Search Results (3,322)

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a significant comorbidity in individuals with type 1 diabetes (T1D), despite its historical association with type 2 diabetes. This review focuses on summarizing current findings regarding the role of insulin resistance in the development of MASLD in T1D, as well as examining the relationship between MASLD and diabetes-related complications. We will also briefly discuss the prevalence, diagnostic challenges, associated complications, and potential mechanisms underlying MASLD in T1D. Although insulin resistance is well established in MASLD among those with type 2 diabetes, its role in T1D requires further clarification. Emerging markers, such as the estimated glucose disposal rate, offer early insight into this relationship. MASLD in T1D is linked to both microvascular and macrovascular complications, including nephropathy, retinopathy, neuropathy, and cardiovascular disease. Variability in prevalence estimates reflects inconsistencies among imaging modalities, emphasizing the need for standardized, non-invasive diagnostic approaches. Recognizing and addressing MASLD and its links to insulin resistance and diabetes complications in T1D is vital for mitigating long-term complications and enhancing clinical outcomes. Full article

Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by persistent hyperglycemia, hyperinsulinemia, and long-term cardiovascular complications. Another hallmark of T2D is disrupted hormonal homeostasis—marked by elevated levels of insulin and leptin and reduced adiponectin—which plays a crucial role in modulating immune cell function. Individuals with T2D exhibit a skewed immune profile, with an elevated secretion of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL17, and IL6, which are well-established drivers of vascular inflammation and dysfunction. Moreover, dysregulated metabolic hormones in T2D promote the acquisition of a pro-inflammatory phenotype in immune cells, suggesting that these hormones not only regulate energy balance but also serve as potent immune activators. Their dysregulation likely plays a significant—and perhaps underappreciated—role in the onset and progression of diabetic cardiovascular complications. Full article

Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

Diabetes mellitus (DM) is one of the leading causes of death and disability worldwide and its prevalence continues to rise. Chronic hyperglycemia exposes patients to severe complications. Among these, diabetic vascular lesions are the most destructive. Their primary driver is the synergistic interaction between hyperglycemia-induced oxidative stress and chronic inflammation. This review systematically elucidates how multiple pathological pathways—namely, metabolic dysregulation, mitochondrial dysfunction, endoplasmic reticulum stress, and epigenetic reprogramming—cooperate to drive oxidative stress and inflammatory cascades. Confronting this complex pathological network, natural products, unlike conventional single-target synthetic drugs, exert multi-target synergistic effects, simultaneously modulating several key pathogenic networks. This enables the restoration of redox homeostasis and the suppression of inflammatory responses, thereby improving vascular function and delaying both microvascular and macrovascular disease progression. However, the clinical translation of natural products still faces multiple challenges and requires comprehensive mechanistic studies and rigorous validation to fully realize their therapeutic potential. Full article

Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (M^pro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of M^pro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of M^pro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 M^pro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the M^pro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under M^pro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 M^pro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article

Diabetes mellitus poses a significant global health challenge, primarily due to its chronic metabolic dysregulation, leading to widespread tissue and organ damage. This systemic impact results in a range of complications that markedly reduce patients’ quality of life. Therefore it is critical to understand the mechanisms underlying these complications. DJ-1 (also known as PARK7) is a highly conserved multifunctional protein involved in antioxidative defense, metabolic equilibrium, and cellular survival. Recent studies have highlighted that DJ-1 is critically involved in the pathogenesis and progression of diabetic complications, including macrovascular issues like cardiovascular disease and microvascular conditions such as diabetic nephropathy, retinopathy, and neuropathy, suggesting that it may serve as a promising therapeutic target. Importantly, drugs targeting DJ-1 have shown therapeutic effects. This review provides a comprehensive overview of the current under-standing of DJ-1’s role in diabetes-related complications, emphasizing recent research advances. Full article

Skin autofluorescence (SAF) detection technology represents a noninvasive, convenient, and cost-effective optical detection approach. It can be employed for the differentiation of various diseases, including metabolic diseases and dermatitis, as well as for monitoring the treatment efficacy. Distinct from diffuse reflection signals, the autofluorescence signals of biological tissues are relatively weak, making them challenging to be captured by photoelectric sensors. Moreover, the absorption and scattering properties of biological tissues lead to a substantial attenuation of the autofluorescence of biological tissues, thereby worsening the signal-to-noise ratio. This has also imposed limitations on the development and application of compact-sized autofluorescence detection systems. In this study, a compact LED light source and a CMOS sensor were utilized as the excitation and detection devices for skin tissue autofluorescence, respectively, to construct a mobile and wireless skin tissue autofluorescence detection system. This system can achieve the detection of skin tissue autofluorescence with a high signal-to-noise ratio under the drive of a simple power supply and a single-chip microcontroller. The detection time is less than 0.1 s. To enhance the stability of the system, a pressure sensor was incorporated. This pressure sensor can monitor the pressure exerted by the skin on the detection system during the testing process, thereby improving the accuracy of the detection signal. The developed system features a compact structure, user-friendliness, and a favorable signal-to-noise ratio of the detection signal, holding significant application potential in future assessments of skin aging and the risk of diabetic complications. Full article

Background: Obesity and its complications have increased in both adults and children, with pediatric populations developing metabolic disorders at earlier ages. Long non-coding RNAs, particularly MEG3, are involved in obesity through regulation of lipogenic genes including ATF4, FTO, SREBP1, FASN, and ACACA. However, data on MEG3 expression in pediatric obesity are limited. This study evaluated MEG3, FTO, and ATF4 expression in PBMCs from children with obesity and their associations with added sugar intake and lipid metabolism genes. Methods: In this cross-sectional study 71 children within the age range of 6 to 12 years were included (28 normal weight and 43 with obesity). Anthropometrical and clinical parameters and dietary added sugar consumption were analyzed. Real-time PCR was performed to assess MEG3, FTO, ATF4, SREBP1, FASN, and ACACA gene expression in peripheral blood mononuclear cells. Results: The expression of MEG3, ATF4, FTO, SREBP1, FASN, and ACACA was decreased in children with obesity. MEG3 and FTO showed sex-dependent expression in children without obesity, while additional sex-related differences were observed for SREBP1, FASN, ACACA, FTO, and MEG3 in children with obesity. MEG3 was associated with the expression of SREBP1, FASN, ACACA, FTO, and ATF4. In insulin-resistant (IR) children, MEG3, ATF4, FTO, ACACA, and SREBP1 were reduced, while FASN was increased. Added sugar intake negatively correlated with FTO, SREBP1, and ACACA. Conclusions: The MEG3, FTO, and ATF4 expression was altered in children with obesity, showing sex- and IR-related differences. Added sugar intake correlated negatively with lipogenic gene expression. Full article

Gestational diabetes mellitus (GDM) and iron deficiency anemia (IDA) are the most common pregnancy-related conditions resulting in adverse maternal and fetal complications. MicroRNAs (miRNAs), particularly miR-182-3p and miR-24-3p, are promising biomarkers as they act as regulatory elements in various diseases; however, their roles in GDM and IDA are unclear. The present study aimed to analyze the expression and functional relevance of miR-182-3p and miR-24-3p in GDM and IDA. Experimental validation via RT-PCR revealed significant upregulation of both miRNAs in GDM and IDA samples. We identified common target genes and signaling pathways associated with these miRNAs, using a combination of data mining, bioinformatic tools (miRDB, TargetScan, miRTarBase, and miRWalk), and differentially expressed gene (DEGs) analysis using the GEO, OMIM, MalaCards, and GeneCards datasets. GO and KEGG pathway analyses revealed that the shared miRNA–mRNA in target genes were enriched in insulin signaling, apoptosis, and inflammatory pathways—key mechanisms implicated in GDM and IDA. Furthermore, hub genes such as IRS1, PIK3CA, CASP3, MAPK7, and PDGFRB were identified, supporting their central role in metabolic dysregulation during pregnancy. These findings demonstrate the potential of miR-182-3p and miR-24-3p as diagnostic biomarkers and therapeutic targets in managing GDM and IDA, offering new insights into the molecular interplay underlying pregnancy complications. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with hypercholesterolemia identified as a major, but modifiable risk factor. This review serves as the second part of a comprehensive analysis of dyslipidemia management. The first installment laid the groundwork by detailing the key pathophysiological mechanisms of lipid metabolism, the development of atherosclerosis, major complications of hyperlipidemia, and the importance of cardiovascular risk assessment in therapeutic decision-making. It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe. Building upon that foundation, the present article focuses exclusively on emerging pharmacological therapies designed to overcome limitations of standard treatment. It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate–citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care. Full article

Background/objectives: Polycystic ovary syndrome (PCOS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are common co-morbidities in women of reproductive age. PCOS is highly heterogeneous and is, therefore, divided into four phenotypes. MASLD leads to numerous systemic complications. Studies to date have shown an association between PCOS and MASLD. This study was designed to compare the FIB-4 score (based on age, alanine aminotransferase, aspartate aminotransferase and platelet count) and the results of shear wave elastography in assessing the risk of developing MASLD by patients with PCOS divided by phenotypes. Methods: The study enrolled 242 women age 18–35 years with PCOS diagnosed according to Rotterdam criteria, hospitalized at the Department of Gynaecological Endocrinology of the University Clinical Centre in Katowice. The study subjects were assigned to phenotypes A to D. Clinical and biochemical assessments were performed (including androgens and metabolic parameters), and the FIB-4 index was calculated. Liver fibrosis was evaluated by shear wave elastography. To balance the group sizes of phenotypes, oversampling with replacement was applied (PROC SURVEYSELECT, SAS), increasing the number of observations for phenotypes B, C, and D fivefold. Statistical analyses were performed based on data distribution (Shapiro–Wilk test), using ANOVA or the Kruskal–Wallis test with Dunn’s correction. Statistical significance was set at p < 0.05. Results: The FIB-4 score was the highest in phenotype B patients (0.50 ± 0.15), and the lowest in phenotypes A and C (0.42 ± 0.14). The highest rate of positive elastography findings was recorded in phenotype A patients (34.7%) and the lowest in phenotype C group (13.5%). Significant differences between the phenotypes were also found in terms of androgen levels, insulin, HOMA-IR, and the lipid profile. Among patients with positive elastography, the highest FIB-4 scores were recorded in phenotype C group (0.44 ± 0.06), but the differences between the phenotypes were not statistically significant. Conclusions: The FIB-4 score was the highest in phenotype B patients and differed significantly from phenotypes A, C and D. In the elastography exam, the fibrosis index was statistically significantly higher in phenotype A compared to other phenotypes. No correlation was detected between the FIB-4 index and positive elastography. The findings suggest that the FIB-4 index may be used for MASLD screening, but its usefulness as a predictor of eligibility for elastography requires more research. Full article

Background: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed whether metabolic improvements from dietary intervention were accompanied by changes in lung function. Methods: This cross-sectional analysis included 184 individuals (101 with T2D, 33 with prediabetes, and 50 glucose-tolerant individuals). Lung function parameters—vital capacity (VC), total lung capacity by plethysmography (TLC-B), and diffusion capacity for carbon monoxide (TL_CO)—were assessed alongside metabolic markers including HOMA2-IR, fatty liver index (FLI), NAFLD score, and Fibrosis-4 index (FIB-4). In a subset of 54 T2D participants, lung function was reassessed after six months following either a fasting-mimicking diet (FMD, n = 14), Mediterranean diet (n = 13), or no dietary intervention (n = 27). Results: T2D participants had significantly lower VC and TLC-B compared to glucose-tolerant and prediabetic individuals, with 18–21% falling below clinical thresholds for RLD. Lung volumes were negatively correlated with HOMA2-IR, FLI, NAFLD score, and FIB-4 across the cohort and within the T2D group. Although the FMD intervention led to significant improvements in HOMA2-IR and FLI, no corresponding changes in lung function were observed over the six-month period. Conclusions: Restrictive lung impairment in T2D is associated with insulin resistance and markers of liver steatosis and fibrosis. While short-term dietary interventions can improve metabolic parameters, their effect on lung function may require a longer duration or additional interventions and targeted follow-up. These findings highlight the relevance of pulmonary assessment in individuals with metabolic dysfunction. Full article

Obstructive sleep apnea (OSA) is a prevalent disorder linked to metabolic complications such as diabetes and cardiovascular disease. By fragmenting normal sleep architecture, OSA perturbs the growth hormone/insulin-like growth factor (GH/IGF) axis and alters circulating levels of IGF-binding proteins (IGFBPs). A prior clinical observation of elevated IGFBP4 in OSA patients motivated the present investigation in a controlled animal model. Building on the previously reported protocol, OSA was induced in male C57BL/6 mice (9–12 weeks old) through intralingual injection of polytetrafluoroethylene (PTFE), producing tongue hypertrophy, intermittent airway obstruction, and hypoxemia. After 8–10 weeks, the study assessed (1) hypoxia biomarkers—including HIF-1α and VEGF expression—and (2) neurobehavioral outcomes in anxiety and cognition using the open-field and novel object recognition tests. PTFE-treated mice exhibited a significant increase in circulating IGFBP4 versus both baseline and control groups. Hepatic Igfbp4 mRNA was also upregulated. Behaviorally, PTFE mice displayed heightened anxiety-like behavior and impaired novel object recognition, paralleling cognitive deficits reported in human OSA. These findings validate the PTFE-induced model as a tool for studying OSA-related hypoxia and neurocognitive dysfunction, and they underscore IGFBP4 as a promising biomarker and potential mediator of OSA’s systemic effects. Full article