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Bai C, Yang W, Yan J, Qi G, Yang L, Wu Q, Peng J, Luo J, Liu T. Overexpression of hsa-HLA-DRB1 may delay diabetic wound healing and angiogenesis by regulating miRNA_12118 and FLT-1. Sci Rep 2025; 15:18409. [PMID: 40419622 DOI: 10.1038/s41598-025-03906-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 05/23/2025] [Indexed: 05/28/2025] Open
Abstract
We investigated the role and mechanism of hsa-HLA-DRB1 in the development and progression of diabetic foot ulcers. High-throughput sequencing was performed on three normal foot trauma tissues and diabetic foot ulcer tissues. The circRNAs with significant differences were identified. The downstream miRNAs were predicted by miRanda and RNAhybrid databases, and the mRNAs were predicted by the TargetScan database. Validation was performed with CCK8, flow cytometry, trabecular scratch assay, tubule generation assay, Western blot, dual luciferase assay, and RT-qPCR. High-throughput sequencing identified 461 significantly different circRNAs, of which 260 were up-regulated and 201 down-regulated. Compared to normal tissue, hsa-HLA-DRB1 was highly expressed in diabetic foot ulcers. The hsa-HLA-DRB1/miRNA_12118/FLT-1 axis was constructed. In vitro, we found that HLA-DRB1 overexpression inhibited cell viability, wound healing, and tubule formation, promoted apoptosis, and enhanced FLT-1 expression in HUVECs. The upregulation of hsa-HLA-DRB1 may promote diabetic foot development The upregulation of hsa - HLA - DRB1 may inhibit the biological function of endothelial cells by targeting miRNA_12118 and acting on FLT - 1. by targeting miRNA_12118 and acting on FLT-1. Therefore, our study highlights the key role of the hsa-HLA-DRB1/miRNA_12118/FLT-1 axis in diabetic foot trauma.
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Affiliation(s)
- Chao Bai
- Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
- Postdoctoral Research Center of Public Health and Preventive Medicine, Xinjiang Medical University, Urumqi, 830000, P.R. China
| | - Wenwen Yang
- Department of Clinical Nutrition, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Jianghao Yan
- Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Guangwei Qi
- Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Liuyu Yang
- Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Qingrui Wu
- Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Jieguang Peng
- Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Jun Luo
- Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China
| | - Tao Liu
- School of Public Health, Xinjiang Medical University, Urumqi, 830000, P.R. China.
- School of Public Health, Xinjiang Medical University, No. 567 Shangde North Road, Shimogou District, Urumqi, 830017, Xinjiang, China.
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2
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Dong Y, Wang M, Wang Q, Cao X, Chen P, Gong Z. Single-cell RNA-seq in diabetic foot ulcer wound healing. Wound Repair Regen 2024; 32:880-889. [PMID: 39264020 PMCID: PMC11584366 DOI: 10.1111/wrr.13218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 08/20/2024] [Accepted: 08/25/2024] [Indexed: 09/13/2024]
Abstract
Diabetic foot ulcer (DFU) is a chronic and serious complication of diabetes mellitus. It is mainly caused by hyperglycaemia, diabetic peripheral vasculopathy and diabetic peripheral neuropathy. These conditions result in ulceration of foot tissues and chronic wounds. If left untreated, DFU can lead to amputation or even endanger the patient's life. Single-cell RNA sequencing (scRNA-seq) is a technique used to identify and characterise transcriptional subpopulations at the single-cell level. It provides insight into cellular function and the molecular drivers of disease. The objective of this paper is to examine the subpopulations, genes and molecules of cells associated with chronic wounds of diabetic foot by using scRNA-seq. The paper aims to explore the wound-healing mechanism of DFU from three aspects: inflammation, angiogenesis and extracellular matrix remodelling. The goal is to gain a better understanding of the mechanism of DFU wound healing and identify possible DFU therapeutic targets, providing new insights for the application of DFU personalised therapy.
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Affiliation(s)
- Yan Dong
- Medical SchoolNantong UniversityNantongChina
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Mengting Wang
- Medical SchoolNantong UniversityNantongChina
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Qianqian Wang
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Xiaoliang Cao
- Medical SchoolNantong UniversityNantongChina
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Peng Chen
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
| | - Zhenhua Gong
- Medical SchoolNantong UniversityNantongChina
- Department of Burn and Plastic SurgeryAffiliated Hospital 2 of Nantong University, The First People's Hospital of NantongNantongChina
- Nantong Clinical Medical CollegeKangda College of Nanjing Medical UniversityNantongChina
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Norton P, Trus P, Wang F, Thornton MJ, Chang C. Understanding and treating diabetic foot ulcers: Insights into the role of cutaneous microbiota and innovative therapies. SKIN HEALTH AND DISEASE 2024; 4:e399. [PMID: 39104636 PMCID: PMC11297444 DOI: 10.1002/ski2.399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 04/22/2024] [Accepted: 05/18/2024] [Indexed: 08/07/2024]
Abstract
Background Notoriously known as the silent pandemic, chronic, non-healing diabetic foot ulcers (DFUs), pose a significant rate of incidence for amputation and are a major cause of morbidity. Alarmingly, the treatment and management strategies of chronic wounds represent a significant economic and health burden as well as a momentous drain on resources with billions per annum being spent in the US and UK alone. Defective wound healing is a major pathophysiological condition which propagates an acute wound to a chronic wound, further propelled by underlying conditions such as diabetes and vascular complications which are more prevalent amongst the elderly. Chronic wounds are prone to infection, which can exacerbate the condition, occasionally resulting in amputation for the patient, despite the intervention of modern therapies. However, amputation can only yield a 5-year survival rate for 50% of patients, highlighting the need for new treatments for chronic wounds. Findings The dynamic cutaneous microbiota is comprised of diverse microorganisms that often aid wound healing. Conversely, the chronic wound microbiome consists of a combination of common skin commensals such as Staphylococcus aureus and Staphylococcus epidermidis, as well as the opportunistic pathogen Pseudomonas aeruginosa. These bacteria have been identified as the most prevalent bacterial pathogens isolated from chronic wounds and contribute to prolific biofilm formation decreasing the efficiency of antimicrobials and further perpetuating a hyper-inflammatory state. Discussion and Conclusion Here, we review recent advances and provide a new perspective on alternative treatments including phage and microbiome transplant therapies and how the definitive role of the cutaneous microbiota impacts the aetiology of DFUs.
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Affiliation(s)
- Paul Norton
- School of Dental SciencesFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Biosciences InstituteFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Centre for Skin SciencesFaculty of Life SciencesUniversity of BradfordBradfordUK
| | - Pavlos Trus
- School of Dental SciencesFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Biosciences InstituteFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
| | - Fengyi Wang
- School of Dental SciencesFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Biosciences InstituteFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
| | - M. Julie Thornton
- Centre for Skin SciencesFaculty of Life SciencesUniversity of BradfordBradfordUK
| | - Chien‐Yi Chang
- School of Dental SciencesFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
- Biosciences InstituteFaculty of Medical SciencesNewcastle UniversityNewcastle Upon TyneUK
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Li Z, Jian Y, Wei Z. Association between monocyte to lymphocyte ratio and diabetic foot ulcer in the population of the US with diabetes based on the 1999-2004 National Health and Nutrition Examination Survey data: a retrospective cross-sectional study. Front Endocrinol (Lausanne) 2024; 15:1361393. [PMID: 38726344 PMCID: PMC11080649 DOI: 10.3389/fendo.2024.1361393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024] Open
Abstract
Background Diabetic foot ulcer (DFU) is a severe complication that occurs in patients with diabetes and is a primary factor that necessitates amputation. Therefore, the occurrence and progression of DFU must be predicted at an early stage to improve patient prognosis and outcomes. In this regard, emerging evidence suggests that inflammation-related markers play a significant role in DFU. One such potential marker, the monocyte-lymphocyte ratio (MLR), has not been extensively studied in relation to DFU. This study aimed to define a connection between MLR and DFU. Methods A cross-sectional study was conducted using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004. DFU was defined based on survey questionnaires assessing the presence of nonhealing ulcers in the lower extremities for more than 4 weeks in diabetes patients. The MLR was calculated as the ratio of the monocyte count to the lymphocyte count, which was directly obtained from laboratory data files. Logistic regression analysis was performed to assess the relationship between the MLR and DFU. Stratified analysis according to age, sex, body mass index, blood glucose, hemoglobin, and glycated hemoglobin categories was conducted, and multiple imputations were applied to missing data. Results In total, 1246 participants were included; the prevalence of DFU was 9.4% (117/1246). A multivariable regression model revealed a significant association between DFU and a 0.1 unit increase in MLR after adjusting for all covariates (adjusted odds ratio=1.16, 95% confidence interval: 1.02-1.33). Subgroup analyses revealed consistent findings regarding the impact of MLR on the presence of DFU (p > 0.05). Conclusion MLR is significantly associated with DFU in diabetes patients, and can be used as one of the indicators for predicting the occurrence of DFU. MLR assessment may be a valuable component in the follow-up of patients with diabetes.
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Affiliation(s)
- Zirui Li
- Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Yang Jian
- Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Zairong Wei
- Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
- The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, Guizhou, China
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Yang DR, Wang MY, Zhang CL, Wang Y. Endothelial dysfunction in vascular complications of diabetes: a comprehensive review of mechanisms and implications. Front Endocrinol (Lausanne) 2024; 15:1359255. [PMID: 38645427 PMCID: PMC11026568 DOI: 10.3389/fendo.2024.1359255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 03/08/2024] [Indexed: 04/23/2024] Open
Abstract
Diabetic vascular complications are prevalent and severe among diabetic patients, profoundly affecting both their quality of life and long-term prospects. These complications can be classified into macrovascular and microvascular complications. Under the impact of risk factors such as elevated blood glucose, blood pressure, and cholesterol lipids, the vascular endothelium undergoes endothelial dysfunction, characterized by increased inflammation and oxidative stress, decreased NO biosynthesis, endothelial-mesenchymal transition, senescence, and even cell death. These processes will ultimately lead to macrovascular and microvascular diseases, with macrovascular diseases mainly characterized by atherosclerosis (AS) and microvascular diseases mainly characterized by thickening of the basement membrane. It further indicates a primary contributor to the elevated morbidity and mortality observed in individuals with diabetes. In this review, we will delve into the intricate mechanisms that drive endothelial dysfunction during diabetes progression and its associated vascular complications. Furthermore, we will outline various pharmacotherapies targeting diabetic endothelial dysfunction in the hope of accelerating effective therapeutic drug discovery for early control of diabetes and its vascular complications.
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Affiliation(s)
- Dong-Rong Yang
- Department of Endocrinology and Metabolism, Shenzhen University General Hospital, Shenzhen, Guangdong, China
- Department of Pathophysiology, Shenzhen University Medical School, Shenzhen, Guangdong, China
| | - Meng-Yan Wang
- Department of Pathophysiology, Shenzhen University Medical School, Shenzhen, Guangdong, China
| | - Cheng-Lin Zhang
- Department of Pathophysiology, Shenzhen University Medical School, Shenzhen, Guangdong, China
| | - Yu Wang
- Department of Endocrinology and Metabolism, Shenzhen University General Hospital, Shenzhen, Guangdong, China
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Napiórkowska-Mastalerz M, Wybranowski T, Bosek M, Kruszewski S, Rhone P, Ruszkowska-Ciastek B. A Preliminary Evaluation of Advanced Oxidation Protein Products (AOPPs) as a Potential Approach to Evaluating Prognosis in Early-Stage Breast Cancer Patients and Its Implication in Tumour Angiogenesis: A 7-Year Single-Centre Study. Cancers (Basel) 2024; 16:1068. [PMID: 38473424 DOI: 10.3390/cancers16051068] [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: 01/23/2024] [Revised: 02/28/2024] [Accepted: 03/04/2024] [Indexed: 03/14/2024] Open
Abstract
Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 μM and 10.39 μM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan-Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 μM and 10.39 μM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice.
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Affiliation(s)
- Marta Napiórkowska-Mastalerz
- Department of Biophysics, Faculty of Pharmacy, Nicolaus Copernicus University, Collegium Medicum, 85-067 Bydgoszcz, Poland
| | - Tomasz Wybranowski
- Department of Biophysics, Faculty of Pharmacy, Nicolaus Copernicus University, Collegium Medicum, 85-067 Bydgoszcz, Poland
| | - Maciej Bosek
- Department of Biophysics, Faculty of Pharmacy, Nicolaus Copernicus University, Collegium Medicum, 85-067 Bydgoszcz, Poland
| | - Stefan Kruszewski
- Department of Biophysics, Faculty of Pharmacy, Nicolaus Copernicus University, Collegium Medicum, 85-067 Bydgoszcz, Poland
| | - Piotr Rhone
- Clinical Ward of Breast Cancer and Reconstructive Surgery, Oncology Centre Prof. F. Łukaszczyk Memorial Hospital, 85-796 Bydgoszcz, Poland
| | - Barbara Ruszkowska-Ciastek
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University, Collegium Medicum, 85-094 Bydgoszcz, Poland
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Sen CK, Roy S, Khanna S. Diabetic Peripheral Neuropathy Associated with Foot Ulcer: One of a Kind. Antioxid Redox Signal 2023. [PMID: 35850520 DOI: 10.1089/ars.2022.0093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Significance: Diabetic peripheral neuropathy (DPN) associated with a diabetic foot ulcer (DFU) is likely to be complicated with critical factors such as biofilm infection and compromised skin barrier function of the diabetic skin. Repaired skin with a history of biofilm infection is known to be compromised in barrier function. Loss of barrier function is also observed in the oxidative stress affected diabetic and aged skin. Recent Advances: Loss of barrier function makes the skin prone to biofilm infection and cellulitis, which contributes to chronic inflammation and vasculopathy. Hyperglycemia favors biofilm formation as glucose lowering led to reduction in biofilm development. While vasculopathy limits oxygen supply, the O2 cost of inflammation is high increasing hypoxia severity. Critical Issues: The host nervous system can be inhabited by bacteria. Because electrical impulses are a part of microbial physiology, polymicrobial colonization of the host's neural circuit is likely to influence transmission of action potential. The identification of perineural apatite in diabetic patients with peripheral neuropathy suggests bacterial involvement. DPN starts in both feet at the same time. Future Directions: Pair-matched studies of DPN in the foot affected with DFU (i.e., DFU-DPN) compared with DPN in the without ulcer, and intact skin barrier function, are likely to provide critical insight that would help inform effective care strategies. This review characterizes DFU-DPN from a translational science point of view presenting a new paradigm that recognizes the current literature in the context of factors that are unique to DFU-DPN.
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Affiliation(s)
- Chandan K Sen
- Indiana Center for Regenerative Medicine & Engineering, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Sashwati Roy
- Indiana Center for Regenerative Medicine & Engineering, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Savita Khanna
- Indiana Center for Regenerative Medicine & Engineering, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Mahmoudvand G, Karimi Rouzbahani A, Razavi ZS, Mahjoor M, Afkhami H. Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight. Front Bioeng Biotechnol 2023; 11:1158484. [PMID: 37122856 PMCID: PMC10133463 DOI: 10.3389/fbioe.2023.1158484] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/31/2023] [Indexed: 05/02/2023] Open
Abstract
Diabetic foot ulcer (DFU) is considered the most catastrophic complication of diabetes mellitus (DM), leading to repeated hospitalizations, infection, gangrene, and finally amputation of the limb. In patients suffering from diabetes mellitus, the wound-healing process is impaired due to various factors such as endothelial dysfunction and synthesis of advanced glycation end-products, hence, conventional therapeutic interventions might not be effective. With increasing therapeutic applications of mesenchymal stem cells (MSCs) in recent years, their potential as a method for improving the wound-healing process has gained remarkable attention. In this field, mesenchymal stem cells exert their beneficial effects through immunomodulation, differentiation into the essential cells at the site of ulcers, and promoting angiogenesis, among others. In this article, we review cellular and molecular pathways through which mesenchymal stem cell therapy reinforces the healing process in non-healing Diabetic foot ulcers.
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Affiliation(s)
- Golnaz Mahmoudvand
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Arian Karimi Rouzbahani
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Zahra Sadat Razavi
- Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohamad Mahjoor
- Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Afkhami
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
- *Correspondence: Hamed Afkhami,
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Tang YB, Uwimana MMP, Zhu SQ, Zhang LX, Wu Q, Liang ZX. Non-coding RNAs: Role in diabetic foot and wound healing. World J Diabetes 2022; 13:1001-1013. [PMID: 36578864 PMCID: PMC9791568 DOI: 10.4239/wjd.v13.i12.1001] [Citation(s) in RCA: 7] [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: 08/26/2022] [Revised: 10/26/2022] [Accepted: 11/18/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetic foot ulcer (DFU) and poor wound healing are chronic complications in patients with diabetes. The increasing incidence of DFU has resulted in huge pressure worldwide. Diagnosing and treating this condition are therefore of great importance to control morbidity and improve prognosis. Finding new markers with potential diagnostic and therapeutic utility in DFU has gathered increasing interest. Wound healing is a process divided into three stages: Inflammation, proliferation, and regeneration. Non-coding RNAs (ncRNAs), which are small protected molecules transcribed from the genome without protein translation function, have emerged as important regulators of diabetes complications. The deregulation of ncRNAs may be linked to accelerated DFU development and delayed wound healing. Moreover, ncRNAs can be used for therapeutic purposes in diabetic wound healing. Herein, we summarize the role of microRNAs, long ncRNAs, and circular RNAs in diverse stages of DFU wound healing and their potential use as novel therapeutic targets.
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Affiliation(s)
- Yi-Bo Tang
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Muhuza Marie Parfaite Uwimana
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Shu-Qi Zhu
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Li-Xia Zhang
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Qi Wu
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Zhao-Xia Liang
- Department of Obstetrics, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
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Patton D, Avsar P, Wilson P, Mairghani M, O'Connor T, Nugent L, Moore Z. Treatment of diabetic foot ulcers: review of the literature with regard to the TIME clinical decision support tool. J Wound Care 2022; 31:771-779. [PMID: 36113541 DOI: 10.12968/jowc.2022.31.9.771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE The aim of this clinically orientated paper is to offer an overview of diabetic foot ulcer (DFU) dressings generally, and more specifically, their use in the treatment of DFUs. METHOD The TIME clinical decision support tool (CDST) has been used as a clinical tool that can help clinicians bring together the different aspects of dressings for DFU treatment into a holistic approach to patient care. RESULTS DFUs are often difficult to heal, are painful and impact negatively on the individual's quality of life. Most DFU dressings are designed to support the healing of hard-to-heal wounds and represent one part of the management of DFUs. Apart from providing a moist environment, absorbing increased exudate, enhancing granulation and assisting in autolysis, the dressings need to be cost-effective. Wound dressing selection is based on clinical knowledge that ensures the dressing is most appropriate for the individual and the wound, taking into account the comorbidities that the individual may have. CONCLUSION This paper has highlighted how the use of the TIME CDST model can enhance clinical care and is a further tool clinicians should consider when developing and executing DFU treatment plans. Future research needs to focus on large multicentre studies using robust methodologies, given the current gaps in the evidence, to determine the effectiveness of dressing products for DFUs.
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Affiliation(s)
- Declan Patton
- School of Nursing & Midwifery, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin.,Skin, Wounds and Trauma Research Centre, School of Nursing and Midwifery. RCSI University of Medicine and Health Sciences, Dublin.,Adjunct Associate Professor, Fakeeh College of Health Sciences, Jeddah, Saudi Arabia.,Honorary Senior Fellow, Faculty of Science, Medicine and Health, University of Wollongong, Australia.,Adjunct Professor, Griffith University, Australia
| | - Pinar Avsar
- Skin, Wounds and Trauma Research Centre, School of Nursing and Midwifery. RCSI University of Medicine and Health Sciences, Dublin
| | - Pauline Wilson
- Skin, Wounds and Trauma Research Centre, School of Nursing and Midwifery. RCSI University of Medicine and Health Sciences, Dublin
| | - Maisoon Mairghani
- Public Health and Epidemiology, RCSI University of Medicine and Health Sciences
| | - Tom O'Connor
- School of Nursing & Midwifery, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin.,Skin, Wounds and Trauma Research Centre, School of Nursing and Midwifery. RCSI University of Medicine and Health Sciences, Dublin.,Adjunct Professor, Griffith University, Australia.,Honorary Professor, Lida Institute, Shanghai, China.,Professor, Fakeeh College of Health Sciences
| | - Linda Nugent
- School of Nursing & Midwifery, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin.,Adjunct Assistant Professor, Fakeeh College of Health Sciences, Jeddah, Saudi Arabia
| | - Zena Moore
- School of Nursing & Midwifery, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin.,Skin, Wounds and Trauma Research Centre, School of Nursing and Midwifery. RCSI University of Medicine and Health Sciences, Dublin.,Honorary Professor, Lida Institute, Shanghai, China.,Professor, Fakeeh College of Health Sciences.,Professor, Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Belgium.,Visiting Professor, University of Wales, Cardiff, UK
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11
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Xu N, Chen Y, Guo D, Deng Y, Guo W, Liu X, Wang Y, Lu H, Liu A, Zhu J, Li F. Rhein promotes the proliferation of keratinocytes by targeting oestrogen receptors for skin ulcer treatment. BMC Complement Med Ther 2022; 22:209. [PMID: 35932049 PMCID: PMC9354312 DOI: 10.1186/s12906-022-03691-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 07/28/2022] [Indexed: 11/10/2022] Open
Abstract
Background The Sheng-ji Hua-yu (SJHY) formula is a quite effective Traditional Chinese Medicines (TCM) in the treatment of delayed diabetic wounds. Previous research has shown that the SJHY formula has significant anti-inflammatory and wound-healing effects, but the precise mechanism remains unknown. The purpose of this study was to evaluate the effects of rhein, a compound extracted from SJHY formula, in keratinocytes and to investigate the underlying mechanisms. Methods Microscale thermophoresis (MST) technology was used to confirm that rhein binds directly to oestrogen receptors (ERs). Rhein was then used to treat keratinocytes in vitro. Cell cycle and proliferation analysis, Real-time polymerase chain reaction (RT-PCR) and Western-blot were conducted. Results Rhein increased the proportion of cells in the S phase of the cell cycle and promoted keratinocyte proliferation. ICI 182,780, an ER inhibitor, was also used to treat keratinocytes. The expression of c-myc mRNA and protein induced by rhein was antagonized by ICI 182,780, indicating that this induction is ER dependent. Intervention with ICI 182,780 had no effect on the upregulation of FosB and JunD, indicating that activator protein 1 (AP-1) members (FosB and JunD) are involved in rhein-induced c-myc mRNA and protein expression but does not require the ER. Conclusion The present study found that rhein stimulates keratinocyte proliferation by activating the oestrogen signalling pathway via the oestrogen receptor, which induces the expression of c-myc in collaboration with FosB and JunD, thereby accelerating the process of re-epithelialization. Supplementary Information The online version contains supplementary material available at 10.1186/s12906-022-03691-1.
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Wang H, Wang X, Liu X, Zhou J, Yang Q, Chai B, Chai Y, Ma Z, Lu S. miR-199a-5p Plays a Pivotal Role on Wound Healing via Suppressing VEGFA and ROCK1 in Diabetic Ulcer Foot. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:4791059. [PMID: 35432725 PMCID: PMC9010206 DOI: 10.1155/2022/4791059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 03/10/2022] [Indexed: 11/18/2022]
Abstract
Diabetes mellitus (DM) is a growing health problem. As a common complication of DM, diabetic foot ulcer (DFU) results in delayed wound healing and is a leading cause of nontraumatic amputation. miR-199a-5p, a short noncoding RNA, had abnormal expression in DFU wound tissues. The expression of miR-199a-5p was significantly increased in DFU wound tissues, skin tissues of diabetic rats, and high glucose-induced cells. Vascular endothelial growth factor A (VEGFA) and Rho-associated kinase 1 (ROCK1) are directly targets of miR-199a-5p. Inhibiting the expression of miR-199a-5p alleviated the inhibition of VEGFA and ROCK1, thereby rescued impaired proliferation and migration of HG-induced cells, and restored the normal function of the cells to some extent. In diabetic rats, inhibition of miR-199a-5p significantly increased the expression of VEGFA and ROCK1, significantly promoted wound healing, and rescued impaired wound healing. miR-199a-5p and its targets showed therapeutic effect on diabetic wounds.
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Affiliation(s)
- Hongshu Wang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai 200233, China
| | - Xianyi Wang
- Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Xiaomin Liu
- Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China
- Shanghai New Tobacco Product Research Institute, Shanghai 201315, China
| | - Jinbao Zhou
- Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Qianqian Yang
- Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Binshu Chai
- Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Yimin Chai
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai 200233, China
| | - Zhongliang Ma
- Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Shengdi Lu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai 200233, China
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Chia-Jui H, Yu L, Jiang YQ, Tan W, Gao GM, Li HB, Han L. Negative pressure wound therapy, artificial skin and autogenous skin implantation in diabetic foot ulcers. J Wound Care 2022; 31:40-46. [PMID: 35077212 DOI: 10.12968/jowc.2022.31.1.40] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Diabetic foot ulcers (DFUs) are one of the most serious diabetic consequences, leading to amputations. Various therapies have been used to treat DFUs; however, a combination of negative pressure suction, artificial skin and autogenous skin implantation have never been investigated. This study aimed to evaluate the effectiveness of a novel three-step therapy protocol using negative pressure wound therapy (NPWT), artificial skin and autogenous skin implantation in patients with DFUs. METHOD At a single tertiary university hospital between 2015 and 2018, the three-step therapy protocol was applied to patients with DFUs and its safety and efficacy was investigated. RESULTS A total of 21 patients took part in the study. The majority of the patients were female (62%), with a mean age of 65 years and a mean body mass index of 21kg/m2. A third (n=7) of operative sites experienced minor complications, with two requiring re-operation. At a median follow up of 24 months, the average time of complete wound healing was 46 days, and the wound healing rate was 71%. The first-stage wound healing rate was 90%. All patients had achieved remission without any further recurrence of disease. CONCLUSION This comprehensive surgical technique for managing DFUs achieved a high local cure rate, minimal functional morbidity, and acceptable wound complication rates. The three-step therapy protocol has the potential to promote the healing process of DFUs, which is expected to serve as a new method for the treatment and cure of DFUs.
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Affiliation(s)
- Hu Chia-Jui
- Department of Orthopedics, Xiamen ChangGung Hospital, Xiamen City, Fujian Province, China
| | - Lai Yu
- Department of Orthopedics, Xiamen ChangGung Hospital, Xiamen City, Fujian Province, China
| | - Yu-Qing Jiang
- Department of Orthopedics, Xiamen ChangGung Hospital, Xiamen City, Fujian Province, China
| | - Wen Tan
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, China
| | - Gong-Ming Gao
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, China
| | - Hai-Bo Li
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, China
| | - Long Han
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, China
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Guarnotta V, Radellini S, Vigneri E, Cernigliaro A, Pantò F, Scondotto S, Almasio PL, Guercio G, Giordano C. Diabetic foot ulcers: Retrospective comparative analysis from Sicily between two eras. PLoS One 2021; 16:e0259405. [PMID: 34874944 PMCID: PMC8651101 DOI: 10.1371/journal.pone.0259405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 10/18/2021] [Indexed: 12/28/2022] Open
Abstract
Aim The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008–2013 and 2014–2019. Methods We compared the two eras, era1: 2008–13, era2: 2014–19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled. Results In the population hospitalized for DFU in 2008–2013, 59.1% of males and 40.9% of females died, whilst in 2014–2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p < 0.001), just as CKD was severe (14.5% vs. 4%, p < 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07–2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37–2.95, p <0.001) and eGFR less than 92 ml/min (OR 2.84, 95% CI 1.51–5.34, p 0.001) were independently associated with risk of death. Conclusions Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality.
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Affiliation(s)
- Valentina Guarnotta
- Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro” (PROMISE), Università di Palermo, Palermo, Italy
- * E-mail: (CG); (VG)
| | - Stefano Radellini
- Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro” (PROMISE), Università di Palermo, Palermo, Italy
| | - Enrica Vigneri
- Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro” (PROMISE), Università di Palermo, Palermo, Italy
| | | | - Felicia Pantò
- Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro” (PROMISE), Università di Palermo, Palermo, Italy
| | | | - Piero Luigi Almasio
- Sezione di Gastroenterologia ed Epatologia, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro”, PROMISE, Università degli Studi di Palermo, Palermo, Italy
| | - Giovanni Guercio
- Sezione di Chirurgia d’Urgenza, Dipartimento di Chirurgia, Oncologia e Scienza Orale, DICHIRONS, Università degli Studi di Palermo, Palermo, Italy
| | - Carla Giordano
- Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza “G. D’Alessandro” (PROMISE), Università di Palermo, Palermo, Italy
- * E-mail: (CG); (VG)
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Huang L, Cai HA, Zhang MS, Liao RY, Huang X, Hu FD. Ginsenoside Rg1 promoted the wound healing in diabetic foot ulcers via miR-489-3p/Sirt1 axis. J Pharmacol Sci 2021; 147:271-283. [PMID: 34507636 DOI: 10.1016/j.jphs.2021.07.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 07/07/2021] [Accepted: 07/28/2021] [Indexed: 12/27/2022] Open
Abstract
PURPOSE Diabetic foot ulcers (DFUs) are common complications of high severity for diabetes. Ginsenoside Rg1 (Rg1) has the potential for diabetes and cardiovascular diseases therapy. This research aimed at exploring the regulation of Rg1 on DFUs treatment and the underlying mechanism. METHODS Human umbilical vein endothelial cells (HUVECs) incubated with high-glucose culture medium were established for induction of diabetes model. The MTT assay, Annexin V/PI assay and oxidative stress detection were carried out on high-glucose-induced HUVECs. Dual-luciferase reporter assay was performed to prove the interaction of miR-489-3p and Sirt1. DFUs model was established to determine the efficiency of Rg1 and miR-489-3p in wound closure of DFUs in vivo. RESULTS Rg1 promoted cell proliferation, migration and angiogenesis, and reduced cell apoptosis in high-glucose-induced HUVECs. Knockdown of miR-489-3p alleviated the high-glucose-induced damage to HUVECs, while overexpression of miR-489-3p attenuated the protection effects of Rg1. Overexpression Sirt1 promoted wound healing in DFUs and Sirt1 was a direct target of miR-489-3p. In addition, animal experiments demonstrated that Rg1 promoted wound closure by regulating miR-489-3p/Sirt1 axis. CONCLUSIONS Rg1 alleviated the DFUs by increasing Sirt1 expression via miR-489-3p downregulation and promoting activation of PI3K/AKT/eNOS signaling.
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Affiliation(s)
- Liang Huang
- Second Clinical Medical College, Southern Medical University, Guangzhou, 510515, Guangdong Province, PR China; Department of Rehabilitation, Guangdong Provincial People's Hospital, Guangzhou, 510515, Guangdong Province, PR China
| | - Hua-An Cai
- Department of Rehabilitation Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410016, Hunan Province, PR China; Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410016, Hunan Province, PR China.
| | - Ming-Sheng Zhang
- Second Clinical Medical College, Southern Medical University, Guangzhou, 510515, Guangdong Province, PR China; Department of Rehabilitation, Guangdong Provincial People's Hospital, Guangzhou, 510515, Guangdong Province, PR China.
| | - Ruo-Yi Liao
- First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, 410004, Hunan Province, PR China
| | - Xing Huang
- Department of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410016, Hunan Province, PR China
| | - Feng-Dan Hu
- Department of Rehabilitation Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410016, Hunan Province, PR China
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Schönborn M, Łączak P, Pasieka P, Borys S, Płotek A, Maga P. Pro- and Anti-Angiogenic Factors: Their Relevance in Diabetic Foot Syndrome-A Review. Angiology 2021; 73:299-311. [PMID: 34541892 DOI: 10.1177/00033197211042684] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Peripheral arterial disease can involve tissue loss in up to 50% of patients with diabetic foot syndrome (DFS). Consequently, revascularization of narrowed or occluded arteries is one of the most common forms of comprehensive treatment. However, technically successful angioplasty does not always result in the healing of ulcers. The pathomechanism of this phenomenon is still not fully understood, but inadequate angiogenesis in tissue repair may play an essential role. Changes in pro- and anti-angiogenic factors among patients with DFS are not always clear and conclusive. In particular, some studies underline the role of decreased concentration of pro-angiogenic factors and higher levels of anti-angiogenic mediators. Nevertheless, there are still controversial issues, including the paradox of impaired wound healing despite high concentrations of some pro-angiogenic factors, dynamics of their expression during the healing process, and their mutual relationships. Exploring this process among diabetic patients may provide new insight into well-known methods of treatment and show their real benefits and chances for improving outcomes.
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Affiliation(s)
- Martyna Schönborn
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland.,Doctoral School of Medical and Health Sciences, 162261Jagiellonian University, Krakow, Poland
| | - Patrycja Łączak
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
| | - Paweł Pasieka
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
| | - Sebastian Borys
- Department of Metabolic Diseases, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
| | - Anna Płotek
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
| | - Paweł Maga
- Department of Angiology, Faculty of Medicine, 162261Jagiellonian University Medical College, Krakow, Poland
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Zhou DR, Deng HY, Pu LL, Lin SL, Gou R, Wang FL. The effectiveness and safety of recombinant human growth hormone combined with alginate dressing in the treatment of diabetic foot ulcer: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e23984. [PMID: 33592853 PMCID: PMC7870157 DOI: 10.1097/md.0000000000023984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 12/02/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Diabetic foot ulcer (DFU) is one of the serious complications of diabetes. It is the result of a joint effect of lower extremities vascular lesions, neuropathy, and infection, which require amputation and even threaten the life of the patient. At present, the conventional treatment for DFU includes infection control, wound care, wound reduction, reduction of foot pressure, use of dressings that are beneficial to wound surface healing, etc, but the effectiveness is not satisfactory. Recombinant human growth hormone and alginate dressing have been used in clinical, but there is lack of the relevant evidence of its effectiveness and safety, so this study evaluates the clinical effectiveness and safety of recombinant human growth hormone combined with alginate dressing in the treatment of DFU by systematic evaluation, the purpose is to provide a theoretical basis for the treatment of diabetic foot ulcer. METHODS This study mainly retrieves the randomized controlled trial of recombinant human growth hormone combined alginate dressing in the treatment of DFU in 7 electronic databases, such as PubMed, EMbase, Cochrane Library, SinoMed, CNKI, WANGFANG database, and VIP database. All the retrieval dates of database are from the establishment of the database until May 31, 2020. At the same time, searching the related degree papers, conference papers, and other gray literature by manual. The original literature data are independently screened and extracted by 2 researchers on the basis of inclusion and exclusion criteria and literature information sheets, and cross-checked and resolved through group discussions and consultations when there are differences of the opinion. Assessing the methodological quality of inclusion in the study based on the "Bias Risk Assessment Form" of the Cochrane Collaboration Network. Using the software of RevMan 5.3.3 and STATA 13.0 for statistical analysis. RESULTS This study compares the main and secondary outcome indicators by systematic evaluation and it will provide strong evidence of recombinant human growth hormone combined alginate dressing in the treatment of DFU. ETHICS AND DISSEMINATION All data in this study are obtained through the web database and do not involve humans, so ethical approval is not suitable for this study. OSF REGISTRATION NUMBER DOI 10.17605/OSF.IO/W6P24. CONCLUSION This study will give positive conclusions about the effectiveness and safety of recombinant human growth hormone combined alginate dressing in the treatment of DFU.
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Affiliation(s)
| | | | | | | | - Rong Gou
- Department of Encephalopathy, Haikou Hospital of Traditional Chinese Medicine, No. 45 Jinpan Road, Longhua District, Haikou, Hainan Province, 570216, China
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Song M, Chen L, Zhang L, Li C, Coffie JW, Fang Z, Zhang L, Wang S, Gao X, Wang H. Cryptotanshinone enhances wound healing in type 2 diabetes with modulatory effects on inflammation, angiogenesis and extracellular matrix remodelling. PHARMACEUTICAL BIOLOGY 2020; 58:845-853. [PMID: 32870741 PMCID: PMC8641666 DOI: 10.1080/13880209.2020.1803369] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
CONTEXT Cryptotanshinone (CT) is a diterpene quinone compound from Salvia miltiorrhiza Bge. Labiatae has been widely used in cardio-cerebral vascular diseases, which could be potentially effective in treating diabetic wounds. OBJECTIVE This study evaluates the wound healing activity of CT by employing an excisional wound splinting model in db/db mice. MATERIALS AND METHODS Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with sodium carboxymethyl cellulose (CMC-Na) or 300 mg/kg/d CT for 16 days. Wound closure was measured every two days. Body weight, fasting blood glucose, re-epithelialization, granulation, leukocyte infiltration, capillary density, collagen deposition and expressions of CXCL1, CXCL2, VEGF, Ang-1, p-eNOS, eNOS, α-SMA, MMP2 and MMP9 were analysed. Expression of VEGF and tube formation was measured in vitro with human umbilical vein endothelial cells (HUVECs). RESULTS CT significantly accelerated rate of wound closure, as the contraction ratio increased from 68% (non-treated group) to 83% (CT-treated group) at days 16 post-injury. A significant increase was observed in re-epithelialization and granulation tissue formation. Mechanistically, CT suppressed leukocyte infiltration and CXCL1 and CXCL2 expression. CT treatment also increased blood vessel density and expression level of VEGF, Ang-1 and p-eNOS. In vitro, CT boosted expression of VEGF and tube formation of endothelial cells. Moreover, extracellular matrix (ECM) remodelling was enhanced by CT via promoting fibroblast transformation and inhibiting MMP2 and MMP9. CONCLUSIONS Our study provides evidence that CT could be developed as a potential therapeutic agent for the treatment of chronic diabetic wound healing.
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Affiliation(s)
- Min Song
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lu Chen
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lusha Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chunxiao Li
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Joel Wake Coffie
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhirui Fang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Liyuan Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shaoxia Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiumei Gao
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Hong Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- CONTACT Hong Wang , School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Rd., West Area, Tuanbo New Town, Jinghai Dist., Tianjin301617, China
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