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1
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Wang Q, Zhang Y, Cheng X, Guo Z, Liu Y, Xia LH, Liu Z, Zheng J, Zhang Z, Sun K, Shen G. Expert consensus on the use of oropharyngeal probiotic Bactoblis in respiratory tract infection and otitis media: available clinical evidence and recommendations for future research. Front Pediatr 2025; 12:1509902. [PMID: 39935974 PMCID: PMC11810568 DOI: 10.3389/fped.2024.1509902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 11/25/2024] [Indexed: 02/13/2025] Open
Affiliation(s)
- Qiang Wang
- Department of Immunology of College of Medicine, Wuhan Wuchang Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Yatong Zhang
- Department of Pharmacy, Beijing Hospital, Beijing, China
| | - Xiaoling Cheng
- Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, China
| | - Zhi Guo
- Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
| | - Yang Liu
- Pediatric Department, Wuhan Asian General Hospital, Wuhan, China
| | - Li-hong Xia
- Pediatric Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zhigang Liu
- Pediatric Department, Jinan Maternity and Child Care Hospital, Jinan, China
| | - Junqing Zheng
- Pediatric Department, Jinan Maternity and Child Care Hospital, Jinan, China
| | - Zihe Zhang
- Department of Otolaryngology Head and Neck Surgery, Shandong Maternity and Child Care Hospital, Jinan, China
| | - Kai Sun
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Shandong First Medical University, Jinan, China
| | - Guanxin Shen
- Department of Immunology, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China
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2
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Datta M, Rajeev A, Chattopadhyay I. Application of antimicrobial peptides as next-generation therapeutics in the biomedical world. Biotechnol Genet Eng Rev 2024; 40:2458-2496. [PMID: 37036043 DOI: 10.1080/02648725.2023.2199572] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 03/30/2023] [Indexed: 04/11/2023]
Abstract
Antimicrobial peptide (AMP), also called host defense peptide, is a part of the innate immune system in eukaryotic organisms. AMPs are also produced by prokaryotes in response to stressful conditions and environmental changes. They have a broad spectrum of activity against both Gram positive and Gram negative bacteria. They are also effective against viruses, fungi, parasites, and cancer cells. AMPs are cationic or amphipathic in nature, but in recent years cationic AMPs have attracted a lot of attention because cationic AMPs can easily interact with negatively charged bacterial and cancer cell membranes through electrostatic interaction. AMPs can also eradicate bacterial biofilms and have broad-spectrum activity against multidrug resistant (MDR) bacteria. Although the main target site for AMPs is the cell membrane, they can also disrupt bacterial cell walls, interfere with protein folding and inhibit enzymatic activity. In recent centuries antibiotics are gradually losing their potential because of the continuous rise of antibiotic resistant bacteria. Therefore, there is an urgent need to develop novel therapeutic approaches to treat MDR bacteria, and AMP is such an alternative treatment option over conventional antibiotics. Several communicable diseases like tuberculosis and non-communicable diseases such as cancer can be treated by using AMPs. One of the major advantages of using AMP is that it works with high specificity and does not cause any harm to normal tissue. AMPs can be modified to improve their efficacy. In this narrative review, we are focusing on the potential application of AMPs in medical science.
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Affiliation(s)
- Manjari Datta
- Department of Biotechnology, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India
| | - Ashwin Rajeev
- Department of Biotechnology, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India
| | - Indranil Chattopadhyay
- Department of Biotechnology, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India
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3
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Biswas S, Sarojini S, Jayaram S, Philip I, Umesh M, Mascarenhas R, Pappuswamy M, Balasubramanian B, Arokiyaraj S. Understanding the Role of Antimicrobial Peptides in Neutrophil Extracellular Traps Promoting Autoimmune Disorders. Life (Basel) 2023; 13:1307. [PMID: 37374090 DOI: 10.3390/life13061307] [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: 04/20/2023] [Revised: 05/26/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
AMPs are small oligopeptides acting as integral elements of the innate immune system and are of tremendous potential in the medical field owing to their antimicrobial and immunomodulatory activities. They offer a multitude of immunomodulatory properties such as immune cell differentiation, inflammatory responses, cytokine production, and chemoattraction. Aberrancy in neutrophil or epithelial cell-producing AMPs leads to inflammation culminating in various autoimmune responses. In this review, we have tried to explore the role of prominent mammalian AMPs-defensins and cathelicidins, as immune regulators with special emphasis on their role in neutrophil extracellular traps which promotes autoimmune disorders. When complexed with self-DNA or self-RNA, AMPs act as autoantigens which activate plasmacytoid dendritic cells and myeloid dendritic cells leading to the production of interferons and cytokines. These trigger a series of self-directed inflammatory reactions, leading to the emergence of diverse autoimmune disorders. Since AMPs show both anti- and pro-inflammatory abilities in different ADs, there is a dire need for a complete understanding of their role before developing AMP-based therapy for autoimmune disorders.
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Affiliation(s)
- Soma Biswas
- Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru 560029, India
| | - Suma Sarojini
- Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru 560029, India
| | - Saranya Jayaram
- Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru 560029, India
| | - Indhu Philip
- Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru 560029, India
| | - Mridul Umesh
- Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru 560029, India
| | - Roseanne Mascarenhas
- Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru 560029, India
| | - Manikantan Pappuswamy
- Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru 560029, India
| | | | - Selvaraj Arokiyaraj
- Department of Food Science and Biotechnology, College of Life Science, Sejong University, Seoul 05006, Republic of Korea
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4
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Yang M, Liu S, Zhang C. Antimicrobial peptides with antiviral and anticancer properties and their modification and nanodelivery systems. CURRENT RESEARCH IN BIOTECHNOLOGY 2023. [DOI: 10.1016/j.crbiot.2023.100121] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
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5
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Liu S, Liu F, Zhang Z, Zhuang Z, Yuan X, Chen Y. The SELP, CD93, IL2RG, and VAV1 Genes Associated with Atherosclerosis May Be Potential Diagnostic Biomarkers for Psoriasis. J Inflamm Res 2023; 16:827-843. [PMID: 36876153 PMCID: PMC9983575 DOI: 10.2147/jir.s398862] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 02/16/2023] [Indexed: 03/03/2023] Open
Abstract
Purpose Psoriasis and atherosclerosis are immunometabolic diseases. This study aimed to integrate bioinformatics and updated public resources to find potential biological markers associated with atherosclerosis that can cause psoriasis. Patients and Methods Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened, and functional enrichment analysis was performed. We identified psoriasis and atherosclerosis common immune-related genes (PA-IRGs) by overlapping immune-related genes (IRGs) with genes in the module most associated with psoriasis and atherosclerosis obtained by weighted gene co-expression network analysis (WGCNAs). Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability. The skin expression levels of diagnostic biomarkers were further verified by immunohistochemical staining. CIBERSORT, single-sample gene set enrichment analysis (ssGSEA), and Pearson's correlation analysis were applied to evaluate immune and lipid metabolism relationships in psoriatic tissues. In addition, a lincRNA-miRNA-mRNA network was constructed to find the pathogenesis in which diagnostic markers may be involved. Results Four PA-IRGs (SELP, CD93, IL2RG, and VAV1) demonstrated the optimal diagnostic value, with an AUC above 0.8. The immune cell infiltration analysis showed that dendritic resting cells, NK cell activation, neutrophils, macrophages M2, macrophages M0, and B-cell memory were highly abundant in psoriasis. Immune response analysis showed that TNF family members, chemokine receptors, interferons, natural killer cells, and TGF-β family members might be involved in psoriasis. Diagnostic biomarkers are strongly associated with various infiltrating immune cells, immune responses, and lipid metabolism. A lincRNA-miRNA-mRNA regulatory network consisting of 31 lincRNAs and 23 miRNAs was constructed. LINC00662 is involved in modulating four diagnostic biomarkers. Conclusion This study identified atherosclerosis-related genes SELP, CD93, VAV1, and IL2RG as potential psoriasis diagnostic markers. Provide novel insights into the possible regulatory mechanisms involved in psoriasis.
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Affiliation(s)
- Shougang Liu
- Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People's Republic of China
| | - Fanghua Liu
- Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People's Republic of China.,Department of Dermatology, Guangdong Medical University, Zhanjiang, People's Republic of China
| | - Zeqiao Zhang
- Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People's Republic of China
| | - Zhe Zhuang
- Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People's Republic of China.,Department of Dermatology, Guangdong Medical University, Zhanjiang, People's Republic of China
| | - Xiuqing Yuan
- Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People's Republic of China
| | - Yongfeng Chen
- Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People's Republic of China.,Department of Dermatology, Guangdong Medical University, Zhanjiang, People's Republic of China
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6
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S100 Proteins as Novel Therapeutic Targets in Psoriasis and Other Autoimmune Diseases. Molecules 2022; 27:molecules27196640. [PMID: 36235175 PMCID: PMC9572071 DOI: 10.3390/molecules27196640] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 09/29/2022] [Accepted: 10/01/2022] [Indexed: 01/07/2023] Open
Abstract
Psoriasis is one of the most common inflammatory skin diseases affecting about 1-3% of the population. One of the characteristic abnormalities in psoriasis is the excessive production of antimicrobial peptides and proteins, which play an essential role in the pathogenesis of the disease. Antimicrobial peptides and proteins can be expressed differently in normal and diseased skin, reflecting their usefulness as diagnostic biomarkers. Moreover, due to their very important functions in innate immunity, members of host defense peptides and proteins are currently considered to be promising new therapeutic targets for many inflammatory diseases. Koebnerisin (S100A15) belongs to an S100 family of antimicrobial proteins, which constitute the multigenetic group of calcium-binding proteins involved in ion-dependent cellular functions and regulation of immune mechanisms. S100A15 was first discovered to be overexpressed in 'koebnerized' psoriatic skin, indicating its involvement in the disease phenotype and the same promising potential as a new therapeutic target. This review describes the involvement of antimicrobial peptides and proteins in inflammatory diseases' development and therapy. The discussion focuses on S100 proteins, especially koebnerisin, which may be involved in the underlying mechanism of the Köebner phenomenon in psoriasis, as well as other immune-mediated inflammatory diseases described in the last decade.
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7
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Lin WH, Jiang WP, Chen CC, Lee LY, Tsai YS, Chien LH, Chou YN, Deng JS, Huang GJ. Renoprotective Effect of Pediococcus acidilactici GKA4 on Cisplatin-Induced Acute Kidney Injury by Mitigating Inflammation and Oxidative Stress and Regulating the MAPK, AMPK/SIRT1/NF-κB, and PI3K/AKT Pathways. Nutrients 2022; 14:2877. [PMID: 35889833 PMCID: PMC9323173 DOI: 10.3390/nu14142877] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/11/2022] [Accepted: 07/12/2022] [Indexed: 02/04/2023] Open
Abstract
Acute kidney injury (AKI) describes a sudden loss of kidney function and is associated with a high mortality. Pediococcus acidilactici is a potent producer of bacteriocin and inhibits the growth of pathogens during fermentation and food storage; it has been used in the food industry for many years. In this study, the potential of P. acidilactici GKA4 (GKA4) to ameliorate AKI was investigated using a cisplatin-induced animal model. First, mice were given oral GKA4 for ten days and intraperitoneally injected with cisplatin on the seventh day to create an AKI mode. GKA4 attenuated renal histopathological alterations, serum biomarkers, the levels of inflammatory mediators, and lipid oxidation in cisplatin-induced nephrotoxicity. Moreover, GKA4 significantly decreased the expression of inflammation-related proteins and mitogen-activated protein kinase (MAPK) in kidney tissues. Eventually, GKA4 also increased the levels of related antioxidant enzymes and pathways. Consistently, sirtuin 1 (SIRT1) upregulated the level of autophagy-related proteins (LC3B, p62, and Beclin1). Further studies are needed to check our results and advance our knowledge of the mechanism whereby PI3K inhibition (wortmannin) reverses the effect of GKA4 on cisplatin-treated AKI. Taken together, GKA4 provides a therapeutic target with promising clinical potential after cisplatin treatment by reducing oxidative stress and inflammation via the MAPK, AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) axes.
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Affiliation(s)
- Wen-Hsin Lin
- College of Pharmacy, China Medical University, Taichung 404, Taiwan;
| | - Wen-Ping Jiang
- Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan;
| | - Chin-Chu Chen
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan 330, Taiwan; (C.-C.C.); (L.-Y.L.); (Y.-S.T.)
| | - Li-Ya Lee
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan 330, Taiwan; (C.-C.C.); (L.-Y.L.); (Y.-S.T.)
| | - You-Shan Tsai
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan 330, Taiwan; (C.-C.C.); (L.-Y.L.); (Y.-S.T.)
| | - Liang-Hsuan Chien
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan; (L.-H.C.); (Y.-N.C.)
| | - Ya-Ni Chou
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan; (L.-H.C.); (Y.-N.C.)
| | - Jeng-Shyan Deng
- Department of Food Nutrition and Healthy Biotechnology, Asia University, Taichung 413, Taiwan
| | - Guan-Jhong Huang
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan; (L.-H.C.); (Y.-N.C.)
- Department of Food Nutrition and Healthy Biotechnology, Asia University, Taichung 413, Taiwan
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8
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Bruno F, Malvaso A, Canterini S, Bruni AC. Antimicrobial Peptides (AMPs) in the Pathogenesis of Alzheimer's Disease: Implications for Diagnosis and Treatment. Antibiotics (Basel) 2022; 11:726. [PMID: 35740133 PMCID: PMC9220182 DOI: 10.3390/antibiotics11060726] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 02/04/2023] Open
Abstract
Alzheimer's disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms of the disease: sporadic (SAD)-whose causes are not completely understood-and familial (FAD)-with clear autosomal dominant inheritance. The two main hallmarks of AD are extracellular deposits of amyloid-beta (Aβ) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein (P-tau). An ever-growing body of research supports the infectious hypothesis of sporadic forms of AD. Indeed, it has been documented that some pathogens, such as herpesviruses and certain bacterial species, are commonly present in AD patients, prompting recent clinical research to focus on the characterization of antimicrobial peptides (AMPs) in this pathology. The literature also demonstrates that Aβ can be considered itself as an AMP; thus, representing a type of innate immune defense peptide that protects the host against a variety of pathogens. Beyond Aβ, other proteins with antimicrobial activity, such as lactoferrin, defensins, cystatins, thymosin β4, LL37, histatin 1, and statherin have been shown to be involved in AD. Here, we summarized and discussed these findings and explored the diagnostic and therapeutic potential of AMPs in AD.
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Affiliation(s)
- Francesco Bruno
- Regional Neurogenetic Centre (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, Italy
- Association for Neurogenetic Research (ARN), 88046 Lamezia Terme, Italy;
| | - Antonio Malvaso
- Neurology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy;
| | - Sonia Canterini
- Division of Neuroscience, Department of Psychology, University La Sapienza, 00158 Rome, Italy;
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9
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Abstract
Antimicrobial peptides (AMPs) have recently become widely publicized because they have the potential to function in alternative therapies as “natural” antibiotics, with their main advantage being a broad spectrum of activity. The potential for antimicrobial peptides to treat diabetes mellitus (DM) has been reported. In diabetes mellitus type I (T1D), cathelicidin-related antimicrobial peptide (CRAMP), cathelicidin antimicrobial peptide (CAMP) and mouse-β- defensin 14 (mBD14) are positively affected. Decreased levels of LL-37 and human neutrophil peptide 1-3 (HNP1-3) have been reported in diabetes mellitus type II (T2D) relative to healthy patients. Moreover, AMPs from amphibians and social wasps have antidiabetic effects. In infections occurring in patients with tuberculosis-diabetes or diabetic foot, granulysin, HNP1, HNP2, HNP3, human beta-defensin 2 (HBD2), and cathelicidins are responsible for pathogen clearance. An interesting alternative is also the use of modified M13 bacteriophages containing encapsulated AMPs genes or phagemids.
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10
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Zhang C, Yang M. Antimicrobial Peptides: From Design to Clinical Application. Antibiotics (Basel) 2022; 11:antibiotics11030349. [PMID: 35326812 PMCID: PMC8944448 DOI: 10.3390/antibiotics11030349] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 02/27/2022] [Accepted: 03/04/2022] [Indexed: 02/06/2023] Open
Abstract
Infection of multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, brings public health issues and causes economic burden. Pathogenic bacteria develop several methods to resist antibiotic killing or inhibition, such as mutation of antibiotic function sites, activation of drug efflux pumps, and enzyme-mediated drug degradation. Antibiotic resistance components can be transferred between bacteria by mobile genetic elements including plasmids, transposons, and integrons, as well as bacteriophages. The development of antibiotic resistance limits the treatment options for bacterial infection, especially for MDR bacteria. Therefore, novel or alternative antibacterial agents are urgently needed. Antimicrobial peptides (AMPs) display multiple killing mechanisms against bacterial infections, including directly bactericidal activity and immunomodulatory function, as potential alternatives to antibiotics. In this review, the development of antibiotic resistance, the killing mechanisms of AMPs, and especially, the design, optimization, and delivery of AMPs are reviewed. Strategies such as structural change, amino acid substitution, conjugation with cell-penetration peptide, terminal acetylation and amidation, and encapsulation with nanoparticles will improve the antimicrobial efficacy, reduce toxicity, and accomplish local delivery of AMPs. In addition, clinical trials in AMP studies or applications of AMPs within the last five years were summarized. Overall, AMPs display diverse mechanisms of action against infection of pathogenic bacteria, and future research studies and clinical investigations will accelerate AMP application.
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Affiliation(s)
- Chunye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65212, USA;
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65211, USA
- Correspondence:
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11
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The Immunogenetics of Morphea and Lichen Sclerosus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1367:155-172. [DOI: 10.1007/978-3-030-92616-8_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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12
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Yang M, Zhang C. The role of liver sinusoidal endothelial cells in cancer liver metastasis. Am J Cancer Res 2021; 11:1845-1860. [PMID: 34094657 PMCID: PMC8167702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 03/03/2021] [Indexed: 06/12/2023] Open
Abstract
Liver sinusoidal endothelial cells (LSECs) are the gatekeeper cells in the liver, contributing critical roles in liver physiological and pathological changes. Factors such as dietary macronutrients, toxins, and aging impact LSEC fenestration. Defenestration of LSECs changes their phenotype and function. Under liver injury, capillarized LSECs promote hepatic stellate cells (HSCs) activation and fibrogenesis, while decapillarized LSECs protect the activation of HSCs and liver injury. The expression of chemokines, such as CXCL9 and CXCL16, changes and impacts the infiltration of immune cells in the liver during disease progression, including hepatocellular carcinoma (HCC). As the largest solid organ, liver is one of the most favorable organs into where tumor cells metastasize. The increased interaction and adhesion of circulating tumor cells (CTCs) with LSECs in the local microenvironment and LSEC-induced tolerance of immunity promote cancer liver metastasis. Several strategies can be applied to target LSEC to modulate their function to prevent cancer liver metastasis, including gut microbiota modulation, microRNA therapy, and medical treatment. Delivery of different treatment agents with nanoparticles may promote precise target treatment. Overall, targeting LSECs is a potential strategy for treatment of early liver diseases and prevention of cancer liver metastasis.
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Affiliation(s)
- Ming Yang
- Department of Surgery, University of MissouriColumbia, Missouri, USA
| | - Chunye Zhang
- Department of Veterinary Pathobiology, University of MissouriColumbia, Missouri, USA
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13
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Solanki SS, Singh P, Kashyap P, Sansi MS, Ali SA. Promising role of defensins peptides as therapeutics to combat against viral infection. Microb Pathog 2021; 155:104930. [PMID: 33933603 PMCID: PMC8084285 DOI: 10.1016/j.micpath.2021.104930] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 04/20/2021] [Accepted: 04/21/2021] [Indexed: 12/13/2022]
Abstract
Antimicrobial peptides (AMPs) are ubiquitously present small peptides, which play a critical function in the innate immune system. The defensin class of AMPs represented an evolutionarily ancient family containing cationic cysteine residue and frequently expressed in epithelial or neutrophils cells. It plays myriad functions in host innate immune responses against various infection. Defensin has a broad spectrum of antimicrobial activities, including anti-bacteria, anti-viruses (AVPs), anti-fungi, anti-cancers, and also overcoming bacterial drug resistance. In this review, we compiled the progress on defensin, particularly incorporating the mechanism of action, their application as an antiviral agent, prospects in different areas, and limitations to be solved as an antiviral peptide. Defensins were explored, in particular, their capacity to stimulate innate and adaptive immunity by trigging as anti-coronavirus (COVID-19) peptides. The present review summarised its immunomodulatory and immunoenhancing properties and predominantly focused on its promising therapeutic adjuvant choices for combat against viral infection.
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Affiliation(s)
| | - Parul Singh
- Cell Biology and Proteomics Lab, Animal Biotechnology Centre, National Dairy Research Institute, Karnal, 132001, Haryana, India
| | - Poonam Kashyap
- Animal Genomics Lab, National Dairy Research Institute, Karnal, 132001, India
| | - Manish Singh Sansi
- Animal Biochemistry Division, National Dairy Research Institute, Karnal, 132001, Haryana, India
| | - Syed Azmal Ali
- Cell Biology and Proteomics Lab, Animal Biotechnology Centre, National Dairy Research Institute, Karnal, 132001, Haryana, India; Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
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14
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Yang M, Zhang CY. G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment. World J Gastroenterol 2021; 27:677-691. [PMID: 33716447 PMCID: PMC7934005 DOI: 10.3748/wjg.v27.i8.677] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/24/2020] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a broad-spectrum disease, ranging from simple hepatic steatosis to nonalcoholic steatohepatitis, which can progress to cirrhosis and liver cancer. Abnormal hepatic lipid accumulation is the major manifestation of this disease, and lipotoxicity promotes NAFLD progression. In addition, intermediate metabolites such as succinate can stimulate the activation of hepatic stellate cells to produce extracellular matrix proteins, resulting in progression of NAFLD to fibrosis and even cirrhosis. G protein-coupled receptors (GPCRs) have been shown to play essential roles in metabolic disorders, such as NAFLD and obesity, through their function as receptors for bile acids and free fatty acids. In addition, GPCRs link gut microbiota-mediated connections in a variety of diseases, such as intestinal diseases, hepatic steatosis, diabetes, and cardiovascular diseases. The latest findings show that gut microbiota-derived acetate contributes to liver lipogenesis by converting dietary fructose into hepatic acetyl-CoA and fatty acids. GPCR agonists, including peptides and natural products like docosahexaenoic acid, have been applied to investigate their role in liver diseases. Therapies such as probiotics and GPCR agonists may be applied to modulate GPCR function to ameliorate liver metabolism syndrome. This review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated treatment. Overall, understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD.
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Affiliation(s)
- Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Chun-Ye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65212, United States
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15
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Askari G, Ghavami A, Shahdadian F, Moravejolahkami AR. Effect of synbiotics and probiotics supplementation on autoimmune diseases: A systematic review and meta-analysis of clinical trials. Clin Nutr 2021; 40:3221-3234. [PMID: 33642142 DOI: 10.1016/j.clnu.2021.02.015] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 01/30/2021] [Accepted: 02/08/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND & AIMS Today synbiotics are considered as immunomodulatory agents. The current systematic review and meta-analysis investigated the effect of synbiotics and probiotics on inflammatory and oxidative stress markers in autoimmune disease. MATERIALS & METHODS The English literature search was performed using PubMed, Scopus, Web of Science, and the Central Cochrane Library through March 2020. Random effects models and generic inverse variance methods were used to synthesize quantitative data by STATA14. RESULTS From a total of 623 entries identified via searches, ten RCTs (n = 440; 216 as intervention, 224 as controls) were included. An additional eleven studies with same intervention and different markers were also explained systematically. The pooled effect size showed that Interleukin (IL)-6 (WMD = -7.79 pg/ml; 95% CI = -13.81, -1.77, P = 0.011), Tumor Necrosis Factor (TNF)-α (WMD = -1.05 pg/ml; 95% CI = -2.01, -0.10, P = 0.030), high sensitivity C-Reactive Protein (hs-CRP) (SMD = -0.58; 95% CI = -0.79, -0.37, P < 0.001), Malondialdehyde (MDA) (SMD = -0.36; 95% CI = -0.68, -0.04; P = 0.026), Homeostasis Model of Assessment-estimated Insulin Resistance (HOMA-IR) (WMD = -0.71; 95% CI = -1.05, -0.37, P < 0.001), and beta cell function (HOMA-β) (WMD = -15.18; 95% CI = -22.08, -8.28, P < 0.001) changed following probiotics (or synbiotics) supplementation. Also supplementation with doses more than 2 billion CFU could reduce IL-10 concentrations (WMD = -1.84; 95% CI = -2.23, 1.87; P < 0.001). Glutathione (GSH) and Total Antioxidant Capacity (TAC) levels did not influence by synbiotics and probiotics; insignificancy was remained after subgrouping for participants' age, study duration, and disease duration. CONCLUSION Our findings revealed that synbiotics and probiotics supplementation has significant effect on some inflammatory and oxidative stress markers; although, the number of trials was too small to powerful conclusion and further investigations may be needed.
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Affiliation(s)
- Gholamreza Askari
- Department of Community Nutrition, School of Nutrition & Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Abed Ghavami
- Student Research Committee, Department of Community Nutrition, School of Nutrition & Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Farnaz Shahdadian
- Student Research Committee, Department of Clinical Nutrition, School of Nutrition & Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Amir Reza Moravejolahkami
- Student Research Committee, Department of Clinical Nutrition, School of Nutrition & Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
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Garcia-Fandino R, Piñeiro Á. Delving Into the Origin of Destructive Inflammation in COVID-19: A Betrayal of Natural Host Defense Peptides? Front Immunol 2021; 11:610024. [PMID: 33552069 PMCID: PMC7862704 DOI: 10.3389/fimmu.2020.610024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/03/2020] [Indexed: 01/08/2023] Open
Abstract
In contrast to other pathogenic agents that directly destroy host cells and tissues, the lethal power of SARS-CoV-2 resides in the over-reactive immune response triggered by this virus. Based on numerous evidences indicating that the lipid composition of host membranes is dramatically affected by COVID-19, and in the fact that our endogenous antimicrobial peptides (AMPs) are sensitive to the membrane composition of pathogenic agents, we propose that such destructive immune response is due to the direct action of AMPs. In a scenario where most host cell membranes are dressed by a pathogenic lipid composition, AMPs can indiscriminately attack them. This is why we use the "AMP betrayal" term to describe this mechanism. Previously proposed cytokine/bradykinin storm mechanisms are not incompatible with this new proposal. Interestingly, the harmful action of AMPs could be prevented by new therapies aimed to reestablish the lipid composition or to inhibit the action of specific peptides.
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Affiliation(s)
- Rebeca Garcia-Fandino
- Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
| | - Ángel Piñeiro
- Departamento de Física Aplicada, Facultade de Física, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
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Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation. Int J Mol Sci 2021; 22:ijms22020557. [PMID: 33429882 PMCID: PMC7826692 DOI: 10.3390/ijms22020557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 12/28/2020] [Accepted: 01/05/2021] [Indexed: 12/04/2022] Open
Abstract
Persistent infections, such as those provoked by the Gram-negative bacterium Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) patients, can induce inflammation with lung tissue damage and progressive alteration of respiratory function. Therefore, compounds having both antimicrobial and immunomodulatory activities are certainly of great advantage in fighting infectious diseases and chronic inflammation. We recently demonstrated the potent antipseudomonal efficacy of the antimicrobial peptide (AMP) Esc(1-21) and its diastereomer Esc(1-21)-1c, namely Esc peptides. Here, we confirmed this antimicrobial activity by reporting on the peptides’ ability to kill P. aeruginosa once internalized into alveolar epithelial cells. Furthermore, by means of enzyme-linked immunosorbent assay and Western blot analyses, we investigated the peptides’ ability to detoxify the bacterial lipopolysaccharide (LPS) by studying their effects on the secretion of the pro-inflammatory cytokine IL-6 as well as on the expression of cyclooxygenase-2 from macrophages activated by P. aeruginosa LPS. In addition, by a modified scratch assay we showed that both AMPs are able to stimulate the closure of a gap produced in alveolar epithelial cells when cell migration is inhibited by concentrations of Pseudomonas LPS that mimic lung infection conditions, suggesting a peptide-induced airway wound repair. Overall, these results have highlighted the two Esc peptides as valuable candidates for the development of new multifunctional therapeutics for treatment of chronic infectious disease and inflammation, as found in CF patients.
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18
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Zhang C, Yang M, Ericsson AC. The Potential Gut Microbiota-Mediated Treatment Options for Liver Cancer. Front Oncol 2020; 10:524205. [PMID: 33163393 PMCID: PMC7591398 DOI: 10.3389/fonc.2020.524205] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 09/21/2020] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer is one of the leading causes of cancer death worldwide. Surgical and non-surgical treatments are optional for liver cancer therapy based on the cancer stage. Accumulating studies show that the gut–liver axis influences the progression of liver diseases, including liver inflammation, fibrosis, cirrhosis, and cancer. However, the role of gut microbiota and their derived components and metabolites in liver cancer remains to be further clarified. In this review, we discuss the roles of gut microbiota and specific bacterial species in HCC and the strategies to modulate gut microbiota to improve antitumor therapy. Given the limitation of current treatments, gut microbiota-mediated therapy is a potential option for HCC treatment, including fiber diet and vegetable diet, antimicrobials, probiotics, and pharmaceutical inhibitors. Also, gut microbiota can be used as a marker for early diagnosis of HCC. HCC occurs dependent on various environmental and genetic factors, including diet and sex. Furthermore, gut microbiota impacts the immunotherapy of HCC treatment. Therefore, a better understanding of the role of the gut–liver axis in liver cancer is critically important to improve therapeutic efficacy.
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Affiliation(s)
- Chunye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, United States
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO, United States
| | - Aaron C Ericsson
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, United States.,University of Missouri Metagenomics Center, University of Missouri, Columbia, MO, United States
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