Diabetes mellitus and diabetic foot ulcer: Etiology, biochemical and molecular based treatment strategies via gene and nanotherapy

Mariadoss, Arokia Vijaya Anand; Sivakumar, Allur Subramaniyan; Lee, Chang-Hun; Kim, Sung Jae

doi:10.1016/j.biopha.2022.113134

Cited by 41 publications

(39 citation statements)

References 131 publications

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“…Currently, traditional intervention methods and DFU efficacy are unable to meet expectations ( 12 ). Stem cells can induce differentiation and secrete cytokines to form a capillary network in local ischemic tissues, establish collateral circulation, increase blood perfusion flow, and improve the ischemic condition of patients’ tissues in order to achieve a therapeutic effect ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the microenvironment of diabetic foot ulcers and potential drug identification based on scRNA-seq

et al. 2023

Front. Endocrinol.

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BackgroundDiabetes foot ulcers (DFUs) are a type of foot infection, ulcer, and/or deep tissue destruction caused by neuropathy and vascular disease in the distal extremities of diabetic patients. Its pathogenesis and its microenvironment are not entirely understood.MethodsInitially, the GSE165816 data set from the GEO database was utilized for single cell analysis to reveal the microenvironment and functional status of DFUs. The GSE199939 RNA-seq data set was utilized for external validation. On the basis of the logistic regression machine learning algorithm (OCLR), pseudo time series analysis, dryness index analysis, and drug target gene analysis were then performed. By constructing drug-gene and gene-gene networks, we can locate the most recent DFUs treatments. Finally, immunofluorescence technology was used to detect the cell-related markers of the DFUs microenvironment, and qPCR was used to detect the expression of drug targets in DFUs.ResultsFirstly, we used the Cell Maker database to obtain information about human cells and related gene markers, and manually reviewed a total of 45 kinds of cells and maker information that may appear in the DFUs microenvironment, which were divided into 17 cell clusters after annotation. Subsequently, we counted the proportions of DM and DFUs in different types of cells, and the results showed that the proportions of macrophages, white blood cells, and monocytes were higher in patients with DFUs, while the proportions of pluripotent stem cells and stromal cells were higher in patients with DM. The Pseudo-time series analysis of cells in DFUs showed that the differentiation pathways of immune cells, mesenchymal cells and stem cells were similar in the three states, while the other cells were distributed in different stages. At the level of a single cell, the scores of both multipotential stem cells and hematopoietic stem cells were significantly lower in DFU healing and non-healing than in DM. Additionally, the highly expressed genes in DFU were chosen as drug targets. We identified seven potential target genes and discovered twenty drugs with high significance. Finally, the colocalization relationship between CD19, ITGAM, and HLA-DR expression in monocytes and macrophages of DFU skin tissue and healthy subjects was analyzed by laser confocal microscopy with the immunofluorescence triple labeling method. The results showed that the expressions of CD19, ITGAM, and HLA-DR in the skin of DFUs were significantly higher than those in the skin of healthy subjects, and the co-localization relationship was significant in DFUs.ConclusionThis study can serve as a resource for the treatment of DFUs.

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Section: Introductionmentioning

confidence: 99%

Characterization of the microenvironment of diabetic foot ulcers and potential drug identification based on scRNA-seq

et al. 2023

Front. Endocrinol.

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“…Patients with diabetes are in a high glucose state for a long time, and their glucose metabolism is disordered, resulting in tissue hypoxia, an increase of damaging substances such as thromboxane, and complete vascular endothelial injury and promotion of microcirculation disorder ( 16 ). In addition, a high concentration of glucose glycosylates with protein and nucleic acid molecules inside and outside the blood vessel causes vascular cell dysfunction, promoting coagulation and thrombosis, leading to microangiopathy ( 17 ). As the mobility and phagocytosis of white blood cells (WBCs) are reduced, the immunity of the body is weakened due to peripheral neuropathy and vascular lesion.…”

Section: Introductionmentioning

confidence: 99%

Predicting the Risk of Diabetic Foot Ulcers From Diabetics With Dysmetabolism: A Retrospective Clinical Trial

Jiang

Gan

et al. 2022

Front. Endocrinol.

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BackgroundDiabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2D) often leads to amputation. Early intervention to prevent DFU is urgently necessary. So far, there have been no studies on predictive models associated with DFU risk factors. Our study aimed to quantify the predictive risk value of DFU, promote health education, and further develop behavioral interventions to reduce the incidence of DFU.MethodsData from 973 consecutive patients with T2D was collected from two hospitals. Patients from the Guangxi Medical University First Affiliated Hospital formed the training cohort (n = 853), and those from the Wuming Hospital of Guangxi Medical University formed the validation cohort (n = 120). Independent variable grouping analysis and multivariate logistic regression analysis were used to determine the risk factors of DFUs. The prediction model was established according to the related risk factors. In addition, the accuracy of the model was evaluated by specificity, sensitivity, predictive value, and predictive likelihood ratio.ResultsIn total, 369 of the 853 patients (43.3%) and 60 of the 120 (50.0%) were diagnosed with DFUs in the two hospitals. The factors associated with DFU were old age, male gender, lower body mass index (BMI), longer duration of diabetes, history of foot disease, cardiac insufficiency, no use of oral hypoglycemic agent (OHA), high white blood cell count, high platelet count, low hemoglobin level, low lymphocyte absolute value, and high postprandial blood glucose. After incorporating these 12 factors, the nomogram drawn achieved good concordance indexes of 0.89 [95% confidence interval (CI): 0.87 to 0.91] in the training cohort and 0.84 (95% CI: 0.77 to 0.91) in the validation cohort in predicting DFUs and had well-fitted calibration curves. Patients who had a nomogram score of ≥180 were considered to have a low risk of DFU, whereas those having ≥180 were at high risk.ConclusionsA nomogram was constructed by combining 12 identified risk factors of DFU. These 12 risk factors are easily available in hospitalized patients, so the prediction of DFU in hospitalized patients with T2D has potential clinical significance. The model provides a reliable prediction of the risk of DFU in patients with T2D.

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“…Diabetes brings about a number of acute complications, such as cardiovascular diseases, cerebrovascular diseases, renal disorders, and obesity [ 5 ]. In addition, people with diabetes experience deterioration when it comes to the healing of serious wounds.…”

Section: Introductionmentioning

confidence: 99%

Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds

Alamoudi

Alharbi

Abdel-Naim

et al. 2022

Life

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Diabetic hyperglycemia delays wound healing, leading to serious consequences. Topical antibiotics can reduce the risk of a wound infection during healing; nevertheless, the microbial fight against antibiotics brings about public health challenges. Anti-microbial peptides (AMPs) belong to a novel class of drug that is used to prevent and treat systemic and topical infections. The aim of the current work was to achieve better wound healing in diabetic rats by conjugating the anti-microbial peptide “apamin” (APA) with the broad-spectrum antibiotic “ceftriaxone” (CTX) to form a nanocomplex. The CTX–APA nanoconjugate formulation was optimized using a Box–Behnken design. The optimized CTX–APA nanoconjugate formulation was evaluated for its size and zeta potential, and was then examined using transmission electron microscopy (TEM). The CTX–APA nanoconjugate was loaded onto a hydroxypropyl methylcellulose (2% w/v)-based hydrogel. It was observed that the application of the CTX–APA nanocomplex on the wounded skin of diabetic rats accelerated the regeneration of the epithelium, granulation tissue formation, epidermal proliferation, and keratinization. The nanocomplex was capable of significantly reducing the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), while increasing the expression of transforming growth factor beta-1 (TGF-β1) as well as the angiogenic markers: hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Conclusively, the application of an ion-paired CTX–APA nanocomplex enhances wound healing in diabetic rats.

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Diabetes mellitus and diabetic foot ulcer: Etiology, biochemical and molecular based treatment strategies via gene and nanotherapy

Cited by 41 publications

References 131 publications

Characterization of the microenvironment of diabetic foot ulcers and potential drug identification based on scRNA-seq

Characterization of the microenvironment of diabetic foot ulcers and potential drug identification based on scRNA-seq

Predicting the Risk of Diabetic Foot Ulcers From Diabetics With Dysmetabolism: A Retrospective Clinical Trial

Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds

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