High Glucose Research Articles

Glucose-activated self-cascade antibacterial and pro-angiogenesis nanozyme-functionalized chitosan-arginine thermosensitive hydrogel for chronic diabetic wounds healing

Affected by persistent hyperglycemia, diabetic neuropathy, and vasculopathy hinder the progression of wound healing by exacerbating susceptibility to recurrent bacterial infection and impairing vascularization. In order to cater to the requirements of diabetic chronic wound healing at various stages, we designed an antibacterial and pro-angiogenic wound dressing with localized glucose-lowering capacity. In this study, we constructed a copper-based metal-organic framework (MOF) nanozyme and loaded with glucose oxidase (GOX) to prepare Cu-MOF/GOX, which was subsequently integrated with CS-Arg (chitosan modified by L-Arginine) and Pluronic (F127) to fabricate multifunctional Cu-MOF/GOX-Gel thermosensitive hydrogel. The GOX generated H2O2 (hydrogen peroxide) and gluconic acid by consuming high blood glucose at the wound site, thus initiating an efficient antibacterial self-cascade catalytic in the initial stages of wound healing. With the further catalysis of in situ generated H2O2, NO (nitric oxide) was gradually released from the hydrogel, facilitating angiogenesis and accumulation of collagen, thereby expediting subsequent phases of wound healing. Overall, the Cu-MOF/GOX-Gel exhibits a comprehensive ability to locally regulate blood glucose levels, while also synergistically promoting antibacterial activity and angiogenesis, that effectively chronic diabetic wounds healing.

Exercise intensities and metabolic health: Targeting blood glucose, insulin, and C-peptide levels in adults with prediabetes in the postprandial state

ObjectiveExercise improves postprandial glycemia and insulin sensitivity in individuals with prediabetes, but the optimal intensity for this metabolic regulation remains unclear. The current study explored the impact of various exercise intensities on blood glucose, insulin, and C-peptide levels in prediabetic individuals to identify the optimal intensity for improving these metabolic indicators. MethodsIn this crossover study, 25 individuals with prediabetes participated in exercise sessions at four different intensities 50 %, 60 %, 70 %, and 80 % of their predicted maximum heart rate using a treadmill. Each session lasted 30 min, including a 5-min warm-up and 5-min cool-down period. Blood samples were collected at four time points: during fasting, immediately before exercise, and 30 and 60 min post-exercise. These samples were analyzed for glucose, insulin, and C-peptide levels. The effects of exercise intensity on these parameters were evaluated using repeated measures analysis of variance (ANOVA), with post hoc tests conducted to determine specific differences between the intensities. ResultsThe participants had an average age of 34.88 years, mean height of 170 cm, and body mass index of 30.34 kg/m2. A significant reduction in insulin and glucose levels post-exercise was observed at 70 % intensity (p ≤ 0.001). Despite high fasting blood glucose levels (110–115 mg/dL), significant reductions were noted at 30 and 60 min post-exercise (p ≤ 0.001). Insulin levels approached near baseline at 70 % intensity, from fasting (26.74 ± 20.83) to 60 min post-exercise (28.47 ± 20.79), indicating a positive response at this intensity. C-peptide levels also showed significant changes, with 70 % intensity exercise bringing them closest to fasting levels by 60 min post-exercise. ConclusionThis study highlights the importance of exercise intensities in enhancing metabolic parameters in individuals with prediabetes. Specifically, 70 % of the predicted maximum heart rate was beneficial, optimizing insulin sensitivity and potentially reducing the risk of progressing from prediabetes to diabetes.

Injectable Gelled Multiple Emulsion for Glucose-Responsive Insulin Delivery.

A glucose-responsive insulin delivery system that sustains blood glucose equilibrium for an extended duration can address the low therapeutic window of insulin in diabetes treatment. Herein, insulin is loaded in a water-in-oil-in-water (W1/O/W2) gelled multiple emulsion using poly (4-vinylphenylboronic acid) (PVPBA) homopolymer as an effective emulsifier. The gelled multiple emulsion exhibits a high encapsulation efficiency (99%), enhanced stability and remarkable shear-thinning behavior, making it easy to inject. Under hyperglycemic conditions, the gelled emulsion system instantly binds to glucose molecules and reduces the hydrogen bonds of the PVPBA homopolymer, resulting in insulin release. In a streptozotocin-induced type 1 diabetic mouse model, a single subcutaneous injection of the gelled emulsion rapidly responds to high blood glucose concentration (BGC)and release insulin in a glucose dependent manner, thus prolonging the antihyperglycemic effect compared with free insulin.

Tuberculosis in South Asia: A regional analysis of burden, progress, and future projections using the global burden of disease (1990–2021)

BackgroundTuberculosis (TB) is a major public health issue in South Asia and accounts for a large share of the global TB burden. Despite global efforts to curb TB incidence and mortality, progress in South Asia has been uneven, necessitating focused regional analysis to guide effective interventions. This study aims to analyse the trends in the TB burden in South Asia from 1990 to 2021 and project future TB incidence rates up to 2031. MethodsThis study utilized data from the Global Burden of Disease (GBD) 2021 results to analyse trends in age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) rates (ASDR) associated with TB in South Asia from 1990 to 2021. Joinpoint regression analysis was employed to identify significant trends, whereas ARIMA models were used to project future TB incidence rates up to 2031. ResultsThis study revealed significant declines in the ASIR, ASPR, ASDR, and ASMR related to TB in South Asia over the past three decades. Prominent reductions were found in Bangladesh and Bhutan, whereas India, Pakistan, and Nepal continue to bear the highest TB burdens. The ARIMA model projections indicate a continued decline in TB incidence across the region, although the extent of the decline varies by country, with less favourable trends observed in Nepal and Pakistan. The analysis also highlights tobacco use, high fasting plasma glucose, and high body mass index as significant risk factors contributing to the TB burden. ConclusionsSubstantial progress has been made in reducing the TB burden in South Asia; however, sustained and intensified efforts are needed, particularly in countries with inconsistent progress. These findings emphasize the need for targeted interventions to meet the WHO End TB Strategy (WETS) targets by 2035. Continuous monitoring and adaptive strategies will be crucial in maintaining and accelerating progress toward TB elimination in South Asia.

Cardiovascular risk factors and all-cause mortality in older age (15-year cohort study)

Cardiovascular diseases (CVD) occupy a leading position in the structure of all-cause mortality. Prospective and interventional studies have identified the major risk factors for CVD and shown their associations with the risk of cardiovascular outcomes and all-cause death. The impact on the individual risk of death may vary by age, sex, study design, and may be population-specific. We aimed to study the contribution of major CVD risk factors to the 15-year risk of all-cause death in the Russian (Siberian) population cohort aged 45–69 years.Material and methods. A random population sample (men and women 45–69 years old, n = 9360) was examined at baseline in 2003–2005 (Novosibirsk, Russian branch of the HAPIEE project) and re-examined twice in 2006–2008 and 2015–2018. Current analysis included individuals without baseline CVD (n = 8087), the average follow-up period – 15.6 (SD 0.69) years. The fatal events were registered based on death certificates from the Population Registration Bureau (ZAGS), and using the data received at serial examinations and postal interview. We analyzed the association between CVD risk factors and all-cause death using multivariate Cox regression.Results. In a cohort aged 45–69, in the adjusted model, 15-year risk of all-cause death was positively associated with age (HR = 1.08; 95 % CI 1.07–1.09), male sex (HR = 1.46; 95 % CI 1.24–1.71), hypertension (HT) (HR = 1.39; 95 % CI 1.25–1.55), smoking (HR = 2.37; 95 % CI 2.08–2.70), high WHR (HR = 1.19; 95 % CI 1.06–1.33), and type 2 diabetes (T2DM) (HR = 1.52; 95 % CI 1.34–1.73), and it was negatively associated with elevated total cholesterol (TC) or LDL-C in blood. In age- and sex-adjusted model, the risk was additionally associated with high triglycerides (HTG), obesity and elevated fasting plasma glucose (FPG). In men, the risk of death was independently associated with age, HT, smoking, low HDL-C, high WHR, and T2DM. In women, the risk of death was independently associated with age, HT, T2DM smoking, and, in age-standardized models, obesity, high WHR, and hyperglycemia.Conclusions. In a population cohort of 45 years and older, among CVD risk factors male sex, HT, smoking, central obesity, and T2DM independently contributed to the risk of all-cause death. Among lipid parameters, low HDL-C and high TG levels increased the risk of death in men. Associations between cardiovascular risk factors and the risk of all-cause death in older people have the patterns specific for older age; these features are important to take into account in a strategy to reduce mortality in the population.

High Blood Glucose After Starch Loading in Young Women With Small Increase in Salivary Amylase: Another Crucial Role of Postprandial Salivary Amylase.

Salivary α-amylase plays a crucial role in the glucose metabolism. However, postprandial salivary α-amylase activity (SAA) and its relationship with blood glucose (BG) are poorly understood. Therefore, we investigated SAA and BG after starch loading in healthy young women. In 60 healthy non-obese young women, we investigated SAA, BG, and blood 3-hydroxybutyrate (3HB) after the consumption of 150 g rice (starch 48.8 g). Participants were classified into two groups based on the changes (Δ) in SAA from baseline at 60 min: small- and large-increase in ΔSAA groups (SI-ΔSAA and LI-ΔSAA). BG levels were significantly higher at 60, 90, and 120 min in participants with SI-ΔSAA (n = 31) than LI-ΔSAA (n = 29). Baseline 3HB concentration was also higher in participants with SI-ΔSAA. ΔSAA at 60 min was most closely and inversely correlated with BG and ΔBG at 90 min (r = -0.53 and -0.50, both P < 0.0001). Generalized linear model analysis also indicated that ΔSAA at 60 min was the most predictive of ΔBG at 90 min. Higher levels of BG and ΔBG were observed after starch loading in healthy young women with smaller increase in salivary amylase, suggesting another crucial role of postprandial salivary amylase for the postprandial glucose metabolism.

National burden and risk factors of diabetes mellitus in China from 1990 to 2021: Results from the Global Burden of Disease study 2021.

In recent years, the prevalence and mortality rates of diabetes have been rising continuously, posing a significant threat to public health and placing a heavy burden on the population. This study was conducted to describe and analyze the burden of diabetes in China from 1990 to 2021 and its attributable risk factors. Utilizing data from the Global Burden of Disease Study 2021, we analyzed the incidence, prevalence, and disability-adjusted life years (DALYs) of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in China from 1990 to 2021. We extracted sex- and age-specific data on diabetes, focusing on DALYs, years lived with disability, and years of life lost. Bayesian meta-regression and spatiotemporal Gaussian process regression were used to estimate disease parameters. Age-standardized rates (ASRs) and estimated annual percentage changes (EAPC) were calculated using direct standardization and log-linear regression. The population-attributable fractions were also determined for each risk factor. In 2021, the absolute number of incident diabetes mellitus (DM) cases was estimated at 4003543.82, including 32 000 T1DM and 3971486.24 T2DM cases. The ASRs were 244.57 for DM, 2.67 for T1DM, and 241.9 for T2DM (per 100 000 population). The absolute number of prevalent DM cases was 117288553.93, including 1442775.09 T1DM and 115845778.84 T2DM cases. The ASRs were 6142.29 for DM, 86.78 for T1DM, and 6055.51 for T2DM (per 100 000 population). In 2021, there were 178475.73 deaths caused by DM, with an ASR of mortality of 8.98 per 100 000 population. The DALYs due to DM in 2021 were 11713613.86, with an ASR of 585.43 per 100 000 population and an EAPC of 0.57. This increase can be attributed to several factors, including high body mass index, air pollution, and dietary habits. The burden of diabetes is considerable, with high prevalence and incidence rates, highlighting the urgent need for public health interventions. Addressing factors like high fasting plasma glucose, body mass index, air pollution, and dietary risks through effective interventions is critical.

Protein kinase D2 modulates hepatic insulin sensitivity in male mice

ObjectivesProtein kinase D (PKD) family is emerging as relevant regulator of metabolic homeostasis. However, the precise role of PKD2 in modulating hepatic insulin signaling has not been fully elucidated and it is the aim of this study. MethodsPKD inhibition was analyzed for insulin signaling in mouse and human hepatocytes. PKD2 was overexpressed in Huh7 hepatocytes and mouse liver, and insulin responses were evaluated. Mice with hepatocyte-specific PKD2 depletion (PKD2ΔHep) and PKD2fl/fl mice were fed a chow (CHD) or high fat diet (HFD) and glucose homeostasis and lipid metabolism were investigated. ResultsPKD2 silencing enhanced insulin signaling in hepatocytes, an effect also found in primary hepatocytes from PKD2ΔHep mice. Conversely, a constitutively active PKD2 mutant reduced insulin-stimulated AKT phosphorylation. A more in-depth analysis revealed reduced IRS1 serine phosphorylation under basal conditions and increased IRS1 tyrosine phosphorylation in PKD2ΔHep primary hepatocytes upon insulin stimulation and, importantly PKD co-immunoprecipitates with IRS1. In vivo constitutively active PKD2 overexpression resulted in a moderate impairment of glucose homeostasis and reduced insulin signaling in the liver. On the contrary, HFD-fed PKD2ΔHep male mice displayed improved glucose and pyruvate tolerance, as well as higher peripheral insulin tolerance and enhanced hepatic insulin signaling compared to control PKD2fl/fl mice. Despite of a remodeling of hepatic lipid metabolism in HFD-fed PKD2ΔHep mice, similar steatosis grade was found in both genotypes. ConclusionsResults herein have unveiled an unknown role of PKD2 in the control of insulin signaling in the liver at the level of IRS1 and point PKD2 as a therapeutic target for hepatic insulin resistance.

Association Between Nickel Exposure and Metabolic Syndrome: Data from NHANES 2017-2018.

Previous studies have found a possible association between nickel and metabolic syndrome (MetS), but with conflicting results. No studies have determined whether nickel exposure increases the prevalence of MetS in the general U.S. population. Therefore, we used data from the National Health and Nutrition Examination Survey (NHANES) to assess the association between urinary nickel and MetS. Since urinary nickel levels were presented as a skewed distribution, they were normalized using a logarithmic transformation. Weighted multivariate logistic models, restricted cubic spline, threshold effect analysis, and subgroup analyses were used to examine the association between urinary nickel concentration and the risk of MetS and its components. Based on data from 1577 participants, individuals in the second, third, and fourth quartiles of urinary nickel had an adjusted OR for MetS of 1.42 (95% CI: 0.88, 2.28), 2.00 (95% CI: 1.22, 3.28), and 1.68 (95% CI: 1.05, 2.70), respectively, representing an inverted "L"-shaped nonlinear dose-response relationship with an inflection point at 0.2141ng/L. Patients over the age of 40, males, less educated, and smokers are more susceptible to nickel exposure. In addition, there were significant associations between nickel and most components of the MetS, with the strongest to weakest correlations being high fasting glucose, reduced high-density lipoprotein, abdominal obesity, and elevated blood pressure; however, there was no significant correlation between nickel and hyperlipidemia. In conclusion, environmental nickel exposure increases the prevalence of MetS in U.S. adults, particularly in males over 40years of age, those with less education, and smokers.

Mechanisms and Future Perspectives of Curcumin in Diabetes Management

Background: Diabetes is a chronic metabolic disorder that leads to significant damage to vital organs due to prolonged high blood glucose levels. These complications include cardiovascular disease, peripheral neuropathy, retinopathy (eye damage), nephropathy (kidney damage), myopathy, and foot infections. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, primarily affecting adults when the body becomes resistant to insulin or when insulin production by the pancreas is insufficient. Turmeric (Curcuma longa), a spice widely used around the world, has been traditionally recognized for its numerous health benefits, including antidiabetic, antioxidant, antibacterial, hepatoprotective, and anticancer properties. Among its active compounds, curcumin, a polyphenolic curcuminoid, has garnered significant attention for its potential role in managing diabetes and its complications. Methods: Data for this review were obtained from databases including PubMed, Elsevier, ScienceDirect, and Google Scholar. Search terms utilized included "diabetes," "type 2 diabetes," "diabetic complications," "turmeric," "curcumin," "oxidative stress and curcumin," "curcumin and nephropathy," "curcumin and retinopathy," "curcumin and neuropathy," "curcumin and cardiovascular diseases," "curcumin and cardiomyopathy," “curcumin and pyroptosis,” "curcumin and diabetic foot ulcer," and "curcumin and erectile dysfunction." Results: This review highlights the promising role of curcumin in transforming diabetes treatment and management. The findings demonstrate that curcumin offers protective effects against diabetic complications by modulating key signaling pathways, such as NF-κB, AMPK, MAPK, and AP-1. Its anti-inflammatory properties, inhibition of hepatic gluconeogenesis, and reduction of oxidative stress through antioxidant activity present a strong case for its therapeutic potential in diabetes care. Conclusion: This review provides an in-depth explanation of curcumin's mechanisms of action, detailing its medicinal effects on diabetes-related complications and key outcomes from preclinical and clinical studies supporting its potential benefits. It also outlines future directions for research into curcumin's role in diabetes treatment.

The role of mu-opioid receptors in pancreatic islet α-cells.

Diabetes is a complex disease that impacts more than 500 million people across the world. Many of these individuals will develop diabetic neuropathy as a comorbidity, which is historically treated with exogenous opioids like morphine, oxycodone, or tramadol. Although these opioids are effective analgesics, growing evidence indicates that they may directly impact the endocrine pancreas function in patients. One common feature of these exogenous opioid ligands is their preference for the mu opioid receptor (MOPR), so we aimed to determine if endogenous MOPRs directly regulate pancreatic islet metabolism and hormone secretion. We show that pharmacological antagonism of MOPRs enhances glucagon secretion, but not insulin secretion, from human islets under high glucose conditions. This increased secretion is accompanied by increased cAMP signaling. mRNA expression of MOPRs is robust in non-diabetic human islets, but downregulated in islets from T2D donors, suggesting a link between metabolism and MOPR expression. Conditional genetic knockout of MOPRs in murine α-cells increases glucagon secretion under high glucose conditions without increasing glucagon content. Consistent with downregulation of MOPRs during metabolic disease, conditional MOPR knockout mice treated with a high fat diet show impaired glucose tolerance, increased glucagon secretion, increased insulin content, and increased islet size. Together, these results demonstrate a direct mechanism of action for endogenous opioid regulation of endocrine pancreas.

Pattern recognition of drying lysozyme–glucose droplets using machine learning classifiers

Out-of-equilibrium processes, such as sessile droplet drying, often result in distinctive macroscopic residual patterns in systems containing molecules, proteins, and colloids. Protein–glucose mixtures are particularly effective models for studying the behavior of complex fluids containing biomolecules. This study investigates the drying patterns of lysozyme droplets with varying initial glucose concentrations. Without glucose, the crack patterns are chaotic and dispersed throughout the droplet. Interestingly, cracks predominantly form around the droplet edges at intermediate glucose concentrations, while the deposits become uniform and crack-free at high glucose concentrations. To understand and classify the unique patterns related to the initial compositional changes, we developed an automated pattern recognition pipeline. We used two methods for analyzing images captured throughout the drying process. The first method involved extracting statistical textural parameters from the images as quantitative features for machine learning classifiers. The second method utilized a neural network-based classifier to directly classify the images, achieving an accuracy of 97%. The results demonstrate the effectiveness of using images from the entire drying process, not just the final images, for pattern classification. This approach may be useful in gaining a fundamental understanding of unique crack pattern that emerge when glucose is added to a protein solution.

Enhanced electricity generation in direct glucose alkaline fuel cell combined with microbial fuel cell

The aim of this study was to investigate the feasibility of combining direct glucose alkaline fuel cell (DGAFC) with microbial fuel cell (MFC) process. The system of two DGAFC cells combined with an MFC cell was successfully operated for the first time with 1 g/L glucose in 50 mM carbonate buffer solution at a pH of 10.5. The combined system achieved 99% of Coulombic efficiency and produced 6.68 and 1.80 times the total Coulombs of two DGAFC cells and one MFC cell, respectively. No accumulation of gluconic acid and high glucose mineralization were detected in the combined system within 72 h. High performance of the combined system was attributed to the synergistic effect between glucose conversion to gluconic acid in the DGAFC and its utilization by electrochemically active bacteria and fermenters in the MFC. Our results could be useful for developing novel glucose fuel cell.

Glucose and pH dual-responsive hydrogels with antibacterial, reactive oxygen species scavenging, and angiogenesis properties for promoting the healing of infected diabetic foot ulcers

The healing process of diabetic foot ulcers is challenging due to the presence of a complex and severe inflammatory microenvironment, characterized by hyperglycemia, low pH, susceptibility to infection, vascular dysfunction, and over-expression of reactive oxygen species (ROS), which can potentially lead to amputation or even mortality. Herein, a glucose and pH dual-responsive hydrogel was designed and prepared by crosslinking phenylboronic acid-grafted quaternary chitosan (QF, 4 wt%) with dopamine-grafted oxidized hyaluronic acid (OD, 5 wt%) through phenylboronation, schiff-base reaction, and other techniques. The multifunctional QO/@PV@AB7 hydrogel was prepared by incorporating pravastatin-loaded chitosan nanoparticles (CSNPs@PV, 2 mg/mL) and antimicrobial peptide AMP-AB7 loaded silica nanoparticles (SiO2NPs@AB7, 0.5 mg/mL). The results demonstrate that the QO/@PV@AB7 hydrogel exhibits good responsiveness to acidic conditions and high glucose levels, while effectively scavenging various types of ROS. Moreover, it exerted protective effects against oxidative stress on cells, enhanced HUVECs viability, and promoted angiogenesis. Notably, the QO/@PV@AB7 hydrogel displayed potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Additionally, in an MRSA-infected rat model of diabetic foot wounds, administration of the QO/@PV@AB7 hydrogel led to increased secretion of pro-angiogenic factors such as vascular endothelial nitric oxide synthase (eNOS), vascular endothelial-generating factor (VEGF), and endothelial cell adhesion molecule (CD31). Furthermore, the hydrogel significantly reduced the levels of inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while simultaneously increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10). The findings suggest that multifunctional hydrogels incorporating PV@CSNPs and SiO2NPs@AB7 demonstrate promising potential as a therapeutic approach for the treatment of diabetic foot. Statement of SignificanceHere, a glucose and pH dual-responsive QO/@PV@AB7 hydrogel with antimicrobial and angiogenesis-promoting properties was developed for the treatment of infected wounds in diabetic feet. Our findings demonstrate that the proposed hydrogel exhibits good responsiveness, effectively scavenges various types of reactive oxygen species (DPPH, O2-, -OH, and ABTS+), provides protection against oxidative stress, enhances HUVECs cell viability, and promotes angiogenesis. Notably, it also demonstrates potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Additionally, in vivo experiments demonstrated that the hydrogel exhibited accelerated wound healing in MRSA-infected diabetic foot ulcers, with a reduction of four days compared to the control group.

Astragaloside I from Astragalus Attenuates Diabetic Kidney Disease by Regulating HDAC3/Klotho/TGF-β1 Loop.

Diabetic kidney disease (DKD) has become the primary cause of end-stage renal disease (ESRD), causing an urgent need for preventive strategies for DKD. Astragaloside I (ASI), a bioactive saponin extracted from Astragalus membranaceus (Fisch.) Bunge has been demonstrated to possess a variety of biological activities. This study investigates the therapeutic potential of ASI in DKD and the underlying molecular mechanism using db/db mice in vivo and high glucose (HG)-induced SV40-MES-13 cells in vitro. The results indicated that ASI significantly ameliorated renal dysfunction and mitigated the pathological alterations in the renal tissues of db/db mice. Moreover, ASI was found to reduce the levels of renal fibrosis makers and suppress the activation of TGF-[Formula: see text]1/Smad2/3 pathway in both db/db mice and HG-induced SV40-MES-13 cells. Furthermore, ASI downregulated HDAC3 expression, upregulated Klotho expression, and enhanced Klotho release. ASI is directly bound to HDAC3, and the beneficial effects of ASI on Klotho/TGF-[Formula: see text]1/Smad2/3-mediciated renal fibrosis in DKD were reversed by the HDAC3 agonist ITSA-1. In conclusion, ASI attenuates renal fibrosis in DKD, and may act through concurrently inhibiting HDAC3 and TGF-[Formula: see text]1, thereby regulating HDAC3-mediciated Klotho/TGF-[Formula: see text]1/Smad2/3 pathway.

Rutaecarpine alleviates inflammation and fibrosis by targeting CK2α in diabetic nephropathy

Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. During the progression of DN, the proliferation of glomerular mesangial cells (GMCs) leads to the deposition of excessive extracellular matrix (ECM) in the mesangial region, eventually resulting in glomerulosclerosis. Rutaecarpine (Rut), an alkaloid found in the traditional Chinese medicinal herb Fructus Evodiae (Euodia rutaecarpa (Juss.) Benth.), has many biological activities. However, its mechanism of action in DN remains unknown. This study used db/db mice and high glucose (HG)-treated mouse mesangial cells (SV40 MES-13) to evaluate the protective effects of Rut and underlying mechanisms on GMCs in DN. We found that Rut alleviated urinary albumin and renal function and significantly relieved renal pathological damage. In addition, Rut decreased the ECM production, and renal inflammation and suppressed the activation of TGF-β1/Smad3 and NF-κB signaling pathways in vitro and in vivo. Protein kinase CK2α (CK2α) was identified as the target of Rut by target prediction, molecular docking, and cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR). Furthermore, Rut could not continue to play a protective role in HG-treated SV40 cells after silencing CK2α. In summary, this study is the first to find that Rut can suppress ECM production and inflammation in HG-treated SV40 cells by inhibiting the activation of TGF-β1/Smad3 and NF-κB signaling pathways and targeting CK2α. Thus, Rut can potentially become a novel treatment option for DN.

Prevalence of metabolic syndrome among adults treated at a district hospital outpatient department.

Metabolic syndrome (MetS) is a collection of risk factors, including hypertension, high fasting blood glucose, high fasting triglyceride and low high-density lipoprotein (HDL) cholesterol levels that may increase the risk for cardiovascular disease and type 2 diabetes. The study aimed to determine the prevalence of MetS among adults attending a Free State district hospital's outpatient department. A cross-sectional study included a consecutive sample of consenting patients 18 years and older from 18 October 2021 to 19 November 2021. Patients' waist circumference was measured, and data were extracted from patients' files. The 409 participants were predominantly females (64.2%). The median age was 60 years. Triglyceride and HDL cholesterol levels were available for 27.4% and 26.9% of patients, respectively. Of the 278 (68.0%) patients with sufficient information to determine their MetS status, 187 (67.3%) had MetS. Of the males with sufficient information, 49.1% (n= 56/114) had MetS compared to 79.9% (n= 131/164) of the females with sufficient information (p 0.001). The age group 60-79 years had the highest prevalence (76.7%,p 0.001). In all race groups, at least two-thirds of patients had MetS (p= 0.831). Incomplete patient notes and failure to do investigations led to a third of patients not having sufficient information to determine their MetS status. In patients with sufficient information, a high prevalence of MetS was found.Contribution:This study highlights the challenges of determining MetS retrospectively in an outpatient population and the need for completeness of medical note keeping and routine investigations in high-risk patients. It also notes the high prevalence of MetS.

Balloon-Shaped SMF Blood Glucose Concentration and Temperature Sensor Based on Core-Offset Structure

A blood glucose concentration and temperature sensor with a balloon-shaped single-mode fiber (SMF) based on a core-offset structure is proposed and experimentally demonstrated. The balloon-shaped SMF is created by offset-fusing a straight-line SMF between two other SMFs, thereby forming a Mach–Zehnder interferometer (MZI). The core-offset structure can effectively excite higher-order cladding modes. The experimental results showed that the maximum sensitivity of blood glucose concentration was 0.331 nm/(mmol/l) and the maximum sensitivity of temperature was 0.216 nm/°C when the offset distance was 10 μm. Dual-parameter measurement was achieved through a dual-parameter matrix. In addition, the sensor has characteristics such as simple structure, low cost, good stability, and electromagnetic interference resistance, making it potentially valuable for diagnosing high blood glucose and related conditions.

Modified streptozotocin-induced diabetic model in rodents.

Streptozotocin (STZ)-induced type I diabetes mellitus (DM) models have been pivotal in diabetes research due to their ability to mimic the insulin-dependent hyperglycemia akin to human type I diabetes. However, these models often suffer from poor induction rates and low survival post-STZ induction, especially in long-term experiments, necessitating insulin supplementation, which introduces additional variables to experiments. To address this, we present a novel modification to the STZ-induced DM model in C57BL/6J mice to improve survival rates without insulin supplementation. Our method involves non-fasting, low-dose STZ injections dissolved in pH-neutral phosphate buffer saline instead of acidic sodium citrate buffer, administered over 5 days. We observed hyperglycemia induction in 94.28% of mice within a week post-injection, with stable high blood glucose levels, stable body weight, and minimal mortality up to 21 weeks. Notably, omitting 10% sucrose in water and fasting did not affect hyperglycemia induction. Our findings suggest that the modified protocol not only decreases the experimental effort of the researchers, but reduces animal stress and mortality, thus enhancing experimental outcomes and animal welfare. By optimizing the STZ-induced DM model in C57BL/6J mice, our study provides a valuable resource for researchers aiming to study diabetes and its complications while minimizing experimental variability and animal usage.

Alpha(α)-mangostin (Xanthone of Garcinia mangostana L.): Augmenting Macrophages Activity for an Effective Diabetic Wound Healing

Diabetic wounds are particularly difficult to treat medically because they heal at a slower pace than regular wounds. Macrophages are essential in all stages of normal wound healing, including inflammation, proliferation and rem odelling. When wound healing is affected, macrophages can reduce the level of growth factor and increase the level of interleukin-6 (IL-6), disrupt the balance between tissue inhibitors of metalloproteinase (TIMPs) and matrix metalloproteinase (MMPs), which can slow down healing. Alpha(α)-mangostin, a natural xanthone derived from the pericarp of the mangosteen, has gained considerable attention due to its anti-inflammatory properties, suggesting its potential to promote wound healing. However, its exact role in healing diabetic foot ulcers, common in diabetes, remains unclear. Hence, this study aims to explore how α-mangostin might affect diabetic wound healing by evaluating its impact on PDGF, CTGF, BFGF, VEGF, TGF-β, MMP-9, TIMP-2 and IL-6 secretion in macrophage cells. Human monocytic macrophages (THP-1) were incubated with a 35 mM glucose solution for 72 h to create a glucose-enriched medium. The cells were then incubated with α-mangostin (0.15, 2.5 and 5 µg/mL) together with 35 mM glucose. Carboxymethyl cellulose (CMC) served as positive controls; glucose-enriched media and media-alone served as negative controls. Protein expression was measured using ELISA. α-mangostin (2.5 µg/mL) increased the levels of PDGF and VEGF and decreased the level of MMP-9 compared to glucose controls. There was no significant difference in other growth factors, TIMP-2 and IL-6 protein levels across any of the treatment groups compared to glucose controls. In conclusion, α-mangostin particularly at 2.5 µg/mL demonstrated a significant increase in PDGF and VEGF levels while simultaneously reducing MMP-9 in macrophage cells under glucose-induced conditions. These findings suggest that α-mangostin holds the potential for enhancing the healing of chronic wounds in diabetic conditions. HIGHLIGHTS Treatment of macrophages (THP-1 cells) with 2.5 µg/mL Alpha (α)-mangostin in a high glucose medium led to a significant increase in PDGF and VEGF secretion compared to glucose control. Treatment of the cells with 2.5 µg/mL Alpha (α)-mangostin in a high glucose medium led to a significant reduction of MMP-9 secretion compared to glucose control. There is no significant effects of Alpha (α)-mangostin on IL-6 and TIMP secretion compared to controls This study suggests that Alpha (α)-mangostin may be beneficial in promoting diabetic wound healing via stimulation of PDGF and VEGF secretion and reducing MMP-9 levels. GRAPHICAL ABSTRACT