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Search Results (301)

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Keywords = diabetic foot complication

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18 pages, 914 KiB  
Article
Microvascular, Biochemical, and Clinical Impact of Hyperbaric Oxygen Therapy in Recalcitrant Diabetic Foot Ulcers
by Daniela Martins-Mendes, Raquel Costa, Ilda Rodrigues, Óscar Camacho, Pedro Barata Coelho, Vítor Paixão-Dias, Carla Luís, Ana Cláudia Pereira, Rúben Fernandes, Jorge Lima and Raquel Soares
Cells 2025, 14(15), 1196; https://doi.org/10.3390/cells14151196 - 4 Aug 2025
Viewed by 18
Abstract
Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study [...] Read more.
Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies. Full article
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16 pages, 1159 KiB  
Article
SmartBoot: Real-Time Monitoring of Patient Activity via Remote Edge Computing Technologies
by Gozde Cay, Myeounggon Lee, David G. Armstrong and Bijan Najafi
Sensors 2025, 25(14), 4490; https://doi.org/10.3390/s25144490 - 19 Jul 2025
Viewed by 581
Abstract
Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system—a wearable, real-time remote [...] Read more.
Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system—a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch—for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and compared with staff-recorded adherence logs. Additionally, user experience was assessed using the Technology Acceptance Model (TAM) in healthy participants (n = 12) and patients with DFU (n = 81). The SmartBoot demonstrated high accuracy in cadence and step count across conditions (bias < 5.5%), with an adherence detection accuracy of 96% (Össur) and 97% (Foot Defender). TAM results indicated strong user acceptance and perceived ease of use across both cohorts. These findings support the SmartBoot system’s potential as a valid, scalable solution for real-time remote monitoring of adherence and mobility in DFU management. Further clinical validation in ongoing studies involving DFU patients is underway. Full article
(This article belongs to the Section Wearables)
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19 pages, 2781 KiB  
Review
From Control to Cure: Insights into the Synergy of Glycemic and Antibiotic Management in Modulating the Severity and Outcomes of Diabetic Foot Ulcers
by Idris Ajibola Omotosho, Noorasyikin Shamsuddin, Hasniza Zaman Huri, Wei Lim Chong and Inayat Ur Rehman
Int. J. Mol. Sci. 2025, 26(14), 6909; https://doi.org/10.3390/ijms26146909 - 18 Jul 2025
Viewed by 558
Abstract
Diabetic foot ulcers (DFUs), which affect approximately 15% of individuals with diabetes mellitus (DM), result from complex molecular disturbances involving chronic hyperglycemia, immune dysfunction, and infection. At the molecular level, chronic hyperglycemia promotes the formation of advanced glycation end products (AGEs), activates the [...] Read more.
Diabetic foot ulcers (DFUs), which affect approximately 15% of individuals with diabetes mellitus (DM), result from complex molecular disturbances involving chronic hyperglycemia, immune dysfunction, and infection. At the molecular level, chronic hyperglycemia promotes the formation of advanced glycation end products (AGEs), activates the AGE-RAGE-NF-κB axis, increases oxidative stress, and impairs macrophage polarization from the pro-inflammatory M1 to the reparative M2 phenotype, collectively disrupting normal wound healing processes. The local wound environment is further worsened by antibiotic-resistant polymicrobial infections, which sustain inflammatory signaling and promote extracellular matrix degradation. The rising threat of antimicrobial resistance complicates infection management even further. Recent studies emphasize that optimal glycemic control using antihyperglycemic agents such as metformin, Glucagon-like Peptide 1 receptor agonists (GLP-1 receptor agonists), and Dipeptidyl Peptidase 4 enzyme inhibitors (DPP-4 inhibitors) improves overall metabolic balance. These agents also influence angiogenesis, inflammation, and tissue regeneration through pathways including AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and vascular endothelial growth factor (VEGF) signaling. Evidence indicates that maintaining glycemic stability through continuous glucose monitoring (CGM) and adherence to antihyperglycemic treatment enhances antibiotic effectiveness by improving immune cell function and reducing bacterial virulence. This review consolidates current molecular evidence on the combined effects of glycemic and antibiotic therapies in DFUs. It advocates for an integrated approach that addresses both metabolic and microbial factors to restore wound homeostasis and minimize the risk of severe outcomes such as amputation. Full article
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28 pages, 392 KiB  
Article
Predicting Risk and Complications of Diabetes Through Built-In Artificial Intelligence
by Siana Sagar Bontha, Sastry Kodanda Rama Jammalamadaka, Chandra Prakash Vudatha, Sasi Bhanu Jammalamadaka, Balakrishna Kamesh Duvvuri and Bala Chandrika Vudatha
Computers 2025, 14(7), 277; https://doi.org/10.3390/computers14070277 - 15 Jul 2025
Viewed by 485
Abstract
The global healthcare system faces significant challenges posed by diabetes and its complications, highlighting the need for innovative strategies to improve early diagnosis and treatment. Machine learning models help in the early detection of diseases and recommendations for taking safety measures and treating [...] Read more.
The global healthcare system faces significant challenges posed by diabetes and its complications, highlighting the need for innovative strategies to improve early diagnosis and treatment. Machine learning models help in the early detection of diseases and recommendations for taking safety measures and treating the disease. A comparative analysis of existing machine learning (ML) models is necessary to identify the most suitable model while uniformly fixing the model parameters. Assessing risk based on biomarker measurement and computing overall risk is important for accurate prediction. Early prediction of complications that may arise, based on the risk of diabetes and biomarkers, using machine learning models, is key to helping patients. In this paper, a comparative model is presented to evaluate ML models based on common model characteristics. Additionally, a risk assessment model and a prediction model are presented to help predict the occurrence of complications. Random Forest (RF) is the best model for predicting the occurrence of Type 2 Diabetes (T2D) based on biomarker input. It has also been shown that the prediction of diabetes complications using neural networks is highly accurate, reaching a level of 98%. Full article
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7 pages, 201 KiB  
Brief Report
The Post-Healing Follow-Up of Diabetic Foot Ulcers by a Multidisciplinary Team to Reduce Their Recurrence: An Observational Retrospective Study
by Marie Bouly, Francois-Xavier Laborne, Caroline Tourte, Elodie Henry, Alfred Penfornis and Dured Dardari
J. Clin. Med. 2025, 14(14), 4975; https://doi.org/10.3390/jcm14144975 - 14 Jul 2025
Viewed by 322
Abstract
Background: Diabetic foot disease is a public health problem. The challenges of its management lie in the complexity of wound healing and, in particular, the high rate of lesion recurrence. Objectives: The primary objective of the study was to evaluate whether [...] Read more.
Background: Diabetic foot disease is a public health problem. The challenges of its management lie in the complexity of wound healing and, in particular, the high rate of lesion recurrence. Objectives: The primary objective of the study was to evaluate whether optimized post-healing follow-up by a multidisciplinary team can reduce the recurrence rate of foot ulcers in people living with diabetes. The secondary objectives were to assess patient needs in terms of hospitalization for recurrence, the number of amputations, pedicure care, and the use of adapted footwear. Participants: The study included 129 patients with diabetes presenting a healed foot ulcer. A total of 38 patients underwent an annual post-healing follow-up visit with a multidisciplinary team (optimized follow-up), while 91 had a visit every 2 years (minimum follow-up). Results: Of the 38 patients with optimal follow-up, 8 presented a wound recurrence (21.1%) compared with 38 out of 91 patients (41.8%) receiving minimum follow-up. The recurrence rate decreased significantly between the two groups (p < 0.05). The use of adapted shoes was also significantly better in the group with optimized follow-up (p = 0.02). Conclusions: Regular post-healing follow-up with a multidisciplinary team seems to be a contributing factor to reducing the recurrence of diabetic foot ulcers among people living with diabetes. Full article
16 pages, 1265 KiB  
Review
Novel Treatments for Diabetic Foot Osteomyelitis: A Narrative Review
by Crystal Jing, Julia E. Ralph, Jamie Lim, Jackson M. Cathey, Conor N. O'Neill and Albert T. Anastasio
Microorganisms 2025, 13(7), 1639; https://doi.org/10.3390/microorganisms13071639 - 11 Jul 2025
Viewed by 546
Abstract
Diabetic foot osteomyelitis (DFO) is a severe complication of diabetes mellitus and a leading cause of non-traumatic lower extremity amputation. Treatment remains clinically challenging with high recurrence rates despite standard antibiotic therapy and surgical debridement. This narrative review synthesizes current evidence on novel [...] Read more.
Diabetic foot osteomyelitis (DFO) is a severe complication of diabetes mellitus and a leading cause of non-traumatic lower extremity amputation. Treatment remains clinically challenging with high recurrence rates despite standard antibiotic therapy and surgical debridement. This narrative review synthesizes current evidence on novel operative and nonoperative therapies for DFO, focusing on emerging biomaterials, local antibiotic delivery systems, innovative surgical techniques, and adjunctive topical agents. Studies examining bioabsorbable and nonabsorbable antibiotic carriers, such as calcium sulfate beads, collagen sponges, and bioactive glass, demonstrate promising infection resolution rates and a potential to reduce the surgical burden, though most are limited by small cohorts and observational designs. Similarly, alternative surgical approaches (i.e., cancelloplasty, conservative bone excision, and tibial cortex distraction) have shown early success in limb preservation. Nonoperative strategies, including adjunct antimicrobials, antimicrobial peptides, and topical oxygen, offer additional options, particularly for patients unfit for surgery. While initial outcomes are encouraging, the supporting evidence is heterogeneous and primarily limited to case series and small, noncomparative trials. Overall, these novel therapies show potential as adjuncts to established DFO management, but further prospective research is indicated to define their long-term efficacy, safety, and role in clinical practice. Full article
(This article belongs to the Section Medical Microbiology)
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19 pages, 5784 KiB  
Article
Identification of Exosome-Associated Biomarkers in Diabetic Foot Ulcers: A Bioinformatics Analysis and Experimental Validation
by Tianbo Li, Lei Gao and Jiangning Wang
Biomedicines 2025, 13(7), 1687; https://doi.org/10.3390/biomedicines13071687 - 10 Jul 2025
Viewed by 440
Abstract
Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes and are characterized by impaired wound healing and a high amputation risk. Exosomes—which are nanovesicles carrying proteins, RNAs, and lipids—mediate intercellular communication in wound microenvironments, yet their biomarker potential in DFUs remains [...] Read more.
Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes and are characterized by impaired wound healing and a high amputation risk. Exosomes—which are nanovesicles carrying proteins, RNAs, and lipids—mediate intercellular communication in wound microenvironments, yet their biomarker potential in DFUs remains underexplored. Methods: We analyzed transcriptomic data from GSE134431 (13 DFU vs. 8 controls) as a training set and validated findings in GSE80178 (6 DFU vs. 3 controls). A sum of 7901 differentially expressed genes (DEGs) of DFUs were detected and intersected with 125 literature-curated exosome-related genes (ERGs) to yield 51 candidates. This was followed by GO/KEGG analyses and a PPI network construction. Support vector machine–recursive feature elimination (SVM-RFE) and the Boruta random forest algorithm distilled five biomarkers (DIS3L, EXOSC7, SDC1, STX11, SYT17). Expression trends were confirmed in both datasets. Analyses included nomogram construction, functional and correlation analyses, immune infiltration, GSEA, gene co-expression and regulatory network construction, drug prediction, molecular docking, and RT-qPCR validation in clinical samples. Results: A nomogram combining these markers achieved an acceptable calibration (Hosmer–Lemeshow p = 0.0718, MAE = 0.044). Immune cell infiltration (CIBERSORT) revealed associations between biomarker levels and NK cell and neutrophil subsets. Gene set enrichment analysis (GSEA) implicated IL-17 signaling, proteasome function, and microbial infection pathways. A GeneMANIA network highlighted RNA processing and vesicle trafficking. Transcription factor and miRNA predictions uncovered regulatory circuits, and DGIdb-driven drug repurposing followed by molecular docking identified Indatuximab ravtansine and heparin as high-affinity SDC1 binders. Finally, RT-qPCR validation in clinical DFU tissues (n = 5) recapitulated the bioinformatic expression patterns. Conclusions: We present five exosome-associated genes as novel DFU biomarkers with diagnostic potential and mechanistic links to immune modulation and vesicular transport. These findings lay the groundwork for exosome-based diagnostics and therapeutic targeting in DFU management. Full article
(This article belongs to the Section Cell Biology and Pathology)
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11 pages, 253 KiB  
Article
Association of Nrf2 Single Nucleotide Polymorphism rs35652124 and FABP4 Levels with Peripheral Artery Disease Among Type 2 Diabetes Mellitus Pakistani Population
by Iqra Ayaz, Nakhshab Choudhry, Amna Ihsan, Tehreem Zubair, Aamir Jamal Gondal and Nighat Yasmin
Curr. Issues Mol. Biol. 2025, 47(7), 530; https://doi.org/10.3390/cimb47070530 - 9 Jul 2025
Viewed by 250
Abstract
Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide [...] Read more.
Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide polymorphisms (SNPs) among PAD-T2DM patients. In a case-control study, 123 samples (healthy control HC, T2DM, and PAD-T2DM; n = 41 each) were collected from the diabetic foot clinic at Mayo Hospital, Lahore. Baseline and biochemical data were collected. PAD diagnosis was established by measuring the ankle-brachial index with color Doppler ultrasound. Serum FABP4 levels were measured using an ELISA. Nrf2 SNP rs35652124 analysis was performed by restriction fragment length polymorphism. PAD-T2DM prevalence was higher among male subjects (61.1%). Fasting plasma glucose levels (p = 0.02), total cholesterol (p < 0.0001), and LDL-cholesterol (p = 0.01) were significantly higher in PAD-T2DM as compared to T2DM. SNP association analysis showed that homozygous genotype TT (OR: 3.85, 95% (CI): 1.22–12.11, p = 0.02) and T-allele (OR: 1.31, 95% (CI): 1.31–4.67, p = 0.005) were significantly associated with PAD-T2DM. FABP4 levels were higher in the PAD-T2DM group as compared to T2DM (p < 0.0001) and were significantly associated with Nrf2 SNP genotype TT (p < 0.001) and CT (p = 0.01) in PAD-T2DM. Our results showed, for the first time, that the Nrf2 SNP is significantly associated with PAD-T2DM and FABP4 levels compared to T2DM. Full article
23 pages, 3705 KiB  
Article
Revealing the Multi-Target Mechanisms of Fespixon Cream in Diabetic Foot Ulcer Healing: Integrated Network Pharmacology, Molecular Docking, and Clinical RT-qPCR Validation
by Tianbo Li, Dehua Wei, Jiangning Wang and Lei Gao
Curr. Issues Mol. Biol. 2025, 47(7), 485; https://doi.org/10.3390/cimb47070485 - 25 Jun 2025
Viewed by 760
Abstract
Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese [...] Read more.
Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and relevant literature, and their corresponding targets were standardized using the Universal Protein Resource (UniProt) database. Diabetic foot ulcer (DFU)-related targets were retrieved and filtered from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The intersection of drug and disease targets was identified, and a protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The interaction network was visualized using Cytoscape version 3.7.2 software. The potential mechanisms of the shared targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using R software packages, and results were visualized through Bioinformatics online tools. Molecular docking was performed to validate the binding between key active compounds of Fespixon cream and core DFU targets using AutoDock Vina version 1.1.2 and PyMOL software. Furthermore, RT-qPCR analysis was performed on wound edge tissue samples from DFU patients treated with Fespixon cream to experimentally verify the mRNA expression levels of predicted hub genes. Results: Network pharmacology analysis identified eight active compounds in Fespixon cream, along with 153 potential therapeutic targets related to diabetic foot ulcer (DFU). Among these, 21 were determined as core targets, with the top five ranked by degree value being RAC-αserine/threonine-protein kinase (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Interleukin-6 (IL6), and Mitogen-activated protein kinase 1 (MAPK1). GO enrichment analysis indicated that the targets of Fespixon cream were primarily involved in various biological processes related to cellular stress responses. KEGG pathway enrichment revealed that these targets were significantly enriched in pathways associated with diabetic complications, atherosclerosis, inflammation, and cancer. Molecular docking confirmed stable binding interactions between the five major active compounds—quercetin, apigenin, rosmarinic acid, salvigenin, and cirsimaritin—and the five core targets (AKT1, TP53, TNF, IL6, MAPK1). Among them, quercetin exhibited the strongest binding affinity with AKT1. RT-qPCR validation in clinical DFU tissue samples demonstrated consistent expression trends with computational predictions: AKT1 was significantly upregulated, while TP53, TNF, IL6, and MAPK1 were markedly downregulated in the Fespixon-treated group compared to controls (p < 0.001), supporting the proposed multi-target therapeutic mechanism. Conclusions: Our study reveals the potential mechanisms by which Fespixon cream exerts therapeutic effects on DFUs. The efficacy of Fespixon cream in treating DFUs is attributed to the synergistic actions of its bioactive components through multiple targets and multiple signaling pathways. Full article
(This article belongs to the Section Molecular Pharmacology)
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15 pages, 1477 KiB  
Article
Geopropolis from Melipona fasciculata Smith Accelerates Wound Healing in Diabetic Mice
by Aramys Silva Reis, Gabriel Carvalho de Souza, Guilherme Martins Gomes Fontoura, Luecya Alves de Carvalho Silva, Alberto Jorge Oliveira Lopes, Richard Pereira Dutra, Lucilene Amorim Silva, Rosane Nassar Meireles Guerra, Maria Nilce Sousa Ribeiro and Flávia Raquel Fernandes Nascimento
Metabolites 2025, 15(6), 413; https://doi.org/10.3390/metabo15060413 - 19 Jun 2025
Viewed by 762
Abstract
Background: Diabetic foot ulcers present a significant clinical challenge because of their high prevalence and severe complications. The need for innovative and accessible treatment options is critical. Owing to their medicinal properties, natural products, such as geopropolis, hold promise. However, the wound healing [...] Read more.
Background: Diabetic foot ulcers present a significant clinical challenge because of their high prevalence and severe complications. The need for innovative and accessible treatment options is critical. Owing to their medicinal properties, natural products, such as geopropolis, hold promise. However, the wound healing potential of the geopropolis of Melipona fasciculata, particularly in accelerating the healing of diabetic ulcers, remains unexplored. In this study, we evaluated the ability of the geopropolis of M. fasciculata to promote wound healing in diabetic mice. Methods: Geopropolis was collected, prepared as a hydroalcoholic extract, and formulated into a topical cream. Non-obese diabetic (NOD) mice with induced chronic wounds were treated with this cream daily, and wound healing was assessed through macroscopic measurements, histological analysis, cytokine quantification, and in silico molecular docking studies. Results: The results demonstrated that, compared with the control treatment, the geopropolis cream accelerated wound closure at all the analyzed time points (days 3, 7, and 14), reduced inflammatory infiltrates, and enhanced fibroblast proliferation and collagen deposition. These alterations were particularly pronounced in the final phase of healing, indicating an improvement in wound repair processes. These effects occurred without altering systemic cytokine levels, suggesting a localized treatment action. These results may be partially associated with the theoretical ability of beta-amyrin and cycloartenol to interact with human myeloperoxidase (MPO), as suggested by in silico docking analysis. Conclusions: Overall, the findings indicate that geopropolis cream could represent a viable alternative for managing diabetic ulcers, providing an effective means to enhance wound healing while remaining accessible to low-income populations. Full article
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23 pages, 4049 KiB  
Article
Gut Microbiome Engineering for Diabetic Kidney Disease Prevention: A Lactobacillus rhamnosus GG Intervention Study
by Alaa Talal Qumsani
Biology 2025, 14(6), 723; https://doi.org/10.3390/biology14060723 - 19 Jun 2025
Viewed by 731
Abstract
The gut microbiota has emerged as a critical modulator in metabolic diseases, with substantial evidence supporting its role in attenuating diabetes-related nephropathy. Recent investigations demonstrate that strategic manipulation of intestinal microflora offers novel therapeutic avenues for safeguarding renal function against diabetic complications. This [...] Read more.
The gut microbiota has emerged as a critical modulator in metabolic diseases, with substantial evidence supporting its role in attenuating diabetes-related nephropathy. Recent investigations demonstrate that strategic manipulation of intestinal microflora offers novel therapeutic avenues for safeguarding renal function against diabetic complications. This investigation sought to determine the nephroprotective potential of Lactobacillus rhamnosus GG (LGG) administration in diabetic nephropathy models. Six experimental cohorts were evaluated: control, probiotic-supplemented control, diabetic, diabetic receiving probiotic therapy, diabetic with antibiotics, and diabetic treated with both antibiotics and probiotics. Diabetic conditions were established via intraperitoneal administration of streptozotocin (50 mg/kg) following overnight fasting, according to validated protocols for experimental diabetes induction. Probiotic therapy (3 × 109 CFU/kg, bi-daily) began one month before diabetes induction and continued throughout the study duration. Glycemic indices were monitored at bi-weekly intervals, inflammatory biomarkers, renal function indices, and urinary albumin excretion. The metabolic profile was evaluated through the determination of HOMA-IR and the computation of metabolic syndrome scores. Microbiome characterization employed 16S rRNA gene sequencing alongside metagenomic shotgun sequencing for comprehensive microbial community mapping. L. rhamnosus GG supplementation substantially augmented microbiome richness and evenness metrics. Principal component analysis revealed distinct clustering of microbial populations between treatment groups. The Prevotella/Bacteroides ratio, an emerging marker of metabolic dysfunction, normalized following probiotic intervention in diabetic subjects. Results: L. rhamnosus GG administration markedly attenuated diabetic progression, achieving glycated hemoglobin reduction of 32% compared to untreated controls. Pro-inflammatory cytokine levels (IL-6, TNF-α) decreased significantly, while anti-inflammatory mediators (IL-10, TGF-β) exhibited enhanced expression. The renal morphometric analysis demonstrated preservation of glomerular architecture and reduced interstitial fibrosis. Additionally, transmission electron microscopy confirmed the maintenance of podocyte foot process integrity in probiotic-treated groups. Conclusions: The administration of Lactobacillus rhamnosus GG demonstrated profound renoprotective efficacy through multifaceted mechanisms, including microbiome reconstitution, metabolic amelioration, and inflammation modulation. Therapeutic effects suggest the potential of a combined probiotic and pharmacological approach to attenuate diabetic-induced renal pathology with enhanced efficacy. Full article
(This article belongs to the Section Microbiology)
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20 pages, 1377 KiB  
Review
The Multi-Dimensional Role of Vitamin D in the Pathophysiology and Treatment of Diabetic Foot Ulcers: From Molecular Mechanisms to Clinical Translation
by Weiwei Tang, Shengqiu Chen, Shuxia Zhang and Xingwu Ran
Int. J. Mol. Sci. 2025, 26(12), 5719; https://doi.org/10.3390/ijms26125719 - 14 Jun 2025
Viewed by 781
Abstract
Diabetic foot ulcers (DFUs) constitute a severe and debilitating complication of diabetes, imposing a substantial global health burden due to their intricate pathophysiology and impaired wound healing processes. Vitamin D deficiency is highly prevalent among diabetic populations, and accumulating evidence indicates its potential [...] Read more.
Diabetic foot ulcers (DFUs) constitute a severe and debilitating complication of diabetes, imposing a substantial global health burden due to their intricate pathophysiology and impaired wound healing processes. Vitamin D deficiency is highly prevalent among diabetic populations, and accumulating evidence indicates its potential involvement in the pathogenesis and prognosis of DFUs. This review comprehensively explores the diverse roles of vitamin D in DFUs, encompassing its molecular mechanisms such as immunomodulation, promotion of angiogenesis, neuroprotection, and induction of antimicrobial peptides, as well as the metabolic characteristics associated with various vitamin D forms and compromised vitamin D receptor (VDR) signaling pathways. Although robust observational studies have established an association between vitamin D deficiency and adverse outcomes in DFUs, the clinical validation of supplementation efficacy through randomized controlled trials (RCTs) remains constrained by limitations such as small sample sizes, heterogeneity in study protocols, and insufficient long-term follow-up. This highlights the critical need for large-scale, high-quality studies to ascertain optimal treatment regimens and to cater to individualized patient requirements, particularly for individuals with obesity or those with renal impairments. Innovative strategies, such as the topical administration of vitamin D through intelligent delivery systems leveraging advanced biomaterials like nanofibers and hydrogels, exhibit substantial preclinical potential in enhancing stability, achieving targeted controlled release, and augmenting local biological effects, including the induction of antimicrobial peptides. Nevertheless, significant challenges persist in conclusively establishing clinical efficacy, comprehensively elucidating the underlying mechanisms, ensuring the safe translation of novel delivery systems, and developing personalized therapeutic strategies. The future success of these interventions hinges on meticulous research and interdisciplinary collaboration to seamlessly integrate validated vitamin D-based interventions into a comprehensive multidisciplinary management framework for DFUs, thereby holding promise for improving the clinical outcomes of this debilitating condition. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 4.0)
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12 pages, 694 KiB  
Article
Sudomotor Dysfunction as an Early Marker of Autonomic and Cardiovascular Risk in Diabetes: Insights from a Cross-Sectional Study Using SUDOSCAN
by Larisa Anghel, Claudiu Cobuz, Laura-Cătălina Benchea, Vasile Maciuc, Maricela Cobuz, Radu-Andy Sascău and Cristian Stătescu
Biosensors 2025, 15(6), 372; https://doi.org/10.3390/bios15060372 - 10 Jun 2025
Viewed by 543
Abstract
Background: Diabetic neuropathy, particularly in its autonomic form, is often underdiagnosed despite its clinical significance. Electrochemical skin conductance (ESC), measured by SUDOSCAN, offers a non-invasive way to assess the autonomic dysfunction. Methods: A total of 288 diabetic patients were assessed using SUDOSCAN to [...] Read more.
Background: Diabetic neuropathy, particularly in its autonomic form, is often underdiagnosed despite its clinical significance. Electrochemical skin conductance (ESC), measured by SUDOSCAN, offers a non-invasive way to assess the autonomic dysfunction. Methods: A total of 288 diabetic patients were assessed using SUDOSCAN to measure ESC in the hands and feet. Clinical and laboratory parameters, including glycated hemoglobin (HbA1c), body mass index (BMI), blood pressure, lipid profile, and cardiovascular risk, were analyzed for correlations with ESC. Neuropathy status was evaluated, and ROC analysis was performed to assess diagnostic accuracy. Results: Sudomotor dysfunction was prevalent, particularly in patients with a diabetes duration exceeding 20 years (p < 0.05). Men showed significantly higher right foot ESC than women (76.5 ± 13.1 vs. 74.0 ± 13.5 µS, p = 0.041). A strong inverse correlation was found between cardiovascular risk score and right foot ESC (r = −0.455, p < 0.001). Left foot ESC also correlated inversely with cardiovascular risk (r = −0.401, p < 0.001) and HbA1c (r = −0.150, p = 0.049), while a weak positive correlation was seen with BMI (r = 0.145, p = 0.043). ROC analysis showed the highest area under the curve (AUC) in right foot ESC for autonomic neuropathy (AUC = 0.750, 95% CI: 0.623–0.877, p < 0.001). Conclusions: This study is among the few to systematically correlate ESC with validated cardiovascular risk scores in a diabetic outpatient cohort, highlighting its potential as a novel early screening biomarker for autonomic and cardiovascular complications. Full article
(This article belongs to the Section Biosensors and Healthcare)
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18 pages, 1509 KiB  
Article
Ozone Therapy and Negative Pressure Wound Therapy in the Treatment of Difficult-to-Heal Wounds in Diabetic Foot Syndrome and Charcot Neuroarthropathy
by Agnieszka Białomyzy, Katarzyna Kotrych, Anna Bogacz, Marta Podralska, Aleksandra Górska, Jacek Białecki, Izabela Uzar, Bogusław Czerny and Adam Kamiński
J. Clin. Med. 2025, 14(12), 4017; https://doi.org/10.3390/jcm14124017 - 6 Jun 2025
Viewed by 768
Abstract
Diabetes, as one of the most common diseases of civilization, is a significant factor of mortality worldwide. Undiagnosed and improperly treated, it leads to the development of a number of complications, including diabetic foot syndrome (DFS) and Charcot neuroarthropathy (CN). Charcot neuroarthropathy is [...] Read more.
Diabetes, as one of the most common diseases of civilization, is a significant factor of mortality worldwide. Undiagnosed and improperly treated, it leads to the development of a number of complications, including diabetic foot syndrome (DFS) and Charcot neuroarthropathy (CN). Charcot neuroarthropathy is a complex and devastating disease characterized by the presence of neuropathy, progressive deformities, and joint destruction. Risk factors and epidemiological data emphasize the high prevalence of CN in the diabetic population, drawing attention to typical predisposing factors for the development of this disease. Serious complications, such as foot ulcers or amputations, show the scale of the negative impact of CN and DFS on the quality of life of patients. Background/Objectives: The aim of the study was to assess the treatment of foot ulcers in patients with DFS and CN using ozone therapy with simultaneous negative pressure wound therapy (NPWT). Methods: The study included 30 patients aged 39 to 87 years with DFS and 30 patients with CN. Ozone therapy and negative pressure wound therapy were used for the treatment of chronic wounds. Results: The analysis of the results showed a significant reduction in the wound size in both study groups; in patients with DFS, a reduction from 5 cm3 to 0.40 cm3 observed after 3 weeks and to 0.002 cm3 after 6 weeks of therapy, while in patients with CN, a reduction from 8 cm3 to 1.50 cm3 was observed after 3 weeks and to 0.004 cm3 after 6 weeks of therapy. No statistically significant differences were observed in median wound sizes between the DFS and CN groups. Ozone therapy with a value of 70 μg/mL is an effective method in the treatment of chronic diseases of soft tissue and the skeletal system. In combination with NPWT after cleansing the wound of bone sequestrum, the process increased the density of capillaries by accelerating the synthesis of proteins and collagen and reduced bacterial colonization in the wound. Conclusions: The use of ozone therapy procedures at 70 μg/mL with negative pressure therapy is effective in the prevention and treatment of infectious bone complications in diabetes, such as diabetic foot syndrome and Charcot neuroarthropathy. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Article
Real-World Efficacy of Minimally Invasive Revascularization in Diabetic Foot Ischemia: Impact of Device Selection and Lesion-Specific Factors
by Yue Lin, Fanzhen Lv, Yulong Huang, Gang Chen, Shichai Hong, Xiang Hong, Xinsheng Xie, Weifeng Lu and Weiguo Fu
Biomedicines 2025, 13(6), 1384; https://doi.org/10.3390/biomedicines13061384 - 5 Jun 2025
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Abstract
Objectives: The objective of this study was to evaluate the real-world efficacy of minimally invasive revascularization in diabetic foot ischemia, focusing on novel insights into device selection and lesion-specific predictors. Methods: This retrospective study included 98 patients (101 limbs) undergoing endovascular/hybrid [...] Read more.
Objectives: The objective of this study was to evaluate the real-world efficacy of minimally invasive revascularization in diabetic foot ischemia, focusing on novel insights into device selection and lesion-specific predictors. Methods: This retrospective study included 98 patients (101 limbs) undergoing endovascular/hybrid interventions. The primary endpoints were 1- and 2-year primary patency and freedom from clinically driven target lesion revascularization (CD-TLR). Multivariate Cox regression identified restenosis predictors, with subgroup analysis comparing drug-coated devices (DCDs) versus conventional strategies in chronic limb-threatening ischemia (CLTI). Results: The cohort (mean age 72.1 ± 8.9 years) comprised 51% CLTI limbs (28.5% with tissue loss). The overall 1-year primary patency was 75.6%, declining to 67.6% after 2 years. The rates of freedom from CD-TLR were 87.4% after 1 year and 74.8% after 2 years. CLTI was associated with significantly reduced 1-year (66.5% vs. 84.9%) and 2-year primary patency (56.3% vs. 80.1%; log-rank p = 0.026) compared to non-CLTI. Multivariate analysis identified CLTI as an independent predictor of restenosis (HR 3.375, 95%CI 1.267–8.990, p = 0.015). Although DCDs did not improve 2-year primary patency in CLTI (58.5% vs. 57.3%, p = 0.768), they demonstrated superior 2-year CD-TLR-free survival (78.5% vs. 54.6%, p = 0.048). The total complication rate was 5.9%, with no significant difference between CLTI and non-CLTI groups (11.5% vs. 0%, p = 0.057). Conclusions: This study highlights CLTI’s impact on revascularization durability and the clinical benefits of DCDs in reducing reinterventions, offering evidence-based insights for tailored device selection despite retrospective limitations. Full article
(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (2nd Edition))
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