Serum Low-density Lipoprotein Cholesterol Levels Research Articles

Serum Low-Density Lipoprotein Cholesterol Levels are Associated with Relapse in Neuromyelitis Optica Spectrum Disorder.

The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients. We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan-Meier Plot. Over a mean disease course of 100±87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) (p<0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse (p< 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76-4.04, p<0.001), and 2.38 (1.48-3.83, p<0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795mmol/L with potential benefits to prevent relapse in NMOSD. In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD.

CYP2C19 loss-of-function variants are independent risk factors for premature cerebral infarction: a hospital based retrospective study

ObjectiveCytochrome P450 2C19 (CYP2C19) plays an vital role in the course of cardiovascular and cerebrovascular diseases by affecting lipid metabolism. Triglyceride-glucose (TyG) is a comprehensive index composed of triglyceride and blood glucose, has relationship with some diseases. There was no research report on the association CYP2C19 polymorphisms, TyG with premature cerebral infarction (CI) (onset ≤ 65 years old) susceptibility.MethodsThis study retrospectively analyzed 1953 CI patients aged ≤ 65 years old from December 2018 to March 2024, and 1919 age-matched individuals with non-CI as controls. The relationship between CYP2C19 polymorphisms, TyG and premature CI risk were analyzed.ResultsThe proportion of hypertension, and diabetes mellitus in patients with premature CI was higher than those in controls. The serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and TyG levels in patients with premature CI were significantly higher than those in controls (all p < 0.05). The patients had lower CYP2C19 *1 allele frequency (63.3% vs. 69.6%, p < 0.001) and higher CYP2C19 *2 allele frequency (31.3% vs. 25.4%, p < 0.001) than controls. Logistic regression analysis showed that smoking history (odds ratio (OR): 1.193, 95% confidence interval (CI): 1.002–1.422, p = 0.048), hypertension (OR: 3.371, 95% CI: 2.914–3.898, p < 0.001), diabetes mellitus (OR: 1.911, 95% CI: 1.632–2.237, p < 0.001), CYP2C19 intermediate metabolizer (IM) + poor metabolizer (PM) phenotypes (OR: 1.424, 95% CI: 1.243–1.631, p < 0.001), and dyslipidemia (OR: 1.294, 95% CI: 1.077–1.554, p = 0.006) were independent risk factors for premature CI.ConclusionsHistory of smoking, hypertension, diabetes mellitus, dyslipidemia, and CYP2C19 IM + PM phenotypes were independently associated with premature CI susceptibility.

SHR-1918, a monoclonal antibody against angiopoietin-like 3, in healthy subjects: a randomized, double-blind, placebo-controlled, phase 1 study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) are important risk factors for atherosclerotic cardiovascular disease. Angiopoietin-like 3 (ANGPTL3) is involved in the regulation of lipid metabolism and can increase serum TG and LDL-C levels by reducing their clearance. SHR-1918 is an ANGPTL3 monoclonal antibody developed to inhibit ANGPTL3 activity, thereby reducing the level of TG and LDL-C. Purpose This phase 1 single ascending dose study aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1918 in healthy subjects. Methods Six dose cohorts were planned, including 100, 300, 450, 750, 900 (optional), and 1200 (optional) mg. For each cohort, 12 healthy subjects were enrolled and randomized (9:3) to receive single subcutaneous SHR-1918 or placebo. Subjects were observed for seven days post-dose and followed up to Day 148 for the 100 mg cohort and Day 190 for the other dose cohorts. The primary endpoints were safety and tolerability. Results A total of 72 subjects were enrolled in the six dose cohorts from 100 to 1200 mg (SHR-1918, n = 54; placebo, n = 18). SHR-1918 was well-tolerated at tested doses. Treatment-emergent adverse events (TEAEs) were reported in 49 (90.7%) subjects in the SHR-1918 group and 17 (94.4%) subjects in the placebo group. The most common TEAEs were upper respiratory tract infection (25.9% with SHR-1918 vs. 27.8% with placebo), protein urine present (22.2% vs. 22.2%), and blood uric acid increased (16.7% vs. 16.7%). All TEAEs were mild or moderate in severity. There were no serious adverse events or TEAEs leading to death. Serum concentration of SHR-1918 generally increased with increasing doses. Maximum serum concentration was reached 8.0 to 10.0 days after injection, and mean t½ was 29.4 to 53.3 days across the dose range. SHR-1918 exposure exhibited in a slightly greater-than-dose-proportional manner from 100 to 1200 mg. Serum LDL-C and TG levels markedly and rapidly decreased in all SHR-1918 dose cohorts and remained under the baseline value up to the end of follow-up period for the higher doses, whereas those in the placebo group were above baseline at most follow-up visits (Figure 1 and 2). In the 750 to 1200 mg cohorts, the largest decline in LDL-C from baseline ranged from -46.5% to -49.1%, and the maximum decrease in TG ranged from -67.4% to -82.8%. On Day 85, there remained to be 36.9% to 39.0% reduction in LDL-C and 59.9% to 79.1% reduction in TG for the higher doses. Anti-drug antibody was not detected in SHR-1918-treated subjects. Conclusions SHR-1918 was well-tolerated and showed promising efficacy in healthy subjects. A phase 2 study has initiated to evaluate SHR-1918 in hyperlipidemic patients (NCT06109831).Serum LDL-C after SHR-1918 injectionSerum TG after SHR-1918 injection

The Impact of Acute Ammonia Nitrogen Stress on Serum Biochemical Indicators and Spleen Gene Expression in Juvenile Yellowfin Tuna (Thunnus albacares).

The presence of ammonia nitrogen in water has a significant impact on the serum and spleen of fish, potentially leading to changes in substances such as proteins in the serum while also causing damage to the immune function of the spleen. To investigate the effects of ammonia nitrogen (NH3-N) stress on juvenile yellowfin tuna (Thunnus albacares), this study established three NH3-N concentrations, 0, 5, and 10 mg/L, denoted as L0, L1, and L2, respectively. Serum and spleen samples were collected at 6, 24, and 36 h. The effects of different NH3-N concentrations and exposure times on the physiological status of juvenile fish were investigated by analyzing serum biochemical indices and splenic gene expression. The results indicate that in the L1 group, the serum high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), complement 3 (C3) and complement 4 (C4) levels, and acid phosphatase (ACP) activity showed a trend of initially increasing and then decreasing. In the L2 group, the serum low-density lipoprotein cholesterol (LDL-C), HDL-C, and C4 levels and ACP activity also displayed an initially rising and then declining trend, while TG, C3, and creatinine (CRE) levels and alkaline phosphatase (AKP) activity showed an upward trend. In the L1 group, glutathione peroxidase 1b (GPX1b), interleukin 10 (IL-10), interleukin 6 receptor (IL-6r), and tumor necrosis factor alpha (TNF-α) gene expression levels in the spleen exhibited a trend of first increasing and then decreasing. In the L2 group, IL-10, IL-6r, tumor necrosis factor beta (TNF-β), caspase 2 (casp2), and caspase 9 (casp9) gene expression levels in the spleen also showed an initial increase followed by a decrease. When NH3-N levels are below 5 mg/L, it is recommended to limit stress exposure to no more than 36 h for the juvenile fish. For concentrations ranging from 5 to 10 mg/L, stress should be strictly controlled to within 24 h. Exposure to high NH3-N levels may affect biochemical indicators such as serum lipid metabolism, immunity, and metabolism in juvenile fish, and may damage the expression of antioxidant, immune gene, and apoptosis factors in the spleen. This study aims to deepen our understanding of the effects of NH3-N on juvenile tuna, with the goal of establishing effective water quality monitoring and management strategies. This will ensure the quality of aquaculture water, reduce the harm caused by NH3-N to juvenile yellowfin tuna, and enhance aquaculture efficiency and product quality.

HMGCR as a promising molecular target for therapeutic intervention in aortic aneurisms: a mendelian randomization study

BackgroundDespite the exploration of the connections between serum low-density lipoprotein cholesterol (LDL-C) levels and aneurisms in epidemiological studies, causality remains unclear. Therefore, this study aimed to assess the causal impact of LDL-C-lowering targets (HMGCR, PCSK9, NPC1L1, CETP, APOB, and LDLR) on various forms of aneurisms using Mendelian Randomization (MR) analysis.MethodsTwo genetic instruments acted as proxies for exposure to LDL-C-lowering drugs: expression quantitative trait loci of drug target genes and genetic variants linked to LDL-C near drug target genes. Summary-data-based MR (SMR), inverse-variance-weighted MR (IVW-MR), and multivariable MR (MVMR) methods were employed to compute the effect estimates.ResultsThe SMR analysis revealed substantial associations between increased HMGCR expression and a heightened risk of aortic aneurism (odds ratio [OR] = 1.603, 95% confidence interval [CI] = 1.209–2.124), thoracic aortic aneurism (OR = 1.666, 95% CI = 1.122–2.475), and abdominal aortic aneurism (OR = 1.910, 95% CI = 1.278–2.856). Likewise, IVW-MR analysis demonstrated positive correlations between HMGCR-mediated LDL-C and aortic aneurism (OR = 2.228, 95% CI = 1.702–2.918), thoracic aortic aneurism (OR = 1.751, 95% CI = 1.191–2.575), abdominal aortic aneurism (OR = 4.784, 95% CI = 3.257–7.028), and cerebral aneurism (OR = 1.993, 95% CI = 1.277–3.110). Furthermore, in the MVMR analysis, accounting for body mass index, smoking, and hypertension, a significant positive relationship was established between HMGCR-mediated LDL-C levels and the development of aortic aneurisms, encompassing both thoracic and abdominal subtypes. Similarly, consistent positive associations were observed for PCSK9 and CETP genes, as well as PCSK9-mediated and CETP-mediated LDL-C levels, with the occurrence of aortic aneurism and abdominal aortic aneurism. Nonetheless, the evidence for potential associations between APOB, NPC1L1 and LDLR with specific subtypes of aortic aneurisms lacked consistent support from both SMR and IVW-MR analyses.ConclusionsOur MR analysis offered compelling evidence of a plausible causal link between HMGCR and an increased risk of aortic aneurism, encompassing both thoracic and abdominal types. These groundbreaking findings further bolster the case for the deployment of HMGCR inhibitors in the treatment of aortic aneurisms, including both thoracic and abdominal variants.

Metabolic Effect of Acute Lead and Restraint Stress Exposure on Female Wistar Rats

Lead is a common environmental toxicant while restraint stress is primarily a psychological stressor. Lead exposure and psychological stressors, are known to exert adverse effects on metabolic health independently. The aim of this study is to investigate the metabolic effects of acute lead and restraint stress exposure in female Wistar rats. Twenty-four (24) female Wistar rats weighing 180 - 240 grams were randomly divided into four (4) groups (n=6): Control (CTL), Restraint stress alone (RSA), Lead acetate alone (LDA), Restraint stress + Lead acetate (RSL). The duration of the study was 21 days. The lead acetate alone group were orally administered 100mg/kg of lead acetate, the restraint stress alone group were restrained for 1 hour daily and the restraint stress + lead group were administered lead acetate and restrained for 1 hour daily. Twenty-four hours post last lead administration and restraint stress exposure, all animals were anesthetized and sacrificed. Blood was collected via cardiac puncture for biochemical analysis. Results showed serum low-density lipoprotein (LDL), triglycerides (TAG) and total cholesterol (CHO) levels in lead alone and restraint stress alone groups were significantly increased (p&lt;0.05) compared with control. The restraint + lead group showed a significant increase in serum LDL, TAG and CHO levels when compared with control, lead alone and restraint stress alone groups. Serum HDL levels showed no significant difference across all groups. Serum glucose, insulin and cortisol levels in lead alone and restraint stress alone groups were significantly increased (p&lt;0.05) when compared with control. The restraint + lead group showed a significant increase (p&lt;0.05) in serum glucose, insulin and cortisol levels when compared with control, lead alone and restraint alone groups. In conclusion, this study showed that exposure to restraint stress and lead has a significant effect on the metabolic profile of female Wistar rats.

Cardiovascular Health and Diet Quality among Vegetarians, Vegans and Omnivores: Insights from a Large Urban Population in Poland.

Background/Objectives: Dietary habits are among the most significant determinants of health. The aim of this study was to assess the nutritional quality and cardiovascular profiles of individuals following plant-based diet. Methods: The study population comprised 199 individuals (136 women, 63 men; mean age 33.9 ± 8.9 years) including vegans (VG; n = 50), vegetarians (VN; n = 101) and omnivores (OV; n = 48). In this analysis the following procedures were assessed: a questionnaire interview, anthropometric and blood pressure measurements, and a blood sample collection. Dietary patterns were evaluated using the Food Frequency Questionnaire and a 24-h dietary recall. Results: Vegans exhibited the lowest protein intake relative to the other groups (p < 0.05) and a significantly higher intake of polyunsaturated fatty acids and lower intake of cholesterol compared to VN and OV (p < 0.05). Vegans had significantly lower levels of serum cholesterol, LDL cholesterol, and triglycerides, fasting glucose and high-sensitivity C-reactive protein (p < 0.05). No cases of overweight or obesity were observed among VN and VG participants. No instances of impaired fasting glucose or elevated blood pressure were noted among vegans. Hypercholesterolemia was identified in 56.2% of OV, 26.7% in VN and 16.0% in VG (p < 0.05), elevated blood pressure was recorded in one vegetarian and in 6.2% of OV participants. Conclusions: Our research indicates that plant-based diets are associated with a better cardiovascular profile compared to traditional diets. Moreover, suboptimal intake of essential nutrients, underscores the need for more effective public health interventions and improved nutrition education regardless of dietary patterns.

Comparative study of immune responses and intestinal microbiota in the gut-liver axis between wild and farmed pike perch (Sander Lucioperca).

Pike perch (Sander Lucioperca) is a predatory freshwater fish, which is highly popular amongst consumers, owing to its white flesh with a delicate structure and mild flavor. Compared to wild pike perch, the diet of farmed ones has shifted from natural food to artificial feeds. These changes would affect the gut flora of the pike perch. Endogenous metabolites of the intestinal flora are transferred through the gut-liver axis, which affects the physiological functions of the host. By studying wild and farmed individuals of the pike perch, novel insights into the stability of the intestinal flora can be provided. In this study, we measured various immune parameters in the blood, liver and intestine of wild and farmed pike perch using enzyme activity assays and real-time fluorescence quantitative PCR. Gut microbes were also collected for 16S rRNA gene sequencing. Our results showed that the serum low-density lipoprotein cholesterol (LDL-C) levels were twice as high in the wild group as in the farmed group. Furthermore, the activities of glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) in the intestinal tissues of the wild group were 733.91 U/g and 375.35 U/g, which were significantly higher than those of the farmed group. Expression of IL10 in the liver of farmed pike perch was also 4-fold higher than that of wild pike perch. The expression of genes related to the p53-BAX/Bcl2 signaling pathway was higher in both intestinal and liver tissues of wild pike perch compared with farmed. 16S rRNA gene analysis of the gut microflora showed a high relative abundance of Cetobacterium in the gut of farmed pike perch. As a result, our study indicates that dietary differences affect the diversity, composition and relative abundance of the gut flora of the pike perch. Meanwhile, it affects the glycolipid metabolism and immunomodulation of pike perch.

Study on the Mechanism of Guizhi Fuling Decoction in Treating Hyperlipidemia Based on Network Pharmacology and Experimental Methods

Background Hyperlipidemia, caused by abnormal lipid metabolism, has become a significant health concern, especially in younger populations. While statins are commonly used for treatment, they often cause severe side effects with long-term use, leading to increased interest in finding natural alternatives. Purpose This study aimed to investigate how Guizhi Fuling Decoction (GZFL) treats hyperlipidemia using network pharmacology and experimental validation. Materials and Methods Network pharmacology analyzed GZFL’s active components, targets, and treatment mechanisms for hyperlipidemia. Hyperlipidemia rat and high-fat cell models were established. Experimental validation included enzyme-linked immunosorbent assay, Western blot, quantitative polymerase chain reaction, Oil Red O staining, and other methods. Statistical analysis was performed using one-way analysis of variance followed by Tukey’s post hoc test for multiple comparisons. Pearson correlation analysis was used to identify correlations between key protein expressions and lipid levels. Results GZFL comprises 85 active components and targets 218 proteins. Hyperlipidemia involves 3,852 targets, with 175 overlapping targets. Key targets included estrogen receptor 1, prostaglandin-endoperoxide synthase 2, interleukin-6 (IL-6), protein kinase B (AKT) 1, tumor necrosis factor, interleukin-1 beta, peroxisome proliferator-activated receptor gamma (PPARG), tumor protein p53 (TP53), and fructo oligosaccharide (FOS). Major active components were quercetin, phytosterols, kaempferol, and baicalein. Enrichment analysis highlighted processes like lipopolysaccharide response and lipid signaling pathways. Animal studies showed GZFL significantly reduced serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels, and increased apolipoprotein A1 ( p &lt; 0.05). Western blot indicated that GZFL influenced AKT, TP53, IL-6, PPARγ expression, and mRNA levels in the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway ( p &lt; 0.01). Serum pharmacology experiments demonstrated GZFL-medicated serum reduced lipid droplet formation in high-fat cell models. Conclusion GZFL contains multiple pharmacologically active components, such as quercetin, phytosterols, and kaempferol, which can influence lipid metabolism. It may exert its effects by regulating proteins like AKT, TP53, IL-6, and PPARγ, participating in lipid and atherosclerosis signaling pathways and the PI3K/AKT/mTOR pathway.

Serum ACSL4 levels in prostate cancer patients and its relationship between patient prognosis: A prospective observational study.

In this prospective observational study, our objective was to investigate the serum levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in prostate cancer (PCa) patients and examine its association with other serum biomarkers, and the clinical outcomes of PCa patients. This prospective observational study was conducted from January 2019 to October 2021, including 103 cases of PCa patients and 101 cases of benign prostate hyperplasia (BPH) patients who received treatment at our hospital. All patients had their serum ACSL4 levels measured using enzyme-linked immunosorbent assay before treatment. The clinical outcomes included age, body mass index, gender, systolic blood pressure, diastolic blood pressure, tumor node metastasis stage, Gleason scores, and prostate volume and serum biomarkers were collected. All patients were followed up for 36 months, the overall survival and disease-free survival were recorded for all patients. All data used SPSS 26.0 for analysis. The phosphorus (P) and serum low-density lipoprotein cholesterol levels were significantly higher in PCa patients compared to BPH patients. Furthermore, compared to the BPH patients, the serum ACSL4 and free prostate-specific antigen levels were significantly decreased while serum total prostate-specific antigen (tPSA) levels were significantly elevated in PCa patients. Pearson correlation analysis showed a positive correlation between ACSL4 levels and free prostate-specific antigen levels, while a negative correlation was observed with P and tPSA levels. ACSL4 might serve as a biomarker for diagnosing PCa with the AUC was 0.747, cutoff value of 33.68 ng/mL, sensitivity of 70.3%, and specificity of 60.2%. Finally, we found that ACSL4, tPSA, and P were identified as risk factors associated with PCa patients. Our findings indicated that the serum levels of ACSL4 were significantly decreased in PCa patients compared to BPH patients. Serum ACSL4 could be used as a potential biomarker for early PCa diagnosis and prognosis.

Effects of High-Intensity Training on Complete Blood Count, Iron Metabolism, Lipid Profile, Liver, and Kidney Function Tests of Professional Water Polo Players.

Our goal was to examine the effect of high-intensity physical activity on changes in the lipid profile, complete blood count (CBC), iron metabolism, and kidney and liver function tests of professional water polo players. This study included twenty professional male water polo players. Blood sampling was carried out at the beginning of the season and during periods of high-intensity training. CBCs were determined with a Siemens Advia 2120i hematology analyzer. A Beckman CoulterAU680 chemistry analyzer was used to determine the serum concentrations/activities of lipid profiles and liver and kidney function test analytes. The lipid athlete scores were also determined. The mean corpuscular volume (p = 0.006), platelet count (p = 0.008), and mean platelet volume (p < 0.001) significantly decreased during the high-intensity period, compared with the beginning of the season. The total iron-binding capacity increased (p = 0.001), and ferritin concentrations significantly declined (p = 0.017). The lipid profiles revealed a significant difference between phases, with slight increases in serum total (p = 0.025) and LDL cholesterol (p = 0.002) levels and a decrease in triglyceride concentrations (p = 0.040) in the high-intensity period. During the high-intensity period, the liver and kidney function tests showed a substantial positive effect on lactate dehydrogenase levels (p < 0.001), aspartate aminotransferase (p = 0.028) serum activity, and total protein concentrations (p = 0.033), compared with the beginning of the season. Water polo players might exhibit a decrease in some CBC parameters, an increase in LDL cholesterol, and a decrease in liver function biomarkers due to intense training at the peak of the competitive season. Kidney function biomarkers remain unchanged.

Lipoprotein (a) is a predictor of non-achievement of LDL-C goals in patients with chronic heart disease

Introduction and objectivesLipoprotein (a) [Lp(a)] concentration influences serum low-density lipoprotein cholesterol (LDL-C) levels. How it influences the achievement of LDL-C targets established in the guidelines is not well studied. Our aim was to know the prevalence of elevated Lp(a) levels in patients with coronary artery disease (CAD), and to assess its influence on the achievement of LDL-C targets. MethodWe conducted a cross-sectional study in a Cardiology department in Spain. A total of 870 patients with stable CAD had their lipid profile determined, including Lp(a). Patients were stratified into two groups according to Lp(a) >50 mg/dL and Lp(a) ≤50 mg/dL. The association of Lp(a) >50 mg/dL with achievement of LDL-C targets was assessed by logistic regression analysis. ResultsThe prevalence of Lp(a) >50 mg/dL was 30.8%. Patients with Lp(a) >50 mg/dL had higher baseline (142.30 ± 47.54 mg/dL vs 130.47 ± 40.75 mg/dL; p = 0.0001) and current (72.91 ± 26.44 mg/dL vs 64.72 ± 25.30 mg/dL; p = 0.0001), despite the fact that they were treated with more high-potency statins (77.2% vs 70.9%; p = 0.058) and more combination lipid-lowering therapy (LLT) (37.7% vs 25.7%; p = 0.001). The proportion of patients achieving target LDL-C was lower in those with Lp(a) >50 mg/dL. Independent predictors of having elevated Lp(a) levels >50 mg/dL were the use of high-potency statins (OR 1.5; 95% CI 1.08−2.14), combination LLT with ezetimibe (OR 2.0; 95% CI 1.45−2.73) and failure to achieve a LDL-C ≤55 mg/dL (OR 2.3; 95% CI 1.63−3.23). ConclusionsElevated Lp(a) levels influence LDL-C levels and hinder the achievement of targets in patients at very high cardiovascular risk. New drugs that act directly on Lp(a) are needed in these patients.

Tetramethylpyrazine and paeoniflorin combination (TMP-PF) alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway

Atherosclerosis remains a great threat to human health worldwide. Previous studies found that tetramethylpyrazine (TMP) and paeoniflorin (PF) combination (TMP-PF) exerts anti-atherosclerotic effects in vitro. However, whether TMP-PF improves atherosclerosis in vivo needs further exploration. The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE-/- mice and explore the related molecule mechanisms. Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels, suppressed vascular endothelial growth factor receptor 2 (VEGFR2) and nuclear receptor subfamily 4 group A member 1 (NR4A1) expression in aortic tissues, inhibited plaque angiogenesis, reduced plaque areas, and alleviated atherosclerosis in ApoE-/- mice. Also, TMP-PF exhibited a better modulation effect than TMP or PF alone. However, NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF. In conclusion, TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway, indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

MicroRNA 29a alleviates mitochondrial stress in diet-induced NAFLD by inhibiting the MAVS pathway

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder characterized by fat accumulation in the liver. This leads to aggravated hepatocyte inflammation due to impaired mitochondrial function, mitochondrial double-stranded RNA (mt-dsRNA) release, elevated oxidative stress, and reactive oxygen species (ROS) production.MicroRNA-29a (miR-29a) is used to reduce hepatic fibrosis in cases of cholestatic liver damage and lessen the severity of non-alcoholic steatohepatitis in animal studies by influencing mitochondrial protein balance. However, the effectiveness of miR-29a in diminishing mt-dsRNA-induced exacerbation of NAFLD remains poorly understood, particularly in the context of a Western diet (WD). Our results have found that mice with increased miR-29a levels and fed a WD showed notably decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, and low-density lipoprotein cholesterol levels. They also experienced less weight gain and lower final body and liver weights. In addition, overexpression of miR-29a reduced the severity of fibrosis, alleviated hepatic oxidative stress, misfolded protein aggregates, and the release of mt-dsRNA. Moreover, miR-29a attenuated the innate immune mitochondrial antiviral-signaling protein (MAVS) pathway response. In vitro, the research using HepG2 cells confirmed that miR-29a reduces MAVS expression and decreases the release of mt-dsRNA and superoxide initiated by palmitic acid (PA). Analysis of luciferase activity further established that the specific binding of miR-29a to the 3′UTR of MAVS led to a repression of its expression. In conclusion, these groundbreaking findings underscore the potential of miR-29a in improving the treatment of NAFLD and liver steatofibrosis by inhibiting the MAVS signaling pathway.

LAYING PERFORMANCE, EGG QUALITY, AND SERUM BIOCHEMICAL INDICATORS OF LAYING DUCKS AFFECTED BY DIETARY CHITOSAN OLIGOSACCHARIDES SUPPLEMENTATION

Chitosan oligosaccharides (COs) have varying physiologic activities. This work aims to explore effects of dietary COs on the laying performance, egg quality, and plasma biochemical indicators of laying ducks. Four diets were formulated by supplementing different dosages (0, 25, 50, and 100 mg/kg) of COs in basal diet. A total of 288 Suyou No.2 healthy laying ducks at peak egg production stage with age of 28 weeks, similar weights (1500 ± 106 g) and egg laying rates were randomly evenly assigned to four groups, with 6 replicates in each group. Dietary 50 mg/kg of COs increased daily egg production (EP), egg mass (EM), egg weight (EW), eggshell strength, yolk color, serum superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, and immunoglobulin (Ig) G, Ig A, Ig M, and high-density lipoprotein levels (HDL-C). Conversely, it decreased the feed conversion ratio (FCR), yolk percentage, and serum malondialdehyde (MDA), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels of laying ducks. Nevertheless, a high dosage of COs (100 mg/kg) neither decreased nor improved the efficiency. The optimum dose of COs supplementation required for the maximum egg mass of laying ducks was 61.41 mg/kg. These results indicated that COs supplementation at an appropriate dosage could ameliorate the laying performance, egg quality, and health condition of laying ducks. Keywords: dietary, chitosan oligosaccharides, laying ducks.

Lipid profile and mortality in patients with pulmonary thromboembolism; a systematic review and meta-analysis.

Acute pulmonary thromboembolism (PTE) is a life-threatening disease. Considering the availability and accessibility of assessing the serum lipids, this study aims todefine the predictive value of lipid profile, as well as the history of lipid disorders, for the mortality of PTE patients. Clinical studies, in which the relation of lipid profile, including triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol, as well as history of imbalance of lipids, with mortality of PTE patients was reported, were included. Non-English articles, reviews, letters, editorials, and non-English papers were excluded. A systematic search was conducted in PubMed, Embase, Scopus, and Web of Science databases. Therisk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal tools and CMA 4 was utilized forthe quantitative synthesis. Out of 3,724 records, six studies were included inthis systematic review. Lipid profile is suggested as a prognostic marker for survival in patients with PTE so higher initial serum HDL, LDL, and total cholesterol levels were associated with lower mortality rates in PTE patients. In addition, dyslipidemia was found to be associated withmortality of PTE patients. Based on the quantitative synthesis, there was a greater serum level of HDL in thesurvival group (standardized mean difference:-0.98; 95 %CI:-1.22 to-0.75; p-value<0.01). Mortality is lower in PTE patients with greater serum lipid levels; therefore, the early prognosis of PTE maybe ascertained by measuring serum lipids within the first 24 h of admission.

Serum Phosphatidylcholine Species 32:0 as a Biomarker for Liver Cirrhosis Pre- and Post-Hepatitis C Virus Clearance.

Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis.

Atherosclerotic Cardiovascular Disease Novel and Traditional Risk Factors in Middle Eastern Young Women. The ANCORS-YW Study.

There is paucity of data on the prevalence of novel and traditional cardiovascular risk factors in young women with atherosclerotic cardiovascular disease (ASCVD) in the Middle East. We sought to evaluate clinical profiles and prevalence of novel and traditional risk factors in Middle Eastern young women with ASCVD compared with age-matched controls. Women 18-50 years of age who have ASCVD were enrolled and each was aged-matched with two women with no ASCVD. Prevalence of novel and traditional risk factors was compared in the two groups. Multivariable analyzes examined the independent association of 16 factors with ASCVD. Of 627 young women enrolled mean age 44.1 ± 5.2 years; 209 had ASCVD and 418 served as controls. Women with ASCVD had significantly higher prevalence of five of the studied traditional risk factors (hypertension, type 2 diabetes [T2D], smoking, low-density lipoprotein cholesterol serum levels, and family history of premature ASCVD [FHx]) than women with no ASCVD. Additionally, of the 11 novel and psychosocial risk factors studied, four showed significantly higher prevalence in young women with ASCVD (preterm delivery, hypertensive disease of pregnancy gestational diabetes, and low level of education). Multivariable analyzes showed hypertension, T2D, smoking, FHx, persistent weight gain after pregnancy and low level of education were independently associated with ASCVD. In this study of young Middle Eastern women; traditional risk factors as well as persistent weight gain after pregnancy were more prevalent in women with ASCVD compared with controls.The study is registered with ClinicalTrials.gov, unique identifier number NCT04975503.

Cholesterol-lowering effect of Pediococcus strains isolated from mother’s milk in mice

PurposeThe Pediococcus strains belong to the group of lactic acid bacteria (LAB). This study aims to isolate and identify the Pediococcus spp. from mother’s milk, and investigate their tolerance to low pH and bile salts, antibacterial activity, attachment to HT-29 cells and effect on cholesterol-lowering and digestive enzymes in mice.Design/methodology/approachPediococcus species were isolated from mother’s milk, then tested for tolerance to acid and bile salts, their antibacterial effect and attachment to HT-29 cell line. In mice experiment, the levels of triglyceride (TG), total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C) and digestive enzymes such as amylase and lipase in serum of mice were measured after administration of 108 CFU/mL bacterial suspension.FindingsA total of 24 Pediococcus spp. including 16 isolates of Pediococcus pentosaceus and 8 isolates of Pediococcus acidilactici were isolated. Fifteen isolates (62.5%) were able to survive in low pH and bile salt concentration. Ten isolates (41.6%) exhibited the most powerful inhibitory effects against both Gram-positive and Gram-negative bacterial pathogens. A total of four Pediococcus isolates (16.67%) showed strong attachment to HT-29 cells. In contrast to HDL-C and amylase, the serum levels of TC, TG and LDL-C were reduced and lipase was elevated significantly following administration of mother milk-derived Pediococcus isolates.Originality/valueThe Pediococcus isolates demonstrated good probiotic properties in particular cholesterol-lowering ability in mice. Thus, after more studies they can be considered as probiotic strain(s).

Therapeutic effect of Momordica charantia on cardiomyopathy in a diabetic maternal rat model.

Myocardial structural and functional abnormalities are hallmarks of diabetic cardiomyopathy (DCM), a chronic consequence of diabetes mellitus (DM). Maternal DM affects and increases the risk of heart defects in diabetic mothers compared with nondiabetic mothers. Momordica charantia exhibits antidiabetic effects due to various bioactive compounds that are phytochemicals, a broad group that includes phenolic compounds, alkaloids, proteins, steroids, inorganic compounds, and lipids. Pregnant maternal rats were split into four groups: control (C), M. charantia-treated (MC), type 2 diabetes mellitus (T2DM) (DM), and diabetic (MC + DM) groups. Diabetes mothers had increased serum glucose, insulin, total cholesterol, triglyceride, and low-density lipoprotein cholesterollevels and reduced high-density lipoprotein cholesterollevels. Cardiac biomarkers such as cardiac troponin T (cTnT), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenasewere increased. Hormone levels of follicle-stimulating hormone, luteinizing hormone, progesterone, and estrogen decreased significantly. Inflammatory markers such as interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and vascular adhesion molecule-1 (VCAM-1) were elevated in diabetic mothers. Oxidative stress markers indicated increased malondialdehydeand nitric oxidelevels, while antioxidants such as glutathione, superoxide dismutase, and catalasewere decreased in maternal heart tissue. The levels of apoptotic markers such as tumor suppressor 53 (P53) and cysteine aspartic protease-3 (caspase-3) were significantly greater in diabetic maternal heart tissue. Histopathological analysis revealed heart tissue abnormalities in diabetic maternal rats. M. charantia extract improved maternal diabetes-induced changes in inflammation, antioxidant levels, and heart tissue structure.