Lipoprotein Triglycerides Research Articles

Unifying Theory and Experiments: Multi-Target Pharmacology of Dajihan Pill Against Hyperlipidemia

Background: The increasing incidence of hyperlipidemia (HLP) is attributed to the imbalance in redox homeostasis, aberrant lipid metabolism, and the excessive intake of empty calories. Dajihan Pill (DJHP) is a Traditional Chinese Medicine (TCM) formula composed of Zingiberis Rhizoma (ZR), Piperis Longi Fructus (PLF), Alpiniae Officinarum Rhizome (AOR), and Cinnamomi Cortex (CC) in a ratio of 3:2:3:2. It exhibits a significant preventive effect on HLP. Certainly, the active components and the precise mechanism of action are not fully understood. Therefore, this study aims to elucidate the preventive and ameliorative mechanisms of DJHP against HLP by integrating network pharmacology, molecular docking, and experimental validation. Methods: Based on the pharmacological method, active ingredients in DJHP and targets were extracted from Traditional Chinese Medicine System Pharmacology (TCMSP) and UniProt. Then core compounds and targets were obtained by constructing “compounds-targets-disease” and proteinprotein interaction (PPI) network. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to elucidate further the associated action mechanism. The molecular binding mechanisms between the core ingredients and targets were elucidated through molecular docking. Additionally, the antioxidant capacities of DJHP extracts were investigated by assessing their DPPH, hydroxyl, and ABTS radical scavenging activities. Results: A total of 45 active compounds and 258 targets were identified in DJHP. Network analysis indicated that quercetin, beta-sitosterol, kaempferol, and oleic acid might serve as core bioactive compounds. Seven core targets, including AKT1, INS, and TNF, were identified as potential preventive targets. GO analysis suggested the improvement of HLP by DJHP may be related to the lipid metabolic process, high-density lipoprotein particle, triglyceride binding, and inflammatory response. The KEGG analysis indicated TNF, HIF-1, and AMPK signaling pathways were involved. The observations of active compounds binding with core targets indicated an excellent combination. Additionally, antioxidant results showed that DJHP exhibited significant DPPH, hydroxyl, and ABTS radical scavenging activities. Conclusion: Theoretical and experimental investigations indicate that DJHP can effectively modulate various signaling pathways and enhance the redox system, thus mitigating HLP. Our work provided a basis for the pharmacological study of DJHP in preventing HLP and further research.

Effects of Marine-Derived Components on Cardiovascular Disease Risk Factors and Gut Microbiota Diversity.

Cardiovascular diseases (CVDs), which comprise coronary heart disease, hypertension, and stroke, collectively represent the number one cause of death globally. Atherosclerosis is the dominant cause of CVDs, and its risk factors are elevated levels of low-density lipoprotein cholesterol and triglycerides, hypertension, cigarette smoking, obesity, and diabetes mellitus. In addition, diverse evidence highlights the role played by inflammation and clonal haematopoiesis, eventually leading to immunity involvement. The human microbiota project and subsequent studies using next-generation sequencing technology have indicated that thousands of different microbial species are present in the human gut. Disturbances in the gut microbiota (GM) composition, i.e., gut dysbiosis, have been associated with diseases ranging from localised gastrointestinal disorders to metabolic and cardiovascular illnesses. Of note, experimental studies suggested that GM, host immune cells, and marine-derived ingredients work together to ensure intestinal wall integrity. This review discusses current evidence concerning the links among GM, marine-derived ingredients, and human inflammatory disease. In detail, we summarise the impact of fish-derived proteins/peptides and algae components on CVD risk factors and gut microbiome. Furthermore, we describe the interplay among these dietary components, probiotics/prebiotics, and CVDs.

Chromium supplementation and type 2 diabetes mellitus: an extensive systematic review.

Diabetes is a global public health concern with increasing prevalence worldwide. Chromium (Cr), a trace element found in soil, water, and food, has been proposed to have a possible positive effect in glucose metabolism and diabetes mellitus prevention. However, the relationship between trivalent chromium [Cr(III)] exposure, mainly through the consumption of diet supplements, and type 2 diabetes mellitus (T2DM) remains controversial. An extensive systematic review of the current literature on randomized controlled studies (RCTs) was conducted from 1 January 2000, to January 2024 using the databases PubMed, Scopus, ScienceDirect, and Cochrane, with specific keywords and inclusion as well as exclusion criteria. After close screening of the research studies retrieved from the mentioned websites was conducted, the most related studies were included in the final systematic review. The studies were evaluated for the degree of relevance, quality, and risk bias, using appropriate quality assessment tools. Several of the included RCT studies reported possible benefits of Cr(III) supplementation, mainly in the form of chromium picolinate (CrPic), chromium yeast (CY), chromium chloride (CrCl3), and chromium nicotinate (CrN). The dosage of chromium was between 50 and 1000μg/day and it was consumed from 2 to 6months. Glycemic control markers, including FPG, insulin, HbA1C, and HOMA-IR levels, significantly decrease following chromium supplementation, mainly in studies with a longer intervention period. Supplementing with chromium (Cr) indicated that could significantly improve lipid profile by raising high-density lipoprotein and lowering triglyceride and total cholesterol while having little effect on low-density lipoprotein. However, most research findings include significant limitations, such as inconsistent dosage and type of chromium, formulation of supplements, and study duration. Further well-designed and high-quality research is needed to fully understand the role of chromium dietary supplementation and the potential risks related to its mechanisms of action, type, and dose, in the prevention and treatment of type 2 diabetes mellitus.

Biochemical Studies of Averrhoa carambola Ethanol Leaf and Fruit Extracts on Alloxan-induced Diabetic Rats

The use of herbal medicines has always been an option to treat diseases such as diabetes cancer and other ailments. This study aimed to evaluate the effect of Averrhoa carambola leaf and its fruit ethanol extracts on biochemical parameters and histopathology features. Forty five albino rats were assigned into 9 groups of 5 rats each. Except for the normal control group, others were induced to be diabetic by a single intraperitoneal injection of alloxan. Group 1 (normal control) and Group 2 (diabetic untreated) received water. Group 3 received 2.5mg/kg glibenclamide, Groups 4-9 received graded doses (250mg/kg, 500mg/kg and 750mg/kg) of leaf and fruit extracts of Averrhoa carambola. Treatment lasted 14days. At the end of the treatment, blood samples and organ (pancreas) were collected from the animals for biochemical and histopathological evaluation. Treatment of alloxan-induced diabetic rats significantly (p<0.05) reduced the glucose concentration across all treated groups. Following induction of diabetic mellitus, the serum activities of liver enzymes (Alanine amino transferase, Aspartate aminotransferase and Alkaline phosphatase), low-density lipoprotein cholesterol (LDL-C) and triglyceride were significantly (p<0.05) elevated in diabetic untreated group with corresponding reduction in serum protein, albumin and high-density lipoprotein cholesterol (HDL-C) compared to the normal control and treated groups. However, the fruit extracts exhibited a high increase in urea and creatinine levels especially at dose of 750mg/kg body weight when compared with the leaf though not significantly higher than the diabetic untreated group. From histopathology studies, the groups treated with the leaf extract of Averrhoa carambola showed greater structural improvement and an increase in pancreatic islet cells. Therefore this study showed that although ethanol extracts of Averrhoa carambola leaf and fruit have antidiabetic properties, the leaf extract possesses more antidiabetic effect.

Impact of Controlling Serum Low-Density Lipoprotein Cholesterol and Triglycerides on Long-Term Clinical Outcomes in Diabetic Patients Who Have Undergone Percutaneous Coronary Intervention

Impact of Controlling Serum Low-Density Lipoprotein Cholesterol and Triglycerides on Long-Term Clinical Outcomes in Diabetic Patients Who Have Undergone Percutaneous Coronary Intervention

The Influence of Hyperlipidemia on the Results of Mammography in Postmenopausal Women

Aim: To determine whether hyperlipidemia causes specific or nonspecific changes that can be detected by mammography in postmenopausal women. Materials and Method: This study was conducted retrospectively and designed as a case-control study in the gynecology clinics of Etlik Zubeyde Hanim Women’s Health Education and Training Hospital between January 2017 and January 2020. Healthy postmenopausal women with a total cholesterol (TC) level of 200 mg/dL and above 200 mg/dL, who were examined in our outpatient clinics and whose mammographic controls were performed in our hospital, were included in the study group (Group I). Healthy postmenopausal women with a TC level below 200 mg/dL who were followed up at the same clinic and whose mammographic controls were performed at our clinic were included in the control group (Group II). We analyzed TC, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides with mammography findings. Results: There were no significant differences between the groups in terms of age and body mass index. There were no significant differences between smoking status and family history of breast cancer. The BAC and BI-RADS scoring category scores differed significantly (p=0.006 and p=0.042, respectively). Conclusion: Postmenopausal women with hyperlipidemia have mammographic findings that can lead to breast cancer. Considering that hyperlipidemia may also have other causes of morbidity and mortality, such as hypertension, diabetes mellitus and cardiovascular disease, it is necessary to treat it with lifestyle changes and / or medications. As this was a retrospective study with a limited number of patients, it is clear that future randomized controlled trials could provide more reliable data on this topic.

High-intensity interval training for cardiometabolic health in adults with metabolic syndrome: a systematic review and meta-analysis of randomised controlled trials

ObjectiveTo assess the effectiveness of high-intensity interval training (HIIT) compared with traditional moderate-intensity continuous training (MICT) and/or non-exercise control (CON) for modification of metabolic syndrome (MetS) components and other cardiometabolic...

Associations of Serum Lipid Traits With Fracture and Osteoporosis: A Prospective Cohort Study From the UK Biobank.

Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population. This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women and 191 242 men, aged 37-73 years) with serum lipid measurements: apolipoprotein A (Apo A), apolipoprotein B (Apo B), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid trait with the risks of fractures and osteoporosis. Subgroup analyses by age, sex, BMI categories and pre-existing cardiovascular disease were conducted. Mediation analyses using the g-formula were performed to quantify to which extent bone mineral density (BMD) may mediate the association between serum lipids and fracture risk. Over a median follow-up period of 13.8 years, 25 918 (6.8%) of the 383 530 participants without prior fracture had incident fracture cases, and 7591 (4.1%) of the 184 919 participants with primary care data and without baseline osteoporosis were diagnosed with osteoporosis. TG had nonlinear associations with fractures and osteoporosis, whereas Apo B, TC and LDL-C had linear associations. There were also nonlinear associations of Apo A and HDL-C with fractures. Individuals in the highest quintiles for Apo A (fracture: HR 1.15 [95% CI 1.10, 1.21]; osteoporosis: HR 1.13 [1.02, 1.25]) and HDL-C (fracture: HR 1.27 [1.20, 1.34]; osteoporosis: HR 1.31 [1.18, 1.46]) were associated with higher risks of fractures and osteoporosis. Conversely, those in the highest quintile for Apo B (fracture: HR 0.85 [0.81, 0.89]; osteoporosis: HR 0.86 [0.79, 0.94]), LDL-C (fracture: HR 0.89 [0.85, 0.93]; osteoporosis: HR 0.91 [0.83, 1.00]) and TG (fracture: HR 0.78 [0.74, 0.82]; osteoporosis: HR 0.75 [0.68, 0.82]) were associated with lower risks. The associations of Apo A (ratio of HR [RHR] 1.05 [1.02, 1.09]) and HDL-C (RHR 1.06 [1.03, 1.09]) with fracture risk were more pronounced in men compared to women. Except for TG and Lp(a), the associations between serum lipids and fractures appear to be partially mediated through BMD (mediation proportions: 5.30% to 40.30%), assuming causality. Our study reveals a complex interplay between different lipid markers and skeletal health, potentially partially mediated through BMD. Routine lipid profile assessments, including HDL-C and Apo A among other lipid traits, may be integrated into the strategies for fracture risk stratification.

Small hepatitis B virus surface antigen (SHBs) induces dyslipidemia by suppressing apolipoprotein-AII expression through ER stress-mediated modulation of HNF4α and C/EBPγ.

Persistent infection with hepatitis B virus (HBV) often leads to disruptions in lipid metabolism. Apolipoprotein AII (apoAII) plays a crucial role in lipid metabolism and is implicated in various metabolic disorders. However, whether HBV could regulate apoAII and contribute to HBV-related dyslipidemia and the underlying mechanism remain unclear. This study revealed significant reductions in apoAII expression in HBV-expressing cell lines, the serum, and liver tissues of HBV-transgenic mice. The impact of HBV on apoAII is related to small hepatitis B virus surface antigen (SHBs). Overexpression of SHBs decreased apoAII levels in SHBs-expressing hepatoma cells, transgenic mice, and the serum of HBV-infected patients, whereas suppression of SHBs increased apoAII expression. Mechanistic investigations demonstrated that SHBs repressed the apoAII promoter activity through a HNF4α- and C/EBPγ-dependent manner; SHBs simultaneously upregulated C/EBPγ and downregulated HNF4α by inhibiting the PI3K/AKT signaling pathway through activating endoplasmic reticulum (ER) stress. Serum lipid profile assessments revealed notable decreases in high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) in SHBs-transgenic mice compared to control mice. However, concurrent overexpression of apoAII in these mice effectively counteracted these reductions in lipid levels. In HBV patients, SHBs levels were negatively correlated with serum levels of HDL-C, LDL-C, TC, and TG, whereas apoAII levels positively correlated with lipid content. This study underscores that SHBs contributes to dyslipidemia by suppressing the PI3K/AKT pathway via inducing ER stress, leading to altered expression of HNF4α and C/EBPγ, and subsequently reducing apoAII expression.IMPORTANCEThe significance of this study lies in its comprehensive examination of how the hepatitis B virus (HBV), specifically through its small hepatitis B virus surface antigen (SHBs), impacts lipid metabolism-a key aspect often disrupted by chronic HBV infection. By elucidating the role of SHBs in regulating apolipoprotein AII (apoAII), a critical player in lipid processes and associated metabolic disorders, this research provides insights into the molecular pathways contributing to HBV-related dyslipidemia. Discovering that SHBs downregulates apoAII through mechanisms involving the repression of the apoAII promoter via HNF4α and C/EBPγ, and the modulation of the PI3K/AKT signaling pathway via endoplasmic reticulum (ER) stress, adds critical knowledge to HBV pathogenesis. The research also shows an inverse correlation between SHBs expression and key lipid markers in HBV-infected individuals, suggesting that apoAII overexpression could counteract the lipid-altering effects of SHBs, offering new avenues for understanding and managing the metabolic implications of HBV infection.

Lipids as the link between central obesity and diabetes: perspectives from mediation analysis

BackgroundCentral obesity is a well-recognized risk factor for diabetes, yet the potential role of lipids in the diabetes risk associated with central obesity remains unclear. This study aimed to explore the possible mediating role of 11 lipid parameters [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein cholesterol (Non-HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), remnant cholesterol (RC), and ratios of Non-HDL-C/HDL-C, RC/HDL-C, LDL/HDL-C, TG/HDL-C, TC/HDL-C] in the association of central obesity with diabetes risk.MethodsWe utilized data from 15,453 participants in the NAGALA longitudinal cohort to assess the association of baseline central obesity indicators [waist-height ratio (WHtR), waist circumference (WC)] and the 11 lipid parameters with diabetes risk. Mediation analysis models were constructed to explore the mediating role of lipid parameters in the association of WC/WHtR with diabetes.ResultsConfirmatory associative analysis using multivariable Cox regression showed that, except for Non-HDL-C, TC and LD-C, the remaining eight lipid parameters were significantly associated with WC/WHtR and diabetes risk. Mediation analysis indicated that TG, RC, HDL-C, and lipid ratios such as Non-HDL-C/HDL-C ratio, RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio and LDL/HDL-C ratio are potential lipids affecting the diabetes risk related to central obesity. Among these, the RC/HDL-C ratio seemed to contribute the most in the WC/WHtR-related diabetes risk association, with a mediation percentage of about 37%. Additionally, lipid ratio parameters appeared to play a more mediating role in the association of central obesity-related diabetes risk than individual lipids.ConclusionsIn central obesity-related diabetes risk, most lipids, especially lipid ratio parameters, play a significant mediating role. Given these findings, we advocate for increased efforts in multifactorial risk monitoring and joint management of diabetes. The evaluation of lipids, particularly lipid ratio parameters, may be holds substantial value in the prevention and management of diabetes risk under close monitoring of central obesity.

Fat mass mediating effect on the association of worsening insulin resistance with increased left ventricular mass in 1595 adolescents: a 7-Year Longitudinal and Mediation Study

Abstract Background Fat mass-insulin resistance vicious cycle has been established in the young population and late adolescence has been identified as the critical time when the pathologic cycle begins. However, the independent and synergistic effect of fat mass in the relationship of insulin resistance with cardiac structure remains unexamined in a large cohort of adolescents, possibly due to the scarcity of repeated echocardiography measures. Mounting effective prevention strategies relies on strong evidence of the timing of the earliest cardiovascular alteration induced by insulin resistance. Purpose To investigate the longitudinal association of insulin resistance with left ventricular mass (LVM) and the mediating effect of fat mass in adolescents. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting glucose and insulin measured at 17- and 24-year clinic visits were included. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated from fasting insulin x fasting glucose/22.5 at ages 17 and 24 years. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7) was available at baseline and follow-up. Fat mass was repeatedly measured with dual-energy Xray absorptiometry at both time points. Multivariable adjusted association was examined using generalized linear mixed-effect models and adjusted for sex, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, and time-varying covariates measured at both baseline and follow-up such as age, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, fat mass, lean mass, smoking status, sedentary time, light physical activity, moderate-to-vigorous physical activity, low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol. Mediation analysis was conducted with a structural equation model adjusting for same covariates, except fat mass. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) median insulin resistance increased from 1.46 to 1.74, median fat mass increased from 15.6kg to 19.2kg and the mean LVMI increased from 35.4g/m2.7 to 38.1g/m2.7, over 7 years. In a fully adjusted model, increased insulin resistance from adolescence through young adulthood was significantly associated with increased LVMI (effect estimate 1.01g/m2.7 [95% CI, 0.63 – 1.57], p<0.001) across the 7-year observation period. Increased fat mass mediated (62.3% mediation effect) the longitudinal association between insulin resistance and LVMI from ages 17 – 24 years. Conclusion Worsening insulin resistance from adolescence through young adulthood was associated with increased cardiac mass, contributing 37% to the total increase in LVMI between ages 17 to 24 years but increased fat mass explained two-thirds of the relationship.

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.

Efficacy and pharmacodynamics of herbal medicine in patients with metabolic phenotype of osteoarthritis

High prevalence of the metabolic phenotype of osteoarthritis (MPOA) and unsatisfactory methods of its treatment necessitate the development of novel therapeutic approaches for this phenotype of OA. Turmeric preparations have a wide range of biological activity; their use in patients with MPOA can be effective and reduce the drug burden. In the present paper, we review our own published research findings on the effectiveness and pharmacodynamics of turmeric preparations in patients with MPOA. In the two studies, we evaluated the effects of two curcumin-containing parapharmaceuticals: Epigenorm Antivir (EA) and Curcumin. Forty-one women with MFOA were included in both studies. Twenty-three patients received EA at a daily dose of 1000 mg for 12 weeks, and 18 patients received curcumin from Evalar at a dose of 1000 mg for 8 weeks. The endpoints for both studies were VAS pain, dysfunction and other symptoms of OA measured using the KOOS scale. After 12 weeks of EA treatment, there was a 2.5-fold decrease pain levels. The decrease in pain was associated with an improvement in the patient’s daily and sports activities and quality of life. These effect sizes were classified as moderate to large according to Cohen. No adverse events were observed during the period of taking EA. Clinical improvement was associated with a decrease in the content of MS individual components: low-density lipoprotein cholesterol and triglycerides. The treatment caused a decrease in the level of systemic inflammation, as evidenced by a decrease in the concentration of TNFα, histamine, IL-18, C-reactive protein, and neopterin. The concentrations of IL-10 and adiponectin increased after treatment. In another study, treatment with curcumin for 4 weeks had an analgesic effect, improved measures of function and quality of life. Clinical improvement was associated with the reductions in serum levels of a number of proinflammatory cytokines, C-reactive protein, and lipids. Thus, the results of the pilot studies evaluating efficacy, safety, and pharmacodynamics of parapharmaceuticals EA and Curcumin in patients with MFOA indicate pleiotropic effects of the interventions. The findings provide a rationale for conducting larger, controlled, blind, randomized clinical trials.

Salvia miltiorrhiza and Its Compounds as Complementary Therapy for Dyslipidemia: A Meta-Analysis of Clinical Efficacy and In Silico Mechanistic Insights.

Background/Objectives: Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), a leading cause of death worldwide. Salvia miltiorrhiza Burge is widely used in East Asia for cardiovascular health, showing potential benefits in lowering cholesterol and reducing inflammation. Methods: This study systematically reviewed and conducted a meta-analysis of randomized controlled trials (RCTs) to assess the clinical effectiveness of Salvia miltiorrhiza in treating dyslipidemia. Moreover, network pharmacology and molecular docking analyses were performed to explore the mechanisms underlying the effects of Salvia miltiorrhiza. Results: The meta-analysis revealed that when Salvia miltiorrhiza is combined with statin therapy, it significantly enhances lipid profiles, including reductions in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides and improvements in high-density lipoprotein cholesterol (HDL-C), compared to statin therapy alone. The in silico analyses indicated that Salvia miltiorrhiza may influence key biological pathways, such as the PI3K/Akt, JAK/STAT, and HMGCR pathways, which are involved in inflammation, lipid metabolism, and the development of atherosclerosis. Conclusions:Salvia miltiorrhiza shows potential as a complementary therapy for dyslipidemia, offering additional lipid-lowering and anti-inflammatory benefits.

Phenotype in Individuals with Heterozygous Rare Variants in LIPC Encoding Hepatic Lipase.

Hepatic lipase deficiency is a rare genetic condition caused by biallelic loss-of-function variants in the LIPC gene encoding hepatic lipase. These variants reduce or abolish the protein's lipolytic activity, resulting in elevated plasma lipids. The condition is classified as autosomal recessive, since dyslipidemia is inconsistently observed in heterozygous patients with only one LIPC variant. However, this has been concluded from historical studies encompassing a few families and having very small sample sizes. Here, we conduct a retrospective chart review of 46 heterozygous subjects, each harboring one rare pathogenic LIPC variant. We compare plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B to those of matched controls without LIPC variants. Variant pathogenicity is classified according to the guidelines of the American College of Medical Genetics and Genomics. We observe that levels of total cholesterol, LDL-C, and triglycerides are significantly elevated in the LIPC variant heterozygotes, but HDL-C and apolipoprotein B are not. When filtering solely with respect to pathogenic or likely pathogenic variants, all lipid variables emerge as significantly elevated compared to controls. Thus, hepatic lipase deficiency may not necessarily be a recessive condition, but perhaps semi-dominant since individuals with one variant are phenotypically distinct from the controls. These hypothesis-generating findings regarding LIPC genetic variations observed in a clinical cohort should be evaluated in larger populations and databases.

Investigation of genetic instability in patients with Diabetes Mellitus type I, II and LADA using buccal micronucleus cytome assay

The aim of our pilot study was to investigate the frequency of micronuclei (MN) and other nuclear anomalies in exfoliated cells of the oral mucosa in patients with type I, II, and LADA (Latent Autoimmune Diabetes in Adults, classified as type 1.5 intermediate, slowly progressing diabetes) types of diabetes mellitus (DM) and compare them with healthy individuals of the Armenian population using the MN test. For each participant essential clinical and biochemical parameters were studied, including blood pressure, duration of illness, glycosylated hemoglobin (HbA1c), blood glucose, plasma glucose, urea, total protein, creatinine, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, HOMA-IR (insulin resistance), insulin, and triglycerides, as well as necessary anthropometric, genealogical, and genetic data. All participants were surveyed regarding habits that might affect MN levels, such as smoking, alcohol consumption, drug use, hereditary diseases, and viral infections. Cytogenetic analyses of exfoliated cells showed that the level of MN in exfoliated cells of DM patients was elevated approximately two to three times compared to healthy individuals. However, statistical significance was only reached in type I DM and LADA patients. The levels of other nuclear anomalies in the squamous epithelial cells of DM patients were also analyzed, and a significant increase in their levels was observed in all three DM types, indicating cytotoxic and genotoxic effects. The results of this study also revealed a high correlation between the total number of MN, cells with MN, blood glucose concentration, and glycosylated hemoglobin.

Effects of multicomponent exercise intervention on cardiometabolic risk factors in children and young adults with cerebral palsy: a multiple-baseline trial.

Adults with cerebral palsy (CP) have a high risk of cardiometabolic diseases. It is unknown whether this risk is elevated in young people with CP and whether exercise can reduce this risk. Therefore, we investigated the effects of the EXErcise for Cerebral Palsy (EXECP) intervention on cardiometabolic risk in children and young adults with CP and compared this risk to typically developing children and young adults (TDs). Ambulatory male and female participants with spastic CP, aged 9-24 years, and age- and sex-matched TDs without musculoskeletal disorders were recruited. Participants with CP were measured at baseline, after a three-month control period manifesting normal development, and after the three-month strength, gait, and flexibility training intervention. TDs were measured at baseline and after the control period. They did not attend the intervention. Cardiometabolic risk factors included body weight, body fat percentage, and skeletal muscle mass index assessed with bioimpedance; resting systolic and diastolic blood pressure and aortic pulse wave velocity assessed with a non-invasive oscillometric device; fasting plasma high-density and low-density lipoprotein cholesterol, triglyceride, and glucose levels. Data were analyzed with independent samples t-tests and linear mixed-effects models adjusted for sex and age. The study involved 18 participants with CP (13 males, 9-22year, mean 14.2 ± 4.4) and 17 TDs (12 males, 9-22year, mean 14.6 ± 4.3). At baseline, participants with CP had a 1.0 (95% confidence interval (CI) [-2.0, -0.0]) kg/m2 lower skeletal muscle mass index than TDs. During the control period, no statistically significant between-group differences were observed in the change of any outcome. In the CP group, body weight (β = 1.87, 95% CI [1.04, 2.70]), fat percentage (β = 1.22 [0.07, 2.37], and blood glucose (β = 0.19, 95% CI [0.01, 0.37]) increased, while diastolic blood pressure (β=-2.31, 95% CI [-4.55, -0.06]) and pulse wave velocity (β=-0.44, 95% CI [-0.73, -0.16]) decreased. In the TD group, only body weight increased (β = 0.85, 95% CI [0.01, 1.68]) statistically significantly. In the CP group, no changes were observed during the intervention. Young people with and without CP do not exhibit significant differences in most cardiometabolic risk factors. EXECP intervention may attenuate some adverse development trajectories occurring without the intervention but greater volume and intensity of aerobic exercise may be needed to reduce cardiometabolic risk. ISRCTN69044459; Registration date 21/04/2017.

Mechanistic studies on the alleviation of lipid accumulation and oxidative stress by Majia pomelo seed oil

In this study, hot-pressed Majia pomelo seed oil (MPSO), which has high oxidative stability and antioxidant capacity, was used to study the effects and potential mechanisms of lipid accumulation and oxidative stress. The results indicated that the low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) levels in HepG2 cells were lowest when the MPSO concentration was 0.5 mg/mL. At this concentration, MPSO could alleviate oleic acid (OA)-induced lipid accumulation, reduce intracellular lipid level, and decrease lipid and cholesterol synthesis by increasing AMPK phosphorylation and down-regulating the expression levels of genes and proteins of ACC, SREBP-1c, PPAR-γ, and FAS. Meanwhile, MPSO can reduce reactive oxygen species (ROS) and malondialdehyde (MDA) content and enhance superoxide dismutase (SOD) content in HepG2 cells by down-regulating the expression levels of Nrf2, γ-GCS, and HO-1 genes and proteins, thus acting as an anti-oxidative stress. In addition, molecular docking results indicated that the active ingredients of MPSO could effectively bind AMPK protein and Keap1 protein, which further demonstrated that MPSO could alleviate lipid accumulation and oxidative stress.

Assessment of Paraoxonase 1 and Arylesterase Activities and Lipid Profile in Bodybuilders: A Comparative Study of Physical Activity and Anthropometry on Atherosclerosis.

Background and Objectives: Atherosclerosis, driven by dyslipidaemia and oxidative stress, is a leading cause of cardiovascular morbidity and mortality. This study evaluates the effects of vigorous-intensity bodybuilding exercise (VIBBE) on atherosclerosis biomarkers-including paraoxonase-1 (PON1) and arylesterase (ARE) activities-and lipid profiles in male bodybuilders who do not use anabolic-androgenic steroids. Comparisons were made with individuals engaged in moderate-intensity aerobic exercise (MIAE), as well as overweight/obese sedentary (OOS) and normal-weight sedentary (NWS) individuals. Materials and Methods: A cross-sectional study was conducted involving 122 healthy male participants aged 18-45 years, divided into four groups: VIBBE (n = 31), OOS (n = 30), MIAE (n = 32), and NWS (n = 29). Anthropometric assessments were performed, and fasting blood samples were collected for biochemical analyses, including lipid profiles and PON1 and ARE activities. Statistical analyses compared the groups and evaluated correlations between adiposity measures and atherosclerosis biomarkers. Results: The VIBBE group exhibited significantly lower levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and logarithm of the TG to high-density lipoprotein cholesterol (HDL-C) ratio [log(TG/HDL-C)] compared to the OOS group (p < 0.05 for all), indicating improved lipid profiles. However, these improvements were not significant when compared to the NWS group (p > 0.05), suggesting that VIBBE may not provide additional lipid profile benefits beyond those associated with normal weight status. PON1 and ARE activities were significantly lower in the VIBBE group compared to the MIAE group (p < 0.05 for both), suggesting that VIBBE may not effectively enhance antioxidant defences. Correlation analyses revealed significant inverse relationships between PON1 and ARE activities and adiposity measures, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body fat percentage (BFP), fat mass index (FMI), and obesity degree (OD) (p < 0.05 for all). Positive correlations were observed between oxLDL and log(TG/HDL-C) and adiposity measures (p < 0.05 for all). Conclusions: Vigorous-intensity bodybuilding exercise improves certain lipid parameters compared to sedentary obese individuals but does not significantly enhance antioxidant enzyme activities or further improve lipid profiles beyond those observed in normal-weight sedentary men. Conversely, moderate-intensity aerobic exercise significantly enhances PON1 and ARE activities and improves lipid profiles, offering superior cardiovascular benefits. These findings underscore the importance of incorporating moderate-intensity aerobic exercise into physical activity guidelines to optimize cardiovascular health by balancing improvements in lipid metabolism with enhanced antioxidant defences.