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Farid A, Mohsen A, Nasser B, Alaa H, Abdelaziz M, Mustafa M, Mansour M, Adel N, Magdy S, Mohsen S, Adel S, Ibrahim S, Abdel-Rahman S, Mohamed S, El-Karamany Y. Treatment of Staphylococcus aureus-infected diabetic wounds by melatonin loaded nanocarriers. AMB Express 2025; 15:46. [PMID: 40088373 PMCID: PMC11910460 DOI: 10.1186/s13568-025-01854-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Accepted: 02/20/2025] [Indexed: 03/17/2025] Open
Abstract
One of the complication of diabetes mellitus is chronic wounds. The healing of wounds in diabetic patients is retarded by the elevation in the pro-inflammatory cytokines secretion and free radicles accumulation. Wound management in diabetic patients requires preventing bacterial biofilm development. Due to the wound healing activity of chitosan (CS), lecithin (Le) and melatonin (M), the present study aimed to load melatonin on CS/Le NPs and examine their effect on diabetic wounds infected with Staphylococcus aureus. Melatonin loaded chitosan/lecithin nanoparticles (M-CS/Le NPs) were physically characterized and their antioxidant, anti-inflammatory and antimicrobial activities were examined in vitro. Male Sprague Dawley rats included two division (non-diabetic and diabetic) which were further divided in nine groups. Diabetes induction and follow up throughout the experimental period was confirmed by measuring the levels of fructosamine and blood glucose. Full-thickness wounds was induced in both non-diabetic and diabetic animals followed by infection with Staphylococcus aureus according to the experimental design. The wound healing effect of M-CS/Le NPs was evaluated through measurements of the oxidative stress, inflammatory cytokines and apoptotic proteins. Our results showed the anti-microbial, free radical scavenging and hemolysis inhibition effects of M-CS/Le NPs in vitro. Moreover, the preparation of M-CS/Le NPs decreased the dose of used melatonin (when compared to free melatonin). M-CS/Le NPs significantly decreased the wound area percent in treated infected wounds of both non-diabetic and diabetic rats more than free melatonin or unloaded CS/Le NPs. In conclusion, M-CS/Le NPs promoted the wound healing in Staphylococcus aureus-infected wounds in diabetic rats.
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Affiliation(s)
- Alyaa Farid
- Biotechnology Department, Faculty of Science, Cairo University, Giza, Egypt.
| | - Ayah Mohsen
- Biochemistry Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Bassant Nasser
- Biochemistry Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Habiba Alaa
- Biotechnology/Biomolecular chemistry program, Faculty of Science, Cairo University, Giza, Egypt
| | - Mariam Abdelaziz
- Biotechnology/Biomolecular chemistry program, Faculty of Science, Cairo University, Giza, Egypt
| | - Maryam Mustafa
- Biotechnology/Biomolecular chemistry program, Faculty of Science, Cairo University, Giza, Egypt
| | - Mustafa Mansour
- Biotechnology/Biomolecular chemistry program, Faculty of Science, Cairo University, Giza, Egypt
| | - Nourhan Adel
- Biochemistry Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Salma Magdy
- Biotechnology/Biomolecular chemistry program, Faculty of Science, Cairo University, Giza, Egypt
| | - Salma Mohsen
- Biotechnology/Biomolecular chemistry program, Faculty of Science, Cairo University, Giza, Egypt
| | - Samah Adel
- Biochemistry Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Sarah Ibrahim
- Biochemistry Department, Faculty of Science, Cairo University, Giza, Egypt
| | | | - Sohaila Mohamed
- Biochemistry Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Yomna El-Karamany
- Biotechnology/Biomolecular chemistry program, Faculty of Science, Cairo University, Giza, Egypt
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Ko RF, Davidson OQC, Ahmed MA, Clark RM, Brandenburg JS, Pankratz VS, Sharma G, Hathaway HJ, Prossnitz ER, Howdieshell TR. GPER deficiency impedes murine myocutaneous revascularization and wound healing. Sci Rep 2024; 14:18400. [PMID: 39117675 PMCID: PMC11310200 DOI: 10.1038/s41598-024-68620-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 07/25/2024] [Indexed: 08/10/2024] Open
Abstract
Estrogens regulate numerous physiological and pathological processes, including wide-ranging effects in wound healing. The effects of estrogens are mediated through multiple estrogen receptors (ERs), including the classical nuclear ERs (ERα and ER β ), that typically regulate gene expression, and the 7-transmembrane G protein-coupled estrogen receptor (GPER), that predominantly mediates rapid "non-genomic" signaling. Estrogen modulates the expression of various genes involved in epidermal function and regeneration, inflammation, matrix production, and protease inhibition, all critical to wound healing. Our previous work demonstrated improved myocutaneous wound healing in female mice compared to male mice. In the current study, we employed male and female GPER knockout mice to investigate the role of this estrogen receptor in wound revascularization and tissue viability. Using a murine myocutaneous flap model of graded ischemia, we measured real-time flap perfusion via laser speckle perfusion imaging. We conducted histologic and immunohistochemical analyses to assess skin and muscle viability, microvascular density and vessel morphology. Our results demonstrate that GPER is crucial in wound healing, mediating effects that are both dependent and independent of sex. Lack of GPER expression is associated with increased skin necrosis, reduced flap perfusion and altered vessel morphology. These findings contribute to understanding GPER signaling in wound healing and suggest possible therapeutic opportunities by targeting GPER.
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Affiliation(s)
- Randy F Ko
- Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA
| | - Oliver Q C Davidson
- Department of Surgery, Augusta University/University of Georgia Medical Partnership, Athens, GA, 30602, USA
| | - Michael A Ahmed
- Department of Surgery, Augusta University/University of Georgia Medical Partnership, Athens, GA, 30602, USA
| | - Ross M Clark
- Department of Surgery, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA
- Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA
| | - Jacquelyn S Brandenburg
- Department of Surgery, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA
| | - Vernon S Pankratz
- Division of Epidemiology, Biostatistics, and Preventive Medicine Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA
| | - Geetanjali Sharma
- Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA
| | - Helen J Hathaway
- Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA
- University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA
| | - Eric R Prossnitz
- Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA.
- University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA.
- Center of Biomedical Research Excellence in Autophagy, Inflammation and Metabolism, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA.
| | - Thomas R Howdieshell
- Department of Surgery, Augusta University/University of Georgia Medical Partnership, Athens, GA, 30602, USA.
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Moore SE, Davey CH, Morgan M, Webel A. Symptoms, Lifetime Duration of Estrogen Exposure, and Ovarian Reserve Among Women Living With HIV: A Cross-Sectional Observational Study. J Assoc Nurses AIDS Care 2024; 35:264-280. [PMID: 38949903 PMCID: PMC11221577 DOI: 10.1097/jnc.0000000000000463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/03/2024]
Abstract
ABSTRACT This cross-sectional observational study examined associations among symptom burden, lifetime duration of estrogen exposure, and serum antimüllerian hormone (AMH) levels among women living with HIV (n = 98) using bivariate bias-corrected Pearson correlations and multiple correspondence analyses. The mostly Black (85.6%) sample of women, with a mean age of 50 years (SD 12.6 years), exhibited no significant reproductive history factors and symptom burden interrelationships or significant associations between lifetime duration of estrogen exposure and symptoms. Predictably, serum AMH levels were lower among older women; however, less predictable were its significant relationships with months living with HIV (r = -0.362), months on ART (r = -0.270), and CD4+ T-cell nadir (r = 0.347). Symptom-symptom relationships support a fatigue, pain, sleep, anxiety, and depression symptom cluster. The hypotheses were not supported by cross-sectional observation. Further studies should explore variation in relationships between HIV, estrogen exposure, ovarian reserve, and AMH levels over time.
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Affiliation(s)
- Scott Emory Moore
- Scott Emory Moore, PhD, MSN, RN, AGPCNP-BC, FAAN, is an Assistant Professor, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA
- Christine Horvat Davey, PhD, RN, is an Assistant Professor, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA
- Michael Morgan, BS, is an Outreach & Recruitment Coordinator in the AIDS Clinical Trials Unit, Case Western Reserve University/University Hospitals, Cleveland, Ohio, USA
- Allison Webel, PhD, RN, FAAN, is the Interim Robert G. and Jean A. Reid Executive Dean, and is the Aljoya Endowed Professor in Aging University of Washington School of Nursing, Seattle, Washington, USA
| | - Christine Horvat Davey
- Scott Emory Moore, PhD, MSN, RN, AGPCNP-BC, FAAN, is an Assistant Professor, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA
- Christine Horvat Davey, PhD, RN, is an Assistant Professor, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA
- Michael Morgan, BS, is an Outreach & Recruitment Coordinator in the AIDS Clinical Trials Unit, Case Western Reserve University/University Hospitals, Cleveland, Ohio, USA
- Allison Webel, PhD, RN, FAAN, is the Interim Robert G. and Jean A. Reid Executive Dean, and is the Aljoya Endowed Professor in Aging University of Washington School of Nursing, Seattle, Washington, USA
| | - Michael Morgan
- Scott Emory Moore, PhD, MSN, RN, AGPCNP-BC, FAAN, is an Assistant Professor, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA
- Christine Horvat Davey, PhD, RN, is an Assistant Professor, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA
- Michael Morgan, BS, is an Outreach & Recruitment Coordinator in the AIDS Clinical Trials Unit, Case Western Reserve University/University Hospitals, Cleveland, Ohio, USA
- Allison Webel, PhD, RN, FAAN, is the Interim Robert G. and Jean A. Reid Executive Dean, and is the Aljoya Endowed Professor in Aging University of Washington School of Nursing, Seattle, Washington, USA
| | - Allison Webel
- Scott Emory Moore, PhD, MSN, RN, AGPCNP-BC, FAAN, is an Assistant Professor, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA
- Christine Horvat Davey, PhD, RN, is an Assistant Professor, Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA
- Michael Morgan, BS, is an Outreach & Recruitment Coordinator in the AIDS Clinical Trials Unit, Case Western Reserve University/University Hospitals, Cleveland, Ohio, USA
- Allison Webel, PhD, RN, FAAN, is the Interim Robert G. and Jean A. Reid Executive Dean, and is the Aljoya Endowed Professor in Aging University of Washington School of Nursing, Seattle, Washington, USA
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Zhong Y, Zhou L, Guo Y, Wang F, He F, Cheng Y, Meng X, Xie H, Zhang Y, Li J. Downregulated SPESP1-driven fibroblast senescence decreases wound healing in aged mice. Clin Transl Med 2024; 14:e1660. [PMID: 38764260 PMCID: PMC11103130 DOI: 10.1002/ctm2.1660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 03/23/2024] [Accepted: 04/02/2024] [Indexed: 05/21/2024] Open
Abstract
BACKGROUND Human dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin. METHODS The expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography-mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1-induced senescent HDFs in wound healing. RESULTS Here, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl-binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin. CONCLUSIONS Taken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti-ageing strategies and improve wound healing in the elderly.
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Affiliation(s)
- Yun Zhong
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
| | - Lei Zhou
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Department of DermatologyThe Third Affiliated HospitalSun Yat‐sen UniversityGuangzhouPeoples Republic of China
| | - Yi Guo
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
| | - Fan Wang
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
| | - Fanping He
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
| | - Yufan Cheng
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
| | - Xin Meng
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
| | - Hongfu Xie
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
| | - Yiya Zhang
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanPeoples Republic of China
| | - Ji Li
- Department of DermatologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- Hunan Key Laboratory of Aging BiologyXiangya HospitalCentral South UniversityChangshaPeoples Republic of China
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanPeoples Republic of China
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5
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Uyar I, Aksam E, Kopal C. Nasal Sill Flap for Lip Lifting. Facial Plast Surg 2024; 40:106-111. [PMID: 37402393 DOI: 10.1055/s-0043-1770764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/06/2023] Open
Abstract
BACKGROUND Over the years, different techniques have been developed to reduce the number of incisions and scars in subnasal lip lifting and to increase the amount of lifting. The aim of this study was to present a new technique to hide the scars at the nasal base in subnasal lip lifting procedures and to review the literature. METHODS The file of patients who underwent subnasal lip lifting between January 2019 and January 2021 were examined. In all patients, the nasal sill flap that was designed was elevated, and the nasal sill flap that was prepared was adapted to its new location when the excision had been completed. Two different plastic surgeons evaluated the patients in the postoperative 12-month follow-ups. The scars were evaluated for vascularity, pigmentation, elasticity, thickness, and height. RESULTS The study included 26 patients. While 21 patients had no histories of lip lifting, five patients had had previous lip lifting history. The mean operation time was 37.11 minutes. Patients' skin types were determined as Type 3 in 18 patients and Type 4 in eight patients according to the Fitzpatrick classification. The mean follow-up period of the patients was 13.11 months. At the end of the 12-month period, the mean scar score of the patients was calculated as 11.15. The mean scar score of primary cases was 11.14, and the mean scar score of secondary cases was 11.20 (p = 0.983). There was no statistically significant difference in terms of complications among smokers (p = 0.356). The mean scar score was calculated as 12.17 in patients who had Type 3 skin and 8.88 in patients with Type 4 skin (p = 0.075). CONCLUSIONS This technique is beneficial for patients because the scars are discrete and easier for patients to accept.
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Affiliation(s)
- Ilker Uyar
- Department of Plastic, Reconstructive and Aesthetic Surgery, Izmir Katip Celebi University Medical Faculty, Izmir, Turkey
| | - Ersin Aksam
- Department of Plastic, Reconstructive and Aesthetic Surgery, Izmir Katip Celebi University Medical Faculty, Izmir, Turkey
| | - Can Kopal
- Private Practice, Kultur Mah. Sair Esref Bul. No:61 Bahar Apartmanı K:2 D:5 Alsancak/Izmir, Turkey
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Kaneko H, Maezawa Y, Tsukagoshi‐Yamaguchi A, Koshizaka M, Takada‐Watanabe A, Nakamura R, Funayama S, Aono K, Teramoto N, Sawada D, Maeda Y, Minamizuka T, Hayashi A, Ide K, Ide S, Shoji M, Kitamoto T, Takemoto M, Kato H, Yokote K. Sex differences in symptom presentation and their impact on diagnostic accuracy in Werner syndrome. Geriatr Gerontol Int 2024; 24:161-167. [PMID: 38062994 PMCID: PMC11503585 DOI: 10.1111/ggi.14752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 10/27/2023] [Accepted: 11/09/2023] [Indexed: 01/05/2024]
Abstract
AIM Whether sex differences exist in hereditary progeroid syndromes remains unclear. In this study, we investigated sex differences in patients with Werner syndrome (WS), a model of human aging, using patient data at the time of diagnosis. METHODS The presence of six cardinal signs in the diagnostic criteria was retrospectively evaluated. RESULTS We found that the percentage of patients with all cardinal signs was higher in males than in females (54.2% vs. 21.2%). By the age of 40 years, 57.1% of male patients with WS presented with all the cardinal signs, whereas none of the female patients developed all of them. In particular, the frequency of having a high-pitched, hoarse voice, a characteristic of WS, was lower in female patients. The positive and negative predictive values for clinical diagnosis were 100% for males and females, indicating the helpfulness of diagnostic criteria regardless of sex. More female patients than male (86.7% vs. 64%) required genetic testing for their diagnosis because their clinical symptoms were insufficient, suggesting the importance of genetic testing for females even if they do not show typical symptoms of WS. Finally, the frequency of abnormal voice was lower in patients with WS harboring the c.3139-1G > C homozygous mutation. CONCLUSION These results indicate, for the first time, that there are sex differences in the phenotypes of hereditary progeroid syndromes. The analysis of this mechanism in this human model of aging may lead to the elucidation of sex differences in the various symptoms of normal human aging. Geriatr Gerontol Int 2024; 24: 161-167.
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Affiliation(s)
- Hiyori Kaneko
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Yoshiro Maezawa
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Ayano Tsukagoshi‐Yamaguchi
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Masaya Koshizaka
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Aki Takada‐Watanabe
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Rito Nakamura
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Shinichiro Funayama
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Kazuto Aono
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Naoya Teramoto
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Daisuke Sawada
- Department of PediatricsChiba University Graduate School of MedicineChibaJapan
| | - Yukari Maeda
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Takuya Minamizuka
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Aiko Hayashi
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Kana Ide
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Shintaro Ide
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Mayumi Shoji
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Takumi Kitamoto
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Minoru Takemoto
- Department of DiabetesMetabolism and Endocrinology, International University of Health and WelfareChibaJapan
| | - Hisaya Kato
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
| | - Koutaro Yokote
- Department of EndocrinologyHematology and Gerontology, Chiba University Graduate School of MedicineChibaJapan
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Wu YW, Wang CY, Cheng NC, Lin HJ, Huang HL, Huang JH, Chen CC, Lee JK, Chen PL, Hsu PC, Wu IH, Yeh JT, Tsai HY, Tzeng YS, Cheng CC, Lin CH, Wu SH, Tan JWH, Wu CH, Hsueh SK, Chang CH, Wu HP, Hsu CH, Yen HT, Lin PC, Lin CH, Tai HC, Chen WJ. 2024 TSOC/TSPS Joint Consensus: Strategies for Advanced Vascular Wound Management in Arterial and Venous Diseases. ACTA CARDIOLOGICA SINICA 2024; 40:1-44. [PMID: 38264067 PMCID: PMC10801419 DOI: 10.6515/acs.202401_40(1).20231220a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 12/20/2023] [Indexed: 01/25/2024]
Abstract
The Taiwan Society of Cardiology (TSOC) and Taiwan Society of Plastic Surgery (TSPS) have collaborated to develop a joint consensus for the management of patients with advanced vascular wounds. The taskforce comprises experts including preventive cardiologists, interventionists, and cardiovascular and plastic surgeons. The consensus focuses on addressing the challenges in diagnosing, treating, and managing complex wounds; incorporates the perfusion evaluation and the advanced vascular wound care team; and highlights the importance of cross-disciplinary teamwork. The aim of this joint consensus is to manage patients with advanced vascular wounds and encourage the adoption of these guidelines by healthcare professionals to improve patient care and outcomes. The guidelines encompass a range of topics, including the definition of advanced vascular wounds, increased awareness, team structure, epidemiology, clinical presentation, medical treatment, endovascular intervention, vascular surgery, infection control, advanced wound management, and evaluation of treatment results. It also outlines a detailed protocol for assessing patients with lower leg wounds, provides guidance on consultation and referral processes, and offers recommendations for various wound care devices, dressings, and products. The 2024 TSOC/TSPS consensus for the management of patients with advanced vascular wounds serves as a catalyst for international collaboration, promoting knowledge exchange and facilitating advancements in the field of advanced vascular wound management. By providing a comprehensive and evidence-based approach, this consensus aims to contribute to improved patient care and outcomes globally.
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Affiliation(s)
- Yen-Wen Wu
- Division of Cardiology, Cardiovascular Medical Center, and Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Graduate Institute of Medicine, Yuan Ze University
| | - Chao-Yung Wang
- Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan
- Institute of Cellular and System Medicine, National Health Research Institute, Zhunan
| | - Nai-Chen Cheng
- Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine
| | - Hung-Ju Lin
- Division of Cardiology, Department of Internal Medicine
- Cardiovascular Center, National Taiwan University Hospital, Taipei
| | - Hsuan-Li Huang
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien
| | - Jih-Hsin Huang
- Division of Cardiovascular Surgery, Cardiovascular Center, Far Eastern Memorial Hospital, New Taipei City
| | - Chun-Chi Chen
- Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan
| | - Jen-Kuang Lee
- Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine
- Division of Cardiology, Department of Internal Medicine
- Department of Internal Medicine
- Department of Laboratory Medicine, National Taiwan University College of Medicine
- Telehealth Center, National Taiwan University Hospital, Taipei
| | - Po-Lin Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Cardiovascular Surgery, Department of Surgery, En Chu Kong Hospital, New Taipei City
- Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei
| | - Po-Chao Hsu
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital
- Faculty of Medicine, Kaohsiung Medical University, Kaohsiung
| | - I-Hui Wu
- Department of Cardiovascular Surgery, National Taiwan University Hospital, College of Medicine, National Taiwan University
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
- Department of Trauma Surgery, National Taiwan University Hospital, Taipei
| | - Jiun-Ting Yeh
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan
| | - Hao-Yuan Tsai
- Division of Cardiology, Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City
| | - Yuan-Sheng Tzeng
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei
- Department of Surgery, Zuoying Armed Forces General Hospital, Kaohsiung
| | - Cheng-Chung Cheng
- Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center
| | - Chia-Hsun Lin
- Division of Cardiovascular Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital
| | - Szu-Hsien Wu
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Jimmy Wei Hwa Tan
- Department of Cardiovascular Surgery, An-Nan Hospital, China Medical University, Tainan
| | - Cheng-Hsueh Wu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei
| | - Shu-Kai Hsueh
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung
| | - Chien-Hwa Chang
- Division of Cardiovascular Surgery, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County
| | - Hsu-Ping Wu
- Cardiovascular Center, MacKay Memorial Hospital, Taipei
| | - Chung-Ho Hsu
- Section of Peripheral Artery Disease, Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, Taichung
| | - Hsu-Ting Yen
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Po-Chang Lin
- Department of Internal Medicine, China Medical University Hospital, Taichung
| | - Chih-Hung Lin
- Department of Plastic Reconstructive Surgery, Chang Gung University of Science and Technology, Taoyuan
| | - Hao-Chih Tai
- Institute of Cellular and System Medicine, National Health Research Institute, Zhunan
| | - Wen-Jone Chen
- Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine
- Division of Cardiology, Department of Internal Medicine
- Department of Emergency Medicine, National Taiwan University College of Medicine and Hospital, Taipei
- Min-Sheng General Hospital, Taoyuan, Taiwan
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8
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Zomer HD, Cooke PS. Targeting estrogen signaling and biosynthesis for aged skin repair. Front Physiol 2023; 14:1281071. [PMID: 38028803 PMCID: PMC10645088 DOI: 10.3389/fphys.2023.1281071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 10/16/2023] [Indexed: 12/01/2023] Open
Abstract
Non-healing skin wounds are disproportionally prevalent in older adults. Current treatments do not account for the particularities of aged skin and result in inadequate outcomes. Overall, healing chronic wounds in the elderly remains a major unmet clinical need. Estrogens play a critical role in reproduction but also have important actions in non-reproductive organs. Estrogen biosynthesis and signaling pathways are locally activated during physiological wound healing, processes that are inhibited in elderly estrogen-deprived skin. Estrogen deprivation has been shown to be a critical mediator of impaired wound healing in both postmenopausal women and aged men, and topical estrogen application reverses age-associated delayed wound healing in both elderly men and women. These data indicate that adequate estrogen biosynthesis and properly regulated estrogen signaling pathways are essential for normal wound healing and can be targeted to optimize tissue repair in the elderly. However, due to fundamental questions regarding how to safely restore estrogen signaling locally in skin wounds, there are currently no therapeutic strategies addressing estrogen deficiency in elderly chronic wounds. This review discusses established and recent literature in this area and proposes the hypothesis that estrogen plays a pleiotropic role in skin aging and that targeting estrogen signaling and biosynthesis could promote skin repair in older adults.
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Affiliation(s)
- Helena D. Zomer
- Department of Physiological Sciences, University of Florida, Gainesville, FL, United States
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9
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Tavelli L, Barootchi S, Stefanini M, Zucchelli G, Giannobile WV, Wang HL. Wound healing dynamics, morbidity, and complications of palatal soft-tissue harvesting. Periodontol 2000 2023; 92:90-119. [PMID: 36583690 DOI: 10.1111/prd.12466] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/17/2022] [Accepted: 05/26/2022] [Indexed: 12/31/2022]
Abstract
Palatal-tissue harvesting is a routinely performed procedure in periodontal and peri-implant plastic surgery. Over the years, several surgical approaches have been attempted with the aim of obtaining autogenous soft-tissue grafts while minimizing patient morbidity, which is considered the most common drawback of palatal harvesting. At the same time, treatment errors during the procedure may increase not only postoperative discomfort or pain but also the risk of developing other complications, such as injury to the greater palatine artery, prolonged bleeding, wound/flap sloughing, necrosis, infection, and inadequate graft size or quality. This chapter described treatment errors and complications of palatal harvesting techniques, together with approaches for reducing patient morbidity and accelerating donor site wound healing. The role of biologic agents, photobiomodulation therapy, local and systemic factors, and genes implicated in palatal wound healing are also discussed.
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Affiliation(s)
- Lorenzo Tavelli
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
- Division of Periodontology, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
| | - Shayan Barootchi
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Martina Stefanini
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | - Giovanni Zucchelli
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | | | - Hom-Lay Wang
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
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10
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Kabir A, Sarkar A, Barui A. Acute and Chronic Wound Management: Assessment, Therapy and Monitoring Strategies. Regen Med 2023. [DOI: 10.1007/978-981-19-6008-6_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
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11
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Rai V, Agrawal DK. Male or female sex: considerations and translational aspects in diabetic foot ulcer research using rodent models. Mol Cell Biochem 2022. [PMID: 36574098 DOI: 10.1007/s11010-022-04642-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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12
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Samy AM, El-Halim MA, El-Sabbagh AH. Micropunch grafting for healing of refractory chronic venous leg ulcers. CHINESE JOURNAL OF PLASTIC AND RECONSTRUCTIVE SURGERY 2022; 4:166-170. [DOI: 10.1016/j.cjprs.2022.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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13
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Kermanian CS, Buote NJ, Bergman PJ. Medicinal Leech Therapy in Veterinary Medicine: A Retrospective Study. J Am Anim Hosp Assoc 2022; 58:303-308. [PMID: 36315858 DOI: 10.5326/jaaha-ms-7146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2021] [Indexed: 06/16/2023]
Abstract
The objective of this study was to report the clinical indications, outcomes, and complications associated with medicinal leech therapy (MLT) in dogs and cats. Medical records (2012-2016) of client-owned dogs (n = 9) and cats (n = 3) treated with MLT at one institution were retrospectively reviewed. Retrieved data included the signalment, indications, physical examination findings, laboratory results, methods of leeching, outcomes, and complications associated with MLT. Following MLT sessions, nine patients (75%) visibly showed clear improvement of the affected tissue. One patient (8%) was euthanized before complete healing owing to pulmonary parenchymal disease. Improvement or appearance of tissue following MLT was not recorded in two patients (17%). Results suggest that MLT may be a safe and effective treatment modality for venous congestion and necrosis in compromised skin flaps and wounds with success in resolving 75% of the lesions in this study. This study is suggestive of the value of MLT when more conventional treatment methods fail in dogs and cats. A data collection form was created for veterinarians to use with the goal of obtaining standardized, objective MLT data for future studies.
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Affiliation(s)
- Celine S Kermanian
- From Small Animal Surgery, The Animal Medical Center, New York, New York (C.S.K.)
| | - Nicole J Buote
- VCA West Los Angeles Animal Hospital, Los Angeles, California (N.J.B.)
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14
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Ma H, Peng Y, Zhang S, Zhang Y, Min P. Effects and Progress of Photo-Crosslinking Hydrogels in Wound Healing Improvement. Gels 2022; 8:609. [PMID: 36286110 PMCID: PMC9601727 DOI: 10.3390/gels8100609] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/15/2022] [Accepted: 09/16/2022] [Indexed: 09/18/2023] Open
Abstract
Wound healing is a dynamic physiological process, including three stages: inflammation, tissue formation, and remodeling. The quality of wound healing is affected by many topical and systemic factors, while any small factor may affect the process. Therefore, improving the quality of wound healing is a complex and arduous challenge. Photo-crosslinking reaction using visible light irradiation is a novel method for hydrogel preparation. Photo-crosslinking hydrogels can be controlled in time and space, and are not interfered by temperature conditions, which have been widely used in the fields of medicine and engineering. This review aims to summarize the application of photo-crosslinking hydrogels in improving the quality of wound healing, mainly including the material design, application mechanism, and effect of photo-crosslinking hydrogels applied in wound healing, followed by the applicable animal models for experimental research. Finally, this review analyzes the clinical application prospects of photo-crosslinking hydrogels in the field of wound healing.
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Affiliation(s)
| | | | | | - Yixin Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China
| | - Peiru Min
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China
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Xiong J, Bonney S, Gonçalves RV, Esposito D. Brassinosteroids control the inflammation, oxidative stress and cell migration through the control of mitochondrial function on skin regeneration. Life Sci 2022; 307:120887. [PMID: 35985505 DOI: 10.1016/j.lfs.2022.120887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 08/11/2022] [Accepted: 08/13/2022] [Indexed: 11/20/2022]
Abstract
INTRODUCTION Brassinosteroids (BRs) are the class of phytohormones with great importance in agriculture and potential diverse effects on human welfare, including skin disease treatment. In this sense, BRs are a promising tool for promoting skin regeneration. AIMS Therefore, the objective of the present work was to analyze the effect of BRs in wound repair, mainly the inflammatory and proliferative phases, and their influence on migratory abilities in human dermal fibroblasts (HDFa), and consequently understand the mitochondrial metabolism. MAIN METHODS We measured nine natural and synthetic BRs for the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We further evaluated the migration activity in HDFa modeling promotion of wound closure after BRs exposure. In addition, we evaluated the 84 gene profiles linked to wound healing response using RT2 Profiler PCR Array and examined cellular bioenergetics using an extracellular flux analyzer. KEY FINDINGS Results showed that LPS-induced cells had around 10 % lower reactive oxygen species and nitric oxide accumulation when treated with some BRs compounds. HDFa treated with homobrassinolide-based and homocastasterone-based compounds resulted in the greatest migratory activity and presents the best results for mitochondrial responses. SIGNIFICANCE Together, these results provided strong evidence for BRs' ability to promote skin health, particularly through contributions to both reducing excessive oxidative stress and controlling the inflammation process resulting in the best HDFa cell migration through the control of mitochondrial function.
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Affiliation(s)
- Jia Xiong
- Plants for Human Health Institute, NC State University, North Carolina Research Campus, 600 Laureate Way, Kannapolis, NC 28081, USA; Department of Animal Science, NC State University, 120 Broughton Drive, Raleigh, NC 27695, USA.
| | - Sierra Bonney
- Plants for Human Health Institute, NC State University, North Carolina Research Campus, 600 Laureate Way, Kannapolis, NC 28081, USA; Department of Animal Science, NC State University, 120 Broughton Drive, Raleigh, NC 27695, USA
| | - Reggiani Vilela Gonçalves
- Plants for Human Health Institute, NC State University, North Carolina Research Campus, 600 Laureate Way, Kannapolis, NC 28081, USA; Department of Animal Biology, Federal University of Viçosa, Avenida Ph. Rolfs, 36.570-000, MG, Brazil.
| | - Debora Esposito
- Plants for Human Health Institute, NC State University, North Carolina Research Campus, 600 Laureate Way, Kannapolis, NC 28081, USA; Department of Animal Science, NC State University, 120 Broughton Drive, Raleigh, NC 27695, USA.
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16
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Hart DA, Nakamura N. Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System. Biomedicines 2022; 10:1570. [PMID: 35884875 PMCID: PMC9313221 DOI: 10.3390/biomedicines10071570] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 06/20/2022] [Accepted: 06/27/2022] [Indexed: 11/16/2022] Open
Abstract
Following most injuries to a musculoskeletal tissue which function in unique mechanical environments, an inflammatory response occurs to facilitate endogenous repair. This is a process that usually yields functionally inferior scar tissue. In the case of such injuries occurring in adults, the injury environment no longer expresses the anabolic processes that contributed to growth and maturation. An injury can also contribute to the development of a degenerative process, such as osteoarthritis. Over the past several years, researchers have attempted to use cellular therapies to enhance the repair and regeneration of injured tissues, including Platelet-rich Plasma and mesenchymal stem/medicinal signaling cells (MSC) from a variety of tissue sources, either as free MSC or incorporated into tissue engineered constructs, to facilitate regeneration of such damaged tissues. The use of free MSC can sometimes affect pain symptoms associated with conditions such as OA, but regeneration of damaged tissues has been challenging, particularly as some of these tissues have very complex structures. Therefore, implanting MSC or engineered constructs into an inflammatory environment in an adult may compromise the potential of the cells to facilitate regeneration, and neutralizing the inflammatory environment and enhancing the anabolic environment may be required for MSC-based interventions to fulfill their potential. Thus, success may depend on first eliminating negative influences (e.g., inflammation) in an environment, and secondly, implanting optimally cultured MSC or tissue engineered constructs into an anabolic environment to achieve the best outcomes. Furthermore, such interventions should be considered early rather than later on in a disease process, at a time when sufficient endogenous cells remain to serve as a template for repair and regeneration. This review discusses how the interface between inflammation and cell-based regeneration of damaged tissues may be at odds, and outlines approaches to improve outcomes. In addition, other variables that could contribute to the success of cell therapies are discussed. Thus, there may be a need to adopt a Precision Medicine approach to optimize tissue repair and regeneration following injury to these important tissues.
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Affiliation(s)
- David A. Hart
- Department of Surgery, Faculty of Kinesiology, McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N 4N1, Canada
- Bone & Joint Health Strategic Clinical Network, Alberta Health Services, Edmonton, AB T5J 3E4, Canada
| | - Norimasa Nakamura
- Institute of Medical Science in Sport, Osaka Health Science University, 1-9-27 Tenma, Kita-ku, Osaka 530-0043, Japan;
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Macedo Silva V, Freitas M, Sousa Magalhães R, Cúrdia Gonçalves T, Boal Carvalho P, Marinho C, Cotter J. Gastrostomy Button Diameter and Length Variations after Percutaneous Endoscopic Gastrostomy: One Size Does Not Fit All. Dig Dis 2022; 41:335-342. [PMID: 35508118 DOI: 10.1159/000524310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 03/23/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Percutaneous endoscopic gastrostomy (PEG) is a useful option for long-term enteral nutrition. Low-profile gastrostomy tubes ("buttons") may afterward be placed in the stomach through the abdominal wall following maturation of the preexisting ostomy. Regular verification is essential since inadequate sizing is associated with accidental exteriorization or food leakage. We aimed to evaluate gastrostomy buttons diameter or length variations on the first year after their placement and possible factors associated with these variations. METHODS We analyzed consecutive PEGs between 2016 and 2018. A minimum follow-up of 12 after gastrostomy button placement was required. Diameter or length variations were assessed in a specialized PEG appointment during the follow-up period. RESULTS Final sample included 94 patients, from which 65 (69.1%) were women, and 29 (30.9%) were men, with a mean age of 76.9 ± 13.3 years. Measurements variations occurred in 44 (46.8%) patients. Diameter variation was significantly more frequent in patients living in a nursing home (OR = 5.43; 95% CI = 1.32-22.27; p = 0.019), patients with previous PEG tube dislodgement (OR = 3.84; 95% CI = 1.21-12.20; p = 0.023), and male patients (OR = 3.50; 95% CI = 1.06-11.49, p = 0.039). Length variation occurred more frequently in patients with a weight change during the follow-up period greater than 5 kg (OR = 3.71; 95% CI = 1.14-12.05; p = 0.029). CONCLUSIONS A significant proportion of patients with gastrostomy buttons required a change in their measurements, especially if male, living in nursing homes, having significant weight changes, or accidental tube exteriorization. This emphasizes the importance of having a specialized PEG appointment to regularly assure the best fitted button for each patient and ultimately guarantee an adequate nutritional intake.
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Affiliation(s)
- Vítor Macedo Silva
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Marta Freitas
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui Sousa Magalhães
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Tiago Cúrdia Gonçalves
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Pedro Boal Carvalho
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Carla Marinho
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - José Cotter
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
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de Paiva Gonçalves V, Steffens JP, Junior CR, Spolidorio LC. Supraphysiological testosterone supplementation improves granulation tissue maturation through angiogenesis in the early phase of a cutaneous wound healing model in rats. Inflamm Res 2022; 71:473-483. [PMID: 35355085 DOI: 10.1007/s00011-022-01553-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 02/10/2022] [Accepted: 02/21/2022] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVE The aim of this study was to evaluate the effects of both testosterone depletion and supraphysiological testosterone supplementation in the early phase of an animal cutaneous wound healing model in comparison with the physiological hormonal condition. MATERIAL AND METHODS Forty rats were distributed into the following four groups: Control, Orchiectomy (OCX), Durateston (Dura) and OCX+Dura. On day 1, the testicles were removed (OCX group) and the rats (Dura group) received a supraphysiological dose (250 mg/kg) of exogenous testosterone weekly. After 15 days a full-thickness excisional skin wound was created in all animals, which was healed by the second intention for 7 days. On day 22, the rats were euthanatized and the wounds were harvested for histopathological evaluation, immunohistochemistry analyses and multiplex immunoassay. One-way ANOVA and post-hoc Tukey tests were performed. RESULTS It was found that the supraphysiological testosterone level increased extracellular matrix deposition, promoted higher blood vessel formation and reduced wound contraction (p < 0.05). Additionally, it also stimulated PCNA-positive fibroblasts and KGF-positive cells (p < 0.05), while orchiectomy reduced the expression of IL-6 and TNF-α and increased VEGF and PDGF (p < 0.05) . CONCLUSION In conclusion, the results provide evidence that supraphysiological testosterone supplementation plays a positive role in the early phase of cutaneous wound healing, thus improving granulation tissue maturation through the enhancement of angiogenesis.
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Affiliation(s)
- Vinícius de Paiva Gonçalves
- Department of Physiology and Pathology, Araraquara School of Dentistry, University of São Paulo State, UNESP, Humaitá St., 1680 - Center, Araraquara, SP, 14801-903, Brazil.
| | - João Paulo Steffens
- Department of Stomatology, Federal University of Paraná, UFPR, Pref. Lothário Meissner Av., 632 - Center, Curitiba, PR, 80210-170, Brazil
| | - Carlos Rossa Junior
- Department of Diagnosis and Surgery, Araraquara School of Dentistry, University of São Paulo State, UNESP, Humaitá St., 1680 - Center, Araraquara, SP, 14801-903, Brazil
| | - Luís Carlos Spolidorio
- Department of Physiology and Pathology, Araraquara School of Dentistry, University of São Paulo State, UNESP, Humaitá St., 1680 - Center, Araraquara, SP, 14801-903, Brazil
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Mukai K, Horike SI, Meguro-Horike M, Nakajima Y, Iswara A, Nakatani T. Topical estrogen application promotes cutaneous wound healing in db/db female mice with type 2 diabetes. PLoS One 2022; 17:e0264572. [PMID: 35271602 PMCID: PMC8912242 DOI: 10.1371/journal.pone.0264572] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 02/13/2022] [Indexed: 11/18/2022] Open
Abstract
Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3–14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1–14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes.
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Affiliation(s)
- Kanae Mukai
- Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan
- * E-mail:
| | - Shin-ichi Horike
- Research Center for Experimental Modeling of Human Disease, Kanazawa University, Ishikawa, Japan
| | - Makiko Meguro-Horike
- Research Center for Experimental Modeling of Human Disease, Kanazawa University, Ishikawa, Japan
| | - Yukari Nakajima
- Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan
| | - Arya Iswara
- Division of Health Sciences, Department of Clinical Nursing, Graduate Course of Nursing Science, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan
| | - Toshio Nakatani
- Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan
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Wilkinson HN, Reubinoff B, Shveiky D, Hardman MJ, Menachem-Zidon OB. Epithelial arginase-1 is a key mediator of age-associated delayed healing in vaginal injury. Front Endocrinol (Lausanne) 2022; 13:927224. [PMID: 36034415 PMCID: PMC9410732 DOI: 10.3389/fendo.2022.927224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 07/22/2022] [Indexed: 11/30/2022] Open
Abstract
Pelvic organ prolapse is a disorder that substantially affects the quality of life of millions of women worldwide. The greatest risk factors for prolapse are increased parity and older age, with the largest group requiring surgical intervention being post-menopausal women over 65. Due to ineffective healing in the elderly, prolapse recurrence rates following surgery remain high. Therefore, there is an urgent need to elucidate the cellular and molecular drivers of poor healing in pelvic floor dysfunction to allow effective management and even prevention. Recent studies have uncovered the importance of Arginase 1 for modulating effective healing in the skin. We thus employed novel in vitro and in vivo vaginal injury models to determine the specific role of Arginase 1 in age-related vaginal repair. Here we show, for the first time, that aged rat vaginal wounds have reduced Arginase 1 expression and delayed healing. Moreover, direct inhibition of Arginase 1 in human vaginal epithelial cells also led to delayed scratch-wound closure. By contrast, activation of Arginase 1 significantly accelerated healing in aged vaginal wounds in vivo, to rates comparable to those in young animals. Collectively, these findings reveal a new and important role for Arginase 1 in mediating effective vaginal repair. Targeting age-related Arginase 1 deficiency is a potential viable therapeutic strategy to promote vaginal healing and reduce recurrence rate after surgical repair of pelvic organ prolapse.
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Affiliation(s)
- Holly N. Wilkinson
- Centre for Biomedicine, Hull York Medical School, University of Hull, Hull, United Kingdom
- *Correspondence: Ofra Ben Menachem-Zidon, ; Holly N. Wilkinson,
| | - Benjamin Reubinoff
- The Hadassah Human Embryonic Stem Cell Research Center and the Goldyne Savad Institute of Gene Therapy, Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- Department of Obstetrics and Gynecology, Hadassah – Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel
| | - David Shveiky
- Department of Obstetrics and Gynecology, Hadassah – Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel
- Section of Female Pelvic Medicine & Reconstructive Surgery, Department of Obstetrics & Gynecology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Matthew J. Hardman
- Centre for Biomedicine, Hull York Medical School, University of Hull, Hull, United Kingdom
| | - Ofra Ben Menachem-Zidon
- The Hadassah Human Embryonic Stem Cell Research Center and the Goldyne Savad Institute of Gene Therapy, Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- *Correspondence: Ofra Ben Menachem-Zidon, ; Holly N. Wilkinson,
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Singh SK, Rupa S. Comparison of Autologous Platelet-Rich Fibrin Matrix and Transplantation of Autologous Noncultured Epidermal Cell Suspension in the Treatment of Chronic Non Healing Ulcer: Randomized Comparative Study. Indian J Dermatol 2022; 67:334-342. [PMID: 36578750 PMCID: PMC9792063 DOI: 10.4103/ijd.ijd_911_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Context Chronic non-healing ulcer causes significant morbidity, high cost and reduced quality of life. Aims To compare autologous platelet-rich fibrin matrix and transplantation of autologous non-cultured epidermal cell suspension in the treatment of chronic non-healing ulcers. Methods The study was single-centre, prospective, randomised comparative study conducted in a tertiary care center in North India. Patients with chronic non-healing ulcer were included and randomly divided into two treatment groups- Group 1: Platelet-rich fibrin matrix (PRFM) procedure was done every 2 weeks with maximum three sittings and in Group 2: Transplantation of autologous noncultured epidermal cell suspension (NCES) procedure was done once. Follow-up was done every 2 weeks for 8 weeks then monthly for up to 5 months to evaluate the healing of the ulcer. The data were analysed by statistical package for social science (SPSS) trial version 22. To find out a significant difference in mean value between groups, the Chi-square test, student's t-test, and Mann-Whitney U test were used. Results A total of 41 patients were included in the study. Complete healing of ulcers occurred in 89.5% of the patients in the PRFM group and 93.8% of the patients in the NCES group at the end of 5 months (P = 0.33). The mean duration of complete healing in PRFM was 1.7 months and in NCES was 2.13 months (P = 0.20). Conclusions Both procedures were effective, and there was no significant difference between the two procedures.
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Affiliation(s)
- Satyendra K. Singh
- From the Department of Dermatology and Venereology, Institute of Medical Sciences, Banaras Hindu University, Uttar Pradesh, India
| | - Sri Rupa
- From the Department of Dermatology and Venereology, Institute of Medical Sciences, Banaras Hindu University, Uttar Pradesh, India,Address for correspondence: Dr. Sri Rupa, Room No. 30, Lady Doctor's Hostel, Banaras Hindu University Campus, Varanasi - 221 005, Uttar Pradesh, India. E-mail:
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Yamaguchi R, Guo X, Zheng J, Zhang J, Han J, Shioya A, Uramoto H, Mochizuki T, Yamada S. PRDX4 Improved Aging-Related Delayed Wound Healing in Mice. J Invest Dermatol 2021; 141:2720-2729. [PMID: 34029576 DOI: 10.1016/j.jid.2021.04.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 03/15/2021] [Accepted: 04/14/2021] [Indexed: 01/09/2023]
Abstract
Aging-related delayed wound healing is an issue of concern worldwide. Oxidative stress is involved in wound healing. Antioxidative enzymes have various roles in this process. PRDX4, a member of the PRDX family, is upregulated after injury. To investigate the effects of PRDX4 on aging-related wound healing, we subjected C57BL/6J (wild-type), human Prdx4‒transgenic (i.e., hPrdx4+/+), Prdx4-knockout (i.e., Prdx4-/y) mice of three age groups (young, adult, and aged) to skin wound formation. The overexpression of PRDX4 accelerated wound healing in adult and aged mice but not in young mice. Aged hPrdx4+/+ mice showed reduced oxidative stress and inflammation, lower numbers of neutrophils, increased macrophage infiltration, increased angiogenesis, and increased GF levels. The granulation tissue of adult and aged hPrdx4+/+ mice was richer in fibroblasts than that in the matched wild-type mice. PRDX4 deficiency was associated with mortality in adult and aged mice. In vitro, the overexpression of PRDX4 promoted the proliferation and migration of fibroblasts derived from adult or aged mice and made fibroblasts more resistant to the cytotoxicity of hydrogen peroxide. PRDX4 is essential for wound healing and can improve the healing process from multiple aspects, suggesting that it may be very beneficial to wound treatment, especially for the elderly.
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Affiliation(s)
- Reimon Yamaguchi
- Department of Pathology and Laboratory Medicine, School of Medicine, Kanazawa Medical University, Uchinada, Japan; Department of Dermatology, School of Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Xin Guo
- Department of Pathology and Laboratory Medicine, School of Medicine, Kanazawa Medical University, Uchinada, Japan.
| | - Jianbo Zheng
- Department of Pathology and Laboratory Medicine, School of Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Jing Zhang
- Department of Pathology and Laboratory Medicine, School of Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Jia Han
- Department of Pathology and Laboratory Medicine, School of Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Akihiro Shioya
- Department of Pathology and Laboratory Medicine, School of Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Hidetaka Uramoto
- Department of Thoracic Surgery, School of Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Takashi Mochizuki
- Department of Dermatology, School of Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Sohsuke Yamada
- Department of Pathology and Laboratory Medicine, School of Medicine, Kanazawa Medical University, Uchinada, Japan
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Crompton RA, Williams H, Campbell L, Hui Kheng L, Saville C, Ansell DM, Reid A, Wong J, Vardy LA, Hardman MJ, Cruickshank SM. An Epidermal-Specific Role for Arginase1 during Cutaneous Wound Repair. J Invest Dermatol 2021; 142:1206-1216.e8. [PMID: 34710388 DOI: 10.1016/j.jid.2021.09.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 09/03/2021] [Accepted: 09/10/2021] [Indexed: 10/20/2022]
Abstract
Nonhealing wounds are a major area of unmet clinical need remaining problematic to treat. Improved understanding of prohealing mechanisms is invaluable. The enzyme arginase1 (ARG1) is involved in prohealing responses, with its role in macrophages best characterized. ARG1 is also expressed by keratinocytes; however, ARG1 function in these critical wound repair cells is not understood. We characterized ARG1 expression in keratinocytes during normal cutaneous repair and reveal de novo temporal and spatial expression at the epidermal wound edge. Interestingly, epidermal ARG1 expression was decreased in both human and murine delayed healing wounds. We therefore generated a keratinocyte-specific ARG1-null mouse model (K14-cre;Arg1fl/fl) to explore arginase function. Wound repair, linked to changes in keratinocyte proliferation, migration, and differentiation, was significantly delayed in K14-cre;Arg1fl/fl mice. Similarly, using the arginase inhibitor N(omega)-hydroxy-nor-L-arginine, human in vitro and ex vivo models further confirmed this finding, revealing the importance of the downstream polyamine pathway in repair. Indeed, restoring the balance in ARG1 activity through the addition of putrescine proved beneficial in wound closure. In summary, we show that epidermal ARG1 plays, to our knowledge, a previously unreported intrinsic role in cutaneous healing, highlighting epidermal ARG1 and the downstream mediators as potential targets for the therapeutic modulation of wound repair.
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Affiliation(s)
- Rachel A Crompton
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
| | - Helen Williams
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
| | - Laura Campbell
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
| | - Lim Hui Kheng
- Skin Research Institute of Singapore, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Charis Saville
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
| | - David M Ansell
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom; Faculty of Life Sciences, School of Chemistry and Bioscience, University of Bradford, Bradford, United Kingdom
| | - Adam Reid
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
| | - Jason Wong
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
| | - Leah A Vardy
- Skin Research Institute of Singapore, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore
| | - Matthew J Hardman
- Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, United Kingdom
| | - Sheena M Cruickshank
- Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
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Extracellular Vesicles in Skin Wound Healing. Pharmaceuticals (Basel) 2021; 14:ph14080811. [PMID: 34451909 PMCID: PMC8400229 DOI: 10.3390/ph14080811] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/13/2021] [Accepted: 08/16/2021] [Indexed: 12/13/2022] Open
Abstract
Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signaling takes part in all four wound healing phases: hemostasis, inflammation, proliferation, and remodeling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration, and treatment of dermal diseases, including the stem cell-derived, plant-derived, and engineered EVs.
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25
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El Mohtadi M, Whitehead K, Dempsey-Hibbert N, Belboul A, Ashworth J. Estrogen deficiency - a central paradigm in age-related impaired healing? EXCLI JOURNAL 2021; 20:99-116. [PMID: 33510594 PMCID: PMC7838826 DOI: 10.17179/excli2020-3210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 01/04/2021] [Indexed: 11/10/2022]
Abstract
Wound healing is a dynamic biological process achieved through four sequential, overlapping phases; hemostasis, inflammation, tissue proliferation and remodeling. For effective wound healing, all four phases must occur in the appropriate order and time frame. It is well accepted that the wound healing process becomes disrupted in the elderly, increasing the propensity of non-healing wound states that can lead to substantial patient morbidity and an enormous financial burden on healthcare systems. Estrogen deprivation in the elderly has been identified as the key driver of age-related delayed wound healing in both genders, with topical and systemic estrogen replacement reversing the detrimental effects of aging on wound repair. Evidence suggests estrogen deprivation may contribute to the development of chronic wound healing states in the elderly but research in this area is somewhat limited, warranting further investigations. Moreover, although the beneficial effects of estrogen on cutaneous healing have been widely explored, the development of estrogen-based treatments to enhance wound repair in the elderly have yet to be widely exploited. This review explores the critical role of estrogen in reversing age-related impaired healing and evaluates the prospect of developing more focused novel therapeutic strategies that enhance wound repair in the elderly via activation of specific estrogen signaling pathways in regenerating tissues, whilst leaving non-target tissues largely unaffected.
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Affiliation(s)
- Mohamed El Mohtadi
- Department of Biology, Edge Hill University, Ormskirk, Lancashire, L39 4QP, UK
| | - Kathryn Whitehead
- Centre for Bioscience, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK
| | - Nina Dempsey-Hibbert
- Centre for Bioscience, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK
| | - Amina Belboul
- Centre for Bioscience, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK
| | - Jason Ashworth
- Centre for Bioscience, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK
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26
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Bagood MD, Gallegos AC, Medina Lopez AI, Pham VX, Yoon DJ, Fregoso DR, Yang HY, Murphy WJ, Isseroff RR. Re-Examining the Paradigm of Impaired Healing in the Aged Murine Excision Wound Model. J Invest Dermatol 2020; 141:1071-1075.e4. [PMID: 33259830 DOI: 10.1016/j.jid.2020.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/22/2020] [Accepted: 10/29/2020] [Indexed: 10/22/2022]
Affiliation(s)
- Michelle D Bagood
- Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA
| | - Anthony C Gallegos
- Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA; Dermatology Section, VA Northern California Health Care System, Sacramento, California, USA
| | - Andrea I Medina Lopez
- Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA; Dermatology Section, VA Northern California Health Care System, Sacramento, California, USA
| | - Vincent X Pham
- Department of Molecular and Cellular Biology, University of California Davis, California, USA
| | - Daniel J Yoon
- Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA; Dermatology Section, VA Northern California Health Care System, Sacramento, California, USA
| | - Daniel R Fregoso
- Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA
| | - Hsin-Ya Yang
- Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA
| | - William J Murphy
- Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA; Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, California, USA
| | - R Rivkah Isseroff
- Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA; Dermatology Section, VA Northern California Health Care System, Sacramento, California, USA.
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27
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Rajesh A, Stuart G, Real N, Ahn J, Tschirley A, Wise L, Hibma M. Depletion of langerin + cells enhances cutaneous wound healing. Immunology 2020; 160:366-381. [PMID: 32307696 DOI: 10.1111/imm.13202] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 04/05/2020] [Accepted: 04/10/2020] [Indexed: 12/14/2022] Open
Abstract
Langerin is a C-type lectin receptor that is expressed on Langerhans cells and langerin-positive dermal dendritic cells in the skin. Little is known about the function of langerin+ cells in wound healing. In this study, the effects of ablation of langerin+ cells on healing of a full-thickness excision wound were investigated using the langerin-DTR depletable mouse. Strikingly, depletion of langerin+ cells resulted in more rapid reduction in wound area. Accelerated wound healing in the langerin+ -cell-depleted group was characterized by enhanced neo-epidermis and granulation tissue formation, and increased cellular proliferation within the newly formed tissues. Accelerated healing in the absence of langerin+ cells was associated with increased levels of granulocyte-macrophage colony-stimulating factor, F4/80+ cells and blood vessels within the granulation tissue. These data support an inhibitory role for langerin+ cells during wound healing. Therapies that suppress langerin+ cells or their function may therefore have utility in progressing the healing of wounds in humans.
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Affiliation(s)
- Aarthi Rajesh
- Department of Pathology, University of Otago, Dunedin, New Zealand
| | - Gabriella Stuart
- Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand
| | - Nicola Real
- Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand
| | - Jenny Ahn
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | | | - Lyn Wise
- Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand
| | - Merilyn Hibma
- Department of Pathology, University of Otago, Dunedin, New Zealand
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28
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Kopcewicz M, Walendzik K, Bukowska J, Kur-Piotrowska A, Machcinska S, Gimble JM, Gawronska-Kozak B. Cutaneous wound healing in aged, high fat diet-induced obese female or male C57BL/6 mice. Aging (Albany NY) 2020; 12:7066-7111. [PMID: 32294622 PMCID: PMC7202484 DOI: 10.18632/aging.103064] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 02/25/2020] [Indexed: 12/26/2022]
Abstract
Since there are limited studies analyzing the impact of age, sex and obesity on cutaneous repair, the current study evaluated excisional skin wound healing as a function of age, sex and diet in C57BL/6 mice subjected to either low (LFD) or high (HFD) fat diet. Older mice accumulated increased body fat relative to younger mice under HFD. Skin wound healing at particular stages was affected by age in the aspect of Tgfβ-1, MCP-1, Mmp-9 and Mmp-13 expression. The most profound, cumulative effect was observed for the combination of two parameters: age and sex. While skin of younger males displayed extremely high collagen 1 and collagen 3 expression, younger females showed exceptionally high Mmp-13 expression at day 3 and 7 after injury. Diet as a single variable modified the thickness of dermis due to increased dermal White Adipose Tissue (dWAT) accumulation in mice fed HFD. The combination of age and diet affected the re-epithelialization and inflammatory response of injured skin. Overall, our data indicate that age has the most fundamental impact although all components (age, sex and diet) contribute to skin repair.
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Affiliation(s)
- Marta Kopcewicz
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
| | - Katarzyna Walendzik
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
| | - Joanna Bukowska
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
| | - Anna Kur-Piotrowska
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
| | - Sylwia Machcinska
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
| | - Jeffrey M Gimble
- LaCell LLC, New Orleans, LA 70112, USA.,Obatala Sciences Inc., New Orleans, LA 70148, USA.,Departments of Medicine, Structural and Cellular Biology, and Surgery and Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Barbara Gawronska-Kozak
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
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Time course analysis of large-scale gene expression in incised muscle using correspondence analysis. PLoS One 2020; 15:e0230737. [PMID: 32210454 PMCID: PMC7094855 DOI: 10.1371/journal.pone.0230737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 03/06/2020] [Indexed: 11/23/2022] Open
Abstract
Studying the time course of gene expression in injured skeletal muscle would help to estimate the timing of injuries. In this study, we investigated large-scale gene expression in incision-injured mouse skeletal muscle by DNA microarray using correspondence analysis (CA). Biceps femoris muscle samples were collected 6, 12, and 24 hours after injury, and RNA was extracted and prepared for microarray analysis. On a 2-dimensional plot by CA, the genes (row score coordinate) located farther from each time series (column score coordinate) had more upregulation at particular times. Each gene was situated in 6 subdivided triangular areas according to the magnitude of the relationship of the fold change (FC) value at each time point compared to the control. In each area, genes for which the ratios of two particular FC values were close to 1 were distributed along the two border lines. There was a tendency for genes whose FC values were almost equal to be distributed near the intersection of these 6 areas. Therefore, the gene marker candidates for estimation of the timing of injuries were detectable according to the location on the CA plot. Moreover, gene sets created by a specific gene and its surrounding genes were composed of genes that showed similar or identical fluctuation patterns to the specific gene. In various analyses on these sets, significant gene ontology term and pathway activity may reflect changes in specific genes. In conclusion, analyses of gene sets based on CA plots is effective for investigation of the time-dependent fluctuation in gene expression after injury.
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30
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Loffredo LF, Coden ME, Berdnikovs S. Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice. Nutrients 2020; 12:nu12020343. [PMID: 32012983 PMCID: PMC7071314 DOI: 10.3390/nu12020343] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 01/22/2020] [Accepted: 01/24/2020] [Indexed: 12/18/2022] Open
Abstract
Allergic airway diseases are accompanied by increased permeability and an inflammatory state of epithelial barriers, which are thought to be susceptible to allergen sensitization. Although exogenous drivers (proteases, allergens) of epithelial barrier disruption and sensitization are well studied, endogenous contributors (diet, xenobiotics, hormones, and metabolism) to allergic sensitization are much less understood. Xenoestrogens are synthetic or natural chemical compounds that have the ability to mimic estrogen and are ubiquitous in the food and water supply of developed countries. By interfering with the estrogen produced by the endocrine system, these compounds have the systemic potential to disrupt the homeostasis of multiple tissues. Our study examined the potential of prototypical xenoestrogen bisphenol A (BPA) to disrupt epithelial homeostasis in vitro and promote allergic responses in vivo. We found that BPA exposure in epithelial cultures in vitro significantly inhibited epithelial cell proliferation and wound healing, as well as promoted the expression of the innate alarmin cytokine TSLP in a time-and dose-dependent manner. In vivo, the exposure to BPA through water supply or inhalation induced a systemic para-inflammatory response by promoting the expression of innate inflammatory mediators in the skin, gut, and airway. In a murine tolerogenic antigen challenge model, chronic systemic exposure to BPA was sufficient to induce airway sensitization to innocuous chicken egg ovalbumin in the complete absence of adjuvants. Mechanistic studies are needed to test conclusively whether endocrine disruptors may play an upstream role in allergic sensitization via their ability to promote a para-inflammatory state.
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Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells. Sci Rep 2020; 10:1281. [PMID: 31992765 PMCID: PMC6987096 DOI: 10.1038/s41598-020-57997-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 08/07/2019] [Indexed: 12/11/2022] Open
Abstract
Endometriosis is estrogen-dependent disorder. Two theories provide the explanations for the increased estrogen production. One is the feed-forward loop model linking inflammation and estrogen production. The more recent model evokes the tissue hypoxia resulting from endometrial debris detached and then regurgitated to the peritoneal cavity. Both models tacitly assume that everything occurs within the endometriotic stromal cells, seemingly without the need for exogenous factors. This study was undertaken to investigate as whether platelets may be responsible for local estrogen overproduction. We employed in vitro experimentation that evaluated the 17β-estradiol (E2) levels in endometriotic stromal cells treated with activated platelets, and the genes and protein expression levels of StAR, HSD3B2, aromatase, and HSD17B1, as well as their upstream genes/proteins such as NF-κB, TGF-β1, HIF-1α, SF-1 and phosphorylated CREB. In addition, we conducted 2 animal experimentations using platelet depletion/infusion and also neutralization of NF-κB and TGF-β1, followed by immunohistochemistry analysis of involved in StAR, HSD3B2, aromatase, and HSD17B1, as well as SF-1 and p-CREB. We found that treatment of endometriotic stromal cells by activated platelets increase the E2 production by 4.5 fold, and concomitant with increased gene and protein expression of StAR, HSD3B2, aromatase, and HSD17B1, the four genes/enzymes important to estrogen synthesis, along with their upstream genes HIF-1α, SF-1 and phosphorylated CREB. Moreover, platelets activate these genes through the activation of NF-κB and/or TGF-β1, and antagonism of either signaling pathway can abolish the induction of the 4 genes and thus increased estrogen production. The two animal experimentations confirmed these changes. Thus, platelets increase the E2 production in endometriotic stromal cells through upregulation of StAR, HSD3B2, aromatase, and HSD17B1 via the activation of NF-κB and/or TGF-β1. These findings provide a yet another compelling piece of evidence that endometriotic lesions are indeed wounds undergoing repeated tissue injury and repair. They strongly indicate that non-hormonal therapeutics for endometriosis is theoretically viable, with anti-platelet therapy being one promising avenue.
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Topical estrogen application to wounds promotes delayed cutaneous wound healing in 80-week-old female mice. PLoS One 2019; 14:e0225880. [PMID: 31774863 PMCID: PMC6881033 DOI: 10.1371/journal.pone.0225880] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 11/14/2019] [Indexed: 01/09/2023] Open
Abstract
Topical estrogen application to wounds is effective in promoting cutaneous wound healing. However, whether it promotes cutaneous wound healing in delayed cutaneous wound healing associated with advanced age remains to be elucidated. This study aimed to evaluate the effect of topical estrogen application to wounds in cutaneous wound healing in 80-week-old female mice. C57BL/6J female mice aged 82–85 and 12 weeks old were submitted to two full-thickness wounds. Mice were divided into four groups: aged group, topical estrogen wound treatment aged group (aged-E), vehicle wound treatment aged group (aged-vehicle), and young group. Wound healing was observed until day 14. In the aged group, wound area ratio (wound area / initial wound area) was significantly higher on days 3–14, ratio of re-epithelialization was significantly lower on day 3 and tended to be lower on day 14, and neutrophil number was significantly higher on day 7 compared with the young group. In contrast, in the aged-E group, wound area ratio was significantly smaller on days 1–14, re-epithelialization ratio was significantly higher on days 3–14, and neutrophil and macrophage number was significantly lower on days 3 and 7 compared with the aged group. These results demonstrate that topical estrogen application to wounds in 80-week-old female mice promoted cutaneous wound healing by reducing wound area and inflammatory response and promoting re-epithelialization.
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Pratsinis H, Mavrogonatou E, Kletsas D. Scarless wound healing: From development to senescence. Adv Drug Deliv Rev 2019; 146:325-343. [PMID: 29654790 DOI: 10.1016/j.addr.2018.04.011] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 03/29/2018] [Accepted: 04/09/2018] [Indexed: 12/21/2022]
Abstract
An essential element of tissue homeostasis is the response to injuries, cutaneous wound healing being the most studied example. In the adults, wound healing aims at quickly restoring the barrier function of the skin, leading however to scar, a dysfunctional fibrotic tissue. On the other hand, in fetuses a scarless tissue regeneration takes place. During ageing, the wound healing capacity declines; however, in the absence of comorbidities a higher quality in tissue repair is observed. Senescent cells have been found to accumulate in chronic unhealed wounds, but more recent reports indicate that their transient presence may be beneficial for tissue repair. In this review data on skin wound healing and scarring are presented, covering the whole spectrum from early embryonic development to adulthood, and furthermore until ageing of the organism.
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35
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Gao X, Petricoin EF, Ward KR, Goldberg SR, Duane TM, Bonchev D, Arodz T, Diegelmann RF. Network proteomics of human dermal wound healing. Physiol Meas 2018; 39:124002. [PMID: 30524050 DOI: 10.1088/1361-6579/aaee19] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVE The healing of wounds is critical in protecting the human body against environmental factors. The mechanisms involving protein expression during this complex physiological process have not been fully elucidated. APPROACH Here, we use reverse-phase protein microarrays (RPPA) involving 94 phosphoproteins to study tissue samples from tubes implanted in healing dermal wounds in seven human subjects tracked over two weeks. We compare the proteomic profiles to proteomes of controls obtained from skin biopsies from the same subjects. MAIN RESULTS Compared to previous proteomic studies of wound healing, our approach focuses on wound tissue instead of wound fluid, and has the sensitivity to go beyond measuring only highly abundant proteins. To study the temporal dynamics of networks involved in wound healing, we applied two network analysis methods that integrate the experimental results with prior knowledge about protein-protein physical and regulatory interactions, as well as higher-level biological processes and associated pathways. SIGNIFICANCE We uncovered densely connected networks of proteins that are up- or down-regulated during human wound healing, as well as their relationships to microRNAs and to proteins outside of our set of targets that we measured with proteomic microarrays.
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Affiliation(s)
- Xi Gao
- Department of Computer Science, School of Engineering, Virginia Commonwealth University, Richmond, VA, United States of America
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Thuraisingam T, Mirmirani P. Erosive Pustular Dermatosis: A Manifestation of Immunosenescence A Report of 8 Cases. Skin Appendage Disord 2018; 4:180-186. [PMID: 30197899 DOI: 10.1159/000484488] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 10/20/2017] [Indexed: 11/19/2022] Open
Abstract
Erosive pustular dermatosis (EPD) is a rare condition of the scalp and legs that is marked by crusted erosions or superficial ulcerations that may result in scarring alopecia and chronic wounds. The condition predominantly affects elderly female as compared to male patients. Its pathogenesis remains poorly understood. The majority of the cases in the literature are from the United Kingdom and continental Europe. In this series, we present 8 North American patients with EPD of the scalp, one of whom also had involvement of the legs and another with the involvement of the face. All our patients were advanced in age and had a predisposition to chronic actinic damage, which are common characteristics of EPD previously reported in the literature. We hypothesize that immunosenescence leads to an aberrant immune response to wound healing and, along with other factors such as a loss of the normal epidermal barrier, ultraviolet damage, and hormonal factors, may contribute to the development of this condition.
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Affiliation(s)
| | - Paradi Mirmirani
- The Permanente Medical Group, Vallejo, CA.,Case Western Reserve University, Cleveland, OH.,University of California, San Francisco, CA, USA
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The effect of estrogen on diabetic wound healing is mediated through increasing the function of various bone marrow-derived progenitor cells. J Vasc Surg 2018; 68:127S-135S. [PMID: 30064832 DOI: 10.1016/j.jvs.2018.04.069] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 04/18/2018] [Indexed: 01/07/2023]
Abstract
OBJECTIVE Endothelial progenitor cells (EPCs) are the key cells of postnatal neovascularization, and mesenchymal stem cells (MSCs) possess pluripotent differentiation capacity and contribute to tissue regeneration and wound healing. Both EPCs and MSCs are critical to the wound repair process, which is hindered in diabetes mellitus. Diabetes has been shown to decrease the function of these progenitor cells, whereas estrogen has beneficial wound healing effects. However, the role of estrogen in modulating EPC and MSC biology in diabetes is unknown. We investigated the effect of estrogen on improving bone marrow (BM)-derived EPC and MSC function using a murine diabetic wound healing model. METHODS Female diabetic db+/db+ and nondiabetic control mice were wounded cutaneously and treated with topical estrogen or placebo cream. On day 5 after wounding, BM cells were harvested to quantify EPC number and colony-forming units of EPCs and MSCs. Wound healing rate was concurrently studied. Vessel density and scar density were then quantified using whole body perfusion and laser confocal microscopy. EPC recruitment was documented by immunohistochemistry to identify CD34- and vascular endothelial growth factor receptor 2-positive cells in the vessel wall. Data were analyzed by analysis of variance. RESULTS Topical estrogen significantly increased colony-forming units of both EPCs and MSCs compared with placebo treatment, indicating improved viability and proliferative ability of these cells. Consistently, increased recruitment of EPCs to diabetic wounds and higher vessel density were observed in estrogen-treated compared with placebo-treated mice. Consequently, topical estrogen significantly accelerated wound healing as early as day 6 after wounding. In addition, scar density resulting from collagen deposition was increased in the estrogen-treated group, reflecting increased MSC activity and differentiation. CONCLUSIONS Estrogen treatment increases wound healing and wound neovascularization in diabetic mice. Our data implicate that these beneficial effects may be mediated through improving the function of BM-derived EPCs and MSCs.
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Williams H, Campbell L, Crompton RA, Singh G, McHugh BJ, Davidson DJ, McBain AJ, Cruickshank SM, Hardman MJ. Microbial Host Interactions and Impaired Wound Healing in Mice and Humans: Defining a Role for BD14 and NOD2. J Invest Dermatol 2018; 138:2264-2274. [PMID: 29723492 DOI: 10.1016/j.jid.2018.04.014] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 03/28/2018] [Accepted: 04/09/2018] [Indexed: 12/15/2022]
Abstract
Chronic wounds cause significant patient morbidity and mortality. A key factor in their etiology is microbial infection, yet skin host-microbiota interactions during wound repair remain poorly understood. Microbiome profiles of noninfected human chronic wounds are associated with subsequent healing outcome. Furthermore, poor clinical healing outcome was associated with increased local expression of the pattern recognition receptor NOD2. To investigate NOD2 function in the context of cutaneous healing, we treated mice with the NOD2 ligand muramyl dipeptide and analyzed wound repair parameters and expression of antimicrobial peptides. Muramyl dipeptide treatment of littermate controls significantly delayed wound repair associated with reduced re-epithelialization, heightened inflammation, and up-regulation of murine β-defensins 1, 3, and particularly 14. We postulated that although murine β-defensin 14 might affect local skin microbial communities, it may further affect other healing parameters. Indeed, exogenously administered murine β-defensin 14 directly delayed mouse primary keratinocyte scratch wound closure in vitro. To further explore the role of murine β-defensin 14 in wound repair, we used Defb14-/- mice and showed they had a global delay in healing in vivo, associated with alterations in wound microbiota. Taken together, these studies suggest a key role for NOD2-mediated regulation of local skin microbiota, which in turn affects chronic wound etiology.
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Affiliation(s)
- Helen Williams
- Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, Manchester, UK
| | - Laura Campbell
- Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, Manchester, UK
| | - Rachel A Crompton
- Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, Manchester, UK
| | - Gurdeep Singh
- Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, Manchester, UK
| | - Brian J McHugh
- Medical Research Council Centre for Inflammation Research at the University of Edinburgh, Edinburgh, UK
| | - Donald J Davidson
- Medical Research Council Centre for Inflammation Research at the University of Edinburgh, Edinburgh, UK
| | - Andrew J McBain
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Sheena M Cruickshank
- Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, Manchester, UK.
| | - Matthew J Hardman
- Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, Manchester, UK
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A Modeling Conundrum: Murine Models for Cutaneous Wound Healing. J Invest Dermatol 2018; 138:736-740. [DOI: 10.1016/j.jid.2017.12.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 12/05/2017] [Accepted: 12/06/2017] [Indexed: 11/21/2022]
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Trenti A, Tedesco S, Boscaro C, Trevisi L, Bolego C, Cignarella A. Estrogen, Angiogenesis, Immunity and Cell Metabolism: Solving the Puzzle. Int J Mol Sci 2018; 19:ijms19030859. [PMID: 29543707 PMCID: PMC5877720 DOI: 10.3390/ijms19030859] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 03/09/2018] [Accepted: 03/13/2018] [Indexed: 12/12/2022] Open
Abstract
Estrogen plays an important role in the regulation of cardiovascular physiology and the immune system by inducing direct effects on multiple cell types including immune and vascular cells. Sex steroid hormones are implicated in cardiovascular protection, including endothelial healing in case of arterial injury and collateral vessel formation in ischemic tissue. Estrogen can exert potent modulation effects at all levels of the innate and adaptive immune systems. Their action is mediated by interaction with classical estrogen receptors (ERs), ERα and ERβ, as well as the more recently identified G-protein coupled receptor 30/G-protein estrogen receptor 1 (GPER1), via both genomic and non-genomic mechanisms. Emerging data from the literature suggest that estrogen deficiency in menopause is associated with an increased potential for an unresolved inflammatory status. In this review, we provide an overview through the puzzle pieces of how 17β-estradiol can influence the cardiovascular and immune systems.
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Affiliation(s)
- Annalisa Trenti
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.
| | - Serena Tedesco
- Venetian Institute of Molecular Medicine, 35129 Padua, Italy.
| | - Carlotta Boscaro
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.
| | - Lucia Trevisi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.
| | - Chiara Bolego
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.
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41
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Estrogen Effects on Wound Healing. Int J Mol Sci 2017; 18:ijms18112325. [PMID: 29099810 PMCID: PMC5713294 DOI: 10.3390/ijms18112325] [Citation(s) in RCA: 118] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 10/30/2017] [Accepted: 11/02/2017] [Indexed: 02/07/2023] Open
Abstract
Wound healing is a physiological process, involving three successive and overlapping phases—hemostasis/inflammation, proliferation, and remodeling—to maintain the integrity of skin after trauma, either by accident or by procedure. Any disruption or unbalanced distribution of these processes might result in abnormal wound healing. Many molecular and clinical data support the effects of estrogen on normal skin homeostasis and wound healing. Estrogen deficiency, for example in postmenopausal women, is detrimental to wound healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment may reverse these effects. Understanding the role of estrogen on skin might provide further opportunities to develop estrogen-related therapy for assistance in wound healing.
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From Inflammation to Current and Alternative Therapies Involved in Wound Healing. Int J Inflam 2017; 2017:3406215. [PMID: 28811953 PMCID: PMC5547704 DOI: 10.1155/2017/3406215] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 06/01/2017] [Accepted: 06/06/2017] [Indexed: 02/08/2023] Open
Abstract
Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential.
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Haffner-Luntzer M, Fischer V, Prystaz K, Liedert A, Ignatius A. The inflammatory phase of fracture healing is influenced by oestrogen status in mice. Eur J Med Res 2017; 22:23. [PMID: 28683813 PMCID: PMC5501454 DOI: 10.1186/s40001-017-0264-y] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 06/22/2017] [Indexed: 12/20/2022] Open
Abstract
Background Fracture healing is known to be delayed in postmenopausal, osteoporotic females under oestrogen-deficient conditions. Confirming this, experimental studies demonstrated impaired callus formation in ovariectomised animals. Oestrogen-deficiency is known to affect the immune system and the inflammatory response during wound healing. Because a balanced immune response is required for proper bone healing, we were interested to ascertain whether the early immune response after facture is affected by oestrogen depletion. Methods To address the above question, female mice received either a bilateral ovariectomy (OVX) or were sham-operated, and femur osteotomy was performed 8 weeks after OVX/sham operation. The effects of OVX on the presence of immune cells and pro-inflammatory cytokines were evaluated by flow cytometry and immunohistochemistry of the fracture calli on days 1 and 3 after fracture. Results One day after fracture, immune cell numbers and populations in the fracture haematoma did not differ between OVX- and sham-mice. However, on day 3 after fracture, OVX-mice displayed significantly greater numbers of neutrophils. Local expression of the oestrogen-responsive and pro-inflammatory cytokine midkine (Mdk) and interleukin-6 (IL-6) expression in the fracture callus were increased in OVX-mice on day 3 after fracture compared with sham-mice, indicating that both factors might be involved in the increased presence of neutrophils. Confirming this, Mdk-antibody treatment decreased the number of neutrophils in the fracture callus and reduced local IL-6 expression in OVX-mice. Conclusions These data indicate that oestrogen-deficiency influences the early inflammatory phase after fracture. This may contribute to delayed fracture healing after oestrogen depletion.
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Affiliation(s)
- Melanie Haffner-Luntzer
- Institute of Orthopaedic Research and Biomechanics, University Medical Centre Ulm, Helmholtzstraße 9, 89081, Ulm, Germany.
| | - Verena Fischer
- Institute of Orthopaedic Research and Biomechanics, University Medical Centre Ulm, Helmholtzstraße 9, 89081, Ulm, Germany
| | - Katja Prystaz
- Institute of Orthopaedic Research and Biomechanics, University Medical Centre Ulm, Helmholtzstraße 9, 89081, Ulm, Germany
| | - Astrid Liedert
- Institute of Orthopaedic Research and Biomechanics, University Medical Centre Ulm, Helmholtzstraße 9, 89081, Ulm, Germany
| | - Anita Ignatius
- Institute of Orthopaedic Research and Biomechanics, University Medical Centre Ulm, Helmholtzstraße 9, 89081, Ulm, Germany
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Wilkinson HN, Hardman MJ. The role of estrogen in cutaneous ageing and repair. Maturitas 2017; 103:60-64. [PMID: 28778334 DOI: 10.1016/j.maturitas.2017.06.026] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Revised: 06/13/2017] [Accepted: 06/22/2017] [Indexed: 01/09/2023]
Abstract
Combined advances in modern medical practice and increased human longevity are driving an ever-expanding elderly population. Females are particularly at risk of age-associated pathology, spending more of their lives in a post-menopausal state. Menopause, denoted by a rapid decline in serum sex steroid levels, accelerates biological ageing across the body's tissues. Post-menopause physiological changes are particularly noticeable in the skin, which loses structural architecture and becomes prone to damage. The sex steroid most widely discussed as an intrinsic contributor to skin ageing and pathological healing is 17β-estradiol (or estrogen), although many others are involved. Estrogen deficiency is detrimental to many wound-healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment widely reverses these effects. Over recent decades, many of the molecular and cellular correlates to estrogen's beneficial effect on normal skin homeostasis and wound healing have been reported. However, disparities still exist, particularly in the context of mechanistic studies investigating estrogen receptor signalling and its potential cellular effects. New molecular techniques, coupled with increased understanding of estrogen in skin biology, will provide further opportunities to develop estrogen receptor-targeted therapeutics.
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Affiliation(s)
- Holly N Wilkinson
- The School of Life Sciences, The University of Hull, Hull, HU6 7RX, United Kingdom.
| | - Matthew J Hardman
- The School of Life Sciences, The University of Hull, Hull, HU6 7RX, United Kingdom.
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Novel Locally Active Estrogens Accelerate Cutaneous Wound Healing-Part 2. Sci Rep 2017; 7:2510. [PMID: 28566747 PMCID: PMC5451472 DOI: 10.1038/s41598-017-02820-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 04/19/2017] [Indexed: 11/19/2022] Open
Abstract
Estrogen deprivation is associated with delayed healing, while estrogen replacement therapy (ERT) accelerates acute wound healing and protects against development of chronic wounds. However, current estrogenic molecules have undesired systemic effects, thus the aim of our studies is to generate new molecules for topic administration that are devoid of systemic effects. Following a preliminary study, the new 17β-estradiol derivatives 1 were synthesized. The estrogenic activity of these novel compounds was evaluated in vitro using the cell line ERE-Luc B17 stably transfected with an ERE-Luc reporter. Among the 17β-estradiol derivatives synthesized, compounds 1e and 1f showed the highest transactivation potency and were therefore selected for the study of their systemic estrogenic activity. The study of these compounds in the ERE-Luc mouse model demonstrated that both compounds lack systemic effects when administered in the wound area. Furthermore, wound-healing experiments showed that 1e displays a significant regenerative and anti-inflammatory activity. It is therefore confirmed that this class of compounds are suitable for topical administration and have a clear beneficial effect on wound healing.
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Gupta V, Yeslev M, Winocour J, Bamba R, Rodriguez-Feo C, Grotting JC, Higdon KK. Aesthetic Breast Surgery and Concomitant Procedures: Incidence and Risk Factors for Major Complications in 73,608 Cases. Aesthet Surg J 2017; 37:515-527. [PMID: 28333172 DOI: 10.1093/asj/sjw238] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Background Major complications following aesthetic breast surgery are uncommon and thus assessment of risk factors is challenging. Objectives To determine the incidence and risk factors of major complications following aesthetic breast surgery and concomitant procedures. Methods A prospective cohort of patients who enrolled into the CosmetAssure (Birmingham, AL) insurance program and underwent aesthetic breast surgery between 2008 and 2013 was identified. Major complications (requiring reoperation, readmission, or emergency room visit) within 30 days of surgery were recorded. Risk factors including age, smoking, body mass index (BMI), diabetes, type of surgical facility, and combined procedures were evaluated. Results Among women, augmentation was the most common breast procedure (n = 41,651, 58.6%) followed by augmentation-mastopexy, mastopexy, and reduction. Overall, major complications occurred in 1.46% with hematoma (0.99%) and infection (0.25%) being most common. Augmentation-mastopexy had a higher risk of complications, particularly infection (relative risk [RR] 1.74, P < 0.01), than single breast procedures. Age was the only significant predictor for hematomas (RR 1.01, P < 0.01). Increasing age (RR 1.02, P = 0.03) and BMI (RR 1.09, P < 0.01) were risk factors for infection. Concomitant abdominoplasty was performed in 4162 (5.8%) female patients and was associated with increased risk of complications compared to breast procedures or abdominoplasty performed alone. Among men, correction of gynecomastia was the most common breast procedure (n = 1613, 64.6%) with a complication rate of 1.80% and smoking as a risk factor (RR 2.73, P = 0.03). Conclusions Incidence of major complications after breast cosmetic surgical procedures is low. Risk factors for major complications include increasing age and BMI. Combining abdominoplasty with any breast procedure increases the risk of major complications. Level of Evidence 2.
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Affiliation(s)
- Varun Gupta
- Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Max Yeslev
- Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Julian Winocour
- Plastic Surgery Fellow, Division of Plastic Surgery, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Ravinder Bamba
- Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - James C Grotting
- Clinical Professor, Division of Plastic Surgery, University of Alabama, Birmingham, AL, USA
| | - K Kye Higdon
- Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
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Chenu C, Adlanmerini M, Boudou F, Chantalat E, Guihot AL, Toutain C, Raymond-Letron I, Vicendo P, Gadeau AP, Henrion D, Arnal JF, Lenfant F. Testosterone Prevents Cutaneous Ischemia and Necrosis in Males Through Complementary Estrogenic and Androgenic Actions. Arterioscler Thromb Vasc Biol 2017; 37:909-919. [PMID: 28360090 DOI: 10.1161/atvbaha.117.309219] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 03/13/2017] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Chronic nonhealing wounds are a substantial medical concern and are associated with morbidity and mortality; thus, new treatment strategies are required. The first step toward personalized/precision medicine in this field is probably in taking sex differences into account. Impaired wound healing is augmented by ischemia, and we previously demonstrated that 17β-estradiol exerts a major preventive effect against ischemia-induced skin flap necrosis in female mice. However, the equivalent effects of testosterone in male mice have not yet been reported. We then investigated the role of steroid hormones in male mice using a skin flap ischemia model. APPROACH AND RESULTS Castrated male mice developed skin necrosis after ischemia, whereas intact or castrated males treated with testosterone were equally protected. Testosterone can (1) activate the estrogen receptor after its aromatization into 17β-estradiol or (2) be reduced into dihydrotestosterone, a nonaromatizable androgen that activates the androgen receptor. We found that dihydrotestosterone protected castrated wild-type mice by promoting skin revascularization, probably through a direct action on resistance arteries, as evidenced using a complementary model of flow-mediated outward remodeling. 17β-estradiol treatment of castrated male mice also strongly protected them from ischemic necrosis through the activation of estrogen receptor-α by increasing skin revascularization and skin survival. Remarkably, 17β-estradiol improved skin survival with a greater efficiency than dihydrotestosterone. CONCLUSIONS Testosterone provides males with a strong protection against cutaneous necrosis and acts through both its estrogenic and androgenic derivatives, which have complementary effects on skin survival and revascularization.
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Affiliation(s)
- Caroline Chenu
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Marine Adlanmerini
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Frederic Boudou
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Elodie Chantalat
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Anne-Laure Guihot
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Céline Toutain
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Isabelle Raymond-Letron
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Patricia Vicendo
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Alain-Pierre Gadeau
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Daniel Henrion
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Jean-François Arnal
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.)
| | - Françoise Lenfant
- From the INSERM U1048, Institut de Médecine Moléculaire de Rangueil, CHU Toulouse, Université Toulouse III Paul-Sabatier, France (C.C., M.A., F.B., E.C., C.T., J.-F.A., F.L.); Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse, France (I.R.-L.); Laboratoire des IMRCP, UMR 5623, Université de Toulouse, Université Paul Sabatier, France (P.V.); INSERM U1034, Université de Bordeaux, Pessac, France (A.-P.G.); and MITOVASC, CARFI, INSERM U1083 and CNRS UMR6214, Université d'Angers, France (A.-L.G., D.H.).
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Trauma and endometriosis. A review. May we explain surgical phenotypes and natural history of the disease? J Gynecol Obstet Hum Reprod 2017; 46:219-227. [PMID: 28403918 DOI: 10.1016/j.jogoh.2016.12.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 11/14/2016] [Accepted: 12/06/2016] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The study was performed to evaluate whether trauma is an initial event of development of endometriosis. METHOD Using Medline database from January 1960 up to December 2014, a systematic review was made of all published studies using the keywords trauma, healing, injury, infection, hyperperistaltism, stretch and endometriosis, adenomyosis and trauma. Studies and review articles written in French and/or in English related to the topic were included and reviewed independently by two authors. RESULTS The role of trauma is well-established for endometriotic lesions diagnosed in surgical scars. Various traumas including delivery, uterine curettage or incision, intraperitoneal hemorrhage, or occult pelvic inflammatory diseases could be involved to explain other localizations of the disease. Many data suggested that the healing process, particularly growth factors and the associated estrogen production, may facilitate the implantation and the growth of ectopic endometrial cells. After the initial, a traumatic event, the phenotype of the disease would depend on the tissue in which the endometriotic lesion grows. CONCLUSIONS The present literature review may support a potential role of a trauma as an initial event of endometriosis.
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Midgley AC, Morris G, Phillips AO, Steadman R. 17β-estradiol ameliorates age-associated loss of fibroblast function by attenuating IFN-γ/STAT1-dependent miR-7 upregulation. Aging Cell 2016; 15:531-41. [PMID: 26931423 PMCID: PMC4854905 DOI: 10.1111/acel.12462] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2016] [Indexed: 12/20/2022] Open
Abstract
Age‐related defects in fibroblast differentiation and functionality were previously shown to be associated with impaired hyaluronan (HA) synthase 2 (HAS2) and epidermal growth factor receptor (EGFR) function, as a result of upregulated microRNA‐7 (miR‐7) expression. In aging fibroblasts, inhibiting miR‐7 prevented the dysregulation of the HA‐mediated CD44/EGFR signaling pathway. Here, we investigated transcriptional upregulation of miR‐7 and implicated the age‐associated over‐activation of JAK/STAT1 as a primary candidate. STAT1 binding sites were identified on the putative miR‐7 promoter and stimulation of fibroblasts with the inflammatory cytokine, interferon‐γ (IFN‐γ), significantly increased miR‐7 transcriptional activity and resulted in upregulated miR‐7 and loss of EGFR. Additionally, we demonstrated a role for the anti‐inflammatory steroid, 17β‐estradiol (E2), in the attenuation of miR‐7 expression. E2 stimulation promoted estrogen receptor (ER) interactions with the miR‐7 putative promoter and suppressed miR‐7 expression. E2 also attenuated STAT1 expression and activity. Furthermore, treatments with E2 restored fibroblast functionality, including proliferation, migration and differentiation, key events in effective wound healing. In light of our findings, we propose that the regulation of miR‐7 by pro‐ and anti‐inflammatory mediators plays a wider role than previously thought. The modulation of fibroblast functions and ultimately wound healing by miR‐7 activators or inhibitors could provide realistic targets for the restoration of chronic wound healing capabilities in the elderly.
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Affiliation(s)
- Adam C. Midgley
- Institute of Nephrology, Wales Kidney Research Unit; Division of Infection and Immunity; Cardiff University; College of Biomedical and Life Sciences; University Hospital of Wales; Heath Park Wales CF14 4XN UK
| | - Glyn Morris
- Institute of Nephrology, Wales Kidney Research Unit; Division of Infection and Immunity; Cardiff University; College of Biomedical and Life Sciences; University Hospital of Wales; Heath Park Wales CF14 4XN UK
| | - Aled O. Phillips
- Institute of Nephrology, Wales Kidney Research Unit; Division of Infection and Immunity; Cardiff University; College of Biomedical and Life Sciences; University Hospital of Wales; Heath Park Wales CF14 4XN UK
| | - Robert Steadman
- Institute of Nephrology, Wales Kidney Research Unit; Division of Infection and Immunity; Cardiff University; College of Biomedical and Life Sciences; University Hospital of Wales; Heath Park Wales CF14 4XN UK
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Ghazizadeh Hashemi SA, Barati B, Mohammadi H, Saeidi M, Bahreini A, Kiani MA. Effect of Topical Estrogen in the Mangement of Traumatic Facial Wounds. IRANIAN JOURNAL OF OTORHINOLARYNGOLOGY 2016; 28:45-9. [PMID: 26878003 PMCID: PMC4735616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
INTRODUCTION Acute skin wound healing is a complicated process comprising various phases. Recent animal studies have shown that steroid sex hormones such as estrogen maybe helpful in the regulation of several pathophysiologic stages that are involved in wound healing. In this study we examined the effects of topical estrogen in the treatment of traumatic facial wounds. MATERIALS AND METHODS Patients referred to Luqman Hospital, Tehran with traumatic wounds were enrolled in this case-control study into two groups of equal size. From the second week of the study, topical estrogen (0.625 mg conjugated topical estrogen ointment) was administered in the case group, while the control group received a Eucerin dressing only. The two groups were then compared in terms of wound healing rate on Day 7,14, and 30. RESULTS Thirty patients with mean age of 16.02+36.23 years were compared in the control and estrogen-treated groups. After treatment, no scars or keloids were observed in either group. The wound area in the estrogen group was lower than that in the control group on Day 14 and 30, but the difference was not significant (P>0.05). Healing rates in the control group on Day 14 (7.1+42.3 vs.50.3+4.9 mm2) and Day 30 (1.9+93.5 vs. + 97.3+0.6 mm2) (were lower than those in the estrogen group, but the differences were not significant (P>0.05). Findings show that the required time for wound healing in the estrogen-treated group was lower than that in the control group, but the difference was not significant (P>0.05). CONCLUSION Based on this study, topical estrogen has no effect on the rate of wound healing or the rate of wound area.
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Affiliation(s)
| | - Behrooz Barati
- Department of Otorhinolaryngology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Hosein Mohammadi
- Department of Otorhinolaryngology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Masumeh Saeidi
- Students Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Abbas Bahreini
- Students Research Committee, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.,Corresponding Author: Department of Pediatrics, Mashhad University of Medical Sciences, Mashhad, Iran. Tel: 05138410137, E-mail:
| | - Mohammad Ali Kiani
- Department of Pediatrics, Mashhad University of Medical Sciences, Mashhad, Iran.
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