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Demeuse J, Mackowiak A, Grifnée E, Massonnet P, Huyghebaert L, Dubrowski T, Peeters S, Goff CL, Cavalier E. Latest Advances in Structural Insights and Quantification Techniques for Type I Collagen Biomarkers: A path toward standardization? Biomark Insights 2025; 20:11772719251336274. [PMID: 40417349 PMCID: PMC12103674 DOI: 10.1177/11772719251336274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 04/01/2025] [Indexed: 05/27/2025] Open
Abstract
With an aging population, the demand for sensitive and specific biomarkers to assess bone turnover has surged. Bone turnover involves 2 key processes: bone formation, during which Type I procollagen is cleaved into Type I collagen and subsequently mineralized into bone, and bone resorption, during which Type I collagen is demineralized and degraded into peptides by cathepsin K. To identify biomarkers that accurately reflect these processes, extensive efforts have been made to characterize the peptides generated during both formation and resorption. Over the years, numerous biomarkers have been discovered for various disorders. However, despite their clinical utility, many of these markers lack specificity. This is due to factors such as the degradation of trimers into monomers, the coexistence of multiple peptide species arising from the unpredictable cleavage of Type I collagen/procollagen by cathepsin K and metalloproteinases, and the lack of assay standardization. Standardization is further hindered by the incomplete characterization of many of these peptides. For accurate assay development, a gold-standard technique like LC-MS/MS is essential, requiring full peptide characterization during method development. This review aims to present recent advances in the characterization of Type I collagen-derived peptides, providing a foundation for improved biomarker standardization and application in clinical practice.
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Affiliation(s)
- Justine Demeuse
- Laboratory of Clinical Chemistry, CIRM, University of Liège, Belgium
| | - Alix Mackowiak
- Laboratory of Clinical Chemistry, CIRM, University of Liège, Belgium
| | - Elodie Grifnée
- Department of Clinical Chemistry, University Hospital of Liège, Belgium
| | | | | | - Thomas Dubrowski
- Department of Clinical Chemistry, University Hospital of Liège, Belgium
| | - Stéphanie Peeters
- Department of Clinical Chemistry, University Hospital of Liège, Belgium
| | - Caroline Le Goff
- Laboratory of Clinical Chemistry, CIRM, University of Liège, Belgium
- Department of Clinical Chemistry, University Hospital of Liège, Belgium
| | - Etienne Cavalier
- Laboratory of Clinical Chemistry, CIRM, University of Liège, Belgium
- Department of Clinical Chemistry, University Hospital of Liège, Belgium
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Le LTT, Chien PN, Trinh TTT, Seo JW, Giang NN, Nga PT, Zhang XR, Jin YX, Nam SY, Heo CY. Evaluating the efficacy of intra-articular polydioxanone (PDO) injections as a novel viscosupplement in osteoarthritis treatment. Life Sci 2025; 361:123303. [PMID: 39662776 DOI: 10.1016/j.lfs.2024.123303] [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: 06/19/2024] [Revised: 11/25/2024] [Accepted: 12/06/2024] [Indexed: 12/13/2024]
Abstract
AIMS Osteoarthritis (OA) is a chronic joint disorder marked by cartilage breakdown, bone alterations, and inflammation, leading to significant pain and disability. Current therapeutic strategies, ranging from lifestyle interventions to pharmacological and surgical treatments, offer limited efficacy and are often accompanied by side effects. This study investigates the potential of Polydioxanone (PDO), a biocompatible synthetic polymer, as a novel intra-articular (IA) viscosupplement in OA. MATERIALS AND METHODS A validated rabbit model of OA was employed to compare the therapeutic effects of IA injections of PDO against established viscosupplements like hyaluronic acid (HA) and Conjuran (CJR). Sixty rabbits with collagenase-induced OA were randomized into four groups, receiving respective treatments over 12 weeks. The effect of PDO was analyzed by histopathological examination, immunofluorescence staining (IF), immunoblotting, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). KEY FINDINGS The histopathological examination revealed substantial improvements in the PDO group's cartilage structure and matrix composition. qRT-PCR, IF staining, and Western Blot showed significant downregulation of matrix metalloproteinases (MMPs) and upregulation of type II collagen (COL II) and aggrecan (ACAN). ELISA results corroborated decreased inflammatory mediators- interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in the PDO-treatment group. SIGNIFICANCE Preliminary results indicate that PDO may enhance cartilage regeneration and reduce inflammation, suggesting it is a viable and superior treatment option for OA. These findings merit further investigation to translate into clinical applications.
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Affiliation(s)
- Linh Thi Thuy Le
- Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Hai Phong University of Medicine and Pharmacy, Haiphong 180000, Viet Nam
| | - Pham Ngoc Chien
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Korean Institute of Nonclinical Study Center, Seongnam 13620, Republic of Korea
| | - Thuy-Tien Thi Trinh
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Korean Institute of Nonclinical Study Center, Seongnam 13620, Republic of Korea
| | - Ji-Won Seo
- Korean Institute of Nonclinical Study Center, Seongnam 13620, Republic of Korea
| | - Nguyen Ngan Giang
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Department of Medical Device Development, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Pham Thi Nga
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Korean Institute of Nonclinical Study Center, Seongnam 13620, Republic of Korea
| | - Xin Rui Zhang
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Yong Xun Jin
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Sun-Young Nam
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Department of Medical Device Development, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
| | - Chan-Yeong Heo
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea; Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Department of Medical Device Development, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Korean Institute of Nonclinical Study Center, Seongnam 13620, Republic of Korea.
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Kacprzak B, Stańczak M, Surmacz J, Hagner-Derengowska M. Biophysics of ACL Injuries. Orthop Rev (Pavia) 2024; 16:126041. [PMID: 39911284 PMCID: PMC11798646 DOI: 10.52965/001c.126041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 11/09/2024] [Indexed: 02/07/2025] Open
Abstract
Anterior Cruciate Ligament (ACL) injuries rank among the most prevalent and severe types of injuries, significantly impacting both athletes and non-athletes alike. These injuries not only result in immediate physical impairment, such as intense pain, substantial swelling, and a marked loss of mobility, but also carry long-term health consequences that can alter a person's quality of life. Chronic pain, persistent instability, and an increased risk of developing osteoarthritis are among the lasting effects that can follow an ACL injury. An in-depth understanding of the biophysics behind ACL injuries is paramount for devising effective prevention and treatment protocols. Biophysics, which combines principles from physics with biological systems, provides crucial insights into the mechanical and structural integrity of the ACL and its susceptibility to injury under various conditions. This systematic review aims to collate and synthesize the current knowledge surrounding the biophysical mechanisms that underlie ACL injuries.
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Affiliation(s)
| | - Mikołaj Stańczak
- AECC University College, Bournemouth, UK
- Rehab Performance, Lublin, Poland
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Wang H, You Q, Kang B, Jing H, Shi Z, Krizkova S, Heger Z, Adam V, Chen X, Li N. Pulling the Rug Out from Under: Biomechanical Microenvironment Remodeling for Induction of Hepatic Stellate Cell Quiescence. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2406590. [PMID: 39410721 DOI: 10.1002/adma.202406590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 08/24/2024] [Indexed: 12/06/2024]
Abstract
Hepatic fibrosis progresses concomitantly with a variety of biomechanical alternations, especially increased liver stiffness. These biomechanical alterations have long been considered as pathological consequences. Recently, growing evidence proposes that these alternations result in the fibrotic biomechanical microenvironment, which drives the activation of hepatic stellate cells (HSCs). Here, an inorganic ascorbic acid-oxidase (AAO) mimicking nanozyme loaded with liquiritigenin (LQ) is developed to trigger remodeling of the fibrotic biomechanical microenvironment. The AAO mimicking nanozyme is able to consume intracellular ascorbic acid, thereby impeding collagen I deposition by reducing its availability. Simultaneously, LQ inhibits the transcription of lysyl oxidase like 2 (LOXL2), thus impeding collagen I crosslinking. Through its synergistic activities, the prepared nanosystem efficiently restores the fibrotic biomechanical microenvironment to a near-normal physiological condition, promoting the quiescence of HSCs and regression of fibrosis. This strategy of remodeling the fibrotic biomechanical microenvironment, akin to "pulling the rug out from under", effectively treats hepatic fibrosis in mice, thereby highlighting the importance of tissue biomechanics and providing a potential approach to improve hepatic fibrosis treatment.
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Affiliation(s)
- Haobo Wang
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, 300072, China
| | - Qing You
- Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, 119074, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore
| | - Bei Kang
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, 300072, China
| | - Huaqing Jing
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, 300072, China
| | - Zhiyuan Shi
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, 300072, China
| | - Sona Krizkova
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, CZ-61300, Czech Republic
| | - Zbynek Heger
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, CZ-61300, Czech Republic
- Center of Advanced Innovation Technologies, Faculty of Materials Science and Technology, VSB - Technical University of Ostrava, Ostrava, CZ-708 00, Czech Republic
| | - Vojtech Adam
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, CZ-61300, Czech Republic
| | - Xiaoyuan Chen
- Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, 119074, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore
- Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore
| | - Nan Li
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, 300072, China
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Li XY, Wang LX, Wang JX, Liu SS, Zhu XJ, Yuan YM, Guo YF, Ge Z, Huang LQ. Dissociated urethral plate Onlay and standard Onlay urethroplasty for mid-distal hypospadias: A comparative study. J Plast Reconstr Aesthet Surg 2024; 98:331-336. [PMID: 39326095 DOI: 10.1016/j.bjps.2024.09.046] [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: 05/21/2024] [Revised: 09/06/2024] [Accepted: 09/10/2024] [Indexed: 09/28/2024]
Abstract
BACKGROUND Urethral plate (UP) reserved Onlay urethroplasty is currently used widely in mid-distal hypospadias. However, for children with 15-30° residual curvature after degloving, only dorsal tunica albuginea plication is performed to correct penile ventral curvature (VC), and long-term follow-up showed a high recurrence rate of penile curvature. We developed a modified Onlay urethroplasty, which dissociates the UP and completely removes the tissue beneath the UP to fully correct penile curvature. Furthermore, we compared it with the standard Onlay urethroplasty to explore its rationality and feasibility. METHODS We prospectively collected clinical data from 68 children with hypospadias who underwent standard or modified Onlay urethroplasty between September 2019 and June 2021, and evaluated the interim outcomes to identify the complications between the two groups. Additionally, we conducted histological examination of the tissue beneath the UP. RESULTS A total of 32 patients underwent modified Onlay urethroplasty. Intraoperative curvature measurements showed that 37.5% (12/32) of the patients had completely straightened their penis after UP dissection and removal of the fibrous tissue beneath it. A total of 36 patients underwent standard Onlay urethroplasty. Totally, five fistulas each were reported in the first and second groups, and the complication rates were 15.6% and 13.9%, respectively (P > 0.05). The histological results showed that the tissue below the UP contains a large amount of collagen, mainly type I collagen. CONCLUSION The dissociated UP Onlay urethroplasty can maximally remove factors limiting penis growth and completely correct penile curvature, without increasing the incidence of postoperative complications. Therefore, we recommend the application of the improved Onlay urethroplasty in children with mid-distal hypospadias.
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Affiliation(s)
- Xiao-Yu Li
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China
| | - Li-Xia Wang
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China
| | - Jia-Xuan Wang
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China
| | - Sai-Sai Liu
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China
| | - Xiao-Jiang Zhu
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China
| | - Yi-Min Yuan
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China
| | - Yun-Fei Guo
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China
| | - Zheng Ge
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China
| | - Li-Qu Huang
- Department of Urology, Children's Hospital of Nanjing Medical University, Jiangsu Provincial Children's Medical Center, Nanjing, Jiangsu, China.
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Yan X, Zhang Q, Ma X, Zhong Y, Tang H, Mai S. The mechanism of biomineralization: Progress in mineralization from intracellular generation to extracellular deposition. JAPANESE DENTAL SCIENCE REVIEW 2023; 59:181-190. [PMID: 37388714 PMCID: PMC10302165 DOI: 10.1016/j.jdsr.2023.06.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 06/01/2023] [Accepted: 06/13/2023] [Indexed: 07/01/2023] Open
Abstract
Biomineralization is a highly regulated process that results in the deposition of minerals in a precise manner, ultimately producing skeletal and dental hard tissues. Recent studies have highlighted the crucial role played by intracellular processes in initiating biomineralization. These processes involve various organelles, such as the endoplasmic reticulum(ER), mitochondria, and lysosomes, in the formation, accumulation, maturation, and secretion of calcium phosphate (CaP) particles. Particularly, the recent in-depth study of the dynamic process of the formation of amorphous calcium phosphate(ACP) precursors among organelles has made great progress in the development of the integrity of the biomineralization chain. However, the precise mechanisms underlying these intracellular processes remain unclear, and they cannot be fully integrated with the extracellular mineralization mechanism and the physicochemical structure development of the mineralization particles. In this review, we aim to focus on the recent progress made in understanding intracellular mineralization organelles' processes and their relationship with the physicochemical structure development of CaP and extracellular deposition of CaP particles.
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Affiliation(s)
- Xin Yan
- Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
- Institute of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Qi Zhang
- Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
- Institute of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Xinyue Ma
- Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
- Institute of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Yewen Zhong
- Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
- Institute of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Hengni Tang
- Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
- Institute of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Sui Mai
- Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
- Institute of Stomatology, Sun Yat-sen University, Guangzhou, China
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Hasselbalch HC, Junker P, Skov V, Kjær L, Knudsen TA, Larsen MK, Holmström MO, Andersen MH, Jensen C, Karsdal MA, Willumsen N. Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms. Cancers (Basel) 2023; 15:4323. [PMID: 37686599 PMCID: PMC10486581 DOI: 10.3390/cancers15174323] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/04/2023] [Accepted: 08/07/2023] [Indexed: 09/10/2023] Open
Abstract
Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) arise due to acquired somatic driver mutations in stem cells and develop over 10-30 years from the earliest cancer stages (essential thrombocythemia, polycythemia vera) towards the advanced myelofibrosis stage with bone marrow failure. The JAK2V617F mutation is the most prevalent driver mutation. Chronic inflammation is considered to be a major pathogenetic player, both as a trigger of MPN development and as a driver of disease progression. Chronic inflammation in MPNs is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). Considering that MPNs are acquired clonal stem cell diseases developing in an inflammatory microenvironment in which the hematopoietic cell populations are progressively replaced by stromal proliferation-"a wound that never heals"-we herein aim to provide a comprehensive review of previous promising research in the field of circulating ECM fragments in the diagnosis, treatment and monitoring of MPNs. We address the rationales and highlight new perspectives for the use of circulating ECM protein fragments as biologically plausible, noninvasive disease markers in the management of MPNs.
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Affiliation(s)
- Hans Carl Hasselbalch
- Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark; (V.S.); (L.K.); (T.A.K.); (M.K.L.)
| | - Peter Junker
- Department of Rheumatology, Odense University Hospital, 5000 Odense, Denmark;
| | - Vibe Skov
- Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark; (V.S.); (L.K.); (T.A.K.); (M.K.L.)
| | - Lasse Kjær
- Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark; (V.S.); (L.K.); (T.A.K.); (M.K.L.)
| | - Trine A. Knudsen
- Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark; (V.S.); (L.K.); (T.A.K.); (M.K.L.)
| | - Morten Kranker Larsen
- Department of Hematology, Zealand University Hospital, 4000 Roskilde, Denmark; (V.S.); (L.K.); (T.A.K.); (M.K.L.)
| | - Morten Orebo Holmström
- National Center for Cancer Immune Therapy, Herlev Hospital, 2730 Herlev, Denmark; (M.O.H.); (M.H.A.)
| | - Mads Hald Andersen
- National Center for Cancer Immune Therapy, Herlev Hospital, 2730 Herlev, Denmark; (M.O.H.); (M.H.A.)
| | - Christina Jensen
- Nordic Bioscience A/S, 2730 Herlev, Denmark; (C.J.); (M.A.K.); (N.W.)
| | - Morten A. Karsdal
- Nordic Bioscience A/S, 2730 Herlev, Denmark; (C.J.); (M.A.K.); (N.W.)
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He Y, Chang Q, Lu F. Oxygen-releasing biomaterials for chronic wounds breathing: From theoretical mechanism to application prospect. Mater Today Bio 2023; 20:100687. [PMID: 37334187 PMCID: PMC10276161 DOI: 10.1016/j.mtbio.2023.100687] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 05/09/2023] [Accepted: 06/01/2023] [Indexed: 06/20/2023] Open
Abstract
Chronic wounds have always been considered as "gordian knots" in medicine, in which hypoxia plays a key role in blocking healing. To address this challenge, although tissue reoxygenation therapy based on hyperbaric oxygen therapy (HBOT) has been performed clinically for several years, the bench to bedside still urges the evolution of oxygen-loading and -releasing strategies with explicit benefits and consistent outcome. The combination of various oxygen carriers with biomaterials has gained momentum as an emerging therapeutic strategy in this field, exhibiting considerable application potential. This review gives an overview of the essential relationship between hypoxia and delayed wound healing. Further, detailed characteristics, preparation methods and applications of various oxygen-releasing biomaterials (ORBMs) will be elaborated, including hemoglobin, perfluorocarbon, peroxide, and oxygen-generating microorganisms, those biomaterials are applied to load, release or generate a vast of oxygen to relieve the hypoxemia and bring the subsequent cascade effect. The pioneering papers regarding to the ORBMs practice are presented and trends toward hybrid and more precise manipulation are summarized.
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9
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Mechanochemistry of collagen. Acta Biomater 2023; 163:50-62. [PMID: 36669548 DOI: 10.1016/j.actbio.2023.01.025] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 01/02/2023] [Accepted: 01/10/2023] [Indexed: 01/18/2023]
Abstract
The collagen molecular family is the result of nearly one billion years of evolution. It is a unique family of proteins, the majority of which provide general mechanical support to biological tissues. Fibril forming collagens are the most abundant collagens in vertebrate animals and are generally found in positions that resist tensile loading. In animals, cells produce fibril-forming collagen molecules that self-assemble into larger structures known as collagen fibrils. Collagen fibrils are the fundamental, continuous, load-bearing elements in connective tissues, but are often further aggregated into larger load-bearing structures, fascicles in tendon, lamellae in cornea and in intervertebral disk. We know that failure to form fibrillar collagen is embryonic lethal, and excessive collagen formation/growth (fibrosis) or uncontrolled enzymatic remodeling (type II collagen: osteoarthritis) is pathological. Collagen is thus critical to vertebrate viability and instrumental in maintaining efficient mechanical structures. However, despite decades of research, our understanding of collagen matrix formation is not complete, and we know still less about the detailed mechanisms that drive collagen remodeling, growth, and pathology. In this perspective, we examine the known role of mechanical force on the formation and development of collagenous structure. We then discuss a mechanochemical mechanism that has the potential to unify our understanding of collagenous tissue assembly dynamics, which preferentially deposits and grows collagen fibrils directly in the path of mechanical force, where the energetics should be dissuasive and where collagen fibrils are most required. We term this mechanism: Mechanochemical force-structure causality. STATEMENT OF SIGNIFICANCE: Our mechanochemical-force structure causality postulate suggests that collagen molecules are components of mechanochemically-sensitive and dynamically-responsive fibrils. Collagen molecules assemble preferentially in the path of applied strain, can be grown in place by mechanical extension, and are retained in the path of force through strain-stabilization. The mechanisms that drive this behavior operate at the level of the molecules themselves and are encoded into the structure of the biomaterial. The concept might change our understanding of structure formation, enhance our ability to treat injuries, and accelerate the development of therapeutics to prevent pathologies such as fibrosis. We suggest that collagen is a mechanochemically responsive dynamic element designed to provide a substantial "material assist" in the construction of adaptive carriers of mechanical signals.
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Della Rocca Y, Fonticoli L, Rajan TS, Trubiani O, Caputi S, Diomede F, Pizzicannella J, Marconi GD. Hypoxia: molecular pathophysiological mechanisms in human diseases. J Physiol Biochem 2022; 78:739-752. [PMID: 35870078 PMCID: PMC9684243 DOI: 10.1007/s13105-022-00912-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/14/2022] [Indexed: 12/01/2022]
Abstract
Abstract
Hypoxia, a low O2 tension, is a fundamental feature that occurs in physiological events as well as pathophysiological conditions, especially mentioned for its role in the mechanism of angiogenesis, glucose metabolism, and cell proliferation/survival. The hypoxic state through the activation of specific mechanisms is an aggravating circumstance commonly noticed in multiple sclerosis, cancer, heart disease, kidney disease, liver disease, lung disease, and in inflammatory bowel disease. On the other hand, hypoxia could play a key role in tissue regeneration and repair of damaged tissues, especially by acting on specific tissue stem cells, but their features may result as a disadvantage when it is concerned for neoplastic stem cells. Furthermore, hypoxia could also have a potential role in tissue engineering and regenerative medicine due to its capacity to improve the performance of biomaterials. The current review aims to highlight the hypoxic molecular mechanisms reported in different pathological conditions to provide an overview of hypoxia as a therapeutic agent in regenerative and molecular therapy.
Graphical abstract
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Affiliation(s)
- Ylenia Della Rocca
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
| | - Luigia Fonticoli
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
| | | | - Oriana Trubiani
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
| | - Sergio Caputi
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
| | - Francesca Diomede
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
| | - Jacopo Pizzicannella
- Cardiology Intensive Care Unit, "Ss. Annunziata" Hospital, ASL02 Lanciano-Vasto-Chieti, Chieti, Italy
| | - Guya Diletta Marconi
- Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
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11
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Suki B, Bates JH, Bartolák-Suki E. Remodeling of the Aged and Emphysematous Lungs: Roles of Microenvironmental Cues. Compr Physiol 2022; 12:3559-3574. [PMID: 35766835 PMCID: PMC11470990 DOI: 10.1002/cphy.c210033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Aging is a slow process that affects all organs, and the lung is no exception. At the alveolar level, aging increases the airspace size with thicker and stiffer septal walls and straighter and thickened collagen and elastic fibers. This creates a microenvironment that interferes with the ability of cells in the parenchyma to maintain normal homeostasis and respond to injury. These changes also make the lung more susceptible to disease such as emphysema. Emphysema is characterized by slow but progressive remodeling of the deep alveolar regions that leads to airspace enlargement and increased but disorganized elastin and collagen deposition. This remodeling has been attributed to ongoing inflammation that involves inflammatory cells and the cytokines they produce. Cellular senescence, another consequence of aging, weakens the ability of cells to properly respond to injury, something that also occurs in emphysema. These factors conspire to make alveolar walls more prone to mechanical failure, which can set emphysema in motion by driving inflammation through immune stimulation by protein fragments. Both aging and emphysema are influenced by microenvironmental conditions such as local inflammation, chemical makeup, tissue stiffness, and mechanical stresses. Although aging and emphysema are not equivalent, they have the potential to influence each other in synergistic ways; aging sets up the conditions for emphysema to develop, while emphysema may accelerate cellular senescence and thus aging itself. This article focuses on the similarities and differences between the remodeled microenvironment of the aging and emphysematous lung, with special emphasis on the alveolar septal wall. © 2022 American Physiological Society. Compr Physiol 12:3559-3574, 2022.
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Affiliation(s)
- Béla Suki
- Department of Biomedical Engineering, Boston University, Boston, Massachusetts
| | - Jason H.T. Bates
- Depatment of Medicine, University of Vermont Larner College of Medicine, Burlington, Vermont
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12
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Malik G, Agarwal T, Costantini M, Pal S, Kumar A. Oxygenation therapies for improved wound healing: Current trends and technologies. J Mater Chem B 2022; 10:7905-7923. [DOI: 10.1039/d2tb01498j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Degree of oxygenation is one of the important parameters governing various processes, including cell proliferation, angiogenesis, extracellular matrix production, and even combating the microbial burden at the wound site, all...
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Xiang ZX, Gong JS, Li H, Shi WT, Jiang M, Xu ZH, Shi JS. Heterologous expression, fermentation strategies and molecular modification of collagen for versatile applications. Crit Rev Food Sci Nutr 2021:1-22. [PMID: 34907819 DOI: 10.1080/10408398.2021.2016599] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Collagen is a kind of high macromolecular protein with unique tissue distribution and distinctive functions in the body. At present, most collagen products are extracted from the tissues and organs of mammals or marine fish. However, this method exhibits several disadvantages, including low efficiency and serious waste generation, which makes it difficult to meet the current market demand. With the rapid development of synthetic biology and the deepening of high-density fermentation technology, the collagen preparation by biosynthesis strategy emerges as the times require. Co-expression with the proline hydroxylase gene can solve the problem of non-hydroxylated collagen, but the yield may be affected. Therefore, improving the expression through molecular modification and dynamic regulation of synthesis is an entry point for future research. Due to the defects in certain properties of the natural collagen, modification of properties would be benefit for meeting the requirements of practical application. In this paper, in-depth investigations on recombinant expression, fermentation, and modification studies of collagen are conducted. Also, it summarizes the research progress of collagen in food, medicine, and beauty industry in recent years. Furthermore, the future development trend and application prospect of collagen are discussed, which would provide guidance for its preparation and application.
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Affiliation(s)
- Zhi-Xiang Xiang
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China
| | - Jin-Song Gong
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China
| | - Heng Li
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China
| | - Wei-Ting Shi
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China
| | - Min Jiang
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China
| | - Zheng-Hong Xu
- National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi, PR China.,Jiangsu Provincial Research Center for Bioactive Product Processing Technology, Jiangnan University, Wuxi, PR China
| | - Jin-Song Shi
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China
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Shin HE, Kim M, Won CW. Association between plasma procollagen type III N-terminal peptide (P3NP) levels and physical performance in elderly men: The Korean Frailty and Aging Cohort Study (KFACS). Exp Gerontol 2021; 154:111523. [PMID: 34425203 DOI: 10.1016/j.exger.2021.111523] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/13/2021] [Accepted: 08/14/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Physical performance decline associated with aging is clinically important in the development of disability in the older population. More recently, procollagen type III N-terminal peptide (P3NP) and synaptosomal-associated protein of 25 kDa (SNAP25) have been suggested as potential biomarkers for physical performance decline. OBJECTIVE The objective of this pilot study was to examine plasma P3NP and SNAP25 levels in relation to muscle mass, strength, and performance status, and to investigate the association of plasma P3NP and SNAP25 levels with sarcopenia components. METHODS Seventy-nine community-dwelling elderly men (mean age: 78.1 ± 3.5 years) were randomly selected and matched by age from the Korean Frailty and Aging Cohort Study. The sample was classified into the "normal," "low muscle mass only," "sarcopenia," and "low physical performance only" groups according to the criteria of the Asian Working Group for Sarcopenia 2019. Estimates and 95% confidence intervals (CIs) of log P3NP and log SNAP25 levels by muscle mass, strength, and performance status were obtained using a generalized linear model. Pearson correlations and multiple linear regression analyses were used to assess the association of log P3NP and log SNAP25 levels with appendicular skeletal muscle mass (ASM) index, handgrip strength, and physical performance. RESULTS Log P3NP levels tended to be associated with low physical performance compared with the normal group (estimate = 0.54; 95% CI = -0.05, 1.14; p = 0.072). Log P3NP levels were inversely associated with physical performance (short physical performance battery and five-times sit-to-stand test) after adjusting for potential confounders (all p < 0.05) and tended to have an inverse association with gait speed (p = 0.078). Log P3NP levels tended to have a positive correlation with the ASM index (r2 = 0.042; p = 0.070), but not with handgrip strength (r2 = 0.0009; p = 0.795). However, no significant association between plasma SNAP25 levels and physical performance was observed. CONCLUSION Plasma P3NP levels might be a potential biomarker for decreased physical performance in elderly men. Further studies with larger sample sizes are needed to confirm our findings.
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Affiliation(s)
- Hyung Eun Shin
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Miji Kim
- Department of Biomedical Science and Technology, College of Medicine, East-West Medical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea.
| | - Chang Won Won
- Elderly Frailty Research Center, Department of Family Medicine, College of Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea.
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15
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Saleh NY, Aboelghar HM, Salem SS, Soliman SE, Elian DM. Relation of Procollagen Type III Amino Terminal Propeptide Level to Sepsis Severity in Pediatrics. CHILDREN-BASEL 2021; 8:children8090791. [PMID: 34572223 PMCID: PMC8470333 DOI: 10.3390/children8090791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/03/2021] [Accepted: 09/07/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Sepsis is still the main etiology of mortality in pediatric intensive care units (PICUs). Therefore, we performed this study to evaluate the value of procollagen Type III amino-terminal propeptide (PIIINP) as a biomarker for sepsis severity diagnosis and mortality. METHOD A prospective study was carried out on 170 critically ill children admitted into the PICU and 100 controls. The performed clinical examinations included calculation of the pediatric risk of mortality. Serum PIIINP was withdrawn from patients at admission and from the controls. RESULTS PIIINP level was significantly more increased in sepsis, severe sepsis, and septic shock than among the controls (p < 0.001). PIIINP was significantly higher in severe sepsis and septic shock (568.3 (32.5-1304.7) and 926.2 (460.6-1370), respectively) versus sepsis (149.5 (29.6-272.9)) (p < 0.001). PIIINP was significantly increased in non-survivors (935.4 (104.6-1370)) compared to survivors (586.5 (29.6-1169)) (p < 0.016). ROC curve analysis exhibited an area under the curve (AUC) of 0.833 for PIIINP, which is predictive for sepsis, while the cut-off point of 103.3 ng/mL had a sensitivity of 88% and specificity of 82%. The prognosis of the AUC curve for PIIINP to predict mortality was 0.651; the cut-off of 490.4 ng/mL had a sensitivity of 87.5% and specificity of 51.6%. CONCLUSIONS PIIINP levels are increased in sepsis, with significantly higher levels in severe sepsis, septic shock, and non-survivors, thus representing a promising biomarker for pediatric sepsis severity and mortality.
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Affiliation(s)
- Nagwan Y. Saleh
- Pediatric Department, Faculty of Medicine, Menoufia University Hospital, Shebin El Kom 32511, Egypt; (H.M.A.); (S.S.S.); (D.M.E.)
- Correspondence: ; Tel.: +20-1003961071
| | - Hesham M. Aboelghar
- Pediatric Department, Faculty of Medicine, Menoufia University Hospital, Shebin El Kom 32511, Egypt; (H.M.A.); (S.S.S.); (D.M.E.)
| | - Sherif S. Salem
- Pediatric Department, Faculty of Medicine, Menoufia University Hospital, Shebin El Kom 32511, Egypt; (H.M.A.); (S.S.S.); (D.M.E.)
| | - Shimaa E. Soliman
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine Menoufia University, Shebin El Kom 32511, Egypt;
- Medical Biochemistry Unit, Department of Pathology, College of Medicine, Qassim University, Qassim 51452, Saudi Arabia
| | - Doaa M. Elian
- Pediatric Department, Faculty of Medicine, Menoufia University Hospital, Shebin El Kom 32511, Egypt; (H.M.A.); (S.S.S.); (D.M.E.)
- Pediatric Department, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
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Alt E, Rothoerl R, Hoppert M, Frank HG, Wuerfel T, Alt C, Schmitz C. First immunohistochemical evidence of human tendon repair following stem cell injection: A case report and review of literature. World J Stem Cells 2021; 13:944-970. [PMID: 34367486 PMCID: PMC8316863 DOI: 10.4252/wjsc.v13.i7.944] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/29/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.
CASE SUMMARY A 66-year-old patient suffered from sPTRCT affecting the right supraspinatus and infraspinatus tendon, caused by a bicycle accident. On day 18 post injury [day 16 post magnetic resonance imaging (MRI) examination] approximately 100 g of abdominal adipose tissue was harvested by liposuction, from which approximately 75 × 106 UA-ADRCs were isolated within 2 h. Then, UA-ADRCs were injected (controlled by biplanar X-ray imaging) adjacent to the injured supraspinatus tendon immediately after isolation. Despite fast clinical recovery, a follow-up MRI examination 2.5 mo post treatment indicated the need for open revision of the injured infraspinatus tendon, which had not been treated with UA-ADRCs. During this operation, a biopsy was taken from the supraspinatus tendon at the position of the injury. A comprehensive, immunohistochemical and microscopic analysis of the biopsy (comprising 13 antibodies) was indicative of newly formed tendon tissue.
CONCLUSION Injection of UA-ADRCs can result in regeneration of injured human tendons by formation of new tendon tissue.
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Affiliation(s)
- Eckhard Alt
- Chairman of the Board, Isarklinikum Munich, Munich 80331, Germany
| | - Ralf Rothoerl
- Department of Spine Surgery, Isarklinikum Munich, Munich 80331, Germany
| | - Matthias Hoppert
- Department for Orthopedics and Trauma Surgery, Isarklinikum Munich, Munich 80331, Germany
| | - Hans-Georg Frank
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
| | - Tobias Wuerfel
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
| | - Christopher Alt
- Director of Science and Research, InGeneron GmbH, Munich 80331, Germany
| | - Christoph Schmitz
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
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Oropallo AR, Serena TE, Armstrong DG, Niederauer MQ. Molecular Biomarkers of Oxygen Therapy in Patients with Diabetic Foot Ulcers. Biomolecules 2021; 11:biom11070925. [PMID: 34206433 PMCID: PMC8301753 DOI: 10.3390/biom11070925] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 06/13/2021] [Accepted: 06/19/2021] [Indexed: 12/28/2022] Open
Abstract
Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) including continuous diffuse oxygen therapy (CDOT) are often utilized to enhance wound healing in patients with diabetic foot ulcerations. High pressure pure oxygen assists in the oxygenation of hypoxic wounds to increase perfusion. Although oxygen therapy provides wound healing benefits to some patients with diabetic foot ulcers, it is currently performed from clinical examination and imaging. Data suggest that oxygen therapy promotes wound healing via angiogenesis, the creation of new blood vessels. Molecular biomarkers relating to tissue inflammation, repair, and healing have been identified. Predictive biomarkers can be used to identify patients who will most likely benefit from this specialized treatment. In diabetic foot ulcerations, specifically, certain biomarkers have been linked to factors involving angiogenesis and inflammation, two crucial aspects of wound healing. In this review, the mechanism of how oxygen works in wound healing on a physiological basis, such as cell metabolism and growth factor signaling transduction is detailed. Additionally, observable clinical outcomes such as collagen formation, angiogenesis, respiratory burst and cell proliferation are described. The scientific evidence for the impact of oxygen on biomolecular pathways and its relationship to the outcomes in clinical research is discussed in this narrative review.
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Affiliation(s)
- Alisha R. Oropallo
- Comprehensive Wound Healing Center and Hyperbarics, Department of Vascular Surgery, Zucker School of Medicine Hofstra/Northwell, Hempstead, NY 11549, USA
- Correspondence: ; Tel.: +1-516-233-3780
| | | | - David G. Armstrong
- Limb Preservation Program, Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA;
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18
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Chen S, Gao C, Yu T, Qu Y, Xiao GG, Huang Z. Bioinformatics Analysis of a Prognostic miRNA Signature and Potential Key Genes in Pancreatic Cancer. Front Oncol 2021; 11:641289. [PMID: 34094925 PMCID: PMC8174116 DOI: 10.3389/fonc.2021.641289] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 03/31/2021] [Indexed: 12/11/2022] Open
Abstract
Background In this study, miRNAs and their critical target genes related to the prognosis of pancreatic cancer were screened based on bioinformatics analysis to provide targets for the prognosis and treatment of pancreatic cancer. Methods R software was used to screen differentially expressed miRNAs (DEMs) and genes (DEGs) downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. A miRNA Cox proportional hazards regression model was constructed based on the miRNAs, and a miRNA prognostic model was generated. The target genes of the prognostic miRNAs were predicted using TargetScan and miRDB and then intersected with the DEGs to obtain common genes. The functions of the common genes were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. A protein-protein interaction (PPI) network of the common genes was constructed with the STRING database and visualized with Cytoscape software. Key genes were also screened with the MCODE and cytoHubba plug-ins of Cytoscape. Finally, a prognostic model formed by the key gene was also established to help evaluate the reliability of this screening process. Results A prognostic model containing four downregulated miRNAs (hsa-mir-424, hsa-mir-3613, hsa-mir-4772 and hsa-mir-126) related to the prognosis of pancreatic cancer was constructed. A total of 118 common genes were enriched in two KEGG pathways and 33 GO functional annotations, including extracellular matrix (ECM)-receptor interaction and cell adhesion. Nine key genes related to pancreatic cancer were also obtained: MMP14, ITGA2, THBS2, COL1A1, COL3A1, COL11A1, COL6A3, COL12A1 and COL5A2. The prognostic model formed by nine key genes also possessed good prognostic ability. Conclusions The prognostic model consisting of four miRNAs can reliably predict the prognosis of patients with pancreatic cancer. In addition, the screened nine key genes, which can also form a reliable prognostic model, are significantly related to the occurrence and development of pancreatic cancer. Among them, one novel miRNA (hsa-mir-4772) and two novel genes (COL12A1 and COL5A2) associated with pancreatic cancer have great potential to be used as prognostic factors and therapeutic targets for this tumor.
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Affiliation(s)
- Shuoling Chen
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, China.,The Second School of Clinical Medicine, Guangdong Medical University, Dongguan, China
| | - Chang Gao
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, China.,Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China
| | - Tianyang Yu
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, China.,Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China
| | - Yueyang Qu
- School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China
| | - Gary Guishan Xiao
- School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China
| | - Zunnan Huang
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, Dongguan, China.,Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China
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19
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Sun Y, Liu Z, Huang L, Shang Y. MiR-144-3p inhibits the proliferation, migration and invasion of lung adenocargen cancer cells by targeting COL11A1. J Chemother 2021; 33:409-419. [PMID: 33845716 DOI: 10.1080/1120009x.2021.1906031] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
This study aimed to investigate the regulatory relationship between miR-144-3p and COL11A1, and to explore its effect on the proliferation, migration and invasion of lung adenocarcinoma (LUAD) cells. A series of methods and experiments were applied. miR-144-3p was downregulated in LUAD tissue and cells, whereas COL11A1 was highly expressed. Overexpressing miR-144-3p inhibited the proliferation, migration and invasion of LUAD cells, which could be reversed by overexpression of COL11A1. Overexpressing miR-144-3p inhibits the proliferation, migration and invasion of LUAD cells by silencing COL11A1.
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Affiliation(s)
- Yahong Sun
- Lung and CriticalLy Ill Emergency Medicine, Department of Haining People's Hospital, Haining, China
| | - Zhihao Liu
- Lung and CriticalLy Ill Emergency Medicine, Department of Haining People's Hospital, Haining, China
| | - Lifei Huang
- Lung and CriticalLy Ill Emergency Medicine, Department of Haining People's Hospital, Haining, China
| | - Yan Shang
- Respiratory and Critical Emergency Medicine, Changhai Hospital, Department of Naval Medical University (Second Military Medical University), Shanghai, China
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20
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Tominaga A, Wada K, Kato Y, Nishi H, Terayama Y, Okazaki K. Early clinical effects, safety, and appropriate selection of bone markers in romosozumab treatment for osteoporosis patients: a 6-month study. Osteoporos Int 2021; 32:653-661. [PMID: 32979066 DOI: 10.1007/s00198-020-05639-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/11/2020] [Indexed: 01/22/2023]
Abstract
UNLABELLED Our 6-month study showed the usefulness of romosozumab for preventing fractures and its safety. It was effective in patients with low baseline spine BMD, high TRACP-5b, and high iP1NP. Percent change from baseline of TRACP-5b and iP1NP after 1 month correlated with that from baseline of BMD after four to 6-month treatment. INTRODUCTION Romosozumab appeared as a new osteoporosis medication in Japan in 2019. It is an anti-sclerostin antibody which increases bone formation and suppresses bone resorption. In this study, we analyzed the actual clinical effects, adverse effects, and the optimal way to evaluate the treatment. METHODS Romosozumab was administered as subcutaneous injection of 210 mg once every 4 weeks. We conducted pre-post study in 185 patients treated for 6 months. We focused on the incidence of new vertebral fractures, safety, bone mineral density (BMD) at the spine and total hip, and bone metabolism markers. We evaluated BMD before romosozumab treatment and after 4 to 6 months and performed the serum analysis before romosozumab treatment, after 1, 3, and 6 months. RESULTS There was no new fracture during treatment, and there was no fatal adverse event including cardiovascular disease. Since percent changes from baseline of the spine and total hip BMD were 6.34% and 1.53% after 4- to 6-month treatment, the treatment was effective for spine osteoporosis. Tartrate-resistant acid phosphatase 5b (TRACP-5b) and intact type I procollagen N-terminal propeptide (iP1NP) had significant changes during romosozumab treatment (p < 0.05). Percent change from baseline of TRACP-5b and iP1NP after 1 month correlated with percent change from baseline of BMD after 4 to 6 months of treatment. CONCLUSION Romosozumab is effective in preventing fractures and useful for increasing the spine BMD. Also, romosozumab is relatively safe to use. It is especially effective in patients with low baseline spine BMD, high TRACP-5b, and high iP1NP.
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Affiliation(s)
- A Tominaga
- Department of Orthopedic Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - K Wada
- Department of Orthopedic Surgery, Tokyo Women's Medical University, Tokyo, Japan.
| | - Y Kato
- Kita Shinagawa 3rd Hospital, Tokyo, Japan
| | - H Nishi
- Hasuda Hospital, Saitama, Japan
| | | | - K Okazaki
- Department of Orthopedic Surgery, Tokyo Women's Medical University, Tokyo, Japan
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21
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Younis I. Dehisced abdominal wall reconstruction. J Wound Care 2021; 29:S29-S30. [PMID: 32427032 DOI: 10.12968/jowc.2020.29.sup5b.s29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Ibby Younis
- Consultant Plastic and Reconstructive Surgeon, Royal Free London NHS Foundation Trust, London, UK
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Xu Y, Kirchner M. Collagen Mimetic Peptides. Bioengineering (Basel) 2021; 8:5. [PMID: 33466358 PMCID: PMC7824840 DOI: 10.3390/bioengineering8010005] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/24/2020] [Accepted: 12/31/2020] [Indexed: 12/20/2022] Open
Abstract
Since their first synthesis in the late 1960s, collagen mimetic peptides (CMPs) have been used as a molecular tool to study collagen, and as an approach to develop novel collagen mimetic biomaterials. Collagen, a major extracellular matrix (ECM) protein, plays vital roles in many physiological and pathogenic processes. Applications of CMPs have advanced our understanding of the structure and molecular properties of a collagen triple helix-the building block of collagen-and the interactions of collagen with important molecular ligands. The accumulating knowledge is also paving the way for developing novel CMPs for biomedical applications. Indeed, for the past 50 years, CMP research has been a fast-growing, far-reaching interdisciplinary field. The major development and achievement of CMPs were documented in a few detailed reviews around 2010. Here, we provided a brief overview of what we have learned about CMPs-their potential and their limitations. We focused on more recent developments in producing heterotrimeric CMPs, and CMPs that can form collagen-like higher order molecular assemblies. We also expanded the traditional view of CMPs to include larger designed peptides produced using recombinant systems. Studies using recombinant peptides have provided new insights on collagens and promoted progress in the development of collagen mimetic fibrillar self-assemblies.
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Affiliation(s)
- Yujia Xu
- Department of Chemistry, Hunter College of the City University of New York, 695 Park Ave., New York, NY 10065, USA;
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23
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Siadat SM, Zamboulis DE, Thorpe CT, Ruberti JW, Connizzo BK. Tendon Extracellular Matrix Assembly, Maintenance and Dysregulation Throughout Life. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1348:45-103. [PMID: 34807415 DOI: 10.1007/978-3-030-80614-9_3] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
In his Lissner Award medal lecture in 2000, Stephen Cowin asked the question: "How is a tissue built?" It is not a new question, but it remains as relevant today as it did when it was asked 20 years ago. In fact, research on the organization and development of tissue structure has been a primary focus of tendon and ligament research for over two centuries. The tendon extracellular matrix (ECM) is critical to overall tissue function; it gives the tissue its unique mechanical properties, exhibiting complex non-linear responses, viscoelasticity and flow mechanisms, excellent energy storage and fatigue resistance. This matrix also creates a unique microenvironment for resident cells, allowing cells to maintain their phenotype and translate mechanical and chemical signals into biological responses. Importantly, this architecture is constantly remodeled by local cell populations in response to changing biochemical (systemic and local disease or injury) and mechanical (exercise, disuse, and overuse) stimuli. Here, we review the current understanding of matrix remodeling throughout life, focusing on formation and assembly during the postnatal period, maintenance and homeostasis during adulthood, and changes to homeostasis in natural aging. We also discuss advances in model systems and novel tools for studying collagen and non-collagenous matrix remodeling throughout life, and finally conclude by identifying key questions that have yet to be answered.
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Affiliation(s)
| | - Danae E Zamboulis
- Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
| | - Chavaunne T Thorpe
- Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK
| | - Jeffrey W Ruberti
- Department of Bioengineering, Northeastern University, Boston, MA, USA
| | - Brianne K Connizzo
- Department of Biomedical Engineering, Boston University, Boston, MA, USA.
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24
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Arauz RF, Byun JS, Tandon M, Sinha S, Kuhn S, Taylor S, Zingone A, Mitchell KA, Pine SR, Gardner K, Perez-Stable EJ, Napoles AM, Ryan BM. Whole-Exome Profiling of NSCLC Among African Americans. J Thorac Oncol 2020; 15:1880-1892. [PMID: 32931935 PMCID: PMC7704928 DOI: 10.1016/j.jtho.2020.08.029] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 08/14/2020] [Accepted: 08/15/2020] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States, especially among men. Although significant progress has been made profiling the genomic makeup of lung cancer in EAs, AAs continue to be underrepresented. Our objective was to chart the genome-wide landscape of somatic mutations in lung cancer tumors from AAs. METHODS In this study, we used the whole-exome sequencing of 82 tumor and noninvolved tissue pairs from AAs. Patients were selected from an ongoing case-control study conducted by the National Cancer Institute and the University of Maryland. RESULTS Among all samples, we identified 178 significantly mutated genes (p < 0.05), five of which passed the threshold for false discovery rate (p < 0.1). In lung adenocarcinoma (LUAD) tumors, mutation rates in STK11 (p = 0.05) and RB1 (p = 0.008) were significantly higher in AA LUAD tumors (25% and 13%, respectively) compared with The Cancer Genome Atlas EA samples (14% and 4%, respectively). In squamous cell carcinomas, mutation rates in STK11 (p = 0.002) were significantly higher among AA (8%) than EA tumors from The Cancer Genome Atlas (1%). Integrated somatic mutation data with CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts) data analysis revealed LUAD tumors from AAs carrying STK11 mutations have decreased interferon signaling. CONCLUSIONS Although a considerable degree of the somatic mutation landscape is shared between EAs and AAs, discrete differences in mutation frequency in potentially important oncogenes and tumor suppressors exist. A better understanding of the molecular basis of lung cancer in AA patients and leveraging this information to guide clinical interventions may help reduce disparities.
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Affiliation(s)
- Rony F Arauz
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Jung S Byun
- Division of Intramural Research, National Institute on Minority Health and Health Disparities, Bethesda, Maryland; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Mayank Tandon
- CCR Collaborative Bioinformatics Resource CCBR, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, Maryland
| | - Sanju Sinha
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Skyler Kuhn
- CCR Collaborative Bioinformatics Resource CCBR, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, Maryland
| | - Sheryse Taylor
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Adriana Zingone
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Khadijah A Mitchell
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Sharon R Pine
- Departments of Pharmacology and Medicine, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey
| | - Kevin Gardner
- National Institute of Minority Health and Health Disparities, Bethesda, Maryland; Department of Pathology and Cell Biology, Columbia University Medical Center, Columbia University, New York, New York
| | | | - Anna M Napoles
- National Institute of Minority Health and Health Disparities, Bethesda, Maryland
| | - Bríd M Ryan
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
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25
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Ribeiro IP, Esteves L, Anjo SI, Marques F, Barroso L, Manadas B, Carreira IM, Melo JB. Proteomics-based Predictive Model for the Early Detection of Metastasis and Recurrence in Head and Neck Cancer. Cancer Genomics Proteomics 2020; 17:259-269. [PMID: 32345667 DOI: 10.21873/cgp.20186] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 02/04/2020] [Accepted: 02/07/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIM Head and neck squamous cell carcinoma (HNSCC) presents high morbidity, an overall poor prognosis and survival, and a compromised quality of life of the survivors. Early tumor detection, prediction of its behavior and prognosis as well as the development of novel therapeutic strategies are urgently needed for a more successful HNSCC management. MATERIALS AND METHODS In this study, a proteomics analysis of HNSCC tumor and non-tumor samples was performed and a model to predict the risk of recurrence and metastasis development was built. RESULTS This predictive model presented good accuracy (>80%) and comprises as variables the tumor staging along with DHB12, HMGB3 and COBA1 proteins. Differences at the intensity levels of these proteins were correlated with the development of metastasis and recurrence as well as with patient's survival. CONCLUSION The translation of proteomic predictive models to routine clinical practice may contribute to a more precise and individualized clinical management of the HNSCC patients, reducing recurrences and improving patients' quality of life. The capability of generalization of this proteomic model to predict the recurrence and metastases development should be evaluated and validated in other HNSCC populations.
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Affiliation(s)
- Ilda Patrícia Ribeiro
- Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.,iCBR-CIMAGO - Center of Investigation on Environment, Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Luísa Esteves
- Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Sandra Isabel Anjo
- CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
| | - Francisco Marques
- iCBR-CIMAGO - Center of Investigation on Environment, Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, Coimbra, Portugal.,Stomatology Unit, Coimbra Hospital and University Centre, CHUC, EPE, Coimbra, Portugal.,Department of Dentistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Leonor Barroso
- Maxillofacial Surgery Department, Coimbra Hospital and University Centre, CHUC, EPE, Coimbra, Portugal
| | - Bruno Manadas
- CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
| | - Isabel Marques Carreira
- Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.,iCBR-CIMAGO - Center of Investigation on Environment, Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, Coimbra, Portugal.,CNC.IBILI, Group of Aging and Brain Diseases: Advanced Diagnosis and Biomarkers, Coimbra, Portugal
| | - Joana Barbosa Melo
- Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Coimbra, Portugal .,iCBR-CIMAGO - Center of Investigation on Environment, Genetics and Oncobiology - Faculty of Medicine, University of Coimbra, Coimbra, Portugal.,CNC.IBILI, Group of Aging and Brain Diseases: Advanced Diagnosis and Biomarkers, Coimbra, Portugal
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Abstract
Rates of peri-prosthetic joint infection (PJI) in primary total hip and total knee arthroplasty range between 0.3% and 1.9%, and up to 10% in revision cases. Significant morbidity is associated with this devastating complication, the economic burden on our healthcare system is considerable, and the personal cost to the affected patient is immeasurable. The risk of surgical site infection (SSI) and PJI is related to surgical factors and patient factors such as age, body mass index (BMI), co-morbidities, and lifestyle. Reducing the risk of SSI in primary hip and knee arthroplasty requires a multi-faceted strategy including pre-operative patient bacterial decolonization, screening and avoidance of anaemia, peri-operative patient warming, skin antisepsis, povidone-iodine wound lavage, and anti-bacterial coated sutures. This article also considers newer concepts such as the influence of bearing surfaces on infection risk, as well as current controversies such as the potential effects of blood transfusion, laminar flow, and protective hoods and suits, on infection risk. Cite this article: EFORT Open Rev 2020;5:604-613. DOI: 10.1302/2058-5241.5.200004
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Affiliation(s)
- Philip F Dobson
- Trauma and Orthopaedic Surgery, Royal Victoria Infirmary, Newcastle, UK
| | - Michael R Reed
- Trauma and Orthopaedic Surgery, Royal Victoria Infirmary, Newcastle, UK
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27
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The significance of stromal collagen organization in cancer tissue: An in-depth discussion of literature. Crit Rev Oncol Hematol 2020; 151:102907. [DOI: 10.1016/j.critrevonc.2020.102907] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 02/09/2020] [Accepted: 02/10/2020] [Indexed: 12/12/2022] Open
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28
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Doan ND, Hosseini AS, Bikovtseva AA, Huang MS, DiChiara AS, Papa LJ, Koller A, Shoulders MD. Elucidation of proteostasis defects caused by osteogenesis imperfecta mutations in the collagen-α2(I) C-propeptide domain. J Biol Chem 2020; 295:9959-9973. [PMID: 32482890 DOI: 10.1074/jbc.ra120.014071] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/26/2020] [Indexed: 01/07/2023] Open
Abstract
Intracellular collagen assembly begins with the oxidative folding of ∼30-kDa C-terminal propeptide (C-Pro) domains. Folded C-Pro domains then template the formation of triple helices between appropriate partner strands. Numerous C-Pro missense variants that disrupt or delay triple-helix formation are known to cause disease, but our understanding of the specific proteostasis defects introduced by these variants remains immature. Moreover, it is unclear whether or not recognition and quality control of misfolded C-Pro domains is mediated by recognizing stalled assembly of triple-helical domains or by direct engagement of the C-Pro itself. Here, we integrate biochemical and cellular approaches to illuminate the proteostasis defects associated with osteogenesis imperfecta-causing mutations within the collagen-α2(I) C-Pro domain. We first show that "C-Pro-only" constructs recapitulate key aspects of the behavior of full-length Colα2(I) constructs. Of the variants studied, perhaps the most severe assembly defects are associated with C1163R C-Proα2(I), which is incapable of forming stable trimers and is retained within cells. We find that the presence or absence of an unassembled triple-helical domain is not the key feature driving cellular retention versus secretion. Rather, the proteostasis network directly engages the misfolded C-Pro domain itself to prevent secretion and initiate clearance. Using MS-based proteomics, we elucidate how the endoplasmic reticulum (ER) proteostasis network differentially engages misfolded C1163R C-Proα2(I) and targets it for ER-associated degradation. These results provide insights into collagen folding and quality control with the potential to inform the design of proteostasis network-targeted strategies for managing collagenopathies.
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Affiliation(s)
- Ngoc-Duc Doan
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Azade S Hosseini
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Agata A Bikovtseva
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Michelle S Huang
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Andrew S DiChiara
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Louis J Papa
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Antonius Koller
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Matthew D Shoulders
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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29
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Nair HKR. Non-healing venous leg ulcer. J Wound Care 2020; 29:S26-S27. [DOI: 10.12968/jowc.2020.29.sup5b.s26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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30
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Boey J. Arteriovenous foot ulcer. J Wound Care 2020; 29:S24-S25. [PMID: 32427029 DOI: 10.12968/jowc.2020.29.sup5b.s24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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31
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Boey J. Delayed healing following amputation of the fifth ray. J Wound Care 2020; 29:S23-S24. [PMID: 32427028 DOI: 10.12968/jowc.2020.29.sup5b.s23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Johnson Boey
- Podiatrist, Singapore General Hospital, Singapore
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32
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Abstract
Not only does oxygen play an essential role in each stage of the wound healing process. It also helps to increases host resistance to infection. Any impairment to the oxygen supply can therefore delay healing. This article explores the affects of oxygen on the wound cells and tissue, and explains how an adequate supply is required for granulation tissue formation and epithelialisation to occur
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Affiliation(s)
- Ibby Younis
- Consultant Plastic and Reconstructive Surgeon, Royal Free London NHS Foundation Trust, London, UK
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33
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Hicks L. Diabetic foot ulcer with osteomyelitis. J Wound Care 2020; 29:S27-S29. [DOI: 10.12968/jowc.2020.29.sup5b.s27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Linda Hicks
- Advanced Podiatrist, County Durham and Darlington NHS Foundation Trust, Darlington, UK
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34
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Terzi A, Gallo N, Bettini S, Sibillano T, Altamura D, Madaghiele M, De Caro L, Valli L, Salvatore L, Sannino A, Giannini C. Sub‐ and Supramolecular X‐Ray Characterization of Engineered Tissues from Equine Tendon, Bovine Dermis, and Fish Skin Type‐I Collagen. Macromol Biosci 2020; 20:e2000017. [DOI: 10.1002/mabi.202000017] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 01/23/2020] [Indexed: 12/20/2022]
Affiliation(s)
- Alberta Terzi
- Institute of Crystallography (IC)National Research Council Bari 70126 Italy
| | - Nunzia Gallo
- Department of Engineering for InnovationUniversity of Salento Lecce 73100 Italy
| | - Simona Bettini
- Department of Engineering for InnovationUniversity of Salento Lecce 73100 Italy
| | - Teresa Sibillano
- Institute of Crystallography (IC)National Research Council Bari 70126 Italy
| | - Davide Altamura
- Institute of Crystallography (IC)National Research Council Bari 70126 Italy
| | - Marta Madaghiele
- Department of Engineering for InnovationUniversity of Salento Lecce 73100 Italy
| | - Liberato De Caro
- Institute of Crystallography (IC)National Research Council Bari 70126 Italy
| | - Ludovico Valli
- Department of Biological and Environmental Sciences and TechnologiesUniversity of Salento Lecce 73100 Italy
| | - Luca Salvatore
- Department of Engineering for InnovationUniversity of Salento Lecce 73100 Italy
| | - Alessandro Sannino
- Department of Engineering for InnovationUniversity of Salento Lecce 73100 Italy
| | - Cinzia Giannini
- Institute of Crystallography (IC)National Research Council Bari 70126 Italy
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35
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Macías I, Alcorta-Sevillano N, Rodríguez CI, Infante A. Osteoporosis and the Potential of Cell-Based Therapeutic Strategies. Int J Mol Sci 2020; 21:ijms21051653. [PMID: 32121265 PMCID: PMC7084428 DOI: 10.3390/ijms21051653] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 02/24/2020] [Accepted: 02/25/2020] [Indexed: 12/14/2022] Open
Abstract
Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowledge regarding the mechanisms that underlie the progression of osteoporosis. Emerging clinical and molecular evidence suggests that inflammation exerts a significant influence on bone turnover, thereby on osteoporosis. In this regard, MSCs have proven to possess broad immunoregulatory capabilities, modulating both adaptive and innate immunity. Here, we will discuss the role that MSCs play in the etiopathology of osteoporosis and their potential use for the treatment of this disease.
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36
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Digenis GE, Dombros NV, Christophoraki M, Grapsa I, Savidis N, Datseris J, Samuilidou E, Zerefos N, Tourkaritonis A. Procollagen Type-I in the Serum and Dialysate of Continuous Ambulatory Peritoneal Dialysis Patients. Perit Dial Int 2020. [DOI: 10.1177/089686089301302s120] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Procollagen-1 carboxylterminal extension peptide (PICP) was determined In the serum and dialysate of 26 continuous ambulatory peritoneal dialysis (CAPD) patients and in the serum of 11 healthy controls. PICP serum levels were significantly higher in CAPD patients than in healthy controls (p<0.001). There was no correlation between serum PICP levels and those of calcium, phosphorus, magnesium, alkaline phosphatase, osteocalcin, and intact parathyroid hormone (IPTH). Serum and dialysate levels of osteocalcin and lPTH showed a significant correlation (p<0.001). The dialysate-to-serum PICP ratio in 21 patients was lower than 1.0. In the remaining 5 patients, however, the above ratio was higher than 1.0. We conclude that In CAPD patients serum PICP levels do not correlate with biochemical parameters of renal osteodystrophy. A dialysate-to-serum PICP ratio above 1.0 could implicate an increased local peritoneal fibro blastic activity and could be a useful marker of peritoneal fibrosis In CAPD.
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Affiliation(s)
| | - Nicholas v. Dombros
- “Alexandra” Hospital, Athens, Peritoneal Dialysis Unit, “Alexandra” Hospital, Athens, Greece
| | - Mary Christophoraki
- First Department of Internal Medicine, “AHEPA “ University Hospital, Thessaloniki, and Nuclear Medicine “Alexandra” Hospital, Athens, Greece
| | - Irene Grapsa
- Renal Unit, “Alexandra” Hospital, Athens, Greece
| | - Nicholas Savidis
- “Alexandra” Hospital, Athens, Peritoneal Dialysis Unit, “Alexandra” Hospital, Athens, Greece
| | - John Datseris
- First Department of Internal Medicine, “AHEPA “ University Hospital, Thessaloniki, and Nuclear Medicine “Alexandra” Hospital, Athens, Greece
| | | | - Nicholas Zerefos
- “Alexandra” Hospital, Athens, Peritoneal Dialysis Unit, “Alexandra” Hospital, Athens, Greece
| | - Achilleas Tourkaritonis
- “Alexandra” Hospital, Athens, Peritoneal Dialysis Unit, “Alexandra” Hospital, Athens, Greece
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Muenchow S, Horch RE, Dragu A. Effects of topical negative pressure therapy on perfusion and microcirculation of human skin. Clin Hemorheol Microcirc 2019; 72:365-374. [PMID: 30909192 DOI: 10.3233/ch-180536] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Topical negative pressure wound therapy (TNPWT) is one of the most frequently used techniques in wound treatment. But some of the underlying mechanisms still remain unclear. One possible explanation is an improved microcirculation by TNPWT. OBJECTIVE This study investigated the influence of TNPWT on microcirculation on intact skin in real-time. METHODS In healthy individuals, we performed a combined tissue - laser/photo - spectrometry technique to monitor changes of 4 different microcirculation parameters in real-time: The local blood flow, the capillary-venous oxygen saturation, the blood flow velocity and the relative amount of hemoglobin. We compared these parameters using two different protocols: a continuously (VAC ON 60/OFF 60) and discontinuously (VAC ON 30/OFF 60/ON 5) application. RESULTS Our results demonstrate a significant increase of all four measured parameters during the active TNPWT and the pressure free period. The comparison of two different protocols shows an advantage of the examined parameters using a discontinuous TNPWT application. CONCLUSIONS Our study demonstrated the changes of the microvascular tissue perfusion in intact human skin under the conditions of negative pressure and may thereby offer a broader understanding of mechanisms underlying the TNPWT.
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Mosca A, Comparcola D, Romito I, Mantovani A, Nobili V, Byrne CD, Alisi A, Targher G. Plasma N-terminal propeptide of type III procollagen accurately predicts liver fibrosis severity in children with non-alcoholic fatty liver disease. Liver Int 2019; 39:2317-2329. [PMID: 31436362 DOI: 10.1111/liv.14225] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 07/16/2019] [Accepted: 07/17/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS We examined the diagnostic performance of plasma N-terminal propeptide of type III procollagen (PIIINP) levels, aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for predicting non-alcoholic steatohepatitis (NASH) and liver fibrosis stage in children/adolescents with non-alcoholic fatty liver disease (NAFLD). METHODS We enrolled 204 children/adolescents with biopsy-proven NAFLD at the "Bambino Gesù" Children's Hospital. We measured plasma PIIINP levels using a commercially available enzyme-linked immunosorbent assay kit and calculated APRI and FIB-4 scores using standard methods. RESULTS Children with NASH had higher plasma PIIINP levels, APRI and FIB-4 scores compared with those without NASH (all P < .001). However, PIIINP levels had much better diagnostic performance and accuracy than APRI and FIB-4 scores for predicting liver fibrosis stage. PIIINP levels correlated with the total NAFLD activity score (NAS) and its constituent components (P < .0001). The risk of either NASH or F ≥ 2 fibrosis progressively increased with increasing PIIINP levels (P < .0001), independent of age, gender, adiposity measures, insulin resistance, NAS score and the patatin-like phospholipase domain-containing protein-3 rs738409 polymorphism. For every 3.6 ng/mL increase in PIIINP levels, the likelihood of having F ≥ 2 fibrosis increased by ~14-fold (adjusted-odds ratio 14.1, 95% CI 5.50-35.8, P < .0001) after adjustment for the aforementioned risk factors. The area under the receiver operating characteristics curve was 0.921 (95% CI 0.87-0.97) for F ≥ 2 fibrosis, and 0.993 (95% CI 0.98-1.0) for F3 fibrosis respectively. CONCLUSIONS Unlike APRI and FIB-4 scores, plasma PIIINP levels are a promising, non-invasive biomarker for diagnosing liver fibrosis stage in children/adolescents with biopsy-proven NAFLD.
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Affiliation(s)
- Antonella Mosca
- Hepatology Gastroenterology and Nutrition, Bambino Gesù Children's Hospital, Rome, Italy
| | - Donatella Comparcola
- Hepato-Metabolic Disease Unit, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy
| | - Ilaria Romito
- Research Unit of Molecular Genetics of Complex Phenotypes, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Valerio Nobili
- Hepatology Gastroenterology and Nutrition, Bambino Gesù Children's Hospital, Rome, Italy.,Department of Pediatrics, University La Sapienza, Rome, Italy
| | - Christopher D Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, Southampton General Hospital, University Hospital Southampton, Southampton, UK.,Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Anna Alisi
- Research Unit of Molecular Genetics of Complex Phenotypes, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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39
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van der Spoel E, van Vliet NA, van Heemst D. Viewpoint on the role of tissue maintenance in ageing: focus on biomarkers of bone, cartilage, muscle, and brain tissue maintenance. Ageing Res Rev 2019; 56:100964. [PMID: 31561015 DOI: 10.1016/j.arr.2019.100964] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 08/19/2019] [Accepted: 09/19/2019] [Indexed: 12/14/2022]
Abstract
Specific hallmarks are thought to underlie the ageing process and age-related functional decline. In this viewpoint, we put forward the hypothesis that disturbances in the process of tissue maintenance are an important common denominator that may lie in between specific hallmarks of ageing (i.e. damage and responses to damage) and their ultimate (patho)physiological consequences (i.e. functional decline and age-related disease). As a first step towards verifying or falsifying this hypothesis, it will be important to measure biomarkers of tissue maintenance in future studies in different study populations. The main aim of the current paper is to discuss potential biomarkers of tissue maintenance that could be used in such future studies. Among the many tissues that could have been chosen to explore our hypothesis, to keep the paper manageable, we chose to focus on a selected number of tissues, namely bone, cartilage, muscle, and the brain, which are important for mobility and cognition and affected in several common age-related diseases, including osteoporosis, osteoarthritis, sarcopenia, and neurodegenerative diseases. Furthermore, we discuss the advantages and limitations of potential biomarkers for use in (pre)clinical studies. The proposed biomarkers should be validated in future research, for example by measuring these in humans with different rates of ageing.
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Gutierrez HL, Tsutsumi R, Moore TY, Cooper KL. Convergent metatarsal fusion in jerboas and chickens is mediated by similarities and differences in the patterns of osteoblast and osteoclast activities. Evol Dev 2019; 21:320-329. [PMID: 31631508 DOI: 10.1111/ede.12320] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
In many vertebrate animals that run or leap, the metatarsals and/or metacarpals of the distal limb are fused into a single larger element, likely to resist fracture due to high ground-reaction forces during locomotion. Although metapodial fusion evolved independently in modern birds, ungulates, and jerboas, the developmental basis has only been explored in chickens, which diverged from the mammalian lineage approximately 300 million years ago. Here, we use a bipedal rodent, the lesser Egyptian jerboa (Jaculus jaculus), to understand the cellular processes of metatarsal fusion in a mammal, and we revisit the developing chicken to assess similarities and differences in the localization of osteoblast and osteoclast activities. In both species, adjacent metatarsals align along flat surfaces, osteoblasts cross the periosteal membrane to unite the three elements in a single circumference, and osteoclasts resorb bone at the interfaces leaving a single marrow cavity. However, the pattern of osteoclast activity differs in each species; osteoclasts are highly localized to resorb bone at the interfaces of neighboring jerboa metatarsals and are distributed throughout the endosteum of chicken metatarsals. Each species, therefore, provides an opportunity to understand mechanisms that pattern osteoblast and osteoclast activities to alter bone shape during development and evolution.
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Affiliation(s)
- Haydee L Gutierrez
- Division of Biological Sciences, Section of Cellular and Developmental Biology, University of California San Diego, La Jolla, California
| | - Rio Tsutsumi
- Division of Biological Sciences, Section of Cellular and Developmental Biology, University of California San Diego, La Jolla, California
| | - Talia Y Moore
- Department of Ecology and Evolutionary Biology and Museum of Zoology, University of Michigan, Ann Arbor, Michigan
| | - Kimberly L Cooper
- Division of Biological Sciences, Section of Cellular and Developmental Biology, University of California San Diego, La Jolla, California
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Toss MS, Miligy IM, Gorringe KL, Aleskandarany MA, Alkawaz A, Mittal K, Aneja R, Ellis IO, Green AR, Rakha EA. Collagen (XI) alpha-1 chain is an independent prognostic factor in breast ductal carcinoma in situ. Mod Pathol 2019; 32:1460-1472. [PMID: 31175327 DOI: 10.1038/s41379-019-0286-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 03/31/2019] [Accepted: 03/31/2019] [Indexed: 12/21/2022]
Abstract
Collagen11A1 (COL11A1) is a fibrillary type collagen constituting a minor component of the extracellular matrix and plays role in tissue tensile strength. Overexpression of COL11A1 expression is associated with aggressive behavior and poor outcome in several human malignancies. In this study, we evaluated the association between COL11A1 expression and clinicopathological parameters of the breast ductal carcinoma in situ (DCIS) and its prognostic value. COL11A1 protein expression was assessed immunohistochemically in a large well-characterized cohort of DCIS including pure (n = 776) and DCIS associated with invasive carcinoma (DCIS-mixed, n = 239). COL11A1 expression was assessed in tumor cells and surrounding stromal cells, and correlated with clinicopathological parameters, immunoprofile and disease outcome. In pure DCIS, high COL11A1 expression was observed in tumor cells and surrounding stromal cells in 25 and 13% of cases, respectively. Higher COL11A1 expression within the stromal cells was associated with hormone receptor negative, HER2 enriched and triple negative molecular subtypes and showed a positive linear correlation with proliferation index, dense tumor infiltrating lymphocytes and hypoxia-inducible factor 1 alpha. COL11A1 expression in tumor and stromal cells was significantly higher in DCIS associated with invasive carcinoma than in pure DCIS, and within the DCIS-mixed cohort, the invasive component showed higher COL11A1 expression than the DCIS component (all, p < 0.0001). Overexpression of stromal COL11A1 was an independent predictor of shorter local recurrence-free interval for all recurrences (HR = 13.2, 95% CI = 6.9-25.4, p < 0.0001) and for invasive recurrences (HR = 11.2, 95% CI = 4.9-25.8, p < 0.0001). When incorporated with other risk factors, stromal COL11A1 provided better patient risk stratification. DCIS with higher stromal COL11A1 expression showed poor outcome even with adjuvant radiotherapy management. In conclusion, overexpression of stromal COL11A1 is associated with invasive recurrence in DCIS and is a potential marker to predict the response to radiotherapy.
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Affiliation(s)
- Michael S Toss
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham City Hospital, Nottingham, UK.,Histopathology department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Islam M Miligy
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham City Hospital, Nottingham, UK.,Histopathology department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Kylie L Gorringe
- Cancer Genomics Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
| | - Mohammed A Aleskandarany
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham City Hospital, Nottingham, UK.,Histopathology department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Abdulbaqi Alkawaz
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham City Hospital, Nottingham, UK
| | | | - Ritu Aneja
- Georgia State University, Atlanta, GA, USA
| | - Ian O Ellis
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham City Hospital, Nottingham, UK
| | - Andrew R Green
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham City Hospital, Nottingham, UK
| | - Emad A Rakha
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham City Hospital, Nottingham, UK. .,Histopathology department, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
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Producing Collagen Micro-stripes with Aligned Fibers for Cell Migration Assays. Cell Mol Bioeng 2019; 13:87-98. [PMID: 32030110 DOI: 10.1007/s12195-019-00600-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 09/14/2019] [Indexed: 01/14/2023] Open
Abstract
Introduction The orientation of collagen fibers in native tissues plays an important role in cell signaling and mediates the progression of tumor cells in breast cancer by a contact guidance mechanism. Understanding how migration of epithelial cells is directed by the alignment of collagen fibers requires in vitro assays with standardized orientations of collagen fibers. Methods To address this issue, we produced micro-stripes with aligned collagen fibers using an easy-to-use and versatile approach based on the aspiration of a collagen solution within a microchannel. Glass coverslips were functionalized with a (3-aminopropyl)triethoxysilane/glutaraldehyde linkage to covalently anchor micro-stripes of aligned collagen fibers, whereas microchannels were functionalized with a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nonionic triblock polymer to prevent adhesion of the collagen micro-stripes. Results Using this strategy, microchannels can be peeled off to expose micro-stripes of aligned collagen fibers without affecting their mechanical integrity. We used time-lapse confocal reflection microscopy to characterize the polymerization kinetics of collagen networks for different concentrations and the orientation of collagen fibers as a function of the microchannel width. Our results indicate a non-linear concentration dependence of the area of fluorescence, suggesting that the architecture of collagen networks is sensitive to small changes in concentration. We show the possibility to influence the collagen fibril coverage by adjusting the concentration of the collagen solution. Conclusion We applied this novel approach to study the migration of epithelial cells, demonstrating that collagen micro-stripes with aligned fibers represent a valuable in-vitro assay for studying cell contact guidance mechanisms.
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Licini C, Vitale-Brovarone C, Mattioli-Belmonte M. Collagen and non-collagenous proteins molecular crosstalk in the pathophysiology of osteoporosis. Cytokine Growth Factor Rev 2019; 49:59-69. [PMID: 31543432 DOI: 10.1016/j.cytogfr.2019.09.001] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 09/12/2019] [Accepted: 09/12/2019] [Indexed: 01/07/2023]
Abstract
Collagenous and non-collagenous proteins (NCPs) in the extracellular matrix, as well as the coupling mechanisms between osteoclasts and osteoblasts, work together to ensure normal bone metabolism. Each protein plays one or more critical roles in bone metabolism, sometimes even contradictory, thus affecting the final mechanical, physical and chemical properties of bone tissue. Anomalies in the amount and structure of one or more of these proteins can cause abnormalities in bone formation and resorption, which consequently leads to malformations and defects, such as osteoporosis (OP). The connections between key proteins involved in matrix formation and resorption are far from being elucidated. In this review, we resume knowledge on the crosstalk between collagen type I and selected NCPs (Transforming Growth Factor-β, Insulin-like Growth Factor-1, Decorin, Osteonectin, Osteopontin, Bone Sialoprotein and Osteocalcin) of bone matrix, focusing on their possible involvement and role in OP. The different elements of this network can be pharmacologically targeted or used for the design/development of innovative regenerative strategies to modulate a feedback loop in bone remodelling.
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Affiliation(s)
- Caterina Licini
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129, Torino, Italy; Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/a, 60126, Ancona, Italy
| | - Chiara Vitale-Brovarone
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129, Torino, Italy.
| | - Monica Mattioli-Belmonte
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/a, 60126, Ancona, Italy
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Steplewski A, Fertala J, Tomlinson R, Hoxha K, Han L, Thakar O, Klein J, Abboud J, Fertala A. The impact of cholesterol deposits on the fibrillar architecture of the Achilles tendon in a rabbit model of hypercholesterolemia. J Orthop Surg Res 2019; 14:172. [PMID: 31182124 PMCID: PMC6558834 DOI: 10.1186/s13018-019-1217-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 05/29/2019] [Indexed: 01/29/2023] Open
Abstract
Background Increased tendon pain and tendon damage is a significant complication related to hyperlipidemia. Unlike the well-established pathogenesis associated with increased serum concentrations of total cholesterol, triglycerides, and low-density lipoprotein in atherosclerotic cardiovascular disease, the role of hyperlipidemia in promoting tendon damage remains controversial and requires mechanistic clarity. Methods In this study, we analyzed the consequences of hypercholesterolemia on the integrity of the collagen-based architecture of the Achilles tendon. The Achilles tendons from rabbits fed with normal-cholesterol (nCH) and high-cholesterol (hCH) diets were analyzed. We studied the morphology of tendons, distribution of lipids within their collagen-rich milieu, the relative amounts of fibrillar collagen I and collagen III, and selected biomechanical parameters of the tendons at the macroscale and the nanoscale. Results Histological assays of hCH tendons and tenosynovium demonstrated hypercellular areas with increased numbers of macrophages infiltrating the tendon structure as compared to the nCH tendons. While Oil Red staining revealed lipid-rich deposits in the hCH tendons, hybridization of tendon tissue with the collagen hybridizing peptide (CHP) demonstrated damage to the collagen fibers. Fourier-transform infrared (FTIR) spectra showed the presence of distinct peaks consistent with the presence of cholesterol ester. Additionally, the hCH tendons displayed regions of poor collagen content that overlapped with lipid-rich regions. The hCH tendons had a substantial fourfold increase in the collage III to collagen I ratio as compared to the nCH tendons. Tendons from the hCH rabbits showed poor biomechanical characteristics in comparison with control. The biomechanical changes were evident at the macrolevel and the nanolevel of tendon structure. Conclusions Our findings support the hypothesis that hypercholesterolemia coincides with the weakening of the tendons. It is likely that the intimate contact between collagen fibrils and cholesterol deposits contributes to the weakening of the fibrillar structure of the tendons.
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Affiliation(s)
- Andrzej Steplewski
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, Room 501, 1015 Walnut Street, Philadelphia, PA, 19107, USA
| | - Jolanta Fertala
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, Room 501, 1015 Walnut Street, Philadelphia, PA, 19107, USA
| | - Ryan Tomlinson
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, Room 501, 1015 Walnut Street, Philadelphia, PA, 19107, USA
| | - Kevth'er Hoxha
- School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, PA, USA
| | - Lin Han
- School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, PA, USA
| | - Ocean Thakar
- Rothman Institute of Orthopaedics, Thomas Jefferson University, Philadelphia, PA, USA
| | - Jason Klein
- Rothman Institute of Orthopaedics, Thomas Jefferson University, Philadelphia, PA, USA
| | - Joseph Abboud
- Rothman Institute of Orthopaedics, Thomas Jefferson University, Philadelphia, PA, USA
| | - Andrzej Fertala
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, Room 501, 1015 Walnut Street, Philadelphia, PA, 19107, USA.
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Adeva-Andany MM, Castro-Quintela E, Fernández-Fernández C, Carneiro-Freire N, Vila-Altesor M. The role of collagen homeostasis in the pathogenesis of vascular disease associated to insulin resistance. Diabetes Metab Syndr 2019; 13:1877-1883. [PMID: 31235109 DOI: 10.1016/j.dsx.2019.04.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 04/16/2019] [Indexed: 12/25/2022]
Affiliation(s)
- María M Adeva-Andany
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, 15406, Ferrol, Spain.
| | - Elvira Castro-Quintela
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, 15406, Ferrol, Spain
| | | | - Natalia Carneiro-Freire
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, 15406, Ferrol, Spain
| | - Matilde Vila-Altesor
- Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, 15406, Ferrol, Spain
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46
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Govindaraju P, Todd L, Shetye S, Monslow J, Puré E. CD44-dependent inflammation, fibrogenesis, and collagenolysis regulates extracellular matrix remodeling and tensile strength during cutaneous wound healing. Matrix Biol 2019; 75-76:314-330. [PMID: 29894820 PMCID: PMC6286871 DOI: 10.1016/j.matbio.2018.06.004] [Citation(s) in RCA: 110] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 05/21/2018] [Accepted: 06/08/2018] [Indexed: 12/19/2022]
Abstract
Cutaneous wound healing consists of three main phases: inflammation, re-epithelialization, and tissue remodeling. During normal wound healing, these processes are tightly regulated to allow restoration of skin function and biomechanics. In many instances, healing leads to an excess accumulation of fibrillar collagen (the principal protein found in the extracellular matrix - ECM), and the formation of scar tissue, which has compromised biomechanics, tested using ramp to failure tests, compared to normal skin (Corr and Hart, 2013 [1]). Alterations in collagen accumulation and architecture have been attributed to the reduced tensile strength found in scar tissue (Brenda et al., 1999; Eleswarapu et al., 2011). Defining mechanisms that govern cellular functionality and ECM remodeling are vital to understanding normal versus pathological healing and developing approaches to prevent scarring. CD44 is a cell surface adhesion receptor expressed on nearly all cell types present in dermis. Although CD44 has been implicated in an array of inflammatory and fibrotic processes such as leukocyte recruitment, T-cell extravasation, and hyaluronic acid (the principal glycosaminoglycan found in the ECM) metabolism, the role of CD44 in cutaneous wound healing and scarring remains unknown. We demonstrate that in an excisional biopsy punch wound healing model, CD44-null mice have increased inflammatory and reduced fibrogenic responses during early phases of wound healing. At wound closure, CD44-null mice exhibit reduced collagen degradation leading to increased accumulation of fibrillar collagen, which persists after wound closure leading to reduced tensile strength resulting in a more severe scarring phenotype compared to WT mice. These data indicate that CD44 plays a previously unknown role in fibrillar collagen accumulation and wound healing during the injury response.
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Affiliation(s)
- Priya Govindaraju
- Department of Biomedical Sciences of the University of Pennsylvania, Philadelphia, PA, United States of America; Pharmacology Graduate Group of the University of Pennsylvania, Philadelphia, PA, United States of America
| | - Leslie Todd
- Department of Biomedical Sciences of the University of Pennsylvania, Philadelphia, PA, United States of America
| | - Snehal Shetye
- McKay Orthopaedic Research Laboratory of the University of Pennsylvania, Philadelphia, PA, United States of America
| | - James Monslow
- Department of Biomedical Sciences of the University of Pennsylvania, Philadelphia, PA, United States of America
| | - Ellen Puré
- Department of Biomedical Sciences of the University of Pennsylvania, Philadelphia, PA, United States of America; Pharmacology Graduate Group of the University of Pennsylvania, Philadelphia, PA, United States of America.
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A cysteine-based molecular code informs collagen C-propeptide assembly. Nat Commun 2018; 9:4206. [PMID: 30310058 PMCID: PMC6181919 DOI: 10.1038/s41467-018-06185-2] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 08/23/2018] [Indexed: 11/29/2022] Open
Abstract
Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that the presence or absence of a single cysteine in type-I collagen’s C-propeptide domain is a key factor governing the ability of a given collagen polypeptide to stably homotrimerize. We also identify a critical role for Ca2+ in non-covalent collagen C-propeptide trimerization, thereby priming the protein for disulfide-mediated covalent immortalization. The resulting cysteine-based code for stable assembly provides a molecular model that can be used to predict, a priori, the identity of not just collagen homotrimers, but also naturally occurring 2:1 and 1:1:1 heterotrimers. Moreover, the code applies across all of the sequence-diverse fibrillar collagens. These results provide new insight into how evolution leverages disulfide networks to fine-tune protein assembly, and will inform the ongoing development of designer proteins that assemble into specific oligomeric forms. Collagen proteins assemble into trimers from distinct monomers with high specificity, yet the molecular basis for this specificity remains unclear. Here the authors demonstrate the crucial role of conserved C-terminal domain cysteine residues and calcium in homotrimeric procollagen assembly.
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48
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Morello R. Osteogenesis imperfecta and therapeutics. Matrix Biol 2018; 71-72:294-312. [PMID: 29540309 PMCID: PMC6133774 DOI: 10.1016/j.matbio.2018.03.010] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 03/08/2018] [Accepted: 03/08/2018] [Indexed: 02/08/2023]
Abstract
Osteogenesis imperfecta, or brittle bone disease, is a congenital disease that primarily causes low bone mass and bone fractures but it can negatively affect other organs. It is usually inherited in an autosomal dominant fashion, although rarer recessive and X-chromosome-linked forms of the disease have been identified. In addition to type I collagen, mutations in a number of other genes, often involved in type I collagen synthesis or in the differentiation and function of osteoblasts, have been identified in the last several years. Seldom, the study of a rare disease has delivered such a wealth of new information that have helped our understanding of multiple processes involved in collagen synthesis and bone formation. In this short review I will describe the clinical features and the molecular genetics of the disease, but then focus on how OI dysregulates all aspects of extracellular matrix biology. I will conclude with a discussion about OI therapeutics.
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Affiliation(s)
- Roy Morello
- Department of Physiology & Biophysics, Orthopaedic Surgery, and Division of Genetics, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
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Hu MS, Hong WX, Januszyk M, Walmsley GG, Luan A, Maan ZN, Moshrefi S, Tevlin R, Wan DC, Gurtner GC, Longaker MT, Lorenz HP. Pathway Analysis of Gene Expression in Murine Fetal and Adult Wounds. Adv Wound Care (New Rochelle) 2018; 7:262-275. [PMID: 30087802 DOI: 10.1089/wound.2017.0779] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 01/29/2018] [Indexed: 01/26/2023] Open
Abstract
Objective: In early gestation, fetal wounds heal without fibrosis in a process resembling regeneration. Elucidating this remarkable mechanism can result in tremendous benefits to prevent scarring. Fetal mouse cutaneous wounds before embryonic day (E)18 heal without scar. Herein, we analyze expression profiles of fetal and postnatal wounds utilizing updated gene annotations and pathway analysis to further delineate between repair and regeneration. Approach: Dorsal wounds from time-dated pregnant BALB/c mouse fetuses and adult mice at various time points were collected. Total RNA was isolated and microarray analysis was performed using chips with 42,000 genes. Significance analysis of microarrays was utilized to select genes with >2-fold expression differences with a false discovery rate of <2. Enrichment analysis was performed on significant genes to identify differentially expressed pathways. Results: Our analysis identified 471 differentially expressed genes in fetal versus adult wounds following injury. Utilizing enrichment analysis of significant genes, we identified the top 20 signaling pathways that were upregulated and downregulated at 1 and 12 h after injury. At 24 h after injury, we discovered 18 signaling pathways upregulated in adult wounds and 11 pathways upregulated in fetal wounds. Innovation: These novel target genes and pathways may reveal repair mechanisms of the early fetus that promote regeneration over fibrosis. Conclusion: Our microarray analysis recognizes hundreds of possible genes as candidates for regulators of scarless versus scarring wound repair. Enrichment analysis reveals 109 signaling pathways related to fetal scarless wound healing.
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Affiliation(s)
- Michael S. Hu
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Wan Xing Hong
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Michael Januszyk
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Graham G. Walmsley
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Anna Luan
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Zeshaan N. Maan
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Shawn Moshrefi
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Ruth Tevlin
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Derrick C. Wan
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Geoffrey C. Gurtner
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Michael T. Longaker
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - H. Peter Lorenz
- Division of Plastic Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, California
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50
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Abdel Aziz MT, Abdel Aziz Wassef M, Kamel M, el Zein M, el Hassan H. Clinical Evaluation of Serum Aminoterminal Propeptide of Type III Procollagen as Tumor Marker in Gynecologic Malignancies. TUMORI JOURNAL 2018; 79:219-23. [PMID: 8236508 DOI: 10.1177/030089169307900313] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Aims The aim of this study was to determine the possible usefulness of the assay of the aminoterminal propeptide of type III procollagen and fibronectin in detecting connective tissue changes associated with gynecologic malignancies. Study Design Serum aminoterminal propeptide of type III procollagen and plasma fibronectin were measured in 36 women with gynecologic malignancies, 20 women with benign gynecologic tumors and 10 healthy women serving as controls. Results A significant serum propeptide was significantly high In the group with gynecologic malignancies and normal in the benign tumor group. The serum propeptide levels were related to of disease stage and presence of ascites in patients with ovarian carcinoma but not in those with cervical or endometrial carcinoma. In the follow-up study, a favorable clinical response was associated with normalizing propeptide levels whereas in rapidly progressive disease the levels fell initially but rose again. In partial response with ultimate progression, the propeptide concentration decreased but remained clearly above the normal range. No difference in plasma fibronectin was found among the malignant tumor, benign tumor and control groups. Conclusions The present study indicates that the aminoterminal propeptide of type III procollagen could serve as an additional, non specific marker to follow the clinical behavior of gynecologic malignancies and consequently of connective tissue metabolism reflecting tumor matrix interaction.
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Affiliation(s)
- M T Abdel Aziz
- Medical Biochemistry Department, Faculty of Medicine, Cairo University, Egypt
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