Prospective studies found associations between serum uric acid (SUA) and incident metabolic syndrome (MetS) with high heterogeneity. We investigated the association between SUA and incident MetS and its components in a region highly burdened by cardiometabolic disorders.

The study included 1999 adults (1297 women). MetS was defined according to the Joint Interim Societies' criteria. Multivariate adjusted Cox proportional hazard analyses were applied to examine the association between SUA and outcomes. During a median follow-up of 9.7 years, 833 (510 women) incident MetS cases occurred. Among the whole population, a higher risk of MetS was observed across quartiles (Q1-4) of SUA even after adjustment for Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), [multivariate hazard ratio (95 % confidence interval) in Q4: 1.58 (1.17-2.14), Q1: as reference]. Generally, same association was found for women. Similarly, a 1-standard deviation (SD) increase of SUA was associated with a higher risk of incident MetS in the whole population, and women [1.19 (1.06-1.34) and 1.14 (1.02-1.28), respectively]. Among men, the association was just in the age-adjusted analysis, however, no effect modification of gender was found. Moreover, a 1-SD increase in SUA elevated the risk of incident high-waist circumference (20 %), -fasting plasma glucose (19 %), -triglycerides (17 %), and low-high-density lipoprotein cholesterol (12 %) after adjustment for other MetS components and HOMA-IR in the whole population (all Ps < 0.05).

SUA was associated with incident MetS and its components, excluding hypertension, and might be a potential biomarker for identifying individuals at risk of developing MetS.

The link between oxidative stress and lipid metabolism is widely studied, but their causal relationship in the general population remains unclear.

We utilized weighted regression and propensity score matching (PSM) models to investigate the relationship between endogenous oxidative stress markers (serum bilirubin and uric acid) and lipid metabolism in 11,087 participants of European ancestry from the National Health and Nutrition Examination Survey (NHANES) during the period from 2005 to 2018. Additionally, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) summary statistics from individuals of European ancestry (n = 997 to 575,531) to explore the genetic causal relationship between oxidative stress markers and lipid metabolism profiles (n = 20,430).

Weighted regression showed that serum uric acid significantly increased high cholesterol (OR = 1.11, 95 % CI = 1.06-1.15, P < 0.001) and high triglycerides (OR = 1.25, 95 % CI = 1.20-1.30, P < 0.001). PSM analysis confirmed that serum uric acid increased the incidence of high triglycerides (OR = 1.57, 95 % CI = 1.35-1.82, P < 0.001). Additionally, a strong bidirectional genetic relationship was found between oxidative stress markers and lipid metabolism. For example, serum uric acid increased serum triglycerides (β = 0.1904, Se = 0.05, P < 0.001) and decreased total cholesterol in very large HDL (β = -0.1298, Se = 0.039, P < 0.001). Conversely, total cholesterol reduced direct bilirubin levels (β = -0.1707, Se = 0.018, P < 0.001). No significant horizontal pleiotropy was detected by MR-Egger intercept.

Our findings demonstrate a robust genetic and population-based association between oxidative stress markers and lipid metabolism, suggesting potential therapeutic targets for lipid disorders based on endogenous oxidative stressors.

Acrylamide (AA) has raised concerns throughout the world in recent years because of its potential negative effects on human health. Numerous researches on humans and animals have connected a high dietary exposure to AA to a possible risk of cancer. Additionally, higher consumption of acrylamide has also been associated with dysfunctioning of various organ systems from nervous system to the reproductive system. Acrylamide is primarily metabolised into the glycidamide inside the body which gets accumulated in different tissues including kidney and liver, and chronic exposure to this can lead to the nephrotoxicity and hepatotoxicity through different molecular mechanisms. This review summarizes the various sources, formation and metabolism of the dietary acrylamide along with the different molecular mechanisms such as oxidative stress, inflammation, DNA damage, autophagy, mitochondrial dysfunction and morphological changes in nephron and hepatocytes through which acrylamide exerts its deleterious effect on kidney and liver causing nephrotoxicity and hepatotoxicity. This review summarizes various animal and cellular studies that demonstrate AA-induced nephrotoxicity and hepatotoxicity. Lastly, the article emphasizes on underlying protective molecular mechanisms of various pharmacological interventions against acrylamide induced hepatotoxicity and nephrotoxicity.

The intricate linking between the health of blood vessels and the functioning of neurons has attracted growing attention in the context of disorders that affect the neurological environment. Endothelial cells, forming the blood-brain barrier and blood-retinal barrier, play a fundamental role in maintaining the integrity of the brain-retina microenvironment connection. This review explores the molecular foundations of endothelial cell dysfunction and its implications for the brain-retina interaction. A comprehensive analysis of the complex factors contributing to endothelial dysfunction is presented, including oxidative stress, inflammation, reduced nitric oxide signaling, and disrupted vascular autoregulation. The significance of endothelial dysfunction extends to neurovascular coupling, synaptic plasticity, and trophic support. To our knowledge, there is currently no existing literature review addressing endothelial microvascular dysfunction and its interplay with the brain-retina microenvironment. The review also explains bidirectional communication between the brain and retina, highlighting how compromised endothelial function can disrupt this vital crosstalk and inhibit normal physiological processes. As neurodegenerative diseases frequently exhibit vascular involvement, a deeper comprehension of the interaction between endothelial cells and neural tissue holds promise for innovative therapeutic strategies. By targeting endothelial dysfunction, we may enhance our ability to preserve the intricate dynamics of the brain-retina microenvironment connection and ameliorate the progression of neurological disorders.

Dyslipidemia is a major contributor to various diseases, including atherosclerotic cardiovascular disease and obesity. Treatment strategies for dyslipidemia continue to evolve as our understanding of this metabolic disorder and potential therapeutic candidates advance. Notably, fucoidan demonstrates promising effects in ameliorating dyslipidemia in rodents, although their lipid metabolism differs significantly from humans. This study, investigates the lipid-regulatory effects of Fucus vesiculosus-derived fucoidan (FvF) and elucidates the underlying mechanisms of action using New Zealand rabbits fed a high-fat diet, whose lipid profiles closely resemble those of patients with dyslipidemia. The results demonstrate that FvF intervention ameliorates dyslipidemia and lipid deposition in a dose-dependent manner. Mechanistically, FvF intervention modulates the expression levels of multiple molecules involved in lipid transport, fatty acid synthesis and beta-oxidation, and redox balance, as revealed by quantitative reverse transcription polymerase chain reaction, western blotting, and proteomic analysis. This study is the first to report that FvF, consisting of alternating [→4)-α-L-Fucp(1 → 3)-α-L-Fucp(1→] glycosyls ameliorates dyslipidemia by directly modulating lipid metabolism and indirectly attenuating oxidative stress. These findings suggest that FvF holds significant potential as a candidate for the treatment of lipid disorder-related diseases.

Cuproptosis is a new mode of cell death that is closely related to mitochondrial stress. The purpose of this study is to investigate the amount of copper, copper-associated genes DLAT and FDX1 oxidative stress (OS) status in obesity. Since there is a close relationship between OS and cuproptosis, evaluating the effect of various strategies to reduce OS, including quercetin (QUER) and caloric restriction (CR), is another goal of this study. In this study, 30 male BALB-C mice aged 8 weeks and weighing 25 g, including the groups receiving normal diet (ND), ND with QUER (15 mg/kg, IP) and CR, a high-fat diet (HFD) with the QUER, CR or a combination of both were used. The activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione reductase (GR), amount of copper in the liver and kidney tissues, and expression of DLAT and FDX1 genes were measured in all studied groups. The amount of copper in the liver and kidney tissue as well as the expression of FDX1 and DLAT in the HFD group increased significantly compared with the ND group. QUER, CR or their combination could significantly reduce the amount of copper as well as the expression of FDX1 and DLAT in liver and kidney tissues. QUER and CR, also significantly increased the activity of GR, SOD and GPX in serum, liver, and kidney tissues. Based on the results, QUER, CR and especially the simultaneous use of both, was able to reduce the amount of copper and its related cuproptosis. These effects may reduce cuproptosis-associated cell death. Therefore, the use of antioxidants and CR may be a promising solution to protect the human body against the effects of cuproptosis in conditions like obesity.

Hibiscus sabdariffa L. (HS) has been investigated as an alternative treatment for metabolic syndrome (MetS), as it affects all MetS components with low side effects simultaneously; however, clinical evidence regarding its efficacy compared with placebo is inconsistent. This study assessed how the aqueous calyx extract of HS influences insulin resistance and MetS parameters and examined the safety effects on liver, kidney, and hematological indexes in participants with abdominal obesity and mild MetS symptoms.

In this double-blind, randomized, placebo-controlled trial, 108 participants with MetS were randomly assigned to take 1000-mg HS (45.04 mg/day in total polyphenols) or placebo daily for 12 weeks. Insulin resistance (HOMA-IR), glycemic markers, body mass index (BMI), waist circumference (WC), lipid profiles, and blood pressure were assessed at baseline, 6 weeks, and 12 weeks. Additionally, liver and kidney function indicators along with hematological parameters were evaluated.

Compared with placebo, HS did not significantly affect HOMA-IR, glycemic markers, BMI, WC, lipid profile, or blood pressure. Although HS did not significantly alter the lipid profile overall, serum low-density lipoprotein (LDL) levels decreased significantly at 12 weeks compared with baseline (- 7.98 mg/dL, [95 % CI, - 14.80, - 1.15]). Additionally, HS did not cause significant liver or kidney function or hematological changes compared with placebo.

Taking 1000-mg HS daily for 12 weeks seems to be safe. Placebo and HS groups showed good clinical results, and the extract was not associated with improved metabolic parameters in individuals with abdominal obesity and mild MetS symptoms, with the exception of lower serum LDL.

Overactive bladder (OAB) is a syndrome marked by urinary urgency. Given the crucial role of metabolic anomalies in the pathogenesis of OAB, the aim of this study was to investigate the associations between different triglyceride glucose index (TyG)-related indicators and OAB.

9024 participants aged ≥ 20 years from NHANES 2005-2018 were involved. Weighted multivariate logistic regression was employed to assess the relationship between three TyG-related indicators and OAB with subgroup and interaction analyses. In addition, ROC, DeLong's test and confusion matrix were further utilized to assess the predictive power of different indicators for OAB in the total population versus different subgroups of the population.

TyG-related indicators were positively associated with OAB. The associations were statistically different in age and physical activity subgroups (all p for interaction < 0.1). In the whole population, TyG-WHtR demonstrated the highest predictive ability, with the largest AUC of 0.625 (95 %CI: 0.609, 0.641), and was relatively more predictive in the < 60 years and moderate-to-vigorous physical activity subgroups.

Positive associations of TyG-related indicators with OAB were observed. TyG-WHtR has the strongest predictive performance for OAB in the total population.

Reactive oxygen species (ROS), a class of highly reactive molecules, are closely linked to the pathogenesis of various cancers. While ROS primarily originate from normal cellular processes, external stimuli can also contribute to their production. Cancer cells typically exhibit elevated ROS levels due to disrupted redox homeostasis, characterized by an imbalance between antioxidant and oxidant species. ROS play a dual role in cancer biology: at moderate levels, they facilitate tumor progression by regulating oncogenes and tumor suppressor genes, inducing mutations, promoting proliferation, extracellular matrix remodeling, invasion, immune modulation, and angiogenesis. However, excessive ROS levels can cause cellular damage and initiate apoptosis, necroptosis, or ferroptosis.

This review explores molecular targets involved in redox homeostasis dysregulation and examines the impact of ROS on the tumor microenvironment (TME). Literature from recent in vitro and in vivo studies was analyzed to assess how ROS modulation contributes to cancer development and therapy.

Findings indicate that ROS influence cancer progression through various pathways and cellular mechanisms. Targeting ROS synthesis or enhancing ROS accumulation in tumor cells has shown promising anticancer effects. These therapeutic strategies exhibit significant potential to impair tumor growth while also interacting with elements of the TME.

The ROS serve as both promoters and suppressors of cancer depending on their intracellular concentration. Their complex role offers valuable opportunities for targeted cancer therapies. While challenges remain in precisely modulating ROS for therapeutic benefit, they hold promise as synergistic agents alongside conventional treatments, opening new avenues in cancer management.

Ambient air pollution is a serious public health issue worldwide. A growing number of studies has highlighted the negative effects of air pollution on metabolic syndrome (MetS) and its components, including abdominal obesity, disorders of lipid metabolism, elevated blood pressure, and impaired fasting blood glucose. This review provides a brief overview of epidemiological and genetic interaction studies of the links between chronic exposure to ambient air pollution and MetS and its components, as well as plausible mechanisms underlying these relationships. The cumulative evidence suggests that long-term exposure to air pollution, especially particulate matter, increases the risk of MetS and its components. These associations can be partly modified by baseline characteristics, lifestyle, and health conditions. Gene-by-air-pollution interaction studies, limited to candidate genes in the past, have recently been conducted at an expanded genome-wide level. However, more such studies are needed to comprehensively understand the genetics involved in the association between air pollution and MetS. Mechanistic evidence suggests potential biological pathways, including inflammation, oxidative stress, and endothelial dysfunction.

Calcific aortic valve disease (CAVD) is a progressive disease, of which the 2-year mortality is >50% for symptomatic disease. However, there are currently no pharmacotherapies to prevent the progression of CAVD unless transcatheter or surgical aortic valve replacement is performed. The prevalence of diabetes among CAVD has increased rapidly in recent decades, especially among those undergoing aortic valve replacement. Diabetes and its comorbidities, such as hypertension, hyperlipidemia, chronic kidney disease and ageing, participated jointly in the initiation and progression of CAVD, which increased the management complexity in patients with CAVD. Except from hyperglycemia, the molecular links between diabetes and CAVD included inflammation, oxidative stress and endothelial dysfunction. Traditional cardiovascular drugs like lipid-lowering agents and renin-angiotensin system blocking drugs have proven to be unsuccessful in retarding the progression of CAVD in clinical trials. In recent years, almost all kinds of glucose-lowering medications have been specifically assessed for decelerating the development of CAVD. Based on the efficacy for atherosclerotic cardiovascular disease and CAVD, this review summarized current knowledge about glucose-lowering medications as promising treatment options with the potential to retard CAVD.

Diffuse large B-cell lymphoma (DLBCL) as among the most common lymphomas is associated with insulin resistance (IR). The triglyceride-glucose (TyG) index, generally considered a surrogate marker for IR, has an uncertain prognostic value in DLBCL.

We conducted a retrospective analysis of DLBCL patients who received R-CHOP therapy at the Second Affiliated Hospital of Nanchang University from January 2011 to December 2023. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for overall survival (OS). Boruta algorithm was employed to strengthen the robustness of our analysis. Restricted cubic spline (RCS) analysis was used to explore the potential nonlinear relationship between the TyG index and OS. Subgroup analyses were conducted to assess the prognostic value of the TyG index across different patient subgroups. Finally, a nomogram model based on the TyG index was developed, and its predictive performance was evaluated using the area under the receiver operating characteristic curve (AUROC), calibration curves, and decision curve analysis (DCA).

A total of 186 DLBCL patients were included in this study. Univariate and multivariate Cox regression analyses identified the TyG index, Age, ECOG performance status, Ann Arbor stage, and lactate dehydrogenase levels as independent prognostic factors for DLBCL. The Boruta algorithm confirmed these variables as the most important prognostic factors. Kaplan-Meier analysis revealed significantly poorer OS in the high TyG index group. RCS analysis demonstrated a non-linear relationship between the TyG index and OS. Subgroup analyses further validated the TyG index as a significant prognostic factor across various patient subgroups. The TyG-based nomogram model outperformed the conventional International Prognostic Index (IPI), with AUROCs of 0.878, 0.809, and 0.867 for 1-year, 3-year, and 5-year OS, respectively. Calibration curves showed good agreement between the nomogram predictions and actual outcomes, and DCA highlighted the high clinical utility of the model.

The TyG index is an independent prognostic factor in DLBCL patients, and the TyG-based nomogram model provides enhanced predictive accuracy compared to the IPI. Its simplicity and low cost make it a valuable tool for routine clinical prognostic assessment in DLBCL patients.

Carbohydrate metabolism disorders (CMDs), including prediabetes and type 2 diabetes mellitus (T2DM), are increasingly prevalent in the aging population. Oxidative stress (OxS) plays a pivotal role in CMD pathogenesis, with extracellular superoxide dismutase (SOD3) and catalase (CAT) serving as critical antioxidant defenses. Additionally, microRNAs (miR-21 and miR-30b) regulate the oxidative and inflammatory pathways, yet their roles in elderly CMD patients remain unclear. This study evaluated miR-21 and miR-30b expression alongside SOD3 and CAT plasma levels in individuals aged ≥ 65 years (n = 126) categorized into control (n = 38), prediabetes (n = 37), and T2DM (n = 51) groups. Quantitative PCR assessed miRNA expression, while ELISA measured the enzyme levels. SOD3 levels were significantly reduced in CMDs, particularly in T2DM, whereas miR-21 was upregulated. A negative correlation between SOD3 and miR-21 was strongest in T2DM, suggesting a regulatory interplay. Neither CAT levels nor miR-30b expression differed among groups. Logistic regression indicated SOD3 as a protective biomarker, with each 1 ng/mL increase reducing the CMD risk by ~5-6%. The ROC analysis supported SOD3's diagnostic potential, while miR-21 showed a modest association. These findings highlight SOD3 downregulation and miR-21 upregulation as potential contributors to CMD progression in elderly patients, warranting further research into their mechanistic roles and therapeutic potential.

Diabetic cardiomyopathy (DCM) is a common and fatal cardiac complication caused by diabetes, with its pathogenesis involving various forms of cell death and mitochondrial dysfunction, particularly ferroptosis and mitochondrial injury. Recent studies have indicated that ferroptosis and mitochondrial damage play crucial roles in the onset and progression of DCM, though their precise regulatory mechanisms remain unclear. Of particular interest is the interaction between ferroptosis and mitochondrial damage, as well as their synergistic effects, which are not fully understood. This review summarizes the roles of ferroptosis and mitochondrial injury in the progression of DCM and explores the molecular mechanisms involved, with an emphasis on the interplay between these two processes. Additionally, the article offers an overview of targeted drugs shown to be effective in cellular experiments, animal models, and clinical trials, analyzing their mechanisms of action and potential side effects. The goal is to provide insights for future drug development and clinical applications. Moreover, the review explores the challenges and prospects of multi-target combination therapies and personalized medicine interventions in clinical practice to offer strategic guidance for the comprehensive prevention and management of DCM.

The cultivation and processing of fruits generate a wide range of by-products (e.g., pulp, seeds, pomace, leaves, and stems), which are often underutilized despite being rich sources of phenolic compounds with well-documented bioactive properties. The bioactive potential of these compounds has attracted significant interest from both the pharmaceutical and food sectors, offering opportunities for their use in functional foods, dietary supplements, natural medicines, and additives. Among these, phenolic acids have shown promising potential in modulating risk factors associated with metabolic syndrome (MetS), a condition encompassing hypertension, dyslipidemia, hyperglycemia, and abdominal obesity, and contributing significantly to cardiovascular disease. Given the global burden of MetS and the need for novel preventive strategies, numerous studies have investigated the bioactivity of phenolic acids derived from fruit by-products. In this review, we critically examine recent studies regarding the phenolic acid composition of fruit-derived by-products and their biological activity in relation to MetS-related risk factors. This work aims to synthesize current findings, highlight prevailing research trends, and identify existing gaps in the literature to inform future research and promote the sustainable use of fruit by-products in the prevention and management of MetS.

A high-fat diet is a key factor contributing to hyperlipidemia. Perilla seed oil, a plant-based source of omega-3, has the potential to reduce this risk. However, its effects have not been fully established. This study aimed to evaluate the effects of perilla seed oil on blood lipid levels, oxidative stress, and inflammation in rats induced with hyperlipidemia through a high-fat diet. Male Wistar rats were administered perilla seed oil at a dosage of 0.67 g/kg body weight per day for 8 weeks. The results showed that perilla seed oil significantly reduced triglyceride levels by 38.00% and 41.88% and total cholesterol levels by 17.16% and 15.91% in the high-fat diet and normal diet groups, respectively (p < 0.05). However, perilla seed oil had no significant effect on HDL and LDL levels. Additionally, perilla seed oil supplementation significantly reduced malondialdehyde (MDA) levels, a biomarker of oxidative stress, by 68.18% in the high-fat diet group and 29.72% in the normal diet group. Regarding its anti-inflammatory effects, perilla seed oil reduced interleukin-6 (IL-6) levels by 15.21% and 64.27% in the high-fat diet and normal diet groups, respectively (p < 0.05). These findings suggest that perilla seed oil has the potential to reduce the risk of metabolic syndrome.

Perfluorohexane sulfonate (PFHxS) is a persistent environmental contaminant linked with several health implications. Humans are exposed to PFHxS mainly through ingestion. Studies have reported that a diet deficient in essential nutrients may have confounding effect on the toxicity outcome of chemicals. We evaluated the potential impact of PFHxS exposure on the reproductive damage in animals maintained on the diet deficient in protein. Female Wistar rats (n = 6) were divided as controls and treatment groups (5 ppm and 25 ppm PFHxS, protein deficient, protein deficient +5 ppm PFHxS and protein deficient +25 ppm PFHxS). PFHxS exposure disrupted the estrous cycle with an increased duration of the diestrus stage at 25 ppm and protein deficient + 25 ppm PFHxS showing 55.56 % and 78.77 % disorder, respectively. There was a significant elevation (P < 0.01) in LH/FSH ratio and reduction in testosterone (P < 0.01), estradiol (P < 0.01), and progesterone (P < 0.001) in protein deficient + 25 ppm PFHxS group. A high order of increase in lipid profile parameters was found in protein deficient + 25 ppm PFHxS group. However, high-density lipoprotein decreased in this group. Protein deficient + 25 ppm PFHxS group animals also revealed high level of oxidative stress. Histopathological findings revealed the presence of cystic follicles and theca cell degeneration in ovaries in the protein deficient + 25 ppm PFHxS group with a significant decrease (P < 0.01) in the myometrium and endometrial area of uterus. The combined effect of protein deficiency and PFHxS exposure caused a greater reprotoxicity compared to either factor alone implying an increased vulnerability of reproductive function in malnourished populations to environmental contaminants.

Hyperlipidemia, marked by high levels of fats in the blood, is a major risk factor for non-communicable diseases such as type 2 diabetes, cardiovascular diseases, and cancer. It has been linked to the action of reactive oxygen species and the formation of advanced glycation end products. Current treatments for hyperlipidemia, like orlistat, simvastatin, and atorvastatin, often present undesirable side effects, prompting the need for new therapeutic agents that are safer, more effective, cost-efficient, and have fewer side effects. In this context, new compounds, specifically propano- and butanosulfonic acids with 9-substituted quinobenzothiazinyl substituents, were synthesized through reactions with 9-substituted quinobenzothiazines and propane sultone or butane sultone. These novel quinobenzothiazine derivatives were verified using 1H NMR, 13C NMR, and HR-MS techniques. The research focused on assessing these compounds for their toxicity, ability to prevent glycation, antioxidant properties, and their potential to combat hyperlipidemia. Toxicity was evaluated on the 3T3 L1 fibroblast cell line using the MTT assay. The capacity to prevent glycation was tested with bovine serum albumin-methylglyoxal and bovine serum albumin-glucose systems. This study measured total reactive oxygen species in the 3T3 L1 cell line using 2',7'-dichlorodihydrofluorescein diacetate staining, and antioxidant capacity was assessed through DPPH scavenging and metal ion chelation tests. The effectiveness against hyperlipidemia was determined by targeting cholesterol esterase and pancreatic lipase activities, with concentrations of the compounds 5 to 12 ranging from 0.0245 to 0.268 μM. Standard drugs such as orlistat, simvastatin, statins, and aminoguanidine were used as positive controls in various assays. Additionally, computational docking studies with AutoDock Vina were performed. The resulting findings indicated that the compounds were non-toxic to cells, effectively inhibited key enzymes related to hyperlipidemia, and showed significant antioxidant properties, including the prevention of advanced glycation end-product formation. Compounds 11 and 12 demonstrated the highest activity levels. These promising results highlight the potential of new quinobenzothiazine derivatives as lead compounds for the development of antihyperlipidemic drugs, although further research is necessary to confirm their efficacy and safety.

Diabetes mellitus (DM) is a chronic endocrine and metabolic disorder characterized by persistent hyperglycemia that poses serious threats to human health and quality of life. The morbidity, disability, and mortality rates of cardiovascular complications stemming from chronic hyperglycemia are primary factors affecting the lifespan of patients with diabetes. Currently, there is no cure for DM. Standard biomedical treatments mostly control the symptoms using insulin injections or oral hypoglycemic drugs. Although the effect of standard biomedical therapy is remarkable, its long-term use is prone to toxic side effects. Numerous studies have recently found that Traditional Chinese Medicine (TCM) has strong advantages in the prevention and treatment of DM and cardiovascular complications (DACC). The collection, processing, preparation and clinical use of TCM are guided by the theory of TCM and follow the "holistic concept." Multiple components, pathways, and targets form the basis for the use of TCM in treating multiple parts and organs of the body simultaneously. TCM is mainly derived from natural medicines and their processed products and has fewer side effects. TCM is clinically used as compound prescriptions, botanical drugs, and monomers. TCM, either independently or in combination with standard biomedical treatments, has shown unique therapeutic advantages. This review aimed to explore the recently reported mechanisms of action of TCM in the prevention and treatment of DACC. These findings will aid the optimization of the current therapy or formation of a therapeutic schedule for integrated TCM and standard biomedical treatments.

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating condition characterized by airflow limitations and systemic inflammation. The interaction between the metabolic and inflammatory pathways plays a key role in disease progression, with leptin and insulin emerging as pivotal metabolic regulators. Leptin, an adipokine that regulates energy homeostasis, and insulin, the primary regulator of glucose metabolism, are both altered in COPD patients. This narrative review provides an in-depth examination of the roles of leptin and insulin in COPD pathogenesis, focusing on the molecular mechanisms through which these metabolic regulators interact with inflammatory pathways and how their dysregulation contributes to a spectrum of extrapulmonary manifestations. These disturbances not only exacerbate COPD symptoms but also increase the risk of comorbidities such as metabolic syndrome, diabetes, cardiovascular disease, or muscle wasting. By exploring the underlying mechanisms of leptin and insulin dysregulation in COPD, this review underscores the significance of the metabolic-inflammatory axis, suggesting that restoring metabolic balance through leptin and insulin modulation could offer novel therapeutic strategies for improving clinical outcomes.

Chronic inflammation is an important component of many diseases, including autoimmune diseases, intracellular infections, dysbiosis and degenerative diseases. An important element of this state is the mainly positive feedback between inflammatory cytokines, reactive oxygen species (ROS), nitric oxide (NO), increased intracellular calcium, hypoxia-inducible factor 1-alpha (HIF-1α) stabilisation and mitochondrial oxidative stress, which, under normal conditions, enhance the response against pathogens. Autophagy and the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant response are mainly negatively coupled with the above-mentioned elements to maintain the defence response at a level appropriate to the severity of the infection. The current review is the first attempt to build a multidimensional model of cellular self-regulation of chronic inflammation. It describes the feedbacks involved in the inflammatory response and explains the possible pathways by which inflammation becomes chronic. The multiplicity of positive feedbacks suggests that symptomatic treatment of chronic inflammation should focus on inhibiting multiple positive feedbacks to effectively suppress all dysregulated elements including inflammation, oxidative stress, calcium stress, mito-stress and other metabolic disturbances.

Tamarillo (Solanum betaceum Cav.) is rich in polyphenols, anthocyanins, and carotenoids, making it a promising candidate for functional food development. This study investigated phytochemical profiles and bioactivities in different tamarillo parts. Various parts of tamarillo were extracted using water and ethanol (0-95%), with 95% ethanol yielding the highest content of bioactive compounds in the peel, pulp, mucilage, and whole fruit, while 75% ethanol was more effective for the seeds. Among tamarillo components, the peel exhibited the highest concentrations of hydroxycinnamoyl derivatives, anthocyanins, and carotenoids, along with superior antioxidant capacity, including strong scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (EC50, 45.26 µg extract/mL) and high reducing power (EC50, 113.3 µg extract/mL). The peel extract exhibited the strongest inhibitory effects on α-glucosidase (IC50, 1.623 mg/mL) and angiotensin-converting enzymes (IC50, 1.435 mg/mL). In contrast, the pulp extract demonstrated the highest inhibitory activity against pancreatic lipase (IC50, 0.882 mg/mL) and α-amylase (IC50, 2.369 mg/mL). These findings suggest that tamarillo extracts possess potent antioxidant activity and enzyme-inhibitory properties related to metabolic syndrome (MetS). However, gastrointestinal digestion simulation influenced the bioactive compound content and bioactivities. Overall, tamarillo has promising potential as a functional ingredient for MetS prevention, but processing strategies are needed to retain its bioactive properties.

Background/Objectives: Inflammatory sarcopenia, characterized by muscle weakness exacerbated by chronic systemic inflammation, has emerged as a critical factor in fall risk among older adults. While previous studies have examined sarcopenia and inflammation independently, few have investigated their combined impact on mobility impairments and fall susceptibility, particularly in immunocompromised individuals. This study aimed to assess the role of inflammatory sarcopenia in increasing fall risk by comparing functional performance, muscle strength, and inflammatory biomarkers across three groups: healthy older adults, individuals with non-inflammatory sarcopenia, and those with inflammatory sarcopenia. A secondary objective was to evaluate fall incidence in immunocompromised versus non-immunocompromised individuals. Methods: A prospective observational study was conducted on 250 adults aged ≥65 years, categorized based on inflammatory status and muscle health. Functional assessments included handgrip strength, the Timed Up and Go (TUG) test, and fall frequency analysis. Inflammatory status was determined by measuring C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Multivariate regression models were used to identify predictors of fall risk. Results: Participants with inflammatory sarcopenia exhibited significantly higher CRP and IL-6 levels, greater muscle weakness, poorer mobility performance, and a fourfold increase in fall incidence compared to controls (p < 0.001). Immunocompromised individuals had nearly double the fall risk of their non-immunocompromised counterparts (p < 0.001). TUG test performance was the strongest fall predictor. Conclusions: Our findings highlight the importance of integrating fall prevention strategies that not only focus on muscle-strengthening programs but also include regular screening for inflammatory markers. Given the strong association between systemic inflammation, muscle weakness, and fall risk, identifying and managing chronic inflammation may play a crucial role in reducing mobility impairments and improving outcomes in older adults.

Conventional post-stroke edema management strategies are limitedly successful as in multiple cases of hemorrhagic transformation is being reported. Clinically, acute-ischemic-stroke (AIS) intervention by endovascular mesenchymal stem cells (MSCs) have shown benefits by altering various signaling pathways. Our previous studies have reported that intra-arterial administration of 1*105 MSCs (IA-MSCs) were beneficial in alleviating post-stroke edema by modulating PKCδ/MMP9/AQP4 axis and helpful in preserving the integrity of blood-brain-barrier (BBB). However, the role of mitochondrial dysfunction and ROS generation post-AIS cannot be overlooked in context to the alteration of the BBB integrity and edema formation through the activation of inflammatory pathways. The anti-inflammatory activity of IA-MSCs in stroke has been reported to be regulated by sirtuin-1 (SIRT-1). Hence, the relationship between SIRT-1 and AQP4 towards regulation of post-stroke edema needs to be further explored. Therefore, the present study deciphers the molecular events towards AQP4 upregulation, mitochondrial dysfunction and BBB disruption in context to the modulation of SIRT-1/PKCδ/NFκB loop by IA-MSCs administration.

Ovariectomized SD rats were subjected to focal ischemia. SIRT-1 activator, SIRT-1 inhibitor, NFkB inhibitor and IA-MSCs were administered at optimized dose. At 24 h of reperfusion, behavioral tests were performed, and brains were harvested following euthanasia for molecular studies.

IA-MSCs downregulated AQP4, PKCδ and NFkB expression, and upregulated SIRT-1 expression. SIRT-1 upregulation renders mitochondrial protection via reduction of oxidative stress resulting in BBB protection.

IA-MSCs can modulate SIRT-1 mediated AQP4 expression via mitochondrial ROS reduction and modification of NFkB transcriptional regulation.

Emerging evidence suggests that in-utero exposure to microplastics (MPs) may have physiological consequences for fetal development, yet human data remain limited. This study investigates the association between placental microplastic exposure and umbilical liver enzyme levels as markers of fetal hepatic function. A prospective cohort study was conducted in Shenyang, China, including 1057 pregnant women. Placental microplastic quantification was performed using LD-IR chemical imaging, targeting polyvinyl chloride (PVC), polypropylene (PP), and polybutylene succinate (PBS). Umbilical cord blood was collected at delivery, and liver enzyme levels alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were analyzed using biochemical assays. Associations were assessed via multivariable regression models adjusting for maternal and socioeconomic confounders. Mixture effects were examined using Bayesian Kernel Machine Regression (BKMR) and quantile g-computation (g-comp). Placental microplastics were detected in most samples (PVC: 88.4 %, PP: 88.8 %, PBS: 89.1 %), with a median total MPs of 12 particles per 10 g of tissue (IQR: 8). Higher placental PVC particles was significantly associated with increased ALP levels (β = 28.07, 95 % CI: 6.65-49.49, p = 0.01). PP exposure correlated positively with ALT (β = 0.63, 95 % CI: 0.01-1.25, p = 0.05) and AST (β = 3.42, 95 % CI: 0.87-5.96, p = 0.01). Both PP and total MPs burden exhibited strong associations with GGT elevation (p < 0.01). Mixture analysis revealed significant overall effects on ALP (β = 30.04, 95 % CI: 11.15-48.92, p < 0.01), AST (β = 7.30, 95 % CI: 4.33-10.27, p < 0.01), and GGT (β = 22.98, 95 % CI: 7.49-38.46, p < 0.01), with ALT showing a suggestive positive trend. Our findings provide novel evidence that placental MP exposure is associated with altered fetal liver enzyme levels, particularly ALP, AST, and GGT, indicating potential impacts on hepatic function. These results underscore the need for further investigation into the underlying mechanisms and long-term health implications of prenatal MP exposure.

Despite certain studies indicating hearing impairments in individuals with polycystic ovary syndrome (PCOS), the correlation between PCOS and sensorineural hearing loss (SNHL) remains inconclusive. This study aimed to investigate the association between PCOS and SNHL.

A systematic literature search was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library from inception to June 24, 2024.

This meta-analysis included cross-sectional, case-control, or cohort studies examining the association between PCOS and SNHL without language or regional restrictions. Case reports, case series, animal studies, and in vitro studies were excluded. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and utilized the Newcastle-Ottawa Scale to assess the risk of bias in the included studies.

After performing the systematic review, we conducted a meta-analysis that included 489 patients from 5 studies: 349 patients with PCOS and 140 age- and sex-matched controls without PCOS. The meta-analysis compared the mean differences in frequency-specific pure-tone thresholds between patients with PCOS and matched controls, providing 95% confidence intervals for these differences. Given the expected clinical heterogeneity, we employed the DerSimonian and Laird random-effects model. Our results revealed significant hearing loss at specific frequencies (1000, 4000, 8000, 10,000, 12,000, 14,000, 16,000, 18,000, and 20,000 Hz) in the PCOS group compared to the control group (P < .05). Furthermore, the degree of hearing loss is greater at higher frequencies.

This meta-analysis demonstrated an association between PCOS and SNHL, particularly at higher frequencies.

To examine Hedan tablet (HDT, )'s potential mechanisms in hyperlipidemic rats induced by a high-fat diet (HFD), as well as its regulatory effects and primary active constituents.

By using ultra-performance liquid chromatography (UPLC)-quadrupole-time-of-flight (QTOF)-tandem mass spectrometry (MS/MS), the components of HDT that can enter the circulatory system were found, aiming to investigate its active constituents with pharmacological effects. Based on network pharmacology approaches, the relevant HDT targets in the therapy of hyperlipidemia were anticipated. The possible mechanism of HDT for hyperlipidemia treatment was verified by in-vivo experiments, and the main active components of HDT for hyperlipidemia treatment were analyzed via in-vitro experiments.

UPLC-QTOF-MS/MS identified 30 components of HDT entering the circulatory system, primarily consisting of flavonoids, diterpenoids and alkaloids. The results of a network pharmacology study revealed that 30 active components mostly target 74 genes associated with hyperlipidemia. The primary active ingredients may include quercetin, kaempferol, and epicatechin, and the main gene targets may be tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin 1 beta (IL-1β), etc. The results of animal experiments demonstrated that HDT can significantly regulate the blood lipid level in rats with HFD, improve the degree of inflammatory infiltration in rat liver cells, lower TNF-α, C-reactive protein (CRP), IL-6, matrix metalloproteinase 9 (MMP9) and malondialdehyde (MDA) levels while raising total superoxide dismutase (T-SOD) level. Meanwhile, HDT can considerably lower the expression of sterol regulatory element-binding transcription factor 2 (SREBF2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and MMP9 while significantly increasing the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and PPAR-γ. In vitro study confirmed that quercetin and kaempferol could reduce the levels of IL-6, IL1B, MMP9 and HMGCR in the high-fat model of hepatoma G2 cells.

The mechanism by which HDT treats hyperlipidemia involves modification of the lipid metabolism targets such as downregulating SREBF2, HMGCR and MMP9, and upregulating PPAR-α and PPAR-γ, as well as anti-inflammatory and antioxidant actions. This study provides a pharmacological and biological rationale for the use of HDT in clinical hyperlipidemia management.

Hypertension, a major global health concern, is closely associated with obesity and lipid abnormalities. Remnant cholesterol (RC), a triglyceride-rich lipoprotein component, has been linked to cardiovascular diseases, but its joint impact with body mass index (BMI) on hypertension risk remains unclear.

We analyzed data from 3805 participants (mean age: 57 years; 44.3% male) in the China Health and Retirement Longitudinal Study (CHARLS) from 2011-2020. Inclusion criteria were adults aged over 45 years with complete data on blood lipids and BMI. Participants with baseline hypertension or missing covariate data were excluded. Cox proportional hazard models assessed associations, while mediation analysis explored RC's role in BMI-hypertension linkage.

Over a 9-year follow-up, 590 participants developed hypertension. Obesity (BMI ≥28.0 kg/m²) and high RC levels were independently associated with hypertension (HR: 2.18; 95% CI: 1.48-3.21 for the highest RC tertile). RC mediated 7.07% of BMI's effect on hypertension, and BMI mediated 29.3% of RC's effect.

This study highlights the intertwined roles of BMI and RC in hypertension development. Targeting both risk factors may enhance prevention strategies.

Poor prognosis of maintenance hemodialysis (MHD) patients, including cardiovascular disease (CVD) and protein-energy wasting (PEW), is strongly associated with insulin resistance (IR). Previous studies have revealed that limb ischemic preconditioning (LIPC), as an intervention, is effective in reducing inflammation and oxidative stress levels in patients. The aim of this study was to elucidate the effects of LIPC on IR indirect indices, inflammation and oxidative stress indices, and to further explore the potential mechanisms of LIPC in reducing IR indices.

A retrospective analysis was performed on 62 patients with MHD who had previously undergone limb ischemia preconditioning (LIPC) or sham surgery (Sham). General clinical and laboratory data were collected. Furthermore, to assess the IR status of MHD patients, the following indices were employed: triglyceride-glucose index (TyG), triglyceride-glucose body mass index (TyG-BMI), triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score of insulin resistance (METS-IR). Inflammation and oxidative stress indicators included high-sensitivity C-reactive protein (hs-CRP), hs-CRP /albumin ratio (CAR), serum malondialdehyde (MDA) and superoxide dismutase (SOD). Mediation analysis was conducted using Model 4 in the SPSS PROCESS macro version 4.1.

Following a four-week experiment, hs-CRP (15.46 ± 3.60 vs. 10.53 ± 5.42, p < 0.001), CAR (0.39 ± 0.10 vs. 0.26 ± 0.13, p < 0.001) and MDA (8.46(6.71,9.85) vs. 5.99(5.11,7.89), p = 0.001) indices were significantly decreased in the MHD patients of the LIPC group, whereas SOD indices (215.07(180.27,286.45) vs. 267.76(228.32,319.54), p = 0.012) were significantly higher. Only hs-CRP (-4.93 ± 5.68 vs. 0.16 ± 5.39, p = 0.001) and CAR (-0.14 ± 0.14 vs. -0.001 ± 0.15, p = 0.001) were significantly different in the LIPC group compared to the Sham group. In contrast, the changes in MDA (p = 0.058) and SOD (p = 0.107) were not statistically significant between groups. The intra- and inter-group differences in the four indirect indices of IR were significant (p < 0.05). The heatmap revealed a notable correlation between the changes in hs-CRP and CAR levels and the changes in the IR indirect indices. In addition, The mediation model showed that the inflammatory indicators hs-CRP played a partial mediating role in the improvement of IR indices (TyG-BMI) by LIPC.

LIPC has an excellent ability to inhibit inflammation and peroxidation. In addition, in MHD patients, inflammation plays a significant role in the process of LIPC improving IR index.

Metabolic syndrome (MetS) associated with Osteoarthritis (OA) is an increasingly recognised entity. Whilst the degenerative pattern in cuff-tear arthropathy (CTA) has been well documented, the biological processes behind primary shoulder OA and CTA remain less understood. This study investigates transcriptomic differences in these conditions, alongside the impact of MetS in patients undergoing total shoulder replacement. In a multi-centre study, 20 OA patients undergoing total shoulder replacement were included based on specific treatment indications for OA and cuff-tear arthropathy as well as 25 patients undergoing rotator cuff repair (RCR) as a comparator group. Tissues from subchondral bone, capsule (OA and RCR), and synovium were biopsied, and RNA sequencing was performed using Illumina platforms. Differential gene expression was conducted using DESeq2, adjusting for demographic factors, followed by pathway enrichment using the mitch package. Gene expressions in CTA and primary OA was differentially affected. CTA showed mitochondrial dysfunction, GATD3A downregulation, and increased cartilage degradation, while primary OA was marked by upregulated inflammatory and catabolic pathways. The effect of MetS on these pathologies was further shown. MetS further disrupted WNT/β-catenin signalling in CTA, and in OA. Genes such as ACAN, PANX3, CLU, and VAT1L were upregulated, highlighting potential biomarkers for early OA detection. This transcriptomic analysis reveals key differences between end-stage CTA and primary glenohumeral OA. CTA shows heightened metabolic/protein synthesis activity with less immune-driven inflammation. Under MetS, mitochondrial dysfunction (including GATD3A downregulation) and altered Wnt/β-catenin signalling intensify cartilage and bone damage. In contrast, primary OA features strong complement activation, inflammatory gene expression, and collagen remodelling. MetS worsens both conditions via oxidative stress, advanced glycation end products, and ECM disruption-particularly, increased CS/DS degradation. These distinctions support targeted treatments, from antioxidants and Wnt modulators to aggrecanase inhibitors or clusterin augmentation. Addressing specific molecular disruptions, especially those amplified by MetS, may preserve shoulder function, delay surgical intervention, and improve long-term patient outcomes.

This study aims to compare the efficacy of IL-17 and IL-23 biologics in the treatment of plaque psoriasis (Psoriasis vulgaris) in patients with metabolic syndrome (MetS) and to explore the effects of different biologics on metabolic indicators, particularly regarding the differences in efficacy during long-term treatment. This is a randomized controlled clinical trial involving 120 moderates to severe plaque psoriasis patients, of which 60 have metabolic syndrome and 60 do not. The patients were randomly assigned to three groups: IL-17 biologics group, IL-23 biologics group, and cyclosporine control group. Treatment lasted for three months, with evaluation indicators including psoriatic lesion assessment (PASI score), blood glucose levels, lipid profile (triglycerides, HDL-C), inflammatory markers (CRP, ESR, IL-6), etc. Patients were assessed at baseline, after one month, and after three months of treatment for both clinical efficacy and changes in metabolic indicators. Both IL-17 and IL-23 biologics demonstrated superior efficacy compared to cyclosporine in treating plaque psoriasis. After one month and three months of treatment, PASI scores in the IL-17 and IL-23 groups were significantly lower than in the control group, and the therapeutic effects were more pronounced (P < 0.05). The IL-17 and IL-23 groups also showed better improvements in blood glucose, blood lipids (TG and HDL-C), and inflammatory markers (CRP, ESR, IL-6) compared to the control group. After three months of treatment, fasting blood glucose, fasting insulin, triglycerides, and CRP levels were significantly lower in the IL-17 and IL-23 groups than in the control group (P < 0.05). Metabolic syndrome had some impact on treatment outcomes, with the efficacy of IL-17 and IL-23 biologics being lower in patients with metabolic abnormalities compared to those without metabolic syndrome. However, the IL-23 biologic showed less impact from metabolic syndrome. IL-17 biologics had a rapid effect in the short term, while IL-23 biologics demonstrated superior efficacy in long-term treatment, particularly at the three-month mark, where both efficacy and metabolic improvements were better than the IL-17 group. Both IL-17 and IL-23 biologics are more effective than cyclosporine in treating plaque psoriasis and can improve metabolic indicators in patients. Although metabolic syndrome impacts the efficacy of IL-17 biologics, IL-23 biologics are less affected by metabolic syndrome and demonstrate better long-term efficacy. Therefore, IL-23 biologics are recommended for long-term treatment in plaque psoriasis patients with metabolic syndrome.

Salvia.officinalis (S. officinalis), is recognized for its antihyperlipidemic, metabolism-regulating, and antioxidant properties in diabetic and hyperlipidemic disorders. This study examining its effects on lipid and oxidative stress (OS) markers in patients with Polycystic Ovary Syndrome (PCOS), thereby substantiating its role in managing metabolic disorders.

In this randomized placebo-controlled trial was performed in gynecology clinics affiliated to Iran University of Medical Sciences. Accordingly, 70 Iranian married women aged 15-40 years with newly diagnosed PCOS were included. They were randomized to receive either 330 mg of S. officinalis extract or placebo daily for eight weeks. The study outcomes included lipid profile and OS markers.

The study found a significantly lower triglyceride levels and malondialdehyde after eight weeks of S. officinalis extract intake compared to placebo. Also, the mean change of triglyceride, high-density lipoprotein cholesterol, malondialdehyde, and total antioxidant capacity were statistically significant in intervention group.

The study demonstrates that S. officinalis extract can significantly reduce triglyceride levels and OS in patients with PCOS, suggesting its potential as an adjunctive natural therapy for managing metabolic and oxidative imbalances associated with this condition. While the extract did not significantly alter other lipid profile markers, the observed improvements highlight the therapeutic promise of S. officinalis. These findings support further investigation into the clinical applications S. officinalis for PCOS and its potential benefits for metabolic health.

IRCT201504146917N2 on 2015-10-03 (registered while recruiting).

Colorectal cancer (CRC) remains a principal contributor to oncological mortality worldwide, with chronic inflammation serving as a fundamental driver of its pathogenesis. Protease-activated receptor-2 (PAR-2), a G-protein-coupled receptor, orchestrates inflammation-driven tumorigenesis by potentiating NF-κB and Wnt/β-catenin signaling, thereby fostering epithelial-mesenchymal transition (EMT), immune evasion, and therapeutic resistance. Despite its pathological significance, targeted modulation of PAR-2 remains an underexplored avenue in CRC therapeutics. Oleocanthal (OC), a phenolic constituent of extra virgin olive oil, is recognized for its potent anti-inflammatory and anti-cancer properties; however, its regulatory influence on PAR-2 signaling in CRC is yet to be elucidated. This study interrogates the impact of OC on PAR-2-mediated inflammatory cascades using HT-29 and Caco-2 CRC cell lines subjected to lipopolysaccharide (LPS)-induced activation of PAR-2. Expression levels of PAR-2 and TNF-α were quantified through Western blotting and RT-PCR, while ELISA assessed TNF-α secretion. Intracellular calcium flux, a pivotal modulator of PAR-2-driven oncogenic inflammation, was evaluated via Fluo-4 calcium assays. LPS markedly elevated PAR-2 expression at both mRNA and protein levels in CRC cells (p < 0.01, one-way ANOVA). OC administration (20-150 μg/mL) elicited a dose-dependent suppression of PAR-2, with maximal inhibition at 100-150 μg/mL (p < 0.001, Tukey's post hoc test). Concomitant reductions in TNF-α transcription (p < 0.01) and secretion (p < 0.001) were observed, corroborating the anti-inflammatory efficacy of OC. Additionally, OC ameliorated LPS-induced calcium dysregulation, restoring intracellular calcium homeostasis in a concentration-dependent manner (p < 0.01). Crucially, OC exhibited selectivity for PAR-2, leaving PAR-1 expression unaltered (p > 0.05), underscoring its precision as a therapeutic agent. These findings position OC as a selective modulator of PAR-2-driven inflammation in CRC, disrupting the pro-tumorigenic microenvironment through attenuation of TNF-α secretion, calcium dysregulation, and oncogenic signaling pathways. This study furnishes mechanistic insights into OC's potential as a nutraceutical intervention in inflammation-associated CRC. Given the variability in OC bioavailability and content in commercial olive oil, future investigations should delineate optimal dosing strategies and in vivo efficacy to advance its translational potential in CRC therapy.

Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut-liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD.

Hypertension is a prevalent chronic disease affecting over 1.2 billion people worldwide, representing a major modifiable risk factor for cardiovascular diseases. The Waist-to-Height Ratio (WHtR) and Triglyceride to High-Density Lipoprotein Cholesterol (TG/HDL-C) ratio are established metabolic indicators linked to the risk of cardiovascular and metabolic diseases. Recently, a Cardiometabolic Index (CMI), combining WHtR and TG/HDL-C ratios, has been proposed to provide a comprehensive assessment of metabolic health. This study investigates the association between CMI and hypertension using data from the National Health and Nutrition Examination Survey (NHANES).

The study utilized NHANES data from nine cycles spanning 2001 to 2018, encompassing 20,049 participants aged over 20. Exclusions were made for individuals with incomplete CMI or hypertension data, and pregnant women. CMI was calculated by multiplying the WHtR by the TG/HDL-C ratio. Hypertension was defined according to American Heart Association guidelines. The relationship between CMI and hypertension was evaluated using multivariate logistic regression analyses, with additional subgroup analyses conducted based on demographic factors. Nonlinear relationships were analyzed using smoothing curve fitting techniques.

The study identified a significant positive correlation between CMI and hypertension risk, with an increase of one unit in CMI associated with a 9% heightened risk of hypertension (OR: 1.09, 95% CI: 1.05, 1.13). The association remained significant across various demographic subgroups. A nonlinear relationship was observed, with a critical CMI threshold of 2.64. Below this threshold, higher CMI values were associated with a progressively higher prevalence of hypertension, whereas beyond this threshold, further increases in CMI did not significantly correlate with an elevated risk of hypertension.

The study demonstrates that CMI is significantly associated with hypertension risk and may serve as a valuable tool for early screening and risk assessment, particularly in identifying individuals at higher risk before reaching the critical CMI threshold. These results underscore the importance of addressing metabolic health in the prevention and management of hypertension. Future research should focus on longitudinal studies to establish causality, explore the clinical utility of CMI in hypertension screening, and examine its applicability in diverse populations.

Fulvic acid (FA) acid has many physiological activities, but the specific metabolic responses and changes in mineral element contents of spinach by FA in response to nitrate stress are unknown. Herein, we used liquid chromatography-mass spectrometry (LC-MS) and wet digestion using H2SO4-H2O2 to analyze the metabolic response and changes in the mineral element content of spinach to nitrate stress (150 mM NO3-) after FA (0.15%) foliar spray application. After 2 days of the stress treatment, FA was sprayed thrice (once every 7 days), sampled 4 days after the last spraying, and metabolites and mineral element contents were measured. FA treatment significantly increased organic acid contents (tartaric acid, malic acid, citric acid, and ascorbic acid) and amino acid contents (threonine, asparagine, valine, tyrosine, alanine, glutamate, serine, histidine, arginine, and glutamine) under nitrate stress. FA application also significantly improved mineral element contents (P, Na, Fe, and Zn) under nitrate stress. This study provides comprehensive insights into metabolite accumulation of metabolites and the improvement of nutritional quality in spinach through FA application under nitrate stress. Further research should focus on elucidating additional underlying molecular mechanisms of these metabolic responses for better utilization of this natural compound in agriculture.

Insulin resistance (IR) is a significant factor in the development and progression of metabolic-related diseases like dyslipidemia, T2DM, hypertension, nonalcoholic fatty liver disease, cardiovascular and cerebrovascular disorders, and cancer. The pathogenesis of IR depends on multiple factors, including age, genetic predisposition, obesity, oxidative stress, among others. Abnormalities in the insulin-signaling cascade lead to IR in the host, including insulin receptor abnormalities, internal environment disturbances, and metabolic alterations in the muscle, liver, and cellular organelles. The complex and multifaceted characteristics of insulin signaling and insulin resistance envisage their thorough and comprehensive understanding at the cellular and molecular level. Therapeutic strategies for IR include exercise, dietary interventions, and pharmacotherapy. However, there are still gaps to be addressed, and more precise biomarkers for associated chronic diseases and lifestyle interventions are needed. Understanding these pathways is essential for developing effective treatments for IR, reducing healthcare costs, and improving quality of patient life.

Cardiovascular diseases are a leading cause of death worldwide, and the process of cardiac remodeling lies at the core of most of these diseases. Sustained cardiac remodeling almost unavoidably ends in progressive muscle dysfunction, heart failure, and ultimately death. Therefore, in order to attenuate cardiac remodeling and reduce mortality, different therapies have been used, but it is important to identify adjuvant factors that can help to modulate this process. One of these factors is the inclusion of affordable foods in the diet with potential cardioprotective properties. Orange juice intake has been associated with several beneficial metabolic changes, which may influence cardiac remodeling induced by cardiovascular diseases. Current opinion highlights how the metabolites and metabolic pathways modulated by orange juice consumption could potentially attenuate cardiac remodeling. It was observed that orange juice intake significantly modulates phospholipids, energy metabolism, endocannabinoid signaling, amino acids, and gut microbiota diversity, improving insulin resistance, dyslipidemia, and metabolic syndrome. Specifically, modulation of phosphatidylethanolamine (PE) metabolism and activation of PPARα and PPARγ receptors, associated with improved energy metabolism, mitochondrial function, and oxidative stress, showed protective effects on the heart. Furthermore, orange juice intake positively impacted gut microbiota diversity and led to an increase in beneficial bacterial populations, correlated with improved metabolic syndrome. These findings suggest that orange juice may act as a metabolic modulator, with potential therapeutic implications for cardiac remodeling associated with cardiovascular diseases.

Effective chemical catalysts can artificially control intracellular metabolism. However, in conventional catalytic chemistry, activity and cytotoxicity have a trade-off relationship; thus, driving catalysts in living cells remains challenging. To overcome this critical issue at the interface between catalytic chemistry and biology, we developed cell-driven allosteric catalysts that exert catalytic activity at specific times. The synthesized allosteric redox catalysts up- and downregulated their foldase- and antioxidase-like activities in response to varying Ca2+ concentrations, which is a key factor for maintenance of the redox status in cells. In the absence of Ca2+ or at low Ca2+ concentrations, the compounds were mostly inactive and hence did not affect cell viability. In contrast, under specific conditions with elevated cytosolic Ca2+ concentrations, the activated compounds resisted the redox imbalance induced by the reactive oxygen species generated by Ca2+-stimulated mitochondria. Smart catalysts that crosstalk with biological phenomena may provide a platform for new prodrug development guidelines.

Diminished ovarian reserve (DOR), a major cause of female infertility, is closely linked to insulin resistance (IR). Traditional Chinese Medicine (TCM) approaches, such as the Gengnianchun (GNC) formula, focus on restoring ovarian function by improving IR and regulating hormonal balance. Despite GNC's demonstrated efficacy, its precise therapeutic mechanisms remain unclear.

This study aims to elucidate the mechanisms by which GNC ameliorates IR-induced DOR through comprehensive pharmacological and experimental validation.

The study combined Liquid chromatograph mass spectrometer (LC-MS), ultra-performance liquid chromatography (UPLC-TOF-MS/MS), network pharmacology, and molecular docking to identify active components and key therapeutic targets of GNC. Functional enrichment analyses (GO and KEGG) and molecular docking studies were performed. A high-fat diet-induced mouse model of IR-DOR was established, followed by GNC treatment at varying doses. Therapeutic effects were evaluated via qRT-PCR, western blot, immunofluorescence, and histological analysis.

GNC contains 219 active ingredients targeting 53 genes associated with IR-induced DOR. KEGG analysis revealed the estrogen signaling pathway as a key mechanism. High-dose GNC significantly improved IR and ovarian reserve by increasing AKT1, ESR1, and ESR2 expression, as confirmed by qRT-PCR, western blot and immunofluorescence analysis. These findings indicate that GNC enhances insulin sensitivity, promotes follicular development, and restores ovarian function.

This study demonstrates for the first time that GNC alleviates IR-induced DOR by modulating the estrogen signaling pathway and activating key molecular targets. These results provide a foundation for clinical research and the development of novel therapeutic strategies for DOR.

Not applicable.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with complex pathophysiological mechanisms such as oxidative stress, inflammation, apoptosis, and endothelial dysfunction driving disease progression. MicroRNAs (miRNAs), a class of non-coding RNAs, have emerged as key regulators of gene expression involved in these processes, positioning them as potential biomarkers and therapeutic targets in CVD management. Simultaneously, flavonoids, naturally occurring polyphenolic compounds found in various plant-based foods, have gained attention for their cardioprotective properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. Recent studies suggest a novel intersection between flavonoids and miRNAs, where flavonoids may modulate the expression of specific miRNAs implicated in CVD pathogenesis. This review explores the potential of flavonoids as miRNA modulators, focusing on their ability to regulate miRNAs associated with cardiac fibrosis, hypertrophy, and vascular inflammation. By bridging the therapeutic potential of flavonoids with miRNA targeting, this review highlights innovative pathways for advancing CVD treatment strategies. Additionally, preclinical and clinical evidence supporting these interactions is discussed, alongside the challenges and opportunities in developing flavonoid-based miRNA therapies. Unlocking this synergy could pave the way for more effective, personalized approaches to CVD management, addressing unmet needs in contemporary cardiovascular care.

Obesity and obesity-related metabolic diseases are causally linked to inflammatory activation. Proinflammatory macrophage infiltration and NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation contribute to chronic inflammation and insulin resistance. Alleviating inflammatory responses is a reliable method to restore insulin sensitivity and reduce the severity of metabolic syndrome. Solanesol, rich in anti-inflammatory foods (potato, tomato, eggplant, chili peppers), has demonstrated anti-inflammatory properties, but whether it plays a beneficial role in obesity-induced chronic inflammation remains poorly understood. In this study, we investigated the effects of solanesol on the NLRP3 inflammasome and inflammatory responses both in vitro and in high-fat diet (HFD)-fed mice. We found that oral administration of solanesol reduced weight gain, insulin resistance, and inflammation in epididymal white adipose tissue (eWAT) in both HFD-fed obese mice and mice concurrently treated with a HFD. This effect was involved with reducing macrophage inflammation and inactivating the NLRP3 inflammasome by reducing the K+ efflux and reactive oxygen species (ROS) production in macrophages. Solanesol also reprogrammed the phenotype of inflammatory macrophages. Taken together, our study suggests that solanesol may be a promising candidate for treating obesity and obesity-related metabolic diseases.