Role of miR-125b-5p in modulating placental SIRT7 expression and its implications for lipid metabolism in gestational diabetes.

Gestational diabetes is marked impaired glucose tolerance, poses various adverse outcomes including increased BMI and obesity. These outcomes results from excess lipid accumulation which is marked by elevated triglycerides. In GDM, placenta exhibits altered lipid metabolism, including reduced fatty acid oxidation and increased triglyceride accumulation.

A Co-Culture System for Studying Cellular Interactions in Vascular Disease.

Cardiovascular diseases (CVDs) are leading causes of morbidity and mortality globally, characterized by complications such as heart failure, atherosclerosis, and coronary artery disease. The vascular endothelium, forming the inner lining of blood vessels, plays a pivotal role in maintaining vascular homeostasis. The dysfunction of endothelial cells contributes significantly to the progression of CVDs, particularly through impaired cellular communication and paracrine signaling with other cell types, such as smooth muscle cells and macrophages.

Pathological insights into cell death pathways in diabetic wound healing.

Diabetic foot ulcers (DFUs) are a microvascular complication that affects almost 21 % of the diabetic population. DFUs are characterized by lower limb abnormalities, chronic inflammation, and a heightened hypoxic environment. The challenge of healing these chronic wounds arises from impaired blood flow, neuropathy, and dysregulated cell death processes.

MiR-142-5p mediated Nrf2 dysregulation in gestational diabetes mellitus and its impact on placental angiogenesis.

Introduction: Gestational diabetes mellitus (GDM) presents significant risks during pregnancy, including adverse perinatal outcomes and placental dysfunction. Impaired angiogenesis, involving crucial factors like Vascular Endothelial Growth Factor (VEGF), contributes to these complications. The Nrf2/Keap1 pathway, crucial for vascular redox homeostasis, has been linked to GDM-associated angiogenesis dysregulation.

Neutrophil Migration is a Crucial Factor in Wound Healing and the Pathogenesis of Diabetic Foot Ulcers: Insights into Pharmacological Interventions.

Diabetic foot ulcers (DFUs) pose a significant clinical challenge, characterized by impaired wound healing, chronic inflammation, and increased risk of infection. Neutrophils, as critical components of the innate immune response, play a pivotal role in the initial stages of wound healing, particularly during the inflammatory phase. This review explores the intricate relationship between neutrophil migration, inflammation, and the pathogenesis of DFU and drugs that can impact neutrophil production and migration.

Mangiferin Represses Inflammation in Macrophages Under a Hyperglycemic Environment Through Nrf2 Signaling.

Inflammation in macrophages is exacerbated under hyperglycemic conditions, contributing to chronic inflammation and impaired wound healing in diabetes. This study investigates the potential of mangiferin, a natural polyphenol, to alleviate this inflammatory response by targeting a redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2). Mangiferin, a known Nrf2 activator, was evaluated for its ability to counteract the hyperglycemia-induced inhibition of Nrf2 and enhance antioxidant defenses.

Nrf2 Activation in Keratinocytes: A Central Role in Diabetes-Associated Wound Healing.

Wound healing is a complex biological process crucial for tissue repair, wherein keratinocytes play a pivotal role in initiating, sustaining and completing the cascade. Various local and systemic factors, such as lifestyle, age metabolic disorders and vascular insufficiency, can influence this process, and in the context of diabetic wounds, disrupted biological mechanisms, including inflammation, tissue hypoxia, decrease in collagen production along with increased oxidative stress and keratinocyte dysfunction, contribute to delayed healing. During re-epithelialisation, keratinocytes undergo rapid multiplication and migration, forming a dense hyperproliferative epithelial layer that restores the epidermal barrier.

Copper Dyshomeostasis And Diabetic Complications: Chelation Strategies For Management.

Cuproptosis, An Emerging Concept In The Field Of Diabetes Research, Presents A Novel And Promising Perspective For The Effective Management Of Diabetes Mellitus And Its Associated Complications. Diabetes, Characterized By Chronic Hyperglycemia, Poses A Substantial Global Health Burden, With An Increasing Prevalence Worldwide. Despite Significant Progress In Our Understanding Of This Complex Metabolic Disorder, Optimal Therapeutic Strategies Still Remain Elusive.

Effect of Bis (methyl glycol) phthalate on endoplasmic reticulum stress in endothelial cells.

Phthalate-based polymeric plasticizers are widely used for their durability, transparency, and odorless nature, resulting in human exposure through inhalation, ingestion, or contaminated water. Epidemiological studies have identified bis-phthalate as a potential cardiovascular disease risk factor, though its mechanisms remain unclear. This study investigates the effects of bis-phthalate on endothelial dysfunction (ED), an early event in cardiovascular complications, with a focus on Endoplasmic Reticulum (ER) stress pathways.

Exploring the Therapeutic Potential of Tyrosol and Its Derivatives: A Comprehensive Review.

Tyrosol (Ty) and its derivatives have gathered considerable attention in recent years due to their diverse pharmacological properties and potential therapeutic applications. This comprehensive review aims to summarize the current understanding of the therapeutic potential of Ty and its derivatives in combating various diseases, including cancer, cardiovascular disease (CVD), neurodegenerative diseases, diabetes, and obesity. This review highlights the multifaceted properties of Ty, including its pharmacokinetic profile and pharmacological actions, which contribute to its efficacy against these prevalent health conditions.

Epigenetic regulation of Nrf2-Mediated angiogenesis in diabetic foot ulcer progression: Role of histone deacetylases.

Nuclear factor E2-related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates proangiogenic mediators, and antioxidant and detoxification enzymes. However, hitherto its regulation in the progression of DFU was poorly examined. The regulation of Nrf2 has been reported to be affected by various factors, including histone deacetylase (HDACs) and DNA methylation.

Pterostilbene Reverses Epigenetic Silencing of Nrf2 and Enhances Antioxidant Response in Endothelial Cells in Hyperglycemic Microenvironment.

The epigenetic regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal redox transcription factor, plays a crucial role in maintaining cellular homeostasis. Recent research has underscored the significance of epigenetic modifications of Nrf2 in the pathogenesis of diabetic foot ulcers (DFUs). This study investigates the epigenetic reversal of Nrf2 by pterostilbene (PTS) in human endothelial cells in a hyperglycemic microenvironment (HGM).

Sodium-Glucose Cotransporter-2 Inhibitor Suppresses Endoplasmic Reticulum Stress and Oxidative Stress in Diabetic Nephropathy Through Nrf2 Signaling: A Clinical and Experimental Study.

Diabetic nephropathy (DN), a severe complication of type 2 diabetes mellitus (T2DM), is marked by heightened endoplasmic reticulum stress (ERS) and oxidative stress (OS) due to protein misfolding and free radical generation. We investigated the sodium-glucose co-transporter-2 inhibitor (SGLT2i), canagliflozin (Cana), in alleviating ERS and OS in DN patients and THP-1 cells under hyperglycemic condition. A total of 120 subjects were divided into four groups, with 30 subjects in each group: healthy controls, T2DM individuals, DN patients receiving standard treatment, and those treated with Cana.

Dysregulation of miR-146a is associated with exacerbated inflammation, oxidative and endoplasmic reticulum stress in the progression of diabetic foot ulcer.

Recent evidence has implicated the role of microRNA-146a (miR-146a) in regulating inflammatory responses. In the present study, we investigated the role of miRNA-146a in the progression of diabetic foot ulcer (DFU) in type 2 diabetes mellitus patients (T2DM) and studied its correlation with stress mediators such as Endoplasmic Reticulum (ER) and oxidative stress. Ninety subjects were enrolled and evenly distributed among three groups: Controls (n = 30), T2DM without complications (n = 30) and T2DM with foot ulcers (n = 30).

LncRNA NEAT1/miR-146a-5p Axis Restores Normal Angiogenesis in Diabetic Foot Ulcers by Targeting mafG.

Non-healing lesions in diabetic foot ulcers are a significant effect of poor angiogenesis. Epigenetic regulators, mainly lncRNA and miRNA, are recognized for their important roles in disease progression. We deciphered the regulation of lncRNA NEAT1 through the miR-146a-5p/mafG axis in the progression of DFU.

MicroRNA-125b regulates vitamin D resistance by targeting CYP24A1 in the progression of gestational diabetes mellitus.

Vitamin D deficiency is prevalent in pregnancy and has been associated with increased occurrences of preeclampsia, cesarean delivery, neonatal bacterial vaginosis, and gestational diabetes. CYP24A1, recognized as a key factor in vitamin D metabolism homeostasis, encodes 24-hydroxylase responsible for converting 25(OH)D3 and 1,25(OH)2D3 into inactive metabolites. Recently, we have reported CYP24A1 overexpression in patients with gestational diabetes mellitus (GDM) and trophoblast cells exposed to hyperglycemia.

Exploring Lactoferrin as a novel marker for disease pathology and ferroptosis regulation in gestational diabetes.

Iron overload is linked to heightened susceptibility to ferroptosis, a process increasingly implicated in diabetes pathogenesis. This present study aims to assess the utility of Lactoferrin in predicting different stages of GDM and explore its association with disease pathology and ferroptosis. In this observational study, 72 pregnant women were recruited and categorized into three groups: healthy pregnant women without diabetes (NGDM, n = 24), early gestational diabetes (eGDM, n = 24), and established gestational diabetes (GDM, n = 24), all receiving standard antenatal care at 12 weeks of gestation.

Crosstalk between inflammasomes, inflammation, and Nrf2: Implications for gestational diabetes mellitus pathogenesis and therapeutics.

The role of inflammasomes in gestational diabetes mellitus (GDM) has emerged as a critical area of research in recent years. Inflammasomes, key components of the innate immune system, are now recognized for their involvement in the pathogenesis of GDM. Activation of inflammasomes in response to various triggers during pregnancy can produce pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), contributing to systemic inflammation and insulin resistance.

Pterostilbene accelerates wound healing response in diabetic mice through Nrf2 regulation.

Pterostilbene (PTS), known for its diverse beneficial effects via Nuclear factor erythroid-2 related factor (Nrf2) activation, holds potential for Diabetic Foot Ulcer (DFU) treatment. However, PTS-mediated Nrf2 regulation in diabetic wounds has yet to be elucidated. We used IC21 macrophage-conditioned media to simulate complex events that can influence the fibroblast phenotype using L929 cells during the wound healing process under a hyperglycemic microenvironment.

Quantitative proteomic analyses uncover regulatory roles of Nrf2 in human endothelial cells.

Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional regulator, is the predominant factor in modulating oxidative stress and other cellular signaling responses. Studies from our lab and others highlighted that activation of the Nrf2 pathway by small molecules improves endothelial function by suppressing oxidative and endoplasmic reticulum (ER) stress. However, the exact mechanisms by which Nrf2 elicits these effects are unknown.

MicroRNA-27b Impairs Nrf2-Mediated Angiogenesis in the Progression of Diabetic Foot Ulcer.

Nuclear factor erythroid-2-related factor 2 () is a stress-activated transcription factor regulating antioxidant genes, and a deficiency thereof, slowing lymphangiogenesis, has been reported in diabetic foot ulcer (DFU). The mode of regulation in DFU has been less explored. Emerging studies on miRNA-mediated target regulation show miRNA to be the leading player in the pathogenesis of the disease.

Dysfunctions, molecular mechanisms, and therapeutic strategies of pancreatic β-cells in diabetes.

Pancreatic beta-cell death has been established as a critical mediator in the progression of type 1 and type 2 diabetes mellitus. Beta-cell death is associated with exacerbating hyperglycemia and insulin resistance and paves the way for the progression of DM and its complications. Apoptosis has been considered the primary mechanism of beta-cell death in diabetes.

New Frontiers in Three-Dimensional Culture Platforms to Improve Diabetes Research.

Diabetes mellitus is associated with defects in islet β-cell functioning and consequent hyperglycemia resulting in multi-organ damage. Physiologically relevant models that mimic human diabetic progression are urgently needed to identify new drug targets. Three-dimensional (3D) cell-culture systems are gaining a considerable interest in diabetic disease modelling and are being utilized as platforms for diabetic drug discovery and pancreatic tissue engineering.