Search

Although numerous studies have shown distinctive similarities between osteomyelitis and diabetic foot ulcers (DFU), the common pathogenesis of both is not fully understood. The current research focuses on an in-depth study of the molecular and pathway mechanisms involved in the complication of these 2 diseases. We downloaded clinical information on osteomyelitis (GSE30119) and DFU (GSE29221) from the GEO database, along with gene expression matrices. Differentially expressed genes (DEGs) among normal individuals and patients with osteomyelitis; normal individuals and patients with DFU were identified by R software, and thus common DEGs were confirmed. We then analyzed these differential genes, including the functional pathway analysis, protein-protein interaction (PPI), modules and hub genes establishment, and transcription factor regulatory networks. We identified 109 common DEGs (46 up-regulated and 63 down-regulated genes) for subsequent analysis. The results of PPI network and the functional pathway analysis revealed the importance of immune response and inflammatory response in both diseases. Among them, chemokines and cytokines were found to be closely related to both osteomyelitis and DFU. In addition, the tumor necrosis factor (TNF) pathway and Staphylococcus aureus infection were found to have more significant roles too. The 12 most essential key genes were later screened by cytoHubba, including matrix metalloproteinases (MMP) 1, MMP3, MMP9, IL8, C-X-C chemokine receptor (CXCR) 2, C-X-C motif chemokine ligand (CXCL) 9, CXCL10, CXCL13, FCGR3B, IL1B, LCN2, S100A12. CXCL10, and MMP1 were validated using the least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Osteomyelitis and DFU share similar molecular and pathway mechanisms. These common key genes and pathways may provide new directions toward the future study of osteomyelitis and DFU., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The objective of the present study was to explore the association between intercellular adhesion molecule 1 (ICAM1) polymorphisms (rs5498 and rs3093030) and diabetic foot (DF) susceptibility in a Chinese Han population.128 type 2 diabetes mellitus (T2DM) patients with DF, 147 T2DM patients without DF, and 155 healthy individuals were enrolled in this study. ICAM1 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotypes and alleles of the polymorphisms were compared by χ test between the 2 groups. Association between ICAM1 polymorphisms and DF susceptibility was expressed through odds ratio (OR) with corresponding 95% confidence interval (95%CI). Effects of ICAM1 polymorphisms on DF clinical characteristics were analyzed by t test.GG genotype of rs5498 polymorphism was distinctly correlated with decreased T2DM risk (OR = 0.369, 95%CI = 0.152-0.895) and reduced susceptibility to DF among healthy controls (OR = 0.316, 95%CI = 0.119-0.837). Similar results were discovered between rs5498 G allele and decreased risk of T2DM (OR = 0.676, 95%CI = 0.475-0.963) and DF (OR = 0.656, 95%CI = 0.453-0.950) among healthy controls. Individuals carrying rs3093030 T allele had low susceptibility to DF developed from T2DM (OR = 0.634, 95%CI = 0.412-0.974). DF patients carrying rs5498 AA genotype had significantly higher serum creatinine levels than GG genotype carriers (P = .003).ICAM1 rs3093030 polymorphism may act as a protective factor against DF developed from T2DM, moreover, rs5498 may be involved in onset of T2DM.Clinical trial number: ChiCTR-INR-18010231.

The present study aimed to explore the influence of sirtuin 1 (SIRT1) polymorphisms (rs12778366 and rs3758391) on diabetic foot (DF) susceptibility and severity in patients with type 2 diabetes mellitus (T2DM).This case-control study recruited 142 patients with DF, 148 patients with T2DM, and 148 healthy controls. SIRT1 gene polymorphisms were sequenced by polymerase chain reaction (PCR) and direct sequencing method. The relative expression of SIRT1 mRNA was estimated using quantitative real-time PCR (qRT-PCR) assay. Odds ratio (OR) with 95% confidence interval (95% CI) were used to represent the association of SIRT1 polymorphisms with DF susceptibility and severity. The results were adjusted using logistic regression analysis.C allele of rs12778366 polymorphism was significantly correlated with reduced DF susceptibility which deriving from healthy controls (adjusted OR = 0.364, 95% CI = 0.158-0.835) so was patients with T2DM (P = .047, OR = 0.591, 95%CI = 0.349-0.998), but the results became nonsignificant adjusted by clinical features (adjusted OR = 0.654, 95% CI = 0.391-1.094). We failed to find any significant association between rs3758391 polymorphisms and T2DM, DF susceptibility. No significant association has been discovered between SIRT1 polymorphisms and DF severity or characteristics. In addition, compared to healthy control and T2DM cases, patients with DF exhibited significant downregulation of SIRT1. The 2 studied polymorphisms had no effects on its gene expression (P > .05 for all).SIRT1 rs12778366 polymorphism C allele might act as a protective factor for DF onset.

Monocyte chemotactant protein-1 (MCP-1), a pro-inflammatory cytokine, plays an important role in inflammatory process. In present study, we evaluated the association of MCP-1 gene rs1024611 polymorphism with risk and clinical characteristics of diabetic foot ulcers (DFUs).This study recruited 116 patients with DFUs, 135 patients with diabetes mellitus (DM) without complications (non-DFU), and 149 healthy controls (HCs). MCP-1 gene rs1024611 polymorphism was genotyped by direct sequencing. The expression of MCP-1 was analyzed using quantitative real-time polymerase chain reaction. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assume the association strength.Individuals with rs1024611 AG and GG genotypes exhibited significantly higher susceptibility to DFUs, in the comparison with HCs (AG vs AA, OR = 2.364, 95% CI = 1.021-5.470; GG vs AA, OR = 2.686, 95% CI = 1.154-6.255). Meanwhile, G allele was associated with increased DFUs susceptibility (OR = 1.457, 95% CI = 1.014-2.093). Besides, rs1024611 SNP was slightly correlated with increased DFUs susceptibility in patients with DM. GG genotype of rs1024611 was significantly correlated with higher epidermal thickness and lower dermis thickness in patients with DFUs (P < .01). Patients with DFU exhibited upregulation of MCP-1 mRNA, and GG genotype was correlated with enhanced MCP-1 expression in DFU and non-DFU groups.Rs1024611 polymorphism was significantly associated with MCP-1 expression and individual susceptibility to DFUs.

The purpose of the present study was to investigate distribution of monocyte chemoattractant protein-1 (MCP-1) -2518A/G and vascular endothelial growth factor (VEGF) -634G/C polymorphisms in type 2 diabetes melitus patients (T2DM) presenting diabetic foot ulcer (DFU). Additionally, we evaluated the effects of these 2 polymorphisms on serum levels of MCP-1 and VEGF in the study population.Patients diagnosed with T2DM without or with DFU were recruited in the study. The distribution of MCP-1 -2518A/G and VEGF -634G/C polymorphisms was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the protein levels of MCP-1 and VEGF. The comparisons of protein levels in DFU patients were performed by student t test according to their genotypes.The frequencies of GG genotype and G allele of MCP-1 -2518A/G was increased in DFU patients, compared with T2DM patients (odds ratio [OR] = 2.60, 95% confidence interval [CI] = 1.23-5.50, P = .011 and OR = 1.72, 95% CI = 1.18-2.50, P = .005, respectively). Moreover, the increased frequency of GG was significantly associated with up-regulated MCP-1 level in DFU patients (P < .001). Analysis for VEGF -634G/C polymorphisms indicated that the prevalence of CC genotype and C allele of the polymorphisms was decreased in DFU patients, compared with T2DM patients (OR = 0.36, 95% CI = 0.17-0.77, P = .008 and OR = 0.63, 95% CI = 0.43-0.91, P = .015, respectively). DFU patients carrying CC genotype had a higher level of VEGF than those with other genotypes (P = .007).MCP-1 -2518A/G and VEGF -634G/C polymorphisms may involve in occurrence and progress of DFU through regulating transcription activity of the genes.

The aim of this study was to investigate the association of vascular endothelial growth factor (VEGF) gene polymorphisms with diabetic foot ulcer (DFU) susceptibility in a Chinese Han population.Around 88 type 2 diabetes mellitus (T2DM) patients without DFU and 97 T2DM patients with DFU were enrolled in this study. A total of 103 age and gender matched healthy individuals were recruited as healthy control. VEGF gene polymorphisms rs699947 and rs13207351 were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association between VEGF gene polymorphisms and DFU risk.The frequency of AA and AC genotypes of rs699947 were lower in DFU patients than that in healthy controls (P = .020, P = .031), suggesting that AC and AA genotypes were negatively associated with DFU risk originating from healthy individuals (OR = 0.496, 95%CI = 0.274-0.899; OR = 0.130, 95%CI = 0.015-1.112). Significantly decreased trend of rs699947 A allele was observed in DFU patients when compared to the controls (P = .004), suggesting A allele was distinctly correlated with decreased DFU risk (OR = 0.490, 95%CI = 0.298-0.804). But no significant differences were detected in rs13207351 genotype and allele distributions between patients and control groups (P > .05).Individuals carrying VEGF rs699947 A allele show low susceptibility to DFU in the Chinese Han population.

Toll-like receptors (TLRs) are innate immune receptors that mediate the inflammatory response in diabetes mellitus (DM). The aim of this study is to evaluate the association of TLR2 and TLR9 gene polymorphism in patients with type 2 DM (T2DM) and diabetic foot (DF).The study included 90 subjects divided into group I (30 patients with T2DM and DF), group II (30 patients with T2DM and no evidence of DF), and group III (normal control subjects). TLR2 (1350 T/C, rs3804100) and TLR9 (1237 T/C, rs5743836) genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for all subjects.There was a statistically significant difference in the distribution of TLR9-1237 T/C genotypes between groups I and II (P < .029) as well as between groups I and III (P < .001). Calculated risk estimation revealed that TLR9-1237 polymorphism conferred almost 20 times increased risk of DF disorders in T2DM (OR = 20, 95% CI = 5.38-74.30). There was no statistical difference in the distribution of TLR2-1350T/C genotypes between the 3 groups.TLR9-1237 T/C gene polymorphism may be considered as a molecular risk for DF among patients with T2DM.

Background: In the past two decades, regenerative surgeons have focused increasing attention on the potential of gene therapy for treatment of local disorders and injuries. Gene transfer techniques may provide an effective local and short-term induction of growth factors without the limits of other topical therapies. In 2002, Tepper and Mehrara accurately reviewed the topic: given the substantial advancement of research on this issue, an updated review is provided., Methods: Literature indexed in the National Center for Biotechnology Information database (PubMed) has been reviewed using variable combinations of keywords ("gene therapy," "regenerative medicine," "tissue regeneration," and "gene medicine"). Articles investigating the association between gene therapies and local pathologic conditions have been considered. Attention has been focused on articles published after 2002. Further literature has been obtained by analysis of references listed in reviewed articles., Results: Gene therapy approaches have been successfully adopted in preclinical models for treatment of a large variety of local diseases affecting almost every type of tissue. Experiences in abnormalities involving skin (e.g., chronic wounds, burn injuries, pathologic scars), bone, cartilage, endothelia, and nerves have been reviewed. In addition, the supporting role of gene therapies to other tissue-engineering approaches has been discussed. Despite initial reports, clinical evidence has been provided only for treatment of diabetic ulcers, rheumatoid arthritis, and osteoarthritis., Conclusions: Translation of gene therapy strategies into human clinical trials is still a lengthy, difficult, and expensive process. Even so, cutting-edge gene therapy-based strategies in reconstructive procedures could soon set valuable milestones for development of efficient treatments in a growing number of local diseases and injuries.