Lipid Levels Research Articles

Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Reduces Fat Deposition in Obese Mice by Remodeling the Gut Microbiota

A methionine-restricted diet (MRD) has been shown to reduce body fat deposition and improve obesity-associated metabolic disorders, with emerging evidence implicating the gut microbiota in mediating these effects. This study investigated the effects and underlying mechanisms of fecal microbiota transplantation (FMT) from MRD mouse donors on body fat deposition in obese mice. Five-week-old male C57BL/6J mice were continuously fed a high-fat diet (HFD, 0.86% methionine + 24% fat) to induce obesity, and then randomly divided into three groups. These groups received FMT from 23-week-old male C57BL/6J mice donors continuously fed with normal diet (0.86% methionine + 4.2% fat), HFD, or MRD (0.17% methionine + 24% fat) for eight weeks, respectively. Our results indicate that FMT from MRD mouse donors reduced body weight, plasma lipid levels, and percentage fat mass. Moreover, FMT from MRD mouse donors elevated the abundance of short-chain fatty acid (SCFA)-producing bacteria while decreasing pro-inflammatory bacteria levels in cecal contents. In addition, systemic metabolic processes were altered, featuring heightened SCFA production and enhanced energy metabolism. FMT from MRD mouse donors further facilitated fat catabolism, inhibited fat anabolism, and decreased lipid levels and lipid accumulation in liver. Meanwhile, FMT from MRD mouse donors also promoted fat browning, decreased adipocyte volume, and reduced fat deposition in adipose tissues. These findings underscore the potential of FMT from MRD mouse donors to improve the gut microbiota and reduce body fat deposition in obese mice. Importantly, our results elucidate that MRD intervention in obesity is, in part, mediated by regulating intestinal microbial composition.

Altering plasma lipids and liver enzyme activities via hippocampal injections of hen Lysozyme amyloid aggregates in an Alzheimer's disease mouse model: Insights into the therapeutic role of Bis (Indolyl) phenylmethane.

Alzheimer's disease (AD) is a prevalent form of dementia in the elderly. There is currently no effective treatment available for this disease. Diagnosis of AD typically relies on clinical manifestations and specific biomarkers. The present study investigated the impact of inducing Alzheimer's disease (AD) in mice through the injection of lysozyme amyloids formed in the presence or absence of Bis (Indolyl) phenylmethane (BIPM) on alterations in plasma lipid profiles and liver enzyme activities. 24 adult Wistar rats were divided into control, Scopolamine, Lysozyme, BIPM groups and the blood samples were obtained from the groups for biochemical analysis. The findings of the study revealed significant changes in the plasma lipid profiles and liver enzyme markers of the Lysozyme group compared to the control group. The Lysozyme group exhibited elevated triglycerides (n=6, P<0.02) and LDL levels (n=6, P<0.02), reduced HDL (n=6, P<0.05) and cholesterol levels (n=6, P<0.02), and altered serum glutamic oxaloacetic transaminase (SGOT) level (n=6, P<0.05) compared to controls. While the level of serum glutamic pyruvic transaminase (SGPT) did not change significantly compared to the control. BIPM groups showed no significant changes in lipid or enzyme levels compared to controls. Overall, our research has shown that BIPM has the ability to modify the structure of HEWL aggregates, thereby improving the detrimental effects associated with AD caused by these aggregates. Analyzing lipid profiles and liver enzyme markers presents a promising avenue for targeted therapeutic approaches. These alterations observed in the plasma may potentially serve as candidate biomarkers for diagnosing this disease.

Evaluation of Flavonoid-rich Fraction of Portulaca Grandiflora Aerial Part Extract in Atherogenic Diet-induced Atherosclerosis.

Portulaca grandiflora is a tiny, upright herb that contains a variety of chemical components, including alkaloids, glycosides, mucilage, proteins, tannins, flavonoids, saponins, polysaccharides, and triterpenoids possessing properties that may help with atherosclerosis. The reported pharmacological properties of Portulaca grandiflora are antioxidant, antidiabetic, antiasthmatic, antibacterial, antiulcer and anti-inflammatory properties. The yield of methanol extract is higher than that of ethanol and acetone, and its phytoconstituents, like flavonoids and polyphenols, and has potent antioxidant properties. In order to determine the effectiveness ofPortulaca grandiflora methanol extract fraction against high-fat diet (HFD)-induced hyperlipidemia, hemodynamic change, antioxidant levels, and vascular dysfunction in rats, a study was carried out on a flavonoid-rich methanol extract fraction of the aerial part of Portulaca grandiflora Hook. This method involves a study of 30 days involving male Wistar rats (240-250 g) (n=5) that were fed with an Ath diet. Study groups were divided into (i) The Control Group, (ii) the Diseases Control Group, (iii) Disease + Standard drug (Atorvastatin 20mg/kg, orally, (iv) Disease + Test Extract dose 1 (Portulaca grandiflora 200mg/kg orally), and (v) Disease + Test Extract dose 2 (Portulaca grandiflora 400mg/kg orally). Both the test drug Portulaca grandiflora and the standard drug Atorvastatin were given orally for 30 days. At the end of the study, blood samples were taken to measure the serum lipid profile, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and levels of oxidative tissue stress. Hemodynamic parameters and aortic staining were performed. Portulaca grandiflora treatment improved the lipid profile and considerably reduced oxidative stress levels. Aortic staining examination revealed a marked reduction in atherosclerotic lesions. These results revealed that Portulaca grandiflora is an effective treatment approach in preventing atherosclerotic lesion progression, which is attributed to its protection against oxidative stress and various enzymatic activities in the Atherogenic model.

A nutrition intervention study’s effect to hematology profiles on elderly group in social retirement home

The increase in the elderly brings consequences, including a higher risk of disease. Inappropriate nutritional intake is also known as one of the risk factors related to the elderly's non-communicable diseases, and nutritional intervention is essential to improve the elderly nutritional status and quality of life. It was an interventional study with a before-after one-group approach. The study was conducted for three months (October-December 2021) in three social retirement homes. The intervention given was supplementation with additional protein sources and snacks each day. The biochemistry profiles were taken 2 times: before and after three months of intervention, comprised of HbA1c, lipid, transferrin, creatinine, and blood pressure level. The data will be analyzed for its normality before being processed with paired t-test or Wilcoxon signed rank based on the normality results. The analysis results show that there are significantly lower transferrin levels (p=0.040), an increase in cholesterol level (p=0.000), and low-density lipoprotein (LDL) level increased from 114.05±32.03 to 125.94±31.41 (p=0.000). There is also a remarkable decrease in hemoglobin (p=0.005) and high-density lipoprotein (HDL) levels. Conversely, there are an increase in HbA1C (p=0.007) and triglyceride level (p=0.005). There is no significant difference in creatinine level. We conclude that nutrition interventions have a significant effect on elderly blood profiles. However, to achieve an improvement, the study should consider physical activity and other variables that might be altering the results.

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway

Background:: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. Methods:: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. Results:: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. Conclusion:: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

The association between telomere length and blood lipids: a bidirectional two-sample Mendelian randomization study

BackgroundObservational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa.MethodsWe obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.ResultsIn the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (β=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (β=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (β=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (β=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10–5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).ConclusionsOur study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.

Epigenetic age acceleration is associated with blood lipid levels in a multi-ancestry sample of older U.S. adults.

Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia. We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = 2,531) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids. After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05), although the effect sizes were relatively small (e.g., < 7mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment. Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages.

Risk Factors for Pelvic Organ Prolapse: Wide-Angled Mendelian Randomization Analysis.

We hypothesized that some metabolic factors, lifestyle factors, and socioeconomic factors may have a causal effect on pelvic organ prolapse (POP). We selected instruments from corresponding genome-wide association studies (GWAS), which identified independent single nucleotide polymorphisms strongly associated with 12 potential risk factors. Summary statistics for POP were derived from two GWAS datasets, serving for discovery and replication stage. The primary analysis involved the use of the inverse-variance weighting mendelian randomization (MR) method, with additional sensitivity MR analyses conducted. The univariable mendelian randomization (UVMR) analysis in both the discovery and replication stage provided evidence for significant causal effects between higher waist-to-hip ratio adjusted for body mass index (WHRadjBMI) levels, lower high-density lipoprotein cholesterol (HDL-C) levels, and lower educational attainment and higher POP risk, as well as a suggestive positive causal effect between triglycerides and POP. The multivariable mendelian randomization (MVMR)analysis showed that only HDL-C among the three blood lipid fractions could reduce the risk of POP. Mediation analysis indicated that HDL-C may partially mediate the effect of WHRadjBMI on POP risk, and the causal effect between educational attainment and POP may be mediated through WHRadjBMI and HDL-C. Our study's evidence supported a causal relationship between WHRadjBMI, triglycerides, HDL-C, educational attainment, and POP risk. This highlights that clinicians may guide the general female population to control obesity and blood lipid levels to reduce the risk of POP.

Assessment of post-myocardial infarction lipid levels and management: Results from a tertiary care hospital of Pakistan

BACKGROUND Lipid treatment practices and levels in post-acute myocardial infarction (AMI) patients, which are crucial for secondary prevention. AIM To evaluate the lipid treatment practices and lipid levels in post-myocardial infarction (MI) patients at a tertiary care hospital in Pakistan. METHODS In this cross-sectional study, we analyzed patients who had experienced their first AMI event in the past 3 years. We assessed fasting and non-fasting lipid profiles, reviewed statin therapy prescriptions, and examined patient compliance. The recommended dose was defined as rosuvastatin ≥ 20 mg or atorvastatin ≥ 40 mg, with target total cholesterol levels set at &lt; 160 mg/dL and target low-density lipoprotein cholesterol (LDL-C) at &lt; 55 mg/dL. RESULTS Among 195 patients, 71.3% were male, and the mean age was 57.1 ± 10.2 years. The median duration since AMI was 36 (interquartile range: 10-48) months and 60% were diagnosed with ST-segment elevation MI. Only 13.8% of patients were advised to undergo lipid profile testing after AMI, 88.7% of patients were on the recommended statin therapy, and 91.8% of patients were compliant with statin therapy. Only 11.5% had LDL-C within the target range and 71.7% had total cholesterol within the target range. Hospital admission in the past 12 months was reported by 14.4%, and the re-admission rate was significantly higher among non-compliant patients (37.5% vs 5.6%). Subsequent AMI event rate was also significantly higher among non-compliant patients (43.8% vs 11.7%). CONCLUSION Our study highlights that while most post-AMI patients received the recommended minimum statin therapy dose, the inadequate practice of lipid assessment may compromise therapy optimization and raise the risk of subsequent events.

Mass Spectrometry Imaging Reveals the Morphology-Dependent Toxicological Effects of Nanosilvers on Multiple Organs of Adult Zebrafish (Danio rerio).

Nanosilvers with multifarious morphologies have been extensively used in many fields, but their morphology-dependent toxicity toward nontarget aquatic organisms remains largely unclear. Herein, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the toxicological effects of silver nanomaterials with various morphologies on spatially resolved lipid profiles within multiple organs in adult zebrafish, especially for the gill, liver, and intestine. Integrated with histopathology, enzyme activity, accumulated Ag contents and amounts, as well as MSI results, we found that nanosilvers exhibit morphology-dependent nanotoxicity by disrupting lipid levels and producing oxidative stress. Silver nanospheres (AgNSs) had the highest toxicity toward adult zebrafish, whereas silver nanoflakes (AgNFs) exhibited greater toxicity than silver nanowires (AgNWs). Levels of differential phospholipids, such as PC, PE, PI, and PS, were associated with nanosilver morphology. Notably, we found that AgNSs induced greater toxicity in multiple organs, such as the brain, gill, and liver, while AgNWs and AgNFs caused greater toxicity in the intestine than AgNSs. Lipid functional disturbance and oxidative stress further caused inflammation and membrane damage after exposure to nanosilvers, especially with respect to sphere morphology. Taken together, these findings will contribute to clarifying the toxicological effects and mechanisms of different morphologies of nanosilvers in adult zebrafish.

Risk factors and prediction of hypoglycaemia using the Hypo-RESOLVE cohort: a secondary analysis of pooled data from insulin clinical trials.

The objective of the Hypoglycaemia REdefining SOLutions for better liVES (Hypo-RESOLVE) project is to use a dataset of pooled clinical trials across pharmaceutical and device companies in people with type 1 or type 2 diabetes to examine factors associated with incident hypoglycaemia events and to quantify the prediction of these events. Data from 90 trials with 46,254 participants were pooled. Analyses were done for type 1 and type 2 diabetes separately. Poisson mixed models, adjusted for age, sex, diabetes duration and trial identifier were fitted to assess the association of clinical variables with hypoglycaemia event counts. Tree-based gradient-boosting algorithms (XGBoost) were fitted using training data and their predictive performance in terms of area under the receiver operating characteristic curve (AUC) evaluated on test data. Baseline models including age, sex and diabetes duration were compared with models that further included a score of hypoglycaemia in the first 6 weeks from study entry, and full models that included further clinical variables. The relative predictive importance of each covariate was assessed using XGBoost's importance procedure. Prediction across the entire trial duration for each trial (mean of 34.8 weeks for type 1 diabetes and 25.3 weeks for type 2 diabetes) was assessed. For both type 1 and type 2 diabetes, variables associated with more frequent hypoglycaemia included female sex, white ethnicity, longer diabetes duration, treatment with human as opposed to analogue-only insulin, higher glucose variability, higher score for hypoglycaemia across the 6 week baseline period, lower BP, lower lipid levels and treatment with psychoactive drugs. Prediction of any hypoglycaemia event of any severity was greater than prediction of hypoglycaemia requiring assistance (level 3 hypoglycaemia), for which events were sparser. For prediction of level 1 or worse hypoglycaemia during the whole follow-up period, the AUC was 0.835 (95% CI 0.826, 0.844) in type 1 diabetes and 0.840 (95% CI 0.831, 0.848) in type 2 diabetes. For level 3 hypoglycaemia, the AUC was lower at 0.689 (95% CI 0.667, 0.712) for type 1 diabetes and 0.705 (95% CI 0.662, 0.748) for type 2 diabetes. Compared with the baseline models, almost all the improvement in prediction could be captured by the individual's hypoglycaemia history, glucose variability and blood glucose over a 6 week baseline period. Although hypoglycaemia rates show large variation according to sociodemographic and clinical characteristics and treatment history, looking at a 6 week period of hypoglycaemia events and glucose measurements predicts future hypoglycaemia risk.

Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63–0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.

Unlocking the Nutraceutical Potential of Legumes and Their By-Products: Paving the Way for the Circular Economy in the Agri-Food Industry

Legumes, including beans, peas, chickpeas, and lentils, are cultivated worldwide and serve as important components of a balanced and nutritious diet. Each legume variety contains unique levels of protein, starch, fiber, lipids, minerals, and vitamins, with potential applications in various industries. By-products such as hulls, rich in bioactive compounds, offer promise for value-added utilization and health-focused product development. Various extraction methods are employed to enhance protein extraction rates from legume by-products, finding applications in various foods such as meat analogs, breads, and desserts. Moreover, essential fatty acids, carotenoids, tocols, and polyphenols are abundant in several residual fractions from legumes. These bioactive classes are linked to reduced incidence of cardiovascular diseases, chronic inflammation, some cancers, obesity, and type 2 diabetes, among other relevant health conditions. The present contribution provides a comprehensive review of the nutritional and bioactive composition of major legumes and their by-products. Additionally, the bioaccessibility and bioavailability aspects of legume consumption, as well as in vitro and in vivo evidence of their health effects are addressed.

Effects of Drying Methods on Morphological Characteristics, Metabolite Content, and Antioxidant Capacity of Cordyceps sinensis

Cordyceps sinensis is a rare and endangered medicinal herb in China and a typical medicinal and food plant. Most of the research related to Cordyceps sinensis focuses on its pharmacological effects, artificial cultivation and clinical applications. However, there are few comprehensive evaluations on the quality of Cordyceps sinensis under different drying methods. In this study, the effects of vacuum freeze-drying (DG), oven-drying (HG) and air-drying (YG) on the morphological characteristics, microstructure, antioxidant activity and metabolites of Cordyceps sinensis were investigated using wild Cordyceps sinensis as the research object. The results showed that in their appearance and morphology, the YG- and HG-method Cordyceps sinensis samples were darker in color and wilted, while the DG- method Cordyceps sinensis samples were golden yellow in color and had better fullness. In terms of microstructure, the stomata of the YG and HG method Cordyceps sinensis samples were relatively small and irregularly shaped, whereas those of the DG method Cordyceps sinensis samples were larger and neat. In terms of antioxidant capacity, the HG-method samples were the lowest, followed by the YG group, and the DG group had the highest total antioxidant capacity. A correlation analysis revealed a significant relationship between antioxidant capacity and lipids, lipid molecules, nucleosides, nucleotides, and analogs. A metabolomics analysis identified 1937 metabolites from 18 superclasses, with lipids, lipid-like molecules, organic acids and derivatives, organoheterocyclic compounds, and organic oxygen compounds being the predominant metabolites in Cordyceps sinensis. Differentially accumulated metabolites (DAMs) in DG samples showed higher levels of lipids and lipid molecules, organic oxygen compounds, organic acids and derivatives, and organoheterocyclic compounds compared to the other drying methods, suggesting DG as the optimal preservation method for Cordyceps sinensis. These findings offer insights for selecting appropriate drying methods and maintaining the post-drying quality of Cordyceps sinensis.

Hexadecanoic acid produced in the co-culture of S. cerevisiae and E.coli promotes oxidative stress tolerance of the S.cerevisiae cells.

Co-fermentation performed by Saccharomyces cerevisiae and Escherichia coli or other microbes has been widely used in industrial fermentation. Meanwhile, the co-cultured microbes might regulate each other's metabolisms or cell behaviors including oxidative stress tolerance through secreting molecules. Here, results based on the co-culture system of S. cerevisiae and E. coli suggested the promoting effect of E. coli on the oxidative stress tolerance of S. cerevisiae cells. The co-cultured E. coli could enhance S. cerevisiae cell viability through improving its membrane stability and reducing the oxidized lipid level. Meanwhile, promoting effect of the co-cultured supernatant on the oxidative stress tolerance of S. cerevisiae illustrated by the supernatant substitution strategy suggested that secreted compounds contained in the co-cultured supernatant contributed to the higher oxidative stress tolerance of S. cerevisiae. The potential key regulatory metabolite (i.e., hexadecanoic acid) with high content difference between co-cultured supernatant and the pure-cultured S. cerevisiae supernatant was discovered by GC-MS-based metabolomics strategy. And exogenous addition of hexadecanoic acid did suggest its contribution to higher oxidative stress tolerance of S. cerevisiae. Results presented here would contribute to the understanding of the microbial interactions and provide the foundation for improving the efficiency of co-fermentation performed by S. cerevisiae and E. coli.

Effects of metformin on the glucose regulation, lipid levels and gut microbiota in high-fat diet with streptozotocin induced type 2 diabetes mellitus rats.

Metformin, an anti-diabetic drug, regulates blood glucose by affecting gut microbiotas. However, the potential mechanism underlying this effect remains unclear. This study aimed to evaluate the effect of metformin on glucose regulation, lipid levels, and the gut microbiota in rats with type 2 diabetes mellitus induced by a high-fat diet with streptozotocin. Thirty Wistar rats was using in this experiment. T2DM rats were administered 300 mg/kg metformin for 8 weeks. The glucose regulation, lipid levels, organ coefficients, and gut microbiotawere measured by 16S rDNA. The metformin-gavaged rats exhibited significant improvements in blood glucose and serum lipid levels, accompanied by alterations in short-chain fatty acid levels and the intestinal microbiota (p < 0.05). In the diabetic rats, metformin potentially increased specific probiotics, thus improving the hypoglycaemic effects of the oral anti-diabetic drug. Further, damage to the liver and kidney was effectively alleviated in the metformin-gavaged rats. This study's findings demonstrate that metformin exerts a positive anti-diabetic effect in HFD- and STZ-induced T2DM rats. These findings potentially provide a basis for the recommended use of metformin as a reliable oral drug for T2DM owing to its positive effect on the intestinal microbiota.

#2124 Accuracy and interferences in the T50 test: assessing the reliability of a novel diagnostic tool

Abstract Background and Aims A novel blood-based in vitro diagnostic test determines the calcification propensity in patients, e.g. chronic kidney disease (CKD) patients. This assay is known as the ‘T50 test’ and is based on the one-half maximal transition time (T50; minutes) of calciprotein particle 1 (CPP1) to calciprotein particle 2 (CPP2) in serum (Fig. 1). Numerous studies have associated a lower T50 with cardiovascular and all-cause mortality in chronic kidney disease (CKD) patients at stages 3, 4 and 5, kidney transplant recipients, and in the general population. To date, the T50 test has been performed at a single site (Calciscon AG, Biel, Switzerland). The aim of this study was to determine the accuracy of the T50 test. Additionally, the effect of haemolysis, hyperbilirubinemia and lipidemia interferences on the T50 was studied and compared to the manufacturer's claims. Method The T50 was measured using T50 test kits and according to the protocol of Calciscon AG using an automatic pipetting machine (EVOware Freedom, Tecan) and a nephelometer (NEPHELOstar, BMG). Patient serum samples were spiked with haemoglobin, bilirubin, or lipids (triglyceride) for the interference analysis. In total, three dilution series with interferences and four additional non-spiked patient serum samples were included (n = 32). The T50 of all samples were measured at two laboratory sites: Amsterdam UMC (Amsterdam, The Netherlands) and Calciscon AG. Data were statistically analysed for accuracy using the Passing Bablok regression and the Bland Altman plot. Interference was established with deviations &amp;gt;10% in T50 compared to the control sample. Results The measurements of all samples at both sites were similar with a mean bias of 0.24% (±4.84%) and a great agreement was found (slope = 1.012; 95% CI [0.931 to 1.107]) (Table 1). Interference was observed at higher levels of haemoglobin and triglyceride with concentrations of at least 0.1 g/dL and 1124.8 mg/dL, respectively. The triglyceride interference is in agreement with the manufacturer's claim (&amp;gt;1000 mg/dL) in contrary to haemoglobin (&amp;gt;0.3 g/dL). No interference was detected for bilirubin with concentrations up to 59.8 mg/dL. Conclusion The accuracy of the T50 test was high with nearly identical T50 results between two laboratory sites. Furthermore, no interference was observed within usual clinical ranges of haemoglobin, bilirubin, and lipid levels. Interference was present at extremely high values only.

TSH Trajectories During Levothyroxine Treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort.

Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time. This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period. Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes. GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.

Tartaric acid ameliorates experimental non-alcoholic fatty liver disease by activating the AMP-activated protein kinase signaling pathway

Tartaric acid (TA) has been shown beneficial effects on blood pressure and lipid levels. However, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. This study aimed to investigate the role of TA in experimental NAFLD. Mice were fed a Western diet for 8 weeks, followed by administration of TA or a vehicle for an additional 12 weeks while continuing on the Western diet. Blood biochemistry including transaminases and glucose tolerance test and liver tissue RNA sequencing (RNA-seq), lipid content, and histology were investigated. The HepG2 cell line was used to explore the mechanism by which TA regulates lipid metabolism. We found that TA significantly improved weight gain, insulin resistance, hepatic steatosis, inflammation and fibrosis in Western diet-fed mice. By comparing gene expression differences, we found that TA affects pathways related to lipid metabolism, inflammatory response, and fibrosis. Furthermore, TA effectively reduced oleic acid-induced lipid accumulation in HepG2 cells and downregulated the genes associated with fatty acid synthesis, which were enriched in the AMP-activated protein kinase (AMPK) signaling pathway. TA also enhanced the phosphorylation of AMPK which could be reverted by the AMPK inhibitor Compound C in HepG2 cells. Our study suggests that TA improves experimental NAFLD by activating the AMPK signaling pathway. These findings indicate that TA may serve as a potential therapy for the human NAFLD.

Puerarin alleviates acrolein-induced atherosclerosis by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit the activation of inflammasome.

Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK-8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr-fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome-related proteins, and the inhibition of MYH9 significantly impaired Pue-induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3-mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr-induced AS by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation.