effects-moist-exposed-burn-ointment-on-wound-neovascularization

Effects of Moist Exposed Burn Ointment on Wound Neovascularization and Plasma Exosomal mir-31-5p in Diabetic Mice

Moist-exposed burn ointment (MEBO) is a traditional Chinese medicine used to treat chronic diabetic wounds; however, the underlying mechanism is unclear. ...

The Affiliated Hospital of Youjiang Medical University for Nationalities

Key Laboratory for the Prevention and Treatment of Diabetic Chronic Wounds in Baise City

Key Laboratory of Metabolic Diseases in Baise City

More and more findings illustrate the critical roles of circular RNA (circRNA) in diabetes mellitus (DM) and its complications. A major pathological characteristic for DM is the apoptosis of endothelial cells (ECs) induced by high glucose (HG), however, the function of circRNA in the ECs' phenotypes is still elusive. Here, this study identified an up-regulated circRNA (circVEGFC) in the HG-induced human umbilical vein endothelial cells (HUVECs). Functionally, knockdown of circVEGFC alleviated the apoptosis and recovered the proliferation in HUVECs induced by HG administration. Mechanistically, circVEGFC functioned as the sponge of miR-338-3p, and miR-338-3p was found to target the 3'-Untranslated Regions (3'-UTR) of hypoxia inducible factor 1 alpha (HIF-1α). HIF-1α, a critical transcription factor in DM, could activate the transcription of vascular endothelial growth factor A (VEGFA) and promote its protein product. In conclusion, these findings reveal the promotion of circVEGFC/miR-338-3p/HIF-1α/VEGFA axis in the HG-induced ECs' apoptosis, providing a potential treatment strategy for ECs' damage in DM.

Circular RNA circVEGFC accelerates high glucose-induced vascular endothelial cells apoptosis through miR-338-3p/HIF-1α/VEGFA axis.

Long noncoding RNA MALAT1 is closely related to diabetes and kidney diseases and is expected to be a new target for the diagnosis and treatment of diabetic nephropathy.

Circulating Expression Level of LncRNA Malat1 in Diabetic Kidney Disease Patients and Its Clinical Significance.

Diabetic foot ulcer (DFU) is the main cause of disability in diabetic patients. However, the molecular changes underlying the occurrence and progression of DFU remain unclear. We conducted this study to examine gene alterations in different DFU patients.

IL-1B can serve as a healing process and is a critical regulator of diabetic foot ulcer.

A new label-free method was developed for SERS detection of human apolipoprotein A4. Rolling circle amplification (RCA) was used, which could induce the production of AuNPs (poly adenine and adsorption gold nanoparticles). When there were two DNA labeled antibodies and target protein, MB1 (molecular beacon 1) was unfolded and the substrate was modified in the homogeneous solution, and the proximate complex was formed. The unfolded molecular beacon worked as a primer in the hybridization with the RCA template to start RCA, which could produce many long sequences of DNA containing amounts of adenines. The AuNPs were bound with the long-repeated adenine in the RCA product, causing accumulation of AuNPs on the surface of the electrode. It was indicated that the spectral characteristics of adenine at 736 cm strongly dominated the SERS spectrum of DNA. Adenine worked as an internal marker for detecting human apolipoprotein A4 by using label-free SERS method. When the conditions were optimal, the detection of human apolipoprotein A4 was carried out from 10 pg mL to 1000 ng mL, and the detection limit was low (4.1 pg mL). Meanwhile, the specificity was also excellent because the antibody could specifically bind with the corresponding antigen. In addition, since adenine was dominant in SERS spectra and the affinity between AuNPs and poly adenine was high, the detection procedure could be performed without any sophisticated modification. This method might provide a promising strategy for diagnosis in clinical practice.

Proximity hybridization induced rolling circle amplification for label-free SERS detection of the depression marker human apolipoprotein A4.

Aluminum (Al) exposure can lead to different degrees of damage to various organ systems of the body. It has been previously revealed that Al exposure can damage the liver, causing liver dysfunction. However, the specific mechanism remains unclear. This research aims to uncover the damaging effect of Al exposure on rat liver and to demonstrate the role of autophagy and apoptosis in this effect. Thirty-two Wistar rats were randomly divided into the control group (C group), low-dose Al exposure group (L group), middle-dose Al exposure group (M group), and high-dose Al exposure group (H group) (n = 8). The rats, respectively, received intraperitoneal injections of 0, 5, 10, and 20 mg/kg·day AlCl solution for 4 weeks (5 times/week). After the experiment, changes in the ultrastructure and autolysosome in rat liver were observed; the liver function, apoptosis rate, as well as levels of apoptosis-associated proteins and autophagy-associated proteins were detected. The results indicated that Al exposure damaged rat liver function and structure and resulted in an increase in autolysosomes. TUNEL staining revealed an elevated number of apoptotic hepatocytes after Al exposure. Moreover, we found from Western blotting that the levels of autophagy-associated proteins Beclin1 and LC3-II were increased; apoptotic protein Caspase-3 level was elevated and the Bcl-2/Bax ratio was reduced. Our research suggested that Al exposure can lead to high autophagy and apoptosis levels of rat hepatocytes, accompanied by hepatocyte injury and impaired liver function. This study shows that autophagy and apoptosis pathways participate in Al toxication-induced hepatocyte injury.

Role of Autophagy and Apoptosis in Aluminum Exposure-Induced Liver Injury in Rats.

Intensive glycemic control and exosomal miRNAs have both been reported to improve wound repair in diabetic ulcers. In this study, we aimed to investigate the effects of intensive glycemic control on serum exosome microRNA-126-3p (miR-126-3p), microRNA-125b-1-3p (miR-125b-1-3p), and wound healing in patients with diabetic ulcers.

Effects of Intensive Glycemic Control on Serum Exosome miR-126-3p and miR-125b-1-3p Levels and Wound Healing in Patients with Diabetic Ulcers.

Diabetic foot ulcer (DFU) is one major, common and serious chronic complication of diabetes mellitus, which is characterized by high incidence, high risk, high burden, and high treatment difficulty and is a leading cause of disability and death in patients with diabetes. Long-term hyperglycemia can result in cellular dysfunction of fibroblasts, which play pivotal roles in wound healing. MicroRNAs (miRNAs) were reported to mediate the pathological processes of multiple diseases, including diabetic wound healing. This research aimed to investigate the functional role of miR-145-5p in high-glucose (HG)-exposed fibroblasts and in DFU mouse models. Human foreskin fibroblast cells (HFF-1) were stimulated by HG to induce cell injury. MiR-145-5p level in HG-stimulated HFF-1 cells was detected via RT-qPCR. The binding between miR-145-5p and PDGFD was validated by Luciferase reporter assay. The effects of the miR-145-5p/PDGFD axis on the viability, migration, and apoptosis of HG-exposed HFF-1 cells were determined by CCK-8, wound healing, and flow cytometry assays. DFU mouse models were subcutaneously injected at the wound edges with miR-145-5p inhibitor/mimics. Images of the wounds were captured on day 0 and 8 post-injection, and wound samples were collected after mice were sacrificed for histological analysis by H&E staining. HG decreased cell viability and increased miR-145-5p expression in HFF-1 cells in a dose- and time-dependent manner. MiR-145-5p downregulation promoted cell viability and migration and inhibited cell apoptosis of HG-stimulated HFF-1 cells, while miR-145-5p overexpression exerted an opposite effect on cell viability, migration, and apoptosis. PDGFD was a direct target gene of miR-145-5p, whose silencing reversed the influence of miR-145-5p downregulation on HG-induced cellular dysfunction of HFF-1 cells. Additionally, downregulating miR-145-5p facilitated while overexpressing miR-145-5p inhibited wound healing in DFU mouse models. MiR-145-5p level was negatively associated with PDGFD level in wound tissue samples of DFU mouse models. MiR-145-5p inhibition improves wound healing in DFU through upregulating PDGFD expression.

MicroRNA miR-145-5p Inhibits Cutaneous Wound Healing by Targeting PDGFD in Diabetic Foot Ulcer.

Diabetic foot ulcer (DFU) is the most serious and costly chronic complication that may lead to disability and even death in patients suffering from diabetes mellitus (DM). However, the clinical diagnosis and prognosis of DFU is inadequate. There is still a lack of effective biomarkers for its early diagnosis. We obtained the circRNA expression dataset GSE114248 and mRNA expression dataset GSE80178 from the GEO. R software was used to identify the differentially expressed circRNAs (DECs). The mRNAs associated with DFU were identified by a random forest algorithm and intersected with mRNAs predicted by circRNAs. Then, the circRNA-miRNA-mRNA network was established and the hub genes were screened using GO semantic similarity and were validated by the GSE199939 dataset. Meanwhile, the expression level of the biomarkers was verified by RT-PCR assays and immunohistochemistry. Finally, GSEA was conducted to determine differential immune cell infiltration and the immunological cells' relationships with hub genes. We identified three hub genes including KIAA1109, ENPP5, and NRP1 that might play an important role in DFU. ROC curve results also showed a good performance of these three genes in the validation dataset. Furthermore, RT-PCR assays and immunohistochemistry confirmed the results above. Immune infiltration analysis indicated that DFU had a significant increase in Neutrophils. Moreover, three hub genes were closely correlated with a variety of inflammatory cells. KIAA1109, ENPP5, and NRP1 are key hub genes of DFU. They might play an important role in the development of DFU and could be potential biomarkers in DFU.

Identification of potential diagnostic biomarkers and immune infiltration features in diabetic foot ulcer by bioinformatics analysis and validation.

Diabetic foot ulcers (DFU) are among the fastest-growing diseases worldwide. Recent evidence has emphasized the critical role of microRNA (miRNA)-mRNA networks in various chronic wounds, including DFU. In this study, we aimed to clarify the miRNA-mRNA axes associated with the occurrence of DFU.

Identifying potential pathogenesis and immune infiltration in diabetic foot ulcers using bioinformatics and in vitro analyses.

Chronic exposure to aluminum (Al) can lead to the accumulation of Al in the liver, which negatively impacts liver structure and function. Oxidative stress is extensively identified as a key contributor to Al toxicity. The Nrf2/HO-1 pathway maintains cellular redox homeostasis and protects from oxidative stress through its antioxidative and cytoprotective role. However, its role in Al-induced liver damage remains unclear. In this study, rats were grouped into the control (C), Al exposure (Al), Al exposure + Omaveloxolone (Al+O), and Al exposure + ML385 (Al+M) groups, and their liver function, hepatic Al content, histopathological changes in liver tissue, and hepatocyte apoptosis were assessed. The Nrf2/HO-1 signaling- and apoptosis-associated protein levels were evaluated using Western blotting. In vitro, with BRL3A cells as a model, Al exposure's influence in cell viability, MMP, and Nrf2/HO-1- and apoptosis-associated protein levels was assessed. The Nrf2/HO-1 pathway was also modulated to investigate changes in oxidative stress and apoptosis-related markers following intervention. The results showed that Al accumulation in liver tissue led to rat histopathological changes and liver dysfunction, promoting oxidative stress and hepatocyte apoptosis, while also enhancing Nrf2/HO-1-associated protein levels. Similar findings were observed in in-vitro experiments. Furthermore, the Nrf2/HO-1 signaling activation mitigated Al-triggered oxidative stress and apoptosis, whereas its inhibition reduced these protective effects. This study indicated that Al exposure could induce s oxidative damage in rat livers and BRL3A cells; activation of the Nrf2/HO-1 pathway serves as a critical compensatory mechanism against Al toxicity, but its protective efficacy is limited.

Effect of the Nrf2/HO-1 pathway on aluminum-induced liver injury.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, and current therapeutic options are limited in effectively managing DN progression. Renal tubular epithelial cell (RTEC) ferroptosis has emerged as a critical mechanism contributing to DN pathogenesis. This study aimed to investigate the potential synergistic effects of quercetin (QCT) and rosuvastatin (RSV) on inhibiting RTEC ferroptosis and ameliorating DN progression, providing a novel combinatorial therapeutic strategy.

A Network Pharmacology-Based Investigation into the Mechanism of Quercetin Combined with Rosuvastatin in Delaying Diabetic Nephropathy via Inhibiting NRK-52E Cell Ferroptosis.

Article	Year
Circular RNA circVEGFC accelerates high glucose-induced vascular endothelial cells apoptosis through miR-338-3p/HIF-1α/VEGFA axis. Aging\| PubMed ID: 32680978	2020
Circulating Expression Level of LncRNA Malat1 in Diabetic Kidney Disease Patients and Its Clinical Significance. Journal of diabetes research\| PubMed ID: 32832561	2020
IL-1B can serve as a healing process and is a critical regulator of diabetic foot ulcer. Annals of translational medicine\| PubMed ID: 35280410	2022
Proximity hybridization induced rolling circle amplification for label-free SERS detection of the depression marker human apolipoprotein A4. Talanta\| PubMed ID: 35398633	2022
Role of Autophagy and Apoptosis in Aluminum Exposure-Induced Liver Injury in Rats. Biological trace element research\| PubMed ID: 36600167	2023
Effects of Intensive Glycemic Control on Serum Exosome miR-126-3p and miR-125b-1-3p Levels and Wound Healing in Patients with Diabetic Ulcers. Evidence-based complementary and alternative medicine : eCAM\| PubMed ID: 36756041	2023
MicroRNA miR-145-5p Inhibits Cutaneous Wound Healing by Targeting PDGFD in Diabetic Foot Ulcer. Biochemical genetics\| PubMed ID: 37950842	2024
Identification of potential diagnostic biomarkers and immune infiltration features in diabetic foot ulcer by bioinformatics analysis and validation. Cellular and molecular biology (Noisy-le-Grand, France)\| PubMed ID: 38015522	2023
Identifying potential pathogenesis and immune infiltration in diabetic foot ulcers using bioinformatics and in vitro analyses. BMC medical genomics\| PubMed ID: 38041124	2023
Effect of the Nrf2/HO-1 pathway on aluminum-induced liver injury. Ecotoxicology and environmental safety\| PubMed ID: 40499352	2025
A Network Pharmacology-Based Investigation into the Mechanism of Quercetin Combined with Rosuvastatin in Delaying Diabetic Nephropathy via Inhibiting NRK-52E Cell Ferroptosis. Diabetes, metabolic syndrome and obesity : targets and therapy\| PubMed ID: 40785752	2025

Biaoliang Wu

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