Fecal virome transplantation: A promising strategy for the treatment of metabolic diseases.

Metabolic diseases are a group of disorders caused by metabolic abnormalities, including obesity, diabetes, non-alcoholic fatty liver disease, and more. Increasing research indicates that, beyond inherent metabolic irregularities, the onset and progression of metabolic diseases are closely linked to alterations in the gut microbiota, particularly gut bacteria. Additionally, fecal microbiota transplantation (FMT) has demonstrated effectiveness in clinically treating metabolic diseases, notably diabetes. Recent attention has also focused on the role of gut viruses in disease onset. This review first introduces the characteristics and influencing factors of gut viruses, then summarizes their potential mechanisms in disease development, highlighting their impact on gut bacteria and regulation of host immunity. We also compare FMT, fecal filtrate transplantation (FFT), washed microbiota transplantation (WMT), and fecal virome transplantation (FVT). Finally, we review the current understanding of gut viruses in metabolic diseases and the application of FVT in treating these conditions. In conclusion, FVT may provide a novel and promising treatment approach for metabolic diseases, warranting further validation through basic and clinical research.

Non-Abelian Braiding of Topological Edge Bands.

Braiding is a geometric concept that manifests itself in a variety of scientific contexts from biology to physics, and has been employed to classify bulk band topology in topological materials. Topological edge states can also form braiding structures, as demonstrated recently in a type of topological insulators known as Möbius insulators, whose topological edge states form two braided bands exhibiting a Möbius twist. While the formation of Möbius twist is inspiring, it belongs to the simple Abelian braid group B_{2}. The most fascinating features about topological braids rely on the non-Abelianness in the higher-order braid group B_{N} (N≥3), which necessitates multiple edge bands, but so far it has not been discussed. Here, based on the gauge enriched symmetry, we develop a scheme to realize non-Abelian braiding of multiple topological edge bands. We propose tight-binding models of topological insulators that are able to generate topological edge states forming non-Abelian braiding structures. Experimental demonstrations are conducted in two acoustic crystals, which carry three and four braided acoustic edge bands, respectively. The observed braiding structure can correspond to the topological winding in the complex eigenvalue space of projective translation operator, akin to the previously established point-gap winding topology in the bulk of the Hatano-Nelson model. Our Letter also constitutes the realization of non-Abelian braiding topology on an actual crystal platform, but not based on the "virtual" synthetic dimensions.

Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis.

Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though the precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors in the chronic social defeat stress (CSDS) model of depression. This study investigated whether the spleen contributes to the antidepressant-like effects of arketamine in the CSDS model. We found that splenectomy significantly inhibited arketamine's antidepressant-like effects in CSDS-susceptible mice. RNA-sequencing analysis identified the oxidative phosphorylation (OXPHOS) pathway in the prefrontal cortex (PFC) as a key mediator of splenectomy's impact on arketamine's effects. Furthermore, oligomycin A, an inhibitor of the OXPHOS pathway, reversed the suppressive effects of splenectomy on arketamine's antidepressant-like effects. Specific genes within the OXPHOS pathways, such as COX11, UQCR11 and ATP5e, may contribute to these inhibitory effects. Notably, transforming growth factor (TGF)-ß1, along with COX11, appears to modulate the suppressive effects of splenectomy and contribute to arketamine's antidepressant-like effects. Additionally, SRI-01138, an agonist of the TGF-ß1 receptor, alleviated the inhibitory effects of splenectomy on arketamine's antidepressant-like effects. Subdiaphragmatic vagotomy also counteracted the inhibitory effects of splenectomy on arketamine's antidepressant-like effects in CSDS-susceptible mice. These findings suggest that the OXPHOS pathway and TGF-ß1 in the PFC play significant roles in the antidepressant-like effects of arketamine, mediated through the spleen-brain axis via the vagus nerve.

Pseudomagnetic suppression of non-Hermitian skin effect.

It has recently been shown that the non-Hermitian skin effect can be suppressed by magnetic fields. In this work, using a two-dimensional tight-binding lattice, we demonstrate that a pseudomagnetic field can also lead to the suppression of the non-Hermitian skin effect. With an increasing pseudomagnetic field, the skin modes are found to be pushed into the bulk, accompanied by the reduction of skin topological area and the restoration of Landau level energies. Our results provide a time-reversal invariant route to localization control and could be useful in various classical wave devices that are able to host the non-Hermitian skin effect but inert to magnetic fields.

4-octyl itaconate inhibits high glucose induced renal tubular epithelial cell fibrosis through TGF-ß-ROS pathway.

Diabetic kidney disease (DKD) is one of the most serious complications of diabetes and has become the leading cause of end-stage kidney disease, causing serious health damage and a huge economic burden. Tubulointerstitial fibrosis play important role in the development of DKD. Itaconate, a macrophage-specific metabolite, has been reported to have anti-oxidant, anti-inflammatory effects. However, it is unknown whether it perform anti-fibrotic effect in renal tubular epithelial cells. In this current study, we observed that in human renal tubular epithelial cells (HK2), high glucose induced an increase in transforming growth factor ß (TGF-ß) production, and upregulated the expressions of fibronectin and collagen I through the TGF-ß receptor as verified by administration of TGF-ß receptor blocker LY2109761. Treatment with 4-octyl itaconate (4-OI), a derivant of itaconic acid, reduced the TGF-ß production induced by high glucose and inhibited the pro-fibrotic effect of TGF-ß in a dose-dependent manner. In addition, we found that 4-OI exerted its anti-fibrotic effect by inhibiting the excessive production of ROS induced by high glucose and TGF-ß. In summary, 4-OI could ameliorate high glucose-induced pro-fibrotic effect in HK2 cell, and blocking the expression of TGF-ß and reducing the excessive ROS production may be involved in its anti-fibrotic effect.

Three-dimensional flat Landau levels in an inhomogeneous acoustic crystal.

When electrons moving in two dimensions (2D) are subjected to a strong uniform magnetic field, they form flat bands called Landau levels (LLs). LLs can also arise from pseudomagnetic fields (PMFs) induced by lattice distortions. In three-dimensional (3D) systems, there has been no experimental demonstration of LLs  as a type of flat band thus far. Here, we report the experimental realization of a flat 3D LL in an acoustic crystal. Starting from a lattice whose bandstructure exhibits a nodal ring, we design an inhomogeneous distortion corresponding to a specific pseudomagnetic vector potential (PVP). This distortion causes the nodal ring states to break up into LLs, including a zeroth LL that is flat along all three directions. These findings suggest the possibility of using nodal ring materials to generate 3D flat bands, allowing access to strong interactions and other attractive physical regimes in 3D.

Survival outcomes and treatment experience of 124 patients with primary central nervous system lymphoma.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a rare malignancy of the central nervous system with high invasiveness. There is little consensus on the treatment of PCNSL. This study retrospectively studied data from PCNSL patients in a single center to summarize treatment experience and explore prognostic factors. METHODS: Survival curves were drawn using the Kaplan-Meier method and prognostic factors were analyzed using Cox's hazards model. RESULTS: In multivariate analysis, cerebrospinal fluid lactic acid dehydrogenase (CSF LDH; p = 0.005 and p = 0.002), neutrophil to lymphocyte ratio (NLR; p = 0.014 and p = 0.038), and completion of four cycles of induction therapy (p < 0.001and p < 0.001) were significant and independent predictors of overall survival (OS) and progression-free survival (PFS), respectively. CONCLUSION: On the basis of this study, we propose that PCNSL patients should receive early induction therapy with sufficient cycles. Subsequent consolidation therapy can prevent relapses and improve survival. In patients with PCNSL, the independent prognostic factors for OS and PFS were CSF LDH level, NLR, and full cycles of induction therapy.

Development of Serum Lactate Level-Based Nomograms for Predicting Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

Purpose: To establish nomograms integrating serum lactate levels and traditional risk factors for predicting diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients. Patients and methods: A total of 570 T2DM patients and 100 healthy subjects were enrolled. T2DM patients were categorized into normal and high lactate groups. Univariate and multivariate logistic regression analyses were employed to identify independent predictors for DKD. Then, nomograms for predicting DKD were established, and the model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA). Results: T2DM patients exhibited higher lactate levels compared to those in healthy subjects. Glucose, platelet, uric acid, creatinine, and hypertension were independent factors for DKD in T2DM patients with normal lactate levels, while diabetes duration, creatinine, total cholesterol, and hypertension were indicators in high lactate levels group (P<0.05). The AUC values were 0.834 (95% CI, 0.776 to 0.891) and 0.741 (95% CI, 0.688 to 0.795) for nomograms in both normal lactate and high lactate groups, respectively. The calibration curve demonstrated excellent agreement of fit. Furthermore, the DCA revealed that the threshold probability and highest Net Yield were 17-99% and 0.36, and 24-99% and 0.24 for the models in normal lactate and high lactate groups, respectively. Conclusion: The serum lactate level-based nomogram models, combined with traditional risk factors, offer an effective tool for predicting DKD probability in T2DM patients. This approach holds promise for early risk assessment and tailored intervention strategies.

Establishment of new transurethral catheterization methods for male mice.

Transurethral catheterization in mice is multifaceted, serving essential functions such as perfusion and drug delivery, and is critical in the development of various urological animal disease models. The complex anatomy of the male mouse urethra presents significant challenges in transurethral catheterization, leading to a predominance of research focused on female specimens. This bias limits the utilization of male mice in lower urinary tract disease studies. Our research aims to develop new reliable methods for transurethral catheterization in adult male mice, thereby expanding their use in relevant disease research. Experiments were conducted on adult male C57BL/6J mice. Utilizing a PE10 catheter measuring 4.5-5 cm in length, the catheter was inserted into the bladder via the mouse's urethra under anesthesia. The intubation technique entailed regulating the insertion force, ensuring the catheter's lubrication, using a trocar catheter, modifying the catheter's trajectory, and accommodating the curvature of the bladder neck. Post-catheter insertion, ultrasound imaging was employed to confirm the catheter's accurate positioning within the bladder. Subsequent to catheterization, the bladder was perfused using trypan blue. This method was further validated through its successful application in establishing an acute urinary retention (AUR) model, where the mouse bladder was infused with saline to a pressure of 50 or 80 cm H2O, maintained steadily for 30 min. A thorough morphological assessment of the mouse bladder was conducted after the infusion. Our study successfully pioneered methods for transurethral catheterization in male mice. This technique not only facilitates precise transurethral catheterization but also proves applicable to male mouse models for lower urinary tract diseases, such as AUR.

Effect of proanthocyanidins on blood lipids: A systematic review and meta-analysis.

Proanthocyanidins (PCs) are natural antioxidant polyphenols and their effect on the regulation of blood lipids is still controversial. This study was conducted to evaluate the effect of PCs on lipid metabolism. We searched PubMed, Embase, Web of Science, Chinese biomedical literature service system, China National Knowledge Internet, and Wanfang Data with no time restriction until March 18, 2022, using various forms of "proanthocyanidins" and "blood lipid" search terms. Randomized controlled trials investigating the relationship between PCs and lipid metabolism were included. The standard system of Cochrane Collaboration was used to assess the quality of studies. We standardized mean differences (SMDs) with 95% confidence interval (CI) using the random-effects model, Cohen approach. Seventeen studies (17 trials, N = 1138) fulfilled the eligibility criteria. PCs significantly reduced triglyceride, and increased recombinant apolipoprotein A1. Subgroup analysis showed a significant reduction in triglycerides in older adults (≥60 years) and total cholesterol for participants who were not overweight or obese (body mass index <24). An intervention duration of greater than 8 weeks reduced triglyceride and low-density lipoprotein cholesterol levels but increased high-density lipoprotein cholesterol. Different doses of PCs could regulate triglycerides, high-density lipoprotein cholesterol and total cholesterol. PCs have beneficial effects on circulating lipids and may represent a new approach for treating or preventing lipid metabolism disorders. However, more high-quality studies are needed to confirm these results.

Effects of SGLT2 inhibitors on cardiac function and health status in chronic heart failure: a systematic review and meta-analysis.

PURPOSE: Numerous clinical studies have explored sodium-glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes mellitus (T2DM), and SGLT2i were proved to significantly reduce CHF hospitalization, cardiovascular death, cardiovascular mortality, all-cause mortality and myocardial infarction in patients with or without T2DM. However, only a limited few have investigated the effects of SGLT-2i on HF disease-specific health status and cardiac function. This meta-analysis aims to assess the effects of SGLT2i on disease-specific health status and cardiac function in CHF patients. METHODS: A comprehensive search was conducted of trials by searching in PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, and two Chinese databases (CNKI and Wanfang), Clinical Trials ( http://www. CLINICALTRIALS: gov ) were also searched. RESULTS: A total of 18 randomized controlled trials (RCTs) involving 23,953 participants were included in the meta-analysis. The effects of SGLT2 inhibitors were compared with control or placebo groups in CHF with or without T2DM. The SGLT2 inhibitors group exhibited a significant reduction in pro b-type natriuretic peptide (NT-proBNP) levels by 136.03 pg/ml (95% confidence interval [CI]: -253.36, - 18.70; P = 0.02). Additionally, a greater proportion of patients in the SGLT2 inhibitors group showed a ≥ 20% decrease in NT-proBNP (RR = 1.45, 95% CI [0.92, 2.29], p = 0.072). However, no statistically significant difference was observed for the effects on B-type natriuretic peptide (BNP). The use of SGLT-2 inhibitors led to a noteworthy improvement in LVEF by 2.79% (95% CI [0.18, 5.39];P = 0.036). In terms of health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6-minute walk distance, SGLT2 inhibitors led to a significant improvement in KCCQ clinical summary (KCCQ-CS) score (WMD = 1.7, 95% CI [1.67, 1.73], P < 0.00001), KCCQ overall summary (KCCQ-OS) score (WMD = 1.73, 95% CI [0.94, 2.52], P < 0.00001), and KCCQ total symptom (KCCQ-TS) score (WMD = 2.88, 95% CI [1.7, 4.06], P < 0.00001). Furthermore, the occurrence of KCCQ-CS and KCCQ-OS score increases ≥ 5 points had relative risks (RR) of 1.25 (95% CI [1.11, 1.42], P < 0.00001) and 1.15 (95% CI [1.09, 1.22], P < 0.00001), respectively. Overall, SGLT2 inhibitors increased the 6-minute walk distance by 23.98 m (95% CI [8.34, 39.62]; P = 0.003) compared to control/placebo from baseline. CONCLUSIONS: The SGLT2 inhibitors treatment offers an effective strategy for improving NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance in CHF with or without T2DM. These findings indicate that SGLT2i improve cardiac function and health status in CHF with or without T2DM, and provide valuable guidance for clinicians making treatment decisions for patients with CHF.

The Prognostic Value of the Age-D-Dimer-Albumin Score in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The Age-D-dimer-Albumin (ADA), the CREDO-Kyoto, and the PARIS scores have been established to predict thrombotic events. However, the prognostic performance of these scores compared to the GRACE score in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) has not been reported. METHODS: Consecutive AMI patients treated with PCI were retrospectively enrolled at a teaching hospital in China from January 2016 to December 2019. The primary endpoint was all-cause mortality and the secondary endpoint was cardiac death. Harrell's C-index and net reclassification improvement (NRI) were used to compare the prognostic value of these scores with the GRACE score for mortality. RESULTS: Of the 1,578 patients enrolled, the mean age was 62.5 years, and 23.5% were female. During a median follow-up of 3.8 years, 146 all-cause deaths and 80 cardiac deaths occurred. The ADA score showed a better prognostic performance than the GRACE (Harrell's C-index: 0.800 vs. 0.749; p = 0.003), the CREDO-Kyoto (Harrell's C-index: 0.800 vs. 0.765; NRI = 0.348, p < 0.001), and the PARIS scores (Harrell's C-index: 0.800 vs. 0.694; NRI = 0.556, p < 0.001). In the multivariable Cox regression analysis, the ADA score was independently associated with all-cause mortality (hazard ratio [HR] = 1.641 per 10-point increment, 95% confidence interval [CI]: 1.397-1.929) and cardiac death (HR = 1.636 per 10-point increment, 95% CI: 1.325-2.020). The risk of all-cause mortality and cardiac death increased with the rising of the ADA score. CONCLUSION: The ADA score showed a better prognostic performance than the GRACE, the CREDO-Kyoto, and the PARIS scores in patients with AMI undergoing PCI, which was a potential predictive tool for mortality.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

First report on female monozygotic twins discordant for congenital nephrogenic diabetes insipidus.

Ninety percent of congenital nephrogenic diabetes insipidus (NDI) are X-linked inherited and are caused by mutations in the vasopressin type 2 receptor gene (AVPR2). Most affected individuals are males. Only sporadic female cases have been reported. Here, we first reported a female monozygotic twin with discordant phenotypes for NDI carrying a missense variant c.845T>C (p.Leu282Pro) in exon 4 of AVPR2. Intracellular cAMP concentrations in COS7 cells transfected with AVPR2-L282P were significantly decreased by about 60% compared with those in wild-type AVPR2 plasmid transfected cells, suggesting this variation was pathogenic. The X-inactivation pattern was investigated in peripheral leukocytes and urine sediments in both the unaffected and affected pair. Results showed that the affected pair had a skewed X chromosome inactivation (XCI) pattern in urine sediments and a random XCI pattern in leukocytes, while the unaffected pair showed a random XCI pattern both in leukocytes and urine sediments. This was the first report of monozygotic twins who developed different phenotypes of NDI. Our study suggested that the development of NDI symptoms is more closely associated with the XCI pattern in urine sediments compared with the XCI pattern in peripheral leukocytes. Analysis of XCI in peripheral leukocytes may not be enough to explore possible mechanisms.

Talin mechanotransduction in disease.

Talin protein (Talin 1/2) is a mechanosensitive cytoskeleton protein. The unique structure of the Talin plays a vital role in transmitting mechanical forces. Talin proteins connect the extracellular matrix to the cytoskeleton by linking to integrins and actin, thereby mediating the conversion of mechanical signals into biochemical signals and influencing disease progression as potential diagnostic indicators, therapeutic targets, and prognostic indicators of various diseases. Most studies in recent years have confirmed that mechanical forces also have a crucial role in the development of disease, and Talin has been found to play a role in several diseases. Still, more studies need to be done on how Talin is involved in mechanical signaling in disease. This review focuses on the mechanical signaling of Talin in disease, aiming to summarize the mechanisms by which Talin plays a role in disease and to provide references for further studies.

MRL-Seg: Overcoming Imbalance in Medical Image Segmentation With Multi-Step Reinforcement Learning.

Medical image segmentation is a critical task for clinical diagnosis and research. However, dealing with highly imbalanced data remains a significant challenge in this domain, where the region of interest (ROI) may exhibit substantial variations across different slices. This presents a significant hurdle to medical image segmentation, as conventional segmentation methods may either overlook the minority class or overly emphasize the majority class, ultimately leading to a decrease in the overall generalization ability of the segmentation results. To overcome this, we propose a novel approach based on multi-step reinforcement learning, which integrates prior knowledge of medical images and pixel-wise segmentation difficulty into the reward function. Our method treats each pixel as an individual agent, utilizing diverse actions to evaluate its relevance for segmentation. To validate the effectiveness of our approach, we conduct experiments on four imbalanced medical datasets, and the results show that our approach surpasses other state-of-the-art methods in highly imbalanced scenarios. These findings hold substantial implications for clinical diagnosis and research.

A Comparison of the Prognostic Value of Liver Fibrosis Scores in Acute Myocardial Infarction Patients With and Without Type 2 Diabetes.

Liver fibrosis scores have been demonstrated to be associated with poor prognosis after percutaneous coronary intervention (PCI). However, no studies have compared the prognostic value of these scores in acute myocardial infarction (AMI) patients with and without diabetes. We retrospectively enrolled 1576 AMI patients who underwent PCI. There were 177 all-cause deaths and 111 cardiac deaths during follow-up (median 3.8 years). The non-alcoholic fatty liver disease fibrosis score (NFS) showed a better prognostic value than the fibrosis-8 (FIB-8) score (Harrell's C-index: 0.703 vs 0.671, P = .014) and the fibrosis-4 (FIB-4) score (Harrell's C-index: 0.703 vs 0.648, P < .001) in the overall population. In the time-dependent receiver operating characteristic analysis, the NFS also had the highest area under the curve across all time points. Consistent results were observed in diabetic and non-diabetic populations. Adding the NFS to traditional cardiovascular risk factors significantly improved the prediction both for all-cause mortality (Harrell's C-index: 0.806 vs 0.771, P < .001) and cardiac death (Harrell's C-index: 0.800 vs 0.771, P = .014). The NFS showed a better prognostic value than the FIB-8 score and the FIB-4 score in patients with AMI undergoing PCI, which might be preferable for estimating the risk of mortality regardless of the presence or absence of diabetes.

Sodium benzoate induces pancreatic inflammation and ß cell apoptosis partially via benzoylation.

Epigenetics, specifically histone post-translational modification (HPTM) induced by environmental factors, plays a crucial role in the development of diabetes. Sodium benzoate (NAB) is a widely used additive, however, its potential contribution to diabetes has been largely overlooked. In 2018, a novel HPTM called benzoylation (Kbz) induced by NAB was discovered. This modification can be catalyzed by ACSS2 (acyl-CoA synthetase short-chain member 2) and acyltransferase P300/CBP, and can be reversed by erase enzymes SIRT2. Studies have indicated that Kbz may regulate insulin secretion, although the exact molecular mechanism remains unclear. In our study, C57BL/6J mice were divided into two groups: the NC group and the 1g/kg NAB water feeding group. In vivo experiments were conducted using ß-TC-6 cells, with 6 mM NAB or 100 µM benzoyl-CoA as stimuli, and 10 µM A485 (P300 inhibitor), 5 µM ACSS2 inhibitor (inhibiting benzoyl-CoA synthesis), or 5 µM AGK2 (SIRT2 inhibitor) as intervention factors. Our study found that, although the experimental concentration of NAB is below the maximum allowable concentration in food, it still damaged the insulin secretion function of C57BL/6J mice and induced inflammation and apoptosis of islet ß cells. We observed significant differences in serum benzoyl-CoA levels between healthy individuals and patients with type 2 diabetes. Furthermore, NAB concentration-dependently increases benzoyl-CoA and Kbz levels. When Kbz is down-regulated using A485 and ACSS2 inhibitor, we observed a reduction in ß cell inflammation, apoptosis, and insulin secretion damage. Conversely, up-regulating Kbz using AGK2 resulted in increased levels of ß cell inflammation and apoptosis. In conclusion, our data suggest that NAB, despite being within the safe dose range, may be an overlooked environmental risk factor contributing to the pathogenesis of diabetes through its impact on Kbz.

Gynura divaricata (L.) DC. promotes diabetic wound healing by activating Nrf2 signaling in diabetic rats.

THE ETHNOPHARMACOLOGICAL SIGNIFICANCE: Diabetic chronic foot ulcers pose a significant therapeutic challenge as a result of the oxidative stress caused by hyperglycemia. Which impairs angiogenesis and delays wound healing, potentially leading to amputation. Gynura divaricata (L.) DC. (GD), a traditional Chinese herbal medicine with hypoglycemic effects, has been proposed as a potential therapeutic agent for diabetic wound healing. However, the underlying mechanisms of its effects remain unclear. AIM OF THE STUDY: In this study, we aimed to reveal the effect and potential mechanisms of GD on accelerating diabetic wound healing in vitro and in vivo. MATERIALS AND METHODS: The effects of GD on cell proliferation, apoptosis, reactive oxygen species (ROS) production, migration, mitochondrial membrane potential (MMP), and potential molecular mechanisms were investigated in high glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) using CCK-8, flow cytometry assay, wound healing assay, immunofluorescence, DCFH-DA staining, JC-1 staining, and Western blot. Full-thickness skin defects were created in STZ-induced diabetic rats, and wound healing rate was tracked by photographing them every day. HE staining, immunohistochemistry, and Western blot were employed to investigate the effect and molecular mechanism of GD on wound healing in diabetic rats. RESULTS: GD significantly improved HUVEC survival, decreased apoptosis, lowered ROS production, restored MMP, improved migration ability, and raised VEGF expression. The use of Nrf2-siRNA completely abrogated these effects. Topical application of GD promoted angiogenesis and granulation tissue growth, resulting in faster healing of diabetic wounds. The expression of VEGF, CD31, and VEGFR was elevated in the skin tissue of diabetic rats after GD treatment, which upregulated HO-1, NQO-1, and Bcl-2 expression while downregulating Bax expression via activation of the Nrf2 signaling pathway. CONCLUSION: The findings of this study indicate that GD has the potential to serve as a viable alternative treatment for diabetic wounds. This potential arises from its ability to mitigate the negative effects of oxidative stress on angiogenesis, which is regulated by the Nrf2 signaling pathway. The results of our study offer valuable insights into the therapeutic efficacy of GD in the treatment of diabetic wounds, emphasizing the significance of directing interventions towards the Nrf2 signaling pathway to mitigate oxidative stress and facilitate the process of angiogenesis.