Metabolic Markers Research Articles

The relationship between iron metabolism markers and parameters of carbohydrate and lipid metabolism in patients with overweight and obesity

Background: Hyperferritinemia associated with obesity and insulin resistance is a link between the components of the metabolic syndrome and a possible triggering factor in the pathogenesis of carbohydrate metabolism disorders and dyslipidemia.Aim: To establish possible relationships between ferrokinetic parameters, parameters of lipid and carbohydrate metabolism in overweight and obese patients, and to analyze the possibility of using iron metabolism parameters (ferritin and serum iron) as predictors of carbohydrate metabolism disorders in this cohort of patients.Material and Methods. The study included 52 overweight or obese patients. In the course of the study, patients were stratified into groups depending on the presence of carbohydrate metabolism disorders (CMD), and depending on the state of iron metabolism. Among all patients included in the study, an assessment of anthropometric data, a study of glycated hemoglobin, a standard glucose tolerance test with 75 g of glucose, a study of hematological parameters, as well as biochemical parameters of iron metabolism – the concentration of serum iron, transferrin and ferritin, was carried out.Results. Patients with CMD – impaired glucose tolerance or impaired fasting glycaemia – had significantly higher serum ferritin levels than obese patients without CMD (p = 0.019). In persons with a high level of ferritin, CMD developed significantly more often than in patients with a ferritin content in the range below the 75th percentile (χ2 = 5.278, p = 0.022). According to the ROC analysis, ferritin showed a rather high sensitivity – 75%, and specificity – 84.4% at a diagnostic threshold of 126.65 ng/ml (area under the curve = 0.738; p = 0.016) in the diagnosis of prediabetes (IGT/IFG) in overweight and obese individuals.Conclusion. High concentrations of iron and ferritin are positively associated with CMD, with ferritin being a promising predictor of prediabetes and type 2 diabetes mellitus.

Effects of calcium phosphate and phosphorus-dissolving bacteria on microbial structure and function during Torreya Grandis branch waste composting

Background Burkholderiais a phosphorus solubilizing microorganism discovered in recent years, which can dissolve insoluble phosphorus compounds into soluble phosphorus. To investigate the effects of Burkholderia and calcium phosphate on the composting of Torreya grandis branches and leaves, as well as to explain the nutritional and metabolic markers related to the composting process.MethodsIn this study, we employed amplicon sequencing and untargeted metabolomics analysis to examine the interplay among phosphorus (P) components, microbial communities, and metabolites during T. grandis branch and leaf waste composting that underwent treatment with calcium phosphate and phosphate-solubilizing bacteria (Burkholderia). There were four composting treatments, 10% calcium phosphate (CaP) or 5 ml/kg (1 × 108/ml Burkholderia) microbial inoculum (WJP) or both (CaP + WJP), and the control group (CK).ResultsThe results indicated that Burkholderia inoculation and calcium phosphate treatment affected the phosphorus composition, pH, EC, and nitrogen content. Furthermore, these treatments significantly affected the diversity and structure of bacterial and fungal communities, altering microbial and metabolite interactions. The differential metabolites associated with lipids and organic acids and derivatives treated with calcium phosphate treatment are twice as high as those treated with Burkholderia in both 21d and 42d. The results suggest that calcium phosphate treatment alters the formation of some biological macromolecules.ConclusionBoth Burkholderia inoculation and calcium phosphate treatment affected the phosphorus composition, nitrogen content and metabolites of T. grandis branch and leaf waste compost.These results extend our comprehension of the coupling of matter transformation and community succession in composting with the addition of calcium phosphate and phosphate-solubilizing bacteria.

Changes in Transient Elastography with Glucagon-Like Peptide-1 Receptor Agonist Use in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Real-World Retrospective Analysis.

Introduction: Current guidelines recommend the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD), especially in patients with comorbid diabetes and obesity. This study investigated the effects of GLP-1RAs on hepatic steatosis and fibrosis in patients with MASLD, as measured by changes in vibration-controlled transient elastography (VCTE) and other clinical parameters in a real-world clinical setting. Methods: We conducted a single-center, retrospective analysis of 96 patients with MASLD from a multidisciplinary care clinic who completed VCTE at baseline and follow-up within 6-24 months to compare changes in controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as well as other metabolic markers, between GLP-1RA users and nonusers using two-sample t-tests and Wilcoxon rank-sum tests. We also assessed whether improvements in hepatic steatosis, defined as a change in CAP >38 dB/m as previously described in the literature, were associated with improvement in fibrosis. Results: GLP-1RA use resulted in significant improvements in weight (-8.1 kg vs. -3.5 kg, P = 0.009), body mass index (BMI) (-2.9 kg/m2 vs. -1.3 kg/m2, P = 0.012), alanine aminotransferase (-15.0 IU/L vs. -4.0 IU/L, P = 0.017), aspartate aminotransferase (-5.0 IU/L vs. -1.0 IU/L, P = 0.021), glycated hemoglobin (HbA1c) (-0.7% vs. 0.1%, P = 0.019), and CAP (-59.9 dB/m vs. -29.1 dB/m, P = 0.016). Responders also had significant improvements in weight (-9.2 kg vs. -1.9 kg, P < 0.001), BMI (-3.3 kg/m2 vs. -0.7 kg/m2, P < 0.001), diastolic blood pressure (-6.1 mmHg vs. -0.7 mmHg, P = 0.028), HbA1c (-0.8% vs. 0.3%, P < 0.001), and LSM (-1.5 kPa vs. 0.1 kPa, P < 0.001). Conclusions: Patients with MASLD treated with GLP-1RAs showed significant improvements in hepatic steatosis and multiple other metabolic parameters, with weight loss as the proposed mechanism for this liver improvement. In addition, change in CAP >38 dB/m was associated with improvements in LSM and other metabolic parameters, suggesting the clinical utility of VCTE in the surveillance of MASLD.

Response of Circulating Free Cellular DNA to Repeated Exercise in Men with Type 1 Diabetes Mellitus

Background: Intense exercise leads to neutrophil extracellular traps (NETs) formation, which triggers cell disintegration. NET, as well as other processes of apoptosis, necrosis, and spontaneous secretion, result in increased levels of cell-free DNA (cf-DNA) in the circulation. An increment of cf-DNA is also observed in autoimmune diseases, such as type 1 diabetes mellitus (T1DM). Repeated exhaustive exercises are an impulse for physiological adaptation; therefore, in this case–control study, we compared the exercise-induced increase in cf-DNA in men with T1DM and healthy controls to determine the development of the tolerance to exercise. Methods: Volunteers performed a treadmill run to exhaustion at a speed matching 70% of their personal VO2 max at three consecutive visits, separated by a 72 h resting period. Blood was collected before and after exercise for the determination of plasma cell-free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, blood cell count and metabolic markers. Results: Each bout of exhaustive exercise induced a great elevation of cf n-DNA levels. An increase in cf mt-DNA was observed after each run. However, the significance of the increase was noted only after the second bout in T1DM participants (p &lt; 0.02). Changes in cf-DNA concentration were transient and returned to baseline values during 72 h of resting. The exercise-induced increment in circulating cf n-DNA and cf mt-DNA was not significantly different between the studied groups (p &gt; 0.05). Conclusions: Cf-DNA appears to be a sensitive marker of inflammation, with a lower post-exercise increase in individuals with T1DM than in healthy men.

In Vitro Treatment with Metformin Significantly Reduces Senescent B Cells Present in the Adipose Tissue of People with Obesity

BackgroundOur previous work has shown that senescent B cells accumulate in the human adipose tissue (AT) from people with obesity, where they express transcripts for markers associated with the senescence-associated secretory phenotype (SASP) and secrete multiple inflammatory mediators. These functions of AT-derived B cells are metabolically supported. ObjectivesTo show that Metformin (MET), a widely used hypoglycemic and antidiabetic drug, is able at least in vitro to decrease frequencies, secretory profile, and metabolic requirements of senescent B cells isolated from the AT from people with obesity. MethodsWe recruited adult females with obesity (n = 8, age 40 ± 2 y, BMI range: 33–42) undergoing breast reduction surgery, who donated their discarded subcutaneous AT. B cells from stromal vascular fractions isolated after collagenase digestion of the AT were evaluated after in vitro incubation with MET (1 mM × 106 B cells) or with a medium for the following measures. The expression of transcripts for SASP-associated markers (p16INK4a and p21CIP1/WAF1) measured by quantitative polymerase chain reaction (qPCR); secretion of inflammatory cytokines (TNF-α, IL-6, IFN-γ and IL-17A) measured by a Cytometric Bead Array); metabolic characteristics as identified by a glycolytic test and Seahorse technology, and by the expression of transcripts for glucose transporters and metabolic enzymes involved in glucose metabolic pathways, measured by qPCR. To examine differences between MET-treated compared with untreated groups, paired Student’s t tests (two-tailed) were employed. ResultsMET in vitro was able to reduce frequencies and numbers of senescent B cells, as identified by staining with β-galactosidase, as well as the secretion of inflammatory cytokines, the expression of transcripts for SASP, and metabolic markers that support intrinsic B cell inflammation. ConclusionsOur results provide evidence to support the beneficial effects of MET in reducing AT-related inflammation through its effects on senescent B cells.

The Relationship Between Age at Diabetes Onset and Clinical Outcomes in Newly Diagnosed Type 2 Diabetes: A Real-World Two-Center Study.

This study was developed with the goal of clarifying whether there is any relationship between type 2 diabetes mellitus (T2DM) age of onset and clinical outcomes for patients in National Metabolic Management Centers (MMC). From September 2017 - June 2022, 864 total T2DM patients were recruited in MMC and assigned to those with early-onset and late-onset diabetes (EOD and LOD) based on whether their age at disease onset was ≤ 40 or > 40 years. All patients received standardized management. Baseline and 1-year follow-up data from these two groups of patients were assessed. Associations between onset age and other factors were evaluated with a multivariate linear regression approach, adjusting for appropriate covariates. Outcomes in particular subgroups were also assessed in stratified analyses. Markers of dysregulated glucose metabolism and BMI values were significantly higher among EOD patients as compared to LOD patients. Subjects in both groups exhibited significant improvements in several disease-related parameters on 1-year follow-up after undergoing metabolic management. EOD patients exhibited significantly greater percentage reductions in HbA1c levels (-28.49 (-44.26, -6.45)% vs -13.70 (-30.15,-1.60)%, P =0.017) relative to LOD patients following adjustment for confounders. Significant differences were also detected between these groups when focused on subgroups of patients who were male, exhibited a BMI ≥ 25, an HbA1c ≥ 9, or had a follow-up frequency < 2. Data from a 1-year follow-up time point suggest that a standardized metabolic disease management model can promote effective metabolic control in newly diagnosed T2DM patients, particularly among individuals with EOD.

Effects of metformin and curcumin in women with polycystic ovary syndrome: A factorial clinical trial

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder in women, associated with dyslipidemia, insulin resistance, and hormonal imbalances. Metformin and curcumin have shown promise in improving these metabolic and hormonal parameters individually, but their combined effects in PCOS remain unclear. MethodsWe conducted a randomized, double-blind, placebo-controlled, 12-week factorial trial involving 200 women with PCOS. Participants were randomly assigned in a 1:1:1:1 ratio to receive metformin (500-mg/8 h) + placebo, nanocurcumin soft gel capsule (80-mg/8 h) + placebo, metformin (500-mg/8 h) + nanocurcumin (80-mg/8 h), or double placebo. Lipid profiles, glucose metabolism markers, hormonal parameters, body weight, and body mass index (BMI) were assessed at baseline and week 12. ResultsThe combination of metformin and curcumin demonstrated significant improvements in lipid profiles, glucose metabolism, hormonal parameters, body weight, and BMI compared to individual agents or placebo. Greater reductions in low-density lipoproteins (LDL) cholesterol, total cholesterol (TC), and triglyceride (TG) levels were observed with the combination therapy, along with increased high-density lipoproteins (HDL) cholesterol. Additionally, the combination therapy significantly improved markers of glucose metabolism and showed synergistic effects in reducing body weight and BMI. Reductions in testosterone and improvements in Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) levels were also observed with combination therapy. ConclusionThe combination of metformin and curcumin demonstrates superior efficacy in improving lipid profiles, glucose metabolism, hormonal parameters, body weight, and BMI in women with PCOS compared to individual agents or placebo. This highlights the potential synergistic effects of combining these agents for the management of PCOS.

Yi-Qi-Jian-Pi-Xiao-Yu formula inhibits cisplatin-induced acute kidney injury through suppressing ferroptosis via STING-NCOA4-mediated ferritinophagy

BackgroundThe kidneys are the primary excretory organs for platinum drugs, making them susceptible to damage from these drugs. Cisplatin-induced acute kidney injury (CIAKI) is the most common side effect observed in patients undergoing clinical cisplatin treatment. A traditional Chinese medicinal preparation, the Yi-Qi-Jian-Pi-Xiao-Yu formula (YQJPXY), which is a modified formulation of the classical Chinese medicine formula Buyang Huanwu Decoction, has long been used in the treatment of clinical kidney diseases. It is expected to be used to ameliorate cisplatin-induced acute kidney injury. However, the mechanism of this YQJPXY for the treatment of cisplatin-induced acute kidney injury remains unclear. PurposeThe objective of this study is to examine the impact of the YQJPXY on the inhibition of ferroptosis in cisplatin-induced acute kidney injury and to elucidate the underlying mechanisms. MethodsThe active components of YQJPXY were analysed using UPLC-MS/MS. A comprehensive investigation was conducted to elucidate the effects and regulatory mechanisms of YQJPXY on CIAKI and ferroptosis in mice subjected to acute cisplatin treatment and in mice receiving cisplatin treatment after STING expression was inhibited using the STING inhibitor C176. The renoprotective effect of YQJPXY on cisplatin-treated mice was evaluated by measuring tissue damage, inflammation and pro-fibrosis. In addition, we employed network pharmacology and molecular docking methodologies to analyse the principal regulatory targets of YQJPXY. Furthermore, the expression of key proteins and markers of ferroptosis and iron metabolism, as well as the levels of key indicators related to STING-associated ferritinophagy, were examined by immunoblotting, immunohistochemistry, immunoprecipitation, quantitative real-time PCR (qPCR) and specific probes. ResultsThe results demonstrated that YQJPXY reduced the levels of indicators of injury, inflammation and pro-fibrosis in CIAKI mice, with renoprotective effects. Network pharmacological analyses revealed that ferroptosis might be the main biological process regulated by YQJPXY. Furthermore, molecular docking results indicated that STING might be a potential regulatory target of YQJPXY. Furthermore, YQJPXY treatment resulted in a significant reduction in MDA and 4-HNE levels, as well as the inhibition of ferroptosis and improvement in iron metabolic processes. Concomitantly, YQJPXY exhibited a robust protective effect on ferroptosis and iron metabolism homeostasis, as evidenced by its inhibitory action on ferritinophagy. Validation experiments utilising the cisplatin inhibitor C176 demonstrated that YQJPXY inhibits cisplatin-induced ferroptosis in kidney via STING-mediated ferritinophagy. ConclusionThese suggest that YQJPXY alleviates cisplatin-induced acute kidney injury through suppressing ferroptosis via STING-NCOA4-mediated Ferritinophagy.

A Systematic Review Exploring Empirical Pharmacogenomics Research Within Global Indigenous Populations.

This systematic review aims to highlight the scope of pharmacogenomics research within global Indigenous populations. This review also explores the barriers and facilitators of pharmacogenomics research within this population. A systematic review of literature was conducted to identify and present an understanding of current empirical evidence demonstrating the conduct of genomics or pharmacogenomics research within global Indigenous populations (PROSPERO registration: CRD42021257226). Using key search terms, relevant databases were searched for articles published between January 2010 and July 2022. Screening, data extraction, and analysis was conducted using well-defined inclusion criteria. Quality assessment and risk of bias appraisal was conducted using the mixed methods appraisal tool. Indigenous community engagement and participation in genomics research was assessed using the social-ecological framework. From the 427 articles identified, 77 articles met inclusion criteria and underwent full-text screening. Of these, 30 articles were included in the final review, with 16 being quantitative and 14 either qualitative or mixed methods studies. Most studies were conducted with native Indigenous populations from the United States of America (36%). Content analysis revealed that studies either explored genetic variations associated with disease in Indigenous populations (23%) or markers for drug metabolism (30%) or were designed to understand perspectives of genomics research within this population (47%). Perspectives included the exploration of the role of participants in research, benefits or outcomes achieved from participation in genomics research, and levels of Indigenous engagement and participation in genomics research. This review highlights a growing gap in Indigenous genomics research globally. It presents several important considerations from Indigenous participants, identifying how researchers can co-create culturally safe and inclusive design, implementation, analysis, and subsequent outcomes of genomics research involving Indigenous people. Indigenous governance, self-determination and leadership is essential, with researchers required to be responsive to such fundamental partnerships for research to progress.

Swimming exercise regulates indices of skeletal muscle glucose metabolism and attenuates cardiac inflammatory cytokines activity via IL-6/TNF-α pathway in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) manifests with impaired glucose metabolism that affects the musculoskeletal and cardiovascular systems. This study investigated the effects of swimming exercise on some indices of muscle glucose metabolism and cardiac inflammatory markers in diabetic rats induced with streptozotocin. Wistar rats of both sexes (150–200 g) were assigned into five groups of seven (7) rats. Group 1: Control (CON), Group 2: Diabetes only (DM), Group 3: Exercise only (EX), Group 4: Diabetes + Exercise (DM + EX), Group 5: Diabetes + Insulin (DM + IN). Type 1 DM was induced via intraperitoneal injection of streptozotocin (60 mg/kg). Insulin (6 IU/g) was administered (IP) to animals in group 5. Swimming exercise test was done for 27 days after which animals were euthanized. Blood samples were collected while hamstring muscles and heart were harvested and homogenized to assess biochemical parameters. The body weight, serum insulin level, muscle glucose metabolic indices (glycogen, Glut-4, CK-MB), and cardiac troponin-T were significantly (P < 0.05) decreased. In contrast, the random blood glucose, cardiac TNF-α, and IL-6 levels were increased (P < 0.05) in diabetic rats when compared with the control group. Swimming exercise regimen significantly (P < 0.05) reversed these anomalies by reducing blood glucose and cardiac inflammatory cytokines (TNF-α and IL-6) levels, improving serum insulin, muscle glycogen, and GLUT-4 expression in diabetic rats when compared to the DM group. The cardiac inflammatory cytokine levels in DM + EX were comparable to the DM + IN group. In conclusion, swimming exercise improves muscle glucose metabolism and protects the heart against cardiac inflammation in diabetic conditions.

39P Studying markers of metabolism, apoptosis, and necrosis in cullin-3 skeletal muscle knockouts

39P Studying markers of metabolism, apoptosis, and necrosis in cullin-3 skeletal muscle knockouts

Comparison of Denosumab with Romosozumab in the treatment of male osteoporosis: a retrospective cohort study

We aimed to investigate the efficacy of romosozumab treatment compared with that of denosumab in especially male osteoporosis patients. This retrospective cohort study included 174 Japanese male patients receiving either denosumab or romosozumab for 12 months. Propensity score matching extracted 50 patients per treatment group for standardization of group characteristics. The endpoints include the rate of change in the bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck after 12 months of treatment as well as the changes in serum bone metabolism markers. The mean 12-month percentage increase in the lumbar spine BMD from baseline was significantly greater with romosozumab (13.0% ±1.7%) than with denosumab (4.5%±0.6%) (P < 0.01). The total hip and femoral neck BMD exhibited a similar trend at 12 months; however, no significant between-group differences were observed. With denosumab, bone formation, and resorption marker levels significantly decreased at 6 and 12 months. Conversely, with romosozumab, the levels of bone formation markers increased transiently at 6 months before returning to baseline, whereas bone resorption markers significantly decreased at both time points. Romosozumab demonstrated significantly superior effects over denosumab in improving BMD, especially of the lumbar spine, suggesting that romosozumab can be used for treating male osteoporosis.

Dissociation between liver fat content and fasting metabolic markers of selective hepatic insulin resistance in humans.

Fasting hyperglycemia and hypertriglyceridemia are characteristic of insulin resistance (IR) and rodent work has suggested this may be due to selective hepatic IR; defined by increased hepatic gluconeogenesis and de novo lipogenesis (DNL), but this has not been shown in humans. Cross-sectional study in men and women across a range of adiposity. Medication-free participants (n=177) were classified as normoinsulinemic (NI) or hyperinsulinemic (HI) and as having low (LF) or high (HF) liver fat content measured by magnetic resonance spectroscopy. Fractional gluconeogenesis (frGNG) and hepatic DNL were measured using stable isotope tracer methodology following an overnight fast. Although HI and HF groups had higher fasting plasma glucose and triglyceride concentrations when compared to NI and LF groups respectively, there was no difference in frGNG. However, HF participants tended to have lower frGNG than LF participants. HI participants had higher DNL compared to NI participants but there was no difference observed between liver fat groups. Taken together, we found no metabolic signature of selective hepatic IR in fasting humans. DNL may contribute to hypertriglyceridemia in individuals with HI but not those with HF. Glycogenolysis and systemic glucose clearance may have a larger contribution to fasting hyperglycemia than gluconeogenesis, especially in those with HF and these pathways should be considered for therapeutic targeting.

Mapping Age Differences in Brain Energy Metabolites and Metabolic Markers of Cellular Membrane Production and Degradation With 31P Magnetic Resonance Spectroscopy.

Using Phosphorus Magnetic Resonance Spectroscopy (31P MRS), we examined five metabolites associated with brain energy cycle, and cellular membrane production and degradation in 11 brain regions of 48 children (age 6-15), and 80 middle-aged and older adults (age 52-87). Levels of phosphomonoesters (PMEs) and phosphodiesters (PDEs), gamma plus alpha adenosine triphosphate (γαATP), phosphocreatine (PCr) and inorganic phosphate (Pi), were residualized on the total amplitude value. PMEs were greater in children compared to adults, whereas PDEs showed the opposite age difference. Higher γαATP and lower Pi were found in children compared to adults. The age group differences were particularly salient in the association cortices and anterior white matter. Among children, age correlated negatively with PMEs and positively with PDEs in association cortices. Compared to children, adults had lower intracellular pH. The results suggest reduction in membrane synthesis and increase in membrane degradation in adolescents and to a greater degree in adults compared to younger children. Concomitant reduction in γαATP and increase in Pi are consistent with reduced energy consumption in adolescents and further drop in middle-aged and older adults, although it is impossible to distinguish declines in energy supply from reduced demand due to shrinking neuropil, without longitudinal studies.

Association of the Triglyceride-Glucose Index and Related Metabolites with sICAS of the Posterior Circulation

ObjectiveThe triglyceride-glucose index (TyG), a reliable marker of insulin resistance (IR), has an unclear association with symptomatic intracranial atherosclerotic stenosis in the posterior circulation (POC-sICAS). This study aimed to investigate the association between the TyG index, associated metabolites, and POC-sICAS. MethodsA total of 106 patients with POC-sICAS and 81 with asymptomatic intracranial atherosclerotic stenosis of the posterior circulation (POC-aICAS) were retrospectively enrolled. The TyG index was calculated using the formula: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Logistic regression analysis evaluated the correlation between the TyG index and POC-sICAS. Differential metabolic markers were identified using liquid chromatography-tandem mass spectrometry. The predictive value of the TyG index and differential metabolites for POC-sICAS was assessed through receiver operating characteristic (ROC) curve analysis. ResultsPatients with POC-sICAS had a significantly higher TyG index than those with POC-aICAS (9.25 [interquartile range {IQR} 8.79-9.92] vs 8.87 [IQR 8.83-9.26]; P<0.001). The TyG index was an independent risk factor for POC-sICAS (adjusted odds ratio [OR]: 2.20, 95% confidence interval [CI]: 1.09-4.42, P=0.027), particularly in patients with diabetes mellitus (adjusted OR: 14.39, 95% CI: 2.37-87.36, P=0.004). The association was stronger in patients younger than 65 years with a high TyG index (≥8.99) (adjusted OR: 4.35, 95% CI: 1.12-16.94, P=0.034). The TyG index positively correlated with 90-day poor prognosis in those with POC-sICAS (R=0.4042, P=0003), especially in those with diabetes mellitus (R=6405, P<00001) and those younger than 65 years (R=0.4628, P=0002). Moreover, 11 differential metabolites were significantly related to the TyG index. The TyG index combined with pregnanediol showed significant discrimination between patients with POC-sICAS and POC-aICAS (area under the curve [AUC]=1, 95% CI 1.000-1.000; P<0.001). ConclusionsThe TyG index and pregnanediol could help identify patients with a high risk of ischemic stroke in POC-ICAS. Moreover, the TyG index was associated with a poor 90-day prognosis in patients with POC-sICAS.

Association of serum lipid profile with liver fibrosis in HCV‑coinfected HIV patients on suppressive anti‑retroviral therapy.

Hepatitis C virus (HCV) coinfection in individuals living with human immunodeficiency virus (HIV) (PLWH) may affect lipid metabolism and accelerate the progression of chronic hepatitis. Therefore, the identification of risk factors for progressive liver disease is needed. The present study aimed to examine the prevalence and clinical features associated with liver fibrosis in HCV-coinfected HIV patients, including metabolic markers. A total of 105 patients coinfected with HIV and HCV were recruited and liver fibrosis was assessed using the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI). Logistic regression analyses indicated that patients aged >50 years and with a CD4+ cell count <350 cells/µl had an 11.4-times higher (P=0.001) and a 5.7-times higher (P=0.017) risk of liver fibrosis, as determined by FIB-4 score, compared to patients aged ≤40 years and a CD4+ cell count of ≥350 cells/µl, respectively. In addition, patients naïve to HCV treatment or receiving treatment had 5.4- and 12.7-times higher risks for liver fibrosis, as determined by APRI, than those with sustained virologic response (SVR) (P=0.003 and P=0.033, respectively). Univariate analysis indicated lower risks of liver fibrosis, as determined by APRI, in the patients with abnormally high levels of cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) than those with normal levels [odds ratio (OR) 0.3, 95% confidence interval (CI) 0.1-0.9, P=0.037; OR 0.4, 95% CI 0.2-0.9, P=0.041; OR 0.2, 95% CI 0.1-0.5, P=0.001] and multivariate analysis suggested only patients with high levels of LDL had a lower risk for liver fibrosis determined by APRI (OR 0.1, 95% CI 0.3-0.8, P=0.029). Consistently, serum levels of cholesterol, HDL and LDL were significantly lower in the patient groups with more advanced fibrosis, evaluated by FIB-4 score and APRI, than those without liver fibrosis and the levels of cholesterol and LDL in the patients achieving SVR were higher than those with no response or not receiving treatment (all P<0.05). In conclusion, the present study identified serum lipid levels as associated factors of hepatic fibrosis, together with age, CD4+ cell count and HCV treatment status, in HCV-coinfected PLWH on long-term suppressive anti-retroviral therapy.

Multi-omics and bioinformatics for the investigation of therapeutic mechanism of roucongrong pill against postmenopausal osteoporosis

Ethnopharmacological relevanceThe Roucongrong Pill (RCRP), originating from the historical General Medical Collection of Royal Benevolence, is frequently used to treat postmenopausal osteoporosis (PMOP). Despite its prevalent application, the specific anti-osteoporotic mechanisms of RCRP remain to be elucidated. Aim of the studyThis study aims to elucidate the therapeutic mechanism of RCRP in the context of ovariectomy (OVX)-induced PMOP in rats. By employing an integrative approach, the research combines medicinal chemistry, gut microbiota (GM) profiling, metabolomics, MetOrigin traceability, network pharmacology, molecular docking, and molecular dynamics simulations to deliver a comprehensive analysis. Materials and methodsSprague-Dawley (SD) rats underwent bilateral OVX to establish a PMOP model. The therapeutic efficacy of RCRP was evaluated through bone metrics (BMD, bone strength, BV/TV, Tb.Sp), hematoxylin and eosin (H&E) histological assessment, and bone metabolism markers (OPG, BALP, TRACP-5b, β-CTX, RANKL). Fecal metabolomics and 16S rDNA sequencing were employed to assess the influence of RCRP on GM and metabolite profiles. Furthermore, MetOrigin facilitated the traceability analysis of relevant metabolites. Molecular docking identified potential RCRP compounds with anti-PMOP activity, while their stability and protein interactions were assessed through molecular dynamics simulations. Network pharmacology further confirms the targets of action. ResultsRCRP alleviated PMOP in rats, enhancing bone strength, cortical and trabecular BMD, BV/TV, and serum OPG levels, while reducing Tb.Sp, serum BALP, TRACP-5b, β-CTX, and RANKL concentrations. A total of twenty-six distinct metabolites were identified, of which ten—tribufos, sulfoacetic acid, betamethasone dipropionate, 9-oxooctadeca-10,12,15-trienoic acid, menatetrenone, piperlongumine, maltopentaose, enol-phenylpyruvate, catechol, pentaacetate, and (+)-2-methylpropanoic acid—exhibited correlations with six GM species: Turicibacter, Roseburia, Colidextribacter, Helicobacter, Odoribacter, and Lachnoclostridium, as determined by Spearman's correlation analysis. Notably, MetOrigin revealed the microbial metabolism of taurine and hypotaurine, along with host-specific steroid hormone synthesis. Computational docking studies demonstrated robust interactions between five RCRP-derived steroids (hydroxyecdysone, corticosterone, trilostane, 5α-androstan-3,6,17-trione, and cortisol) and key enzymes (estradiol 17α-dehydrogenase and UDP-glucuronosyltransferase), suggesting a potential enhancement of therapeutic efficacy against PMOP. Furthermore, molecular dynamics simulations indicated stable interactions between hydroxyecdysone and two proteins, with binding free energies of −67.427 kJ/mol and −156.948 kJ/mol, respectively. Through network pharmacology and molecular docking approaches, potential targets of these metabolites were identified, including estrogen receptors ESR1 and ESR2, dual specificity phosphatase 6 (DUSP6), sex hormone-binding globulin (SHBG), prostaglandin E receptor 4 (PTGER4), cannabinoid receptor 2 (CNR2), cathepsin K (CTSK), and androgen receptor (AR). ConclusionsRCRP effectively mitigates OVX-induced bone loss in PMOP rats by modulating GM and associated metabolites, along with their potential targets and key metabolic pathways, including taurine and hypotaurine metabolism, as well as steroid hormone biosynthesis. These findings offer new insights into the therapeutic mechanisms by which RCRP may alleviate PMOP.

Mass spectrometry unveils heat-induced changes in yolk oxylipins and key lipid molecules during home cooking

IntroductionOxylipins, as a widespread class of metabolic markers following oxidative stress, and several studies have reported dietary regulation of lipid metabolism. However, there is a lack of investigation of dietary oxylipins, especially cooking-induced changes in food lipid oxidation. ObjectivesInvestigated the effects of cooking methods and lipid profiles on polyunsaturated fatty acids derived oxylipins generation within egg yolks. MethodsThe lipid profile of egg yolk was determined by UPLC-QTOF-MS/MS, oxylipins were detected by HPLC-QTRAP-MS/MS, while the total fatty acid content was quantified by GC-FID. Random Forest (RF) and Partial Least Squares (PLS) regression models were employed to explore the association between oxidized lipids and key lipid species. ResultsHeating reduced egg yolk docosahexaenoic acid (DHA) content, and no consistent trends for arachidonic acid (AA), linoleic acid (LA), and linolenic acid (ALA). Yolk lipid composition affected triacylglycerol (TG), phosphatidylethanolamine (PE), and LA-monoepoxide contents after cooking. 9- and 13-HODE (hydroxyoctadecadienoic acid), 9,10,13-TriHOME (trihydroxyoctadecenoic acid), 9,10- and 12,13-EpOME (epoxyoctadecenoic acid), 9,10- and 12,13-DiHOME (dihydroxyoctadecenoic acid), 5-HETE (hydroxyeicosatetraenoic acid), and 4-HDHA (hydroxydocosahexaenoic acid) were the prevalent oxylipins with high concentrations, accounting for 1.08 %–29.58 % of the total content of 29 oxylipins. Steaming resulted in a 1.9-fold increase in oxylipin concentrations in yolks compared to raw yolks, and boiling with or without shells (poaching) resulted in a 1.30- to 1.76-fold increase in oxylipin concentrations. In contrast, pan-fried yolks exhibited the lowest and least variable levels of total oxylipins, while still retaining some epoxides, including epoxyeicosatrienoic acid (EET) and EpOME. Utilizing big data analysis, we mapped the oxylipin network in both ordinary and DHA-enriched egg yolks, revealing a strong correlation between cooking-induced oxylipin production and variations in 24 lipid species. ConclusionRevealed the potential mechanisms and key lipid molecules for heating-induced oxylipin production of yolk through lipidomics and big data analysis.

White rot fungi as a multifaceted biocontrol agent: Metabolic disruption and algal inhibition in Microcystis aeruginosa

Microcystis aeruginosa is a prevalent cyanobacterium linked to water eutrophication and harmful algal blooms. While bacterial control strategies are well-studied, the effects of white rot fungi on Microcystis aeruginosa are less understood. This study examines the impact of whole fungal liquid, its centrifuged supernatant, and sterilized solutions on the algae’s physiological and biochemical traits. Metabolomics and multivariate analysis identified significant changes in 47 metabolic markers, including carbohydrates, amino acids, and fatty acids, across treatments. The complete fungal liquid exhibited the strongest algicidal effect, likely due to synergistic solubilization mechanisms mediated by extracellular enzymes such as manganese peroxidase, catalase, and laccase. Notably, algicidal activity persisted even after sterilization, suggesting the presence of non-proteinaceous compounds like polysaccharides or lipids. The metabolic disturbances included downregulation of the TCA cycle and reduced fatty acid synthesis, leading to inhibited photosynthesis and compromised nucleic acid integrity in the algal cells. This research enhances our understanding of how white rot fungi disrupt Microcystis aeruginosa metabolism, providing a theoretical basis for their potential use in bioremediation of eutrophic aquatic environments.

Interplay of Adiponectin With Glycemic and Metabolic Risk Metrics in Patients With Diabetes.

Background Type 2 diabetes mellitus (T2DM) is characterized by low insulin production or resistance. Adiponectin, a hormone produced by adipocytes, is essential for regulating glucose metabolism and is correlated with insulin decrease. Aim The aim of this study is to estimate the levels of adiponectin in T2DM patients and their relationship with various metabolic markers (glycated hemoglobin (HbA1c), fasting blood sugar (FBS), fasting insulin, lipid profile, and anthropometric variables in an Indian cohort. Methods This study was conducted at King George's Medical University (KGMU), India, from October 2022 to October 2024. The study (case-control)included 234 subjects: T2DM patients and age-sex-matched healthy controls. Diagnosis of T2DM followedAmerican Diabetes Association criteria. Data collection involved medical history, anthropometric measurements, blood pressure, and biochemical assessments including FBS, HbA1c, lipid profiles, insulin levels, and insulin resistance. Serum adiponectin levels were estimated using an ELISA kit. Results T2DM patients had a significantly higher HbA1c value (7.82±0.96%) compared to controls (5.31±0.39%, p<0.001). Insulin resistance was also significantly higher in T2DM patients (4.31±0.95) than in controls (3.62±0.82, p=0.002). Adiponectin levels were significantly lower in T2DM patients (6.87±3.73 µg/mL) compared to controls (10.18±5.16 µg/mL, p<0.001). Low levels of adiponectin were correlated with HbA1c (r=-0.58, p<0.001), FBS (r=-0.51, p<0.001), and total cholesterol (r=0.38, p<0.001). Adiponectin levels also were correlated with BMI (r=-0.33, p<0.001). Conclusion Lower adiponectin levels in T2DM patients correlate with HbA1c and increased insulin resistance, suggesting that adiponectin may be a biomarker for diabetes management and risk assessment.