Diabetic Conditions Research Articles

Cardiovascular Disease and Diabetes Are Among the Main Underlying Causes of Death in Twenty Healthcare Facilities Across Two Cities in the Democratic Republic of Congo

Introduction: The mortality rates associated with cardiovascular disease (CVD) and diabetes exhibit disparities by region, with Central Africa ranking fourth globally in terms of mortality rate. The Democratic Republic of Congo (DRC) does not possess mortality data pertaining to these specific underlying causes of death. This study aimed to determine the death rate attributable to CVD and diabetes in two cities in the DRC. Methodology: The data on CVD and diabetes utilized in this study were obtained from a pilot project and were registered in the National Health Information System (NHIS). Data quality was initially evaluated using an automated Digital Open Rule Integrated Selection (DORIS), followed by an assessment conducted manually by three assessors. Descriptive and comparative analyses were carried out to determine the proportion of mortality related to CVD and diabetes. Results: CVD accounted for 20.4% (95%CI: 17.7–23.4%) of deaths in the two cities (Kinshasa and Matadi), whereas diabetes accounted for 5.4% (95%CI: 3.9–7.2%). After adjusting for age and city, the proportional mortality from CVD and diabetes was higher for women than men and increased with age. This study recorded 4.4% of deaths among men and 7.0% among women as the proportional mortality from diabetes. Conclusions: Non-communicable diseases (NCDs) continue to be a major cause of death, and CVD and diabetes are among the leading causes of early mortality in adults in urban areas. The proportional mortality related to CVD and diabetes appears to be higher in women than in men. Special emphasis should be placed on women, particularly during adulthood, to ensure the prompt detection of diabetes and cardiovascular conditions.

Using QALYs as an Outcome for Assessing Global Prediction Accuracy in Diabetes Simulation Models.

(1) To demonstrate the use of quality-adjusted life-years (QALYs) as an outcome measure for comparing performance between simulation models and identifying the most accurate model for economic evaluation and health technology assessment. QALYs relate directly to decision making and combine mortality and diverse clinical events into a single measure using evidence-based weights that reflect population preferences. (2) To explore the usefulness of Q2, the proportional reduction in error, as a model performance metric and compare it with other metrics: mean squared error (MSE), mean absolute error, bias (mean residual), and R2. We simulated all EXSCEL trial participants (N = 14,729) using the UK Prospective Diabetes Study Outcomes Model software versions 1 (UKPDS-OM1) and 2 (UKPDS-OM2). The EXSCEL trial compared once-weekly exenatide with placebo (median 3.2-y follow-up). Default UKPDS-OM2 utilities were used to estimate undiscounted QALYs over the trial period based on the observed events and survival. These were compared with the QALYs predicted by UKPDS-OM1/2 for the same period. UKPDS-OM2 predicted patients' QALYs more accurately than UKPDS-OM1 did (MSE: 0.210 v. 0.253; Q2: 0.822 v. 0.786). UKPDS-OM2 underestimated QALYs by an average of 0.127 versus 0.150 for UKPDS-OM1. UKPDS-OM2 predictions were more accurate for mortality, myocardial infarction, and stroke, whereas UKPDS-OM1 better predicted blindness and heart disease. Q2 facilitated comparisons between subgroups and (unlike R2) was lower for biased predictors. Q2 for QALYs was useful for comparing global prediction accuracy (across all clinical events) of diabetes models. It could be used for model registries, choosing between simulation models for economic evaluation and evaluating the impact of recalibration. Similar methods could be used in other disease areas. Diabetes simulation models are currently validated by examining their ability to predict the incidence of individual events (e.g., myocardial infarction, stroke, amputation) or composite events (e.g., first major adverse cardiovascular event).We introduce Q2, the proportional reduction in error, as a measure that may be useful for evaluating and comparing the prediction accuracy of econometric or simulation models.We propose using the Q2 or mean squared error for QALYs as global measures of model prediction accuracy when comparing diabetes models' performance for health technology assessment; these can be used to select the most accurate simulation model for economic evaluation and to evaluate the impact of model recalibration in diabetes or other conditions.

Integrative analysis of gene expression, protein abundance, and metabolomic profiling elucidates complex relationships in chronic hyperglycemia-induced changes in human aortic smooth muscle cells

Type 2 diabetes mellitus (T2DM) is a major public health concern with significant cardiovascular complications (CVD). Despite extensive epidemiological data, the molecular mechanisms relating hyperglycemia to CVD remain incompletely understood. We here investigated the impact of chronic hyperglycemia on human aortic smooth muscle cells (HASMCs) cultured under varying glucose conditions in vitro, mimicking normal (5 mmol/L), pre-diabetic (10 mmol/L), and diabetic (20 mmol/L) conditions, respectively. Normal HASMC cultures served as baseline controls, and patient-derived T2DM-SMCs served as disease controls. Results showed significant increases in cellular proliferation, area, perimeter, and F-actin expression with increasing glucose concentration (p < 0.01), albeit not exceeding the levels in T2DM cells. Atomic force microscopy analysis revealed significant decreases in Young’s moduli, membrane tether forces, membrane tension, and surface adhesion in SMCs at higher glucose levels (p < 0.001), with T2DM-SMCs being the lowest among all the cases (p < 0.001). T2DM-SMCs exhibited elevated levels of selected pro-inflammatory markers (e.g., ILs-6, 8, 23; MCP-1; M-CSF; MMPs-1, 2, 3) compared to glucose-treated SMCs (p < 0.01). Conversely, growth factors (e.g., VEGF-A, PDGF-AA, TGF-β1) were higher in SMCs exposed to high glucose levels but lower in T2DM-SMCs (p < 0.01). Pathway enrichment analysis showed significant increases in the expression of inflammatory cytokine-associated pathways, especially involving IL-10, IL-4 and IL-13 signaling in genes that are up-regulated by elevated glucose levels. Differentially regulated gene analysis showed that compared to SMCs receiving normal glucose, 513 genes were upregulated and 590 genes were downregulated in T2DM-SMCs; fewer genes were differentially expressed in SMCs receiving higher glucose levels. Finally, the altered levels in genes involved in ECM organization, elastic fiber synthesis and formation, laminin interactions, and ECM proteoglycans were identified. Growing literature suggests that phenotypic switching in SMCs lead to arterial wall remodeling (e.g., change in stiffness, calcific deposits formation), with direct implications in the onset of CVD complications. Our results suggest that chronic hyperglycemia is one such factor that leads to morphological, biomechanical, and functional alterations in vascular SMCs, potentially contributing to the pathogenesis of T2DM-associated arterial remodeling. The observed differences in gene expression patterns between in vitro hyperglycemic models and patient-derived T2DM-SMCs highlight the complexity of T2DM pathophysiology and underline the need for further studies.

Representation of Native Hawaiian and Pacific Islander Individuals in Clinical Trials

Having diverse participants in clinical trials ensures new drug products work well across different demographic groups, making health care safer and more effective for everyone. Information on the extent of Native Hawaiian and Pacific Islander participation in clinical trials is limited. To examine representation of Native Hawaiian and Pacific Islanders in clinical trials leading to the first US Food and Drug Administration (FDA) approvals for the 10 drug products with the top worldwide sales forecasts in 2024. Cross-sectional secondary analysis of existing data from clinical trials that took place from 2006 to 2021 in the US. All clinical trials that were included in the FDA first approval application for the 10 drug products were evaluated in this study. Data were analyzed from February to August 2024. Participation in a clinical drug trial. Comparison of the proportion of Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts in 2024 to the Native Hawaiian and Pacific Islander population proportion. In this cross-sectional study of 139 062 individuals, Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts was either unknown or low. For 6 of the 10 drug products (60%), the number of Native Hawaiian and Pacific Islander participants was not documented. All trials that reported Native Hawaiian and Pacific Islander participation had fewer Native Hawaiian and Pacific Islander participants than would be expected based on their US population proportion, with 2 of the differences being statistically significant. Of the trials that disaggregated Native Hawaiian and Pacific Islander participants from other racial groups, the number of Native Hawaiian and Pacific Islander participants was 8 for risankizumab-rzaa (0.38% of participants vs 0.49% of the population; percentage point difference, -0.11%; 95% CI, -0.37% to -0.15%), 7 for bictegravir/emtricitabine/tenofovir alafenamide (0.38% of participants vs 0.49% of the population; percentage point difference, -0.10%; 95% CI, -0.39% to 0.18%), 27 for 4vHPV/9vHPV (0.15% of participants vs 0.46% of the population; percentage point difference, -0.31%; 95% CI, -0.37% to -0.26%), and 90 for BNT162B2 COVID-19 vaccine (0.20% of participants vs 0.52% of the population; percentage point difference, -0.32; 95% CI, -0.36% to -0.27%). In this cross-sectional study, limited documentation and participation of Native Hawaiian and Pacific Islander individuals in clinical trials for drug products with top sales forecasts was found. This is especially concerning because Native Hawaiian and Pacific Islander individuals have a higher risk than other racial groups for type 2 diabetes, cancer, and several other conditions the products examined in this study treat. Given the importance of enrolling Native Hawaiian and Pacific Islander participants in clinical trials, sites should be established in key geographic regions, such as Hawai'i, and postmarket studies should be conducted within Native Hawaiian and Pacific Islander populations.

From Orchard to Wellness: Unveiling the Health Effects of Sweet Cherry Nutrients

This review paper explores the multifaceted relationship between sweet cherry nutrients and human health, aiming to uncover the comprehensive impact of these bioactive compounds from orchard to wellness. Furthermore, it highlights how advanced crop techniques can be pivotal in optimizing these beneficial compounds. Synthesizing existing literature, the paper examines the diverse bioactive nutrients in sweet cherries, including antioxidants, polyphenols, vitamins, and minerals, and elucidating their mechanisms of action and potential health benefits. From antioxidant properties to anti-inflammatory effects, the paper elucidates how these nutrients may mitigate chronic diseases such as cardiovascular disorders, diabetes, and neurodegenerative conditions. Additionally, it explores their role in promoting gastrointestinal health, enhancing exercise recovery, and modulating sleep patterns. The review discusses emerging research on the potential anti-cancer properties of sweet cherry compounds, highlighting their promising role in cancer prevention and treatment. Furthermore, it delves into the impact of sweet cherry consumption on metabolic health, weight management, and skin health. By providing a comprehensive overview of the current understanding of sweet cherry nutrients and their health effects, this paper offers valuable insights for researchers, healthcare professionals, and consumers interested in utilizing nature’s bounty for holistic wellness.

BIG DATA AND CHRONIC DISEASE MANAGEMENT THROUGH PATIENT MONITORING AND TREATMENT WITH DATA ANALYTICS

This systematic review investigates the role of predictive analytics in chronic disease management, focusing on its capacity to predict disease progression, reduce hospitalizations, and enhance patient outcomes. A total of 35 peer-reviewed articles were analyzed to evaluate how predictive models, utilizing data from electronic health records (EHRs), wearable devices, and real-time monitoring systems, are applied in managing chronic diseases such as diabetes and cardiovascular conditions. The findings indicate that predictive models have significantly improved early disease detection accuracy, with studies showing improved forecasting of heart failure exacerbations and notable reductions in hospital readmissions due to timely interventions. Additionally, many studies reported a reduction in healthcare utilization through predictive analytics-driven early interventions. However, challenges regarding data quality and model accuracy were frequently cited, particularly concerning data integration and harmonization across various healthcare systems. Ethical and privacy concerns, including data security and algorithmic bias, were also highlighted, underscoring the need to address these issues for responsible and equitable use of predictive analytics. This review affirms the growing impact of predictive analytics in chronic disease management, while calling for advancements in data management and ethical frameworks to maximize its potential.

Endothelial KLF11 is a novel protector against diabetic atherosclerosis

BackgroundAtherosclerotic cardiovascular diseases remain the leading cause of mortality in diabetic patients, with endothelial cell (EC) dysfunction serving as the initiating step of atherosclerosis, which is exacerbated in diabetes. Krüppel-like factor 11 (KLF11), known for its missense mutations leading to the development of diabetes in humans, has also been identified as a novel protector of vascular homeostasis. However, its role in diabetic atherosclerosis remains unexplored.MethodsDiabetic atherosclerosis was induced in both EC-specific KLF11 transgenic and knockout mice in the Ldlr−/− background by feeding a diabetogenic diet with cholesterol (DDC). Single-cell RNA sequencing (scRNA-seq) was utilized to profile EC dysfunction in diabetic atherosclerosis. Additionally, gain- and loss-of-function experiments were conducted to investigate the role of KLF11 in hyperglycemia-induced endothelial cell dysfunction.ResultsWe found that endothelial KLF11 deficiency significantly accelerates atherogenesis under diabetic conditions, whereas KLF11 overexpression remarkably inhibits it. scRNA-seq profiling demonstrates that loss of KLF11 increases endothelial-to-mesenchymal transition (EndMT) during atherogenesis under diabetic conditions. Utilizing gain- and loss-of-function approaches, our in vitro study reveals that KLF11 significantly inhibits EC inflammatory activation and TXNIP-induced EC oxidative stress, as well as Notch1/Snail-mediated EndMT under high glucose exposure.ConclusionOur study demonstrates that endothelial KLF11 is an endogenous protective factor against diabetic atherosclerosis. These findings indicate that manipulating KLF11 could be a promising approach for developing novel therapies for diabetes-related cardiovascular complications.

Does drinking coffee reduce the risk of kidney stone formation?

Introduction: Kidney stones, a prevalent urological issue affecting 2% to 15% of the global population, result from complex physicochemical processes in urine. Untreated stones can lead to severe complications like ureter blockage and kidney damage. Diet plays a crucial role in stone formation, with historical negative views on coffee consumption. However, new research shows potential benefits of coffee. The purpose of this review was to analyze the association between coffee consumption and the risk of developing kidney stones. State of knowledge: Kidney stones develop as solid masses in the kidney's collecting system and can consist of various substances like calcium oxalate, calcium phosphate, uric acid, and cystine. Understanding the formation of kidney stones involves analyzing the role of crystal retention. Coffee consumption has shown potential benefits in reducing the risk of kidney stones by influencing urine composition. Additionally, oxalate and calcium are key dietary components to consider in kidney stone prevention strategies. Coffee has demonstrated diverse health benefits, including protection against cardiovascular disease, type 2 diabetes and neurodegenerative conditions. Its impact on blood pressure, glucose metabolism, and neuroprotection highlights its potential role in promoting overall well-being. Conclusions: Coffee consumption, particularly due to its caffeine content and other compounds like chlorogenic acid, may reduce the risk of kidney stone formation. Caffeine has shown anti-lithogenic properties, decreasing oxalate excretion and increasing magnesium and potassium excretion, potentially preventing stone formation. A study by P. Peerapen and V. Thongboonkerd highlighted caffeine's role in reducing crystal adhesion to renal cells as a key mechanism in preventing kidney stones. In summary, coffee's diverse components could provide protection against kidney stone development.

Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.

Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential for maintaining physiological functions and metabolic homeostasis. However, chronic elevation of BCAAs causes metabolic diseases such as obesity, type 2 diabetes (T2D), and metabolic-associated fatty liver disease (MAFLD). Adipose tissue, skeletal muscle, and the liver are the three major metabolic tissues not only responsible for controlling glucose, lipid, and energy balance but also for maintaining BCAA homeostasis. Under obese and diabetic conditions, different pathogenic factors like pro-inflammatory cytokines, lipotoxicity, and reduction of adiponectin and peroxisome proliferator-activated receptors γ (PPARγ) disrupt BCAA metabolism, leading to excessive accumulation of BCAAs and their downstream metabolites in metabolic tissues and circulation. Mechanistically, BCAAs and/or their downstream metabolites, such as branched-chain ketoacids (BCKAs) and 3-hydroxyisobutyrate (3-HIB), impair insulin signaling, inhibit adipogenesis, induce inflammatory responses, and cause lipotoxicity in the metabolic tissues, resulting in multiple metabolic disorders. In this review, we summarize the latest studies on the metabolic regulation of BCAA homeostasis by the three major metabolic tissues-adipose tissue, skeletal muscle, and liver-and how dysregulated BCAA metabolism affects glucose, lipid, and energy balance in these active metabolic tissues. We also summarize therapeutic approaches to restore normal BCAA metabolism as a treatment for metabolic diseases.

N 6-Methyladenosine demethylase FTO controls macrophage homeostasis in diabetic vasculopathy.

Diabetic vasculopathy, encompassing complications such as diabetic retinopathy, represents a significant source of morbidity, with inflammation playing a pivotal role in the progression of these complications. This study investigates the influence of m6A modification and the m6A demethylase FTO on macrophage polarization and its subsequent effects on diabetic microvasculopathy. We found that diabetes induces a shift in macrophage polarization towards a pro-inflammatory M1 phenotype, which is associated with a reduction in m6A modification levels. Notably, FTO emerges as a critical regulator of m6A under diabetic conditions. In vitro experiments reveal that FTO not only modulates macrophage polarization but also mediates their interactions with vascular endothelial cells. In vivo experiments demonstrate that FTO deficiency exacerbates retinal inflammation and microvascular dysfunction in diabetic retinas. Mechanistically, FTO stabilizes mRNA through an m6A-YTHDF2-dependent pathway, thereby activating the PI3K/AKT signaling cascade. Collectively, these findings position FTO as a promising therapeutic target for the management of diabetic vascular complications.

The Therapeutic Potential of GLP-1 Receptor Agonists in the Management of Hidradenitis Suppurativa: A Systematic Review of Anti-Inflammatory and Metabolic Effects

Background: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are synthetic peptides that mimic the natural activity of GLP-1, widely known for lowering blood glucose levels and promoting weight reduction. These characteristics make them a valuable tool in managing type 2 diabetes and obesity-related conditions. Recent findings indicate that GLP1-RAs may also offer therapeutic benefits in managing hidradenitis suppurativa (HS), a chronic inflammatory skin disorder closely associated with metabolic abnormalities, including obesity, diabetes, and dyslipidemia. This review explores the potential role of GLP1-RAs in managing HS. Methods: A systematic review was conducted by searching electronic databases, including MEDLINE and Google Scholar, without date limitations. Key search terms included “GLP-1” or “GLP-1 agonists” combined with “hidradenitis suppurativa” or “acne inversa”. Inclusion criteria were set for studies reporting on the use of GLP1-RAs as a treatment for HS, with articles discussing theoretical applications excluded. Data synthesis included findings from 25 relevant studies. Results: The analysis revealed that GLP1-RAs, specifically liraglutide and semaglutide, led to significant reductions in weight and systemic inflammation in HS patients. Notably, improvements in lesion severity and quality of life were reported. The anti-inflammatory effects of GLP1-RAs were attributed to the suppression of key inflammatory pathways involving TNF-α, IL-17, and NF-κB. Conclusions: GLP1-RAs demonstrate significant potential as an adjunct therapy for HS, addressing both the metabolic and inflammatory aspects of the condition. While early results are promising, further research is necessary to determine their long-term efficacy in managing HS.

Two Endogenous Endophthalmitis Cases Accompanying Nephrological Condition in Diabetic Patients

Aims: This report aims to highlight the importance of prompt diagnosis and intervention in cases of endogenous endophthalmitis, with particular focus on its nephrological etiology and associated systemic infections. Presentation of Case: Two cases of endogenous endophthalmitis were observed in patients with nephrological complications. Case 1 involved a 50-year-old man with end-stage renal disease on hemodialysis, who presented with severe visual impairment in the right eye due to Staphylococcus aureus sepsis from a hemodialysis catheter infection. Despite aggressive treatment with intravitreal and systemic antibiotics, the patient’s visual prognosis was poor. Case 2 involved a 65-year-old woman with acute pyelonephritis and undiagnosed diabetes, presenting with unilateral visual loss and ocular inflammation. Systemic and intravitreal antibiotics, alongside corticosteroids, led to a favorable outcome with a final visual acuity of 7/10. Discussion: Diabetic patients with nephrological conditions are particularly susceptible to endogenous endophthalmitis due to compromised immunity and increased risk of systemic infections. Both cases underscore the link between systemic infections, particularly in patients with renal or diabetic conditions, and endogenous endophthalmitis. Prompt recognition of ocular symptoms in patients with systemic infections is critical, as appropriate intervention can preserve visual function. The role of broad-spectrum antibiotics, intravitreal injections, and systemic infection control is emphasized. Conclusion: These cases illustrate the importance of multidisciplinary intervention in managing endogenous endophthalmitis secondary to nephrological infections. While outcomes vary depending on disease severity and patient health, rapid diagnosis and treatment are vital to improving prognosis and preserving vision.

Application of Fourier Transform Infrared (FTIR) spectroscopy for the analysis of legume seeds

Legume seeds are highly valued for their rich nutritional profile and many culinary applications, making them essential to human diets in many civilizations worldwide. Legume seeds have lower protein content comparable to that found in animal sources. Legumes have many health benefits, such as improved blood sugar control, weight management, cardiovascular health, and a reduced risk of developing chronic diseases, including diabetes, cancer, and heart conditions. The functional groups in legume seeds such as black chickpea, cowpea, white chickpea, small red bean, and red lentil were analyzed using FTIR spectroscopy combined with principal compound analysis. The findings indicated that five samples had O-H stretching, C-H stretching, and N-H stretching bonds in the wave number range of 2924 cm- 1, which implies the presence of alcohol, carboxylic acid, amine salt, and alkane. The nitro compound having N-O stretching was observed in all samples except white chickpea. All the samples have C-F stretching bonds, representing the presence of fluoro compound in the wave range of 1002- 1115 cm-1, except for red beans. It is worth noting that the properties of red lentils differ significantly from those of black chickpeas and cowpeas, and the properties of cowpeas differ from those of small red beans.

From ROS scavenging to boosted osseointegration: cerium-containing mesoporous bioactive glass nanoparticles functionalized implants in diabetes

Excessive production of reactive oxygen species (ROS) around titanium implants under diabetic conditions causes persistent inflammation, leading to poor osseointegration and even implant failure. Surface modification is an effective way to promote ROS clearance, alleviate inflammation, and stimulate bone formation. In this study, a multifunctional coating is fabricated by introducing cerium (Ce)-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) onto the titanium surface via an electrophoretic deposition method. The incorporation of Ce-MBGNs remarkably improves surface hydrophilicity by increasing the surface areas. The bioactive ions are appropriately released, thereby promoting mesenchymal stem cell proliferation and differentiation under diabetic conditions. The conversion between Ce(III) and Ce(IV) endows Ce-MBGNs coating with antioxidative nanoenzymes properties to scavenge diabetes-induced ROS, resulting in macrophage polarization towards the anti-inflammatory phenotype. The therapeutic effect of Ce-MBGNs-modified titanium implants is also verified in diabetic rats by inhibiting inflammatory responses and accelerating early osseointegration. Taken together, the findings reveal that the ROS-scavenging and immunomodulation activity of the Ce-MBGNs coating contributes to enhanced osseointegration, and provides a novel implant surface for diabetic patients.

The function of p97/valosin-containing protein (VCP) and small VCP-interacting protein (SVIP) in invasion and migration of pancreatic cancer cells.

Misfolded proteins are eliminated by a process known as endoplasmic reticulum-associated protein degradation (ERAD). ERAD has an impact on a variety of illnesses, such as diabetes, cystic fibrosis, cancer, and neurological conditions. As one of the many proteins involved in ERAD, this study is focused on p97/valosin-containing protein (VCP) and small VCP-interacting protein (SVIP). The existence and function of SVIP and p97/VCP in various types of pancreatic cancer have not yet been investigated. The study's objectives are to examine the expressions of SVIP and p97/VCP in two pancreatic cancer types and to show whether these proteins aid in the invasion and migration of pancreatic cancer cells. In this work, MIA PaCa-2 and PANC-1 human cell lines were examined. Immunocytochemistry and immunofluorescence were performed to detect the cellular localization and presence of p97/VCP and SVIP in pancreatic cancer cells. Following p97/VCP siRNA and SVIP siRNA transfection of the cells, protein expressions were assessed using Western blot analysis. The effects of this suppression on cell invasion and migration were determined using the xCELLigence real-time analysis system (RTAC). In the nucleus and cytoplasm of MIA PaCa-2 and PANC-1 cells, p97/VCP and SVIP immunoexpressions were seen. The decrease in protein expressions of p97/VCPsi and SVIPsi was significant in pancreatic cells compared to the controlsi. The p97/VCP siRNA transfection reduced the invasion and migration of MIA PaCa-2 and PANC-1 cells. In addition, the SVIP siRNA suppression resulted in increasing the invasion and migration ability of both cells. This study also demonstrated, for the first time, SVIP expression in MIA PaCa-2 and PANC-1 cells. Overall, the findings show the differential expression and function of p97/VCP and SVIP in pancreas ductal adenocarcinoma cells. The potential of the pancreatic cancer cells to migrate and invade altered when the two cell lines were transfected with p97/VCPsi and SVIPsi.

Renal microRNA-144-3p is associated with transforming growth factor-β1-induced oxidative stress and fibrosis by suppressing the NRF2 pathway in hypertensive diabetic kidney disease

Chronic kidney disease (CKD) is a global health problem characterized by progressive renal fibrosis and excessive extracellular matrix deposition. Oxidative stress and epigenetic regulation, particularly through microRNAs (miRNAs), play crucial roles in the pathogenesis of CKD. In this study, we investigated the role of urinary miR-144-3p, which is upregulated in rats with CKD induced by diabetes and hypertension, in renal fibrosis progression, particularly its regulation of the nuclear factor erythroid-2-related factor 2 (NRF2) pathway. Our findings revealed elevated miR-144-3p levels and reduced NRF2 and target gene levels in kidney tissues of streptozotocin-treated spontaneously hypertensive rats. In vitro experiments demonstrated that miR-144-3p directly binds to the 3'-untranslated region of nrf2, suppressing the NRF2 pathway in renal tubular epithelial cells. Additionally, the profibrogenic factor transforming growth factor (TGF)-β1 increased miR-144-3p expression. TGF-β1-induced NRF2 suppression and reactive oxygen species elevation were found to be mediated through miR-144-3p upregulation. In vivo, cilostazol, an antiplatelet drug with an NRF2-activating effect, ameliorated renal injury in diabetic hypertensive rats by decreasing TGF-β1 and miR-144-3p levels while increasing NRF2 and its target gene levels in the kidneys. These findings highlight the potential therapeutic value of targeting the miR-144-3p/NRF2 pathway to attenuate CKD progression in hypertensive diabetic conditions.

Precisely Engineering a ROS‐Regulatable Decellularized Matrix to Rejuvenate Endogenous Repair for Heart Valve Remodeling in Diabetic Cohort

AbstractThe reconstruction of a heart valve through in situ tissue engineering remains a formidable challenge, particularly for patients with diabetes mellitus, because the pathophysiological alterations associated with diabetes substantially impair the cardiovascular system's intrinsic repair capacity. In this study, reactive oxygen species (ROS) regulation are integrated into the fabrication of pro‐endothelialization interfaces to counteract the adverse repair environment. Specifically, a heparin‐mimicking alginate‐derived glycopeptide and the natural ROS scavenger melanin are modified onto the surface of a decellularized extracellular matrix (dECM). This tailored interface significantly enhances endothelial cell (EC) adhesion while reducing platelet adhesion. The incorporation of melanin effectively suppresses ROS elevation in ECs and macrophages under hyperglycemic conditions. Consequently, this intervention promotes EC rejuvenation by enhancing proliferation, migration, and anti‐apoptotic capabilities, while concurrently attenuating the release of inflammatory and pro‐fibrotic factors by macrophages. The dECM is intravascularly implanted in a diabetic rabbit model after being fabricated into a covered stent, demonstrating favorable remodeling characteristics such as enhanced endothelialization and reduced fibrotic deposition. This scaffold design, specifically tailored to the pathological conditions of diabetes, offers a precise biomaterial strategy for in situ heart valve tissue engineering.

Impacts of Hyperglycemia on Epigenetic Modifications in Human Gingival Fibroblasts and Gingiva in Diabetic Rats

Periodontal disease is considered one of the diabetic complications with high morbidity and severity. Recent studies demonstrated the involvement of the epigenome on diabetic complications. Histone modifications change chromatin architecture and gene activation. Histone modifications have been reported to alter chromatin structure and regulate gene transcription. In this study, we investigated the impacts of H3 lysine 4 trimethylation (H3K4me3) and specific histone methyltransferases of H3K4 methylation, su(var)3-9, enhancer-of-zeste, and trithorax domain 1A (SETD1A) on periodontal tissue affected by the diabetic condition. We observed the increase in H3K4me3 and SETD1A in gingival tissue of diabetic rats compared with the normal rats. Cultured human fibroblasts (hGFs) confirmed a high glucose-induced increase in H3K4me3 and SETD1A. We further demonstrated that high glucose increased the gene expression of matrix metalloproteinase (MMP) 1 and MMP13, which were canceled by sinefungin, an SETD1A inhibitor. Our investigation suggests that diabetes triggers histone modifications in the gingival tissue, resulting in gingival inflammation. Histone modifications may play crucial roles in the development of periodontal disease in diabetes.

Ferroptosis-associated alterations in diabetes following ischemic stroke: Insights from RNA sequencing

ObjectiveFerroptosis is an iron-dependent form of programmed cell death associated with lipid peroxidation. Though diabetes worsens cerebral injury and clinical outcomes in stroke, it is poorly understood whether ferroptosis contributes to diabetes-exacerbated stroke. This study aimed to identify ferroptosis-associated differentially expressed genes in ischemic stroke under diabetic condition and then explore their roles using comprehensive bioinformatics analyses. MethodsType 1 diabetes (T1D) model was established in male mice at 8–10 weeks of age by one intraperitoneal injection of streptozotocin (110 mg/kg). Ischemic stroke was induced by a transient 45-minute middle cerebral artery occlusion and evaluated three days thereafter. Ischemic brain cortex was dissected 24 h after the reperfusion and subjected to bulk tissue RNA sequencing followed by bioinformatics analysis and verification of key findings via quantitative real-time PCR. ResultsEnlarged infarct size was seen in diabetic, as compared with non-diabetic mice, in conjunction with worsened neurological behaviors. Both body and spleen weights were reduced in diabetic as compared with non-diabetic mice. There was a trend for reduced survival rate in diabetic mice following the stroke. In RNA sequencing analysis, we identified 1299 differentially expressed genes in ischemic brain between diabetic and non-diabetic mice, with upregulation and downregulation for 732 and 567 genes, respectively. Among these genes, 27 genes were associated with ferroptosis. Further analysis reveals that solute carrier family 25 member 28(SLC25A28) and sterol carrier protein 2(SCP2) were the top genes associated with ferroptosis in diabetic mice following ischemic stroke. In several bioinformatics analyses, we found SLC25A28, one of the top ferroptosis-related genes, is involved in several metabolic and regulatory pathways as well as the regulatory complexity of microRNAs and circular RNAs, which demonstrates the potential role of SLC25A28 in diabetes-exacerbated stroke. Drug network analysis suggests SLC25A28 as a potential therapeutic target for ameliorating ischemic injury in diabetes. ConclusionsOur bulk RNA sequencing and bioinformatics analyses show that altered ferroptosis signaling pathway was associated with the exacerbation of experimental stroke injury under diabetic condition. Especially, additional investigation into the mechanisms of SLC25A28 and SCP2 in diabetes-exacerbated stroke will be explored in the future study.

Epidermal Growth Factor Intralesional Delivery in Chronic Wounds: The Pioneer and Standalone Technique for Reversing Wound Chronicity and Promoting Sustainable Healing.

The early expectations about growth factors' (GFs') discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology was a conundrum at that time. Diabetes undermines keratinocytes' and fibroblasts' physiology, impairing skin healing abilities. Diabetic ulcers, as other chronic wounds, are characterized by hyperinflammation, unbalanced proteolytic activity, catabolism, and free radical cytotoxicity. This hostile scenario for the chemical stability, integrity, and functionality of GFs led to the conclusion that topical administration may jeopardize GFs' clinical effectiveness. Epidermal growth factor (EGF) has a proximal position in tissues homeostasis by activating survival and mitogenic pathways from embryonic life to adulthood. Seminal experiments disclosed unprecedented pharmacological bounties of parenterally administered EGF. Accordingly, the experience accumulated for more than 20 years of EGF intralesional infiltration of diabetic wound bottoms and edges has translated into sustained healing responses, such as low recurrences and amputation rates. This delivery route, in addition to being safe and tolerated, has shown to restore a variety of circulating biochemical markers ordinarily disturbed in diabetic conditions. EGF infiltration triggers a cascade of local fibroblast reactions, supporting its molecular integrity, prolonged mean residence time, and ultimately eliciting its receptor trafficking and nuclear translocation. The intralesional delivery route seems to warrant that EGF reaches wound fibroblasts' epigenetic core, mitigating the consequences of metabolic memory imprinting.