Serum Cholesterol Levels Research Articles

Evaluation of Changes in Laboratory Parameters from a Phase 2b Trial of Zasocitinib (TAK-279), an Oral, Selective TYK2 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis

Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective tyrosine kinase 2 inhibitor. In a recent phase 2b trial (NCT04999839), more patients with moderate-to-severe plaque psoriasis treated with zasocitinib 15 and 30 mg once daily achieved 75% improvement in the psoriasis area and severity index at Week 12 (primary endpoint) than those receiving placebo (PBO; p < 0.001). Here we report an assessment of laboratory parameters from this study. Methods: In this randomized, multicenter, double-blinded, PBO-controlled study, adults with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30 mg) or PBO once daily for 12 weeks. The safety analysis set included all patients who received ≥1 dose of the assigned study treatment. Laboratory parameters assessed throughout the trial included creatine kinase (CK), as well as hematologic (neutrophils, lymphocytes, hemoglobin, platelets), hepatic and renal (alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, estimated glomerular filtration rate), and lipid (cholesterol, triglycerides) parameters. Results: In total, 259 patients were included in the safety analysis set. Longitudinal changes in all laboratory parameters were generally similar in the PBO and zasocitinib groups. Mean values of most laboratory parameters remained within normal ranges during the study. There was no relationship between zasocitinib treatment and cytopenia. Some CK elevations were observed in both the PBO and zasocitinib groups, but most were transient or reversible and of Common Terminology Criteria for Adverse Events Grade 1 or 2 (Grade ≥2 events occurred in 2 [3.8%], 2 [4.0%], 6 [11.5%], 4 [7.5%] and 3 [5.8%] patients, in the PBO, and 2, 5, 15 and 30 mg groups, respectively), and were not associated with rhabdomyolysis. Mean triglyceride values were slightly higher than normal ranges at baseline and Week 12 in all treatment groups, including PBO, and were mainly asymptomatic, mild-to-moderate elevations. These changes were not accompanied by increases in serum cholesterol levels. Conclusion: Zasocitinib treatment did not result in adverse changes in hematologic, hepatic, renal or lipid parameters that are associated with Janus kinase (JAK) inhibition, suggesting that the mechanism of action of zasocitinib is distinct from that of JAK1/2/3 inhibition. Further phase 3 studies of zasocitinib in psoriasis are ongoing to confirm these observations (NCT06088043; NCT06108544).

Study the role of xanthine oxidase inhibitor, allopurinol in experimentally induced steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease which can lead to cirrhosis and hepatic failure. It is observed in patients with both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Allopurinol, a xanthine oxidase inhibitor that is widely used in clinical practice, has been demonstrated to reduce hepatic oxidative stress and attenuate acute liver injury which may be through activation of antioxidant pathways. This work aimed at investigating the role of Allopurinol (ALP) in attenuation of type 1 diabetes associated with Nonalcoholic fatty liver disease (NAFLD) and exploring the possible molecular mechanism by which ALP attenuates NASH in type 1 diabetes. Forty-five adult male albino rats were included in the study. They were randomly allocated to 3 equal groups: group I (control), Group II (diabetic animals), Group III (diabetic animals with allopurinol treatment). At the end of this experimental study measurements of serum glucose, ALT, AST, cholesterol, triglyceride, serum levels of uric acid, malondialdehyde (MDA), serum superoxide dismutase (SOD) were done. Histological analysis of liver tissue to diagnose steatohepatitis and gene expression of nuclear factor-erythroid-2- related factor-2 (Nrf2) & TNFα were done. Diabetic rates treated with allopurinol (group III) showed decrease in serum levels of ALT, AST, cholesterol, uric acid and MDA compared to diabetic rat group. As regards TNF, gene expression was significantly decreased in group III compared to group II. This study also demonstrated that Nrf2α was significantly increased in group III compared to group II. Allopurinol also, ameliorated the histopathological changes observed in group II. In conclusion, allopurinol treatment increases the Nrf2 gene expression in the liver of STZ-induced diabetic rats and ameliorates steatohepatitis through modulation of TNF-α gene expression. Allopurinol could be a candidate for prevention or treatment of NAFLD.

Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways

Abstract Background and objective In northern China’s cold regions, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) exceeds 50%, significantly higher than the national and global rates. MASLD is an important risk factor for cardiovascular and cerebrovascular diseases, including coronary heart disease, stroke, and tumors, with no specific therapeutic drugs currently available. The ethanol extract of cassia seed (CSEE) has shown promise in lowering blood lipids and improving hepatic steatosis, but its mechanism in treating MASLD remains underexplored. This study aims to investigate the therapeutic effects and mechanisms of CSEE. Methods MASLD models were established in male Wistar rats and golden hamsters using a high fat diet (HFD). CSEE (10, 50, 250 mg/kg) was administered via gavage for six weeks. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as liver TC and TG, were measured using biochemical kits. Histopathological changes in the liver were evaluated using Oil Red O staining, Hematoxylin-eosin (H&E) staining, and transmission electron microscopy (TEM). HepG2 cell viability was assessed using the cell counting kit-8 (CCK8) and Calcein-AM/PI staining. Network pharmacology was used to analyze drug-disease targets, and western blotting was used to confirm these predictions. Results CSEE treatment significantly reduced serum levels of TC, TG, LDL-C, ALT, and AST, and improved liver weight, liver index, and hepatic lipid deposition in rats and golden hamsters. In addition, CSEE alleviated free fatty acid (FFA)-induced lipid deposition in HepG2 cells. Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK, p-ACC, PPARα, CPT1A, PI3K P110 and p-AKT, while decreasing the protein levels of SREBP1, FASN, C/EBPα, and PPARγ, thus improving hepatic lipid metabolism and reducing lipid deposition. The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro. Conclusion CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK, PPARα, and PI3K/AKT signaling pathways.

Inducible global knockout of surfeit locus protein 4 in adult mice results in hypolipidemia, intestinal lipid accumulation, liver injury, and increased mortality.

Surfeit locus protein 4 (SURF4) acts as a cargo receptor to mediate endoplasmic reticulum export of various cargos. We have shown that SURF4 is essential for secretion of hepatic very low-density lipoprotein and intestinal chylomicron. Knockdown of hepatic Surf4 also significantly reduces the development of atherosclerosis and liver fibrosis without causing overt liver damage. However, constitutive global Surf4 knockout results in embryonic lethality. To further understand the physiological role of Surf4, we generated tamoxifen-inducible global Surf4 knockout mice. We found that conditional knockout of Surf4 in adult mice (Surf4ig-ko) significantly reduced mouse body weight. Male and female Surf4ig-ko mice died approximately 30 and 50 days after tamoxifen administration, respectively. Triglyceride secretion and serum levels of total cholesterol, triglycerides, free fatty acids, apolipoprotein B-100, and apolipoprotein-48 were significantly reduced in Surf4ig-ko mice compared with Surf4flox mice. Proteomics analysis of mouse serum samples revealed 308 proteins with significantly altered expression in Surf4ig-ko mice that have unique functions and are involved in various biological processes. In addition, Surf4ig-ko mice exhibited lipid accumulation in the intestine but not in the liver. However, in Surf4ig-ko mice, liver weight was significantly reduced, and serum transaminase activity was significantly increased, indicating liver damage. Therefore, SURF4 is essential for survival in adult mice, suggesting that the therapeutic use of SURF4 requires precise tissue/cell type-specific targeting.

A review on the treatment of hyperlipidemia with Erchen Decoction

Hyperlipidemia, commonly referred to as dyslipidemia, is characterized by elevated serum cholesterol and/or triglyceride levels. This condition contributes significantly to the high mortality rates associated with cardiovascular diseases, posing a serious threat to global health. Although statins remain the predominant pharmacological treatment for hyperlipidemia, their associated side effects have led to a growing interest in alternative therapeutic approaches. Traditional Chinese Medicine (TCM) is exploring these alternatives, with the Erchen Decoction (ECD) emerging as a promising candidate. This review aims to summarize current clinical research, elucidate the mechanisms of action, and assess the compatibility of ECD in the management of hyperlipidemia. By doing so, we hope to provide valuable insights and references for clinical practice and future research.

Abstract 4135712: Mortality and Cardiovascular Complications Associated with Weight Loss Drugs among Breast Cancer Females Under Cardiotoxic Therapies: A Real-World Populational Study in the United States

Background: Obesity is an adverse prognostic factor for breast cancer (BC). While liraglutide and semaglutide, derived from antidiabetic glucagon-like peptide-1 receptor agonists (GLP1RA), are established weight loss drugs known for their cardiovascular safety in the general obese population, their safety in BC patients undergoing cardiotoxic antineoplastic therapies remains less understood. Objective: To investigate the mortality and cardiovascular outcomes related to GLP1RA used for weight loss among the highly susceptible BC females. Methods: This retrospective cohort study was based on the TrinetX network, comprising real-time health records from over 60 US healthcare organizations. The study population included obese females (≥18 years old) who received at least three prescriptions of either exclusive GLP1RA (liraglutide or semaglutide) or non-GLP1RA weight loss drugs (phentermine, bupropion-naltrexone, orlistat) upon BC diagnosis between 01/01/2015 and 01/01/2022. The index date was the initiation of systemic anti-cancer treatment, including chemotherapy (anthracycline, taxane, or cyclophosphamide), and/or anti-HER2 agents (trastuzumab, pertuzumab, or lapatinib). We used 1:1 propensity score-matching (PSM) to balance demographics, BMI, comorbidities, concurrent medications for cardiovascular diseases and metabolic disorders, BC receptor status and prior treatment, and levels of serum cholesterol (LDL, HDL) and hemoglobin A1c. Cox regression models were applied to compute hazard ratios (HR) and 95% confidence intervals (CIs). Follow-up continued until 05/24/2024, or until adverse cardiovascular events or death occurred. Results: Among 380 PSM-balanced pairs, the GLP1RA group (mean age: 57.6±11) showed significantly lower risks of all-cause mortality (HR 0.593, 95% CI 0.457-0.77), acute heart failure (HR 0.496, 95% CI 0.286-0.859), angina pectoris (HR 0.566, 95% CI 0.343-0.936), and acute stroke (HR 0.661, 95% CI 0.46-0.951) than the non-GLP1RA group (mean age: 57.5±12). Otherwise, no significant difference was shown in acute myocardial infarction (HR 0.787, 95% CI 0.495-1.251), pulmonary hypertension (HR 0.777, 95% CI 0.55-1.099), or arrhythmias (HR 0.829, 95% CI 0.566-1.215). Conclusion: Compared to non-GLP1RA weight loss agents, GLP1RA offers better survival and cardiovascular protection for BC patients undergoing cardiotoxic therapies. Future studies are warranted to validate the safety of these weight loss drugs during the BC treatment continuum.

Effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice.

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities on the manifestation and severity of immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether sex and prevalent cardio-metabolic co-morbidities affect ICI-induced cardiotoxicity, we randomized 17-month-old male and female mice to receive control diet (CON) or high-fat diet (HFD) + L-NAME-a well-established mouse model of cardio-metabolic co-morbidities-for 17weeks (n = 5-7), and evaluated markers of T-cell function in the spleen. As expected, HFD + L-NAME significantly increased body- and heart weight, and serum cholesterol levels, and caused no systolic dysfunction, however, led to diastolic dysfunction, cardiomyocyte hypertrophy, and increased fibrosis only in males compared to corresponding CON. Western blot analyses of splenic immune checkpoint protein levels showed differential expression depending on sex and prevalent cardio-metabolic co-morbidities, suggesting T-cell exhaustion in both sexes on HFD + L-NAME, but more pronounced in males. In a sub-study with a similar setup, we tested cardiotoxic manifestations of ICI by treating mice with anti-PD-1 monoclonal antibody (ICI) for the last 2weeks of diet administration (n = 5-7). After 2weeks of ICI treatment, cardiac systolic functions significantly decreased in CON, but not in HFD + L-NAME groups of both sexes compared to baseline (before ICI administration). In conclusion, in this exploratory study using aged mice, we describe for the first time that ICI-related systolic dysfunction is diminished in both sexes when obesity and hypercholesterolemia are present, possibly due to obesity-related T-cell exhaustion.

Predictive Value of NT-proBNP, FGF21, Galectin-3 and Copeptin in Advanced Heart Failure in Patients with Preserved and Mildly Reduced Ejection Fraction and Type 2 Diabetes Mellitus

Background and Objectives: Heart failure (HF) is one of the most common initial presentations of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). There are different cardiac biomarkers related to the pathophysiological mechanisms of HF in T2DM. The current research aims to identify additional biomarkers that could improve the diagnosis and prognosis of HFpEF, which is currently assessed using NT pro-BNP levels. NT pro-BNP is a valuable tool for diagnosing heart failure but may not always correlate with clinical symptom severity or can present normal levels in certain cases, such as obesity. Biomarkers like FGF-21 and galectin-3 could provide greater insight into heart failure severity, especially in diabetic patients. The main objective of the current study is to assess the performance of NT-proBNP, FGF21, Galectin-3 and Copeptin to discriminate between advanced and mild HF. Materials and Methods: A total of 117 patients were enrolled in this study and divided into two groups: 67 patients in NYHA functional class I-II (mild HF) and 50 patients in NYHA III-IV (advanced HF). NT-pro BNP, FGF21, Galectin 3 and Copeptin serum levels were determined with the ELISA method. Receiver operating characteristic (ROC) analysis and binomial logistic regression analysis were used to measure the ability of the studied biomarkers to distinguish between advanced and mild HF patients. Results: In patients with T2DM with advanced HF, serum FGF21 level was significantly positively correlated with eGFR (ρ = 0.35, p = 0.0125) and triglycerides (ρ = 0.28, p = 0.0465) and significantly negatively correlated with serum levels of HDL cholesterol (ρ = −0.29, p = 0.0386) and with RV-RA gradient (ρ = −0.30, p = 0.0358). In patients with mild HF, serum FGF21 level was significantly negatively correlated with NT-proBNP levels (ρ = −0.37, p = 0.0022), E/e’ ratio (ρ = −0.29, p = 0.0182), TR velocity (ρ = −0.24, p = 0.0470) and RV-RA gradient (ρ = −0.24, p = 0.0472). FGF21 (AUC = 0.70, 95% CI: 0.60−0.79) and NT-proBNP (AUC = 0.73, 95% CI: 0.63–0.82) demonstrated significant predictive value to discriminate T2DM patients with advanced HF from those with mild HF. Elevated values for FGF21 (≥377.50 ng/mL) or NTproBNP (≥2379 pg/mL) were significantly associated with increased odds of advanced HF after adjusting for demographic and clinical covariates. Conclusions: NTpro-BNP and FGF21 have a similar ability to discriminate T2DM patients with advanced HF from those with mild HF. Univariable and multivariable logistic models showed that, FGF21 and NTproBNP were independent predictors for advanced HF in patients with preserved and mildly reduced ejection fraction and T2DM.

The Relationship Between Serum Cholesterol, Triglycerides, and Self-Reported Appetitive and Reactive Aggression, as Well as Violent Crimes in Male Forensic Patients with Substance Use Disorder

Numerous studies have linked lower levels of serum cholesterol with heightened aggression, violent crimes, and violent deaths across diverse populations, including forensic psychiatric patients, criminals, and the broad public. Interestingly, this association appears to be more pronounced in men than in women. Conversely, findings regarding serum triglycerides present a more nuanced picture, with some studies indicating heightened aggression with elevated levels and others suggesting the opposite. However, most studies have neglected to examine this phenomenon in conjunction with psychological traits. Additionally, no prior research has explored the association between serum lipid levels and different types of aggression, e.g., reactive, instrumental, or appetitive. Considering these gaps, our study aimed to assess serum cholesterol and triglyceride levels upon clinic admission and correlate them with scores from the Appetitive and Facilitative Aggression Scale (AFAS), a self-rating questionnaire assessing reactive and appetitive aggression. We conducted our investigation on a cohort of 135 forensic psychiatric patients undergoing drug addiction treatment under Section 64 of the German Criminal Code. This provision offers a nearly unique opportunity worldwide for individuals who have committed crimes under the influence of drugs or in the context of their addiction to receive specialized treatment. Using non-linear Spearman correlation analyses, we observed an inverse relationship between serum concentrations of both cholesterol and triglycerides and AFAS appetitive violence scores but not for reactive aggression. Additionally, triglyceride levels exhibited an inverse association with the prevalence of violent crimes as an index crime. In conclusion, blood lipids may affect numerous areas of health and disease beyond what is currently known, offering a potential shift in how we understand their role in aggression.

The influence of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra on rat liver function and structure

Background. Tea mistletoe (Scurrula atropurpurea (Blume)) and mango mistletoe (Dendrophthoe pentandra) have been known as a potential medicine for several diseases.Objective: to investigate the effect of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra (MESA-DP) on rat liver function and structure using serological and histopathological analysis.Material and methods. This study was experimental during 28 days using 20 rats divided into four groups (Group 1 as a control, while Groups 2, 3, and 4 were given MESA-DP at doses 250, 500, and 1,000 mg/kg of body weight, respectively). The liver histopathological structure was observed using hematoxylin-eosin staining. The liver function assessment included total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total protein, albumin, globulin, cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. Data were analyzed using a one-way ANOVA analysis (ANalysis Of VAriance) and performed via SPSS Statistics 17.0 (IBM, USA).Results. The administration of MESA-DP did not show significant differences at all doses for the liver rat function in total bilirubin, SGOT, SGPT, albumin, cholesterol and triglycerides (p>0.05), while globulin, total protein, HDL and LDL showed significant results (p<0.05). The liver histopathological structure showed the number of pyknotic, karyorrhectic and karyolytic cells in rats after MESA-DP administration compared to controls, which grew with increasing dose.Conclusion. The liver function in rats after being exposed to MESA-DP was not affected in terms of total bilirubin, SGOT, SGPT, albumin, cholesterol, and triglyceride levels. However, using MESA-DP increased the necrotic liver cells. It may be beneficial for the liver health of experimental animals taking into account the correct dosage.

Fibrinogen-Like Protein 2 Protects the Aggravation of Hypertriglyceridemia on the Severity of Hypertriglyceridemia Acute Pancreatitis by Regulating Macrophages.

The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP. Both wild-type and FGL2 gene knockout C57BL/6 mice were utilized to establish HTG, AP, and HTG-AP models using P-407 and/or caerulein. Serum levels of triglycerides, total cholesterol, amylase, and lipase were assessed via biochemical analysis. Pancreatic and lung tissue injuries were evaluated using hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels in serum and pancreatic tissues were quantified using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of FGL2, the macrophage marker CD68, and M1/M2 macrophage markers iNOS/CD163. The animal models were successfully established. Compared to wild-type mice, FGL2 knockout resulted in increased pathological injury scores in the pancreas and lungs, as well as elevated TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissue in the HTG group, with more pronounced effects observed in the HTG-AP group. The AP group alone did not exhibit significant changes due to FGL2 knockout. Further analysis revealed that FGL2 knockout increased CD68 expression but reduced CD163 expression in the pancreatic tissues in the HTG group. In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression. FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.

Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes.

Lipid droplets (LDs) serve as crucial hubs for lipid trafficking and metabolic regulation through their numerous interactions with various organelles. While the interplay between LDs and the Golgi apparatus has been recognized, their roles and underlying mechanisms remain poorly understood. Here, we reveal the role of Ras-related protein Rab-2A (Rab2A) in mediating LD-Golgi interactions, thereby contributing to very-low-density lipoprotein (VLDL) lipidation and secretion in hepatocytes. Mechanistically, our findings identify a selective interaction between Golgi-localized Rab2A and 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) protein residing on LDs. This complex facilitates dynamic organelle communication between the Golgi apparatus and LDs, thus contributing to lipid transfer from LDs to the Golgi apparatus for VLDL2 lipidation and secretion. Attenuation of Rab2A activity via AMP-activated protein kinase (AMPK) suppresses the Rab2A-HSD17B13 complex formation, impairing LD-Golgi interactions and subsequent VLDL secretion. Furthermore, genetic inhibition of Rab2A and HSD17B13 in the liver reduces the serum triglyceride and cholesterol levels. Collectively, this study provides a new perspective on the interactions between the Golgi apparatus and LDs.

Teriparatide administration is osteoanabolic but does not impact atherosclerotic plaque calcification and progression in a mouse model of menopause

Menopause exacerbates osteoporosis and increases the risk of atherosclerotic plaque rupture, leading to cardiovascular mortality. Osteoporotic women are increasingly treated with teriparatide (TPTD, 1–34 parathyroid hormone), one of the few treatments that stimulate bone formation. Despite the fact that atherosclerotic plaque calcification is a hallmark of plaque development, the impact of TPTD administration on plaque calcification remain unclear. In this context, we sought to determine the effects of TPTD administration on atherosclerosis in ovariectomized (OVX) apolipoprotein E deficient mice (ApoE−/−), as a model of postmenopausal osteoporosis. OVX ApoE−/− mice, fed a high fat, high cholesterol diet to induce atherosclerosis, received either vehicle or TPTD daily injections (40 μg/kg/d) for 4 or 10 weeks, at which points plaques are respectively weakly and heavily calcified. After sacrifice, bone remodeling was evaluated by serum markers and bone histomorphometry. Bone architectural parameters were measured by μCT. Aortic plaques were analyzed histologically, and their calcification with von Kossa staining and the calcium tracer Osteosense. Plaque inflammation and calcification markers were measured by RT-qPCR. Intermittent TPTD increased bone volume in OVX mice, due to a higher stimulation of bone formation relatively to bone resorption. These effects were not accompanied by changes in serum levels of cholesterol, triglycerides, glucose or insulin. TPTD neither significantly affected aortic plaque size, inflammation, and calcification, even if it slightly increased vascular smooth muscle cell transdifferentiation into calcifying cells. In conclusion, TPTD exhibits osteoanabolic effects in OVX ApoE−/− mice, without significantly influencing atherosclerotic plaque progression or calcification in the short term.

Leukemia Inhibitory Factor Receptor inhibition by EC359 reduces atherosclerotic stenosis grade in Ldlr-/- mice

Cytokines are involved in all stages of atherosclerosis, generally contributing to disease progression. Previously, members of the IL-6 cytokine family, such as Interleukin-6, oncostatin M, and cardiotrophin-1, have been extensively studied in atherosclerosis. However, the role of leukemia inhibitory factor (LIF), member of the IL-6 family, and its receptor (LIFR), remains to be further elucidated. Therefore, the aim of this study is to provide insight in LIF receptor signalling in atherosclerosis development.Single-cell RNA sequencing analysis of human carotid artery plaques revealed that mast cells highly express LIF, whereas LIFR was specifically expressed on activated endothelial cells. A similar expression pattern of Lifr was observed in mouse atherosclerotic plaques. Next, female Western-type diet fed Ldlr-/- mice were treated with LIF receptor inhibitor EC359 (5 mg/kg s.c., n=15) or control solvent (n=15) three times per week for eight weeks. Stenosis grade was reduced in the aortic root of EC359 treated mice compared to control mice, but treatment did not affect plaque composition. Serum cholesterol levels were significantly reduced in EC359 treated mice, likely attributed to a reduction in VLDL cholesterol levels. Furthermore, LIF receptor inhibition reduced Pecam1 and Vcam1 expression in the aorta. Consequently, immune cell infiltration was reduced in aortic plaques of EC359 treated mice compared to control mice.Conclusively, we demonstrated that LIF receptor is a potential therapeutic target in atherosclerosis by reducing plaque size, attributed to lower serum cholesterol levels, reduced endothelial activation and less immune cell infiltration in the plaque.

Evaluation of the Efficacy of Diosmin and Chrysin against Tau-fluvalinate Exposure in Rats

Tau-fluvalinate is a type 2 pyrethroid insecticide. Diosmin and chrysin are flavonoids with antioxidant and anti-apoptotic effects. Role of diosmin and chrysin against infavorable toxic effects caused by tau-fluvalinate and the underlying mechanisms of these effects were investigated. A total of 6 groups were formed and diosmin, chrysin, tau-fluvalinate, tau-fluvalinate+diosmin and tau-fluvalinate+chrysin were administered orally to rats at a dose of 20 mg/kg.bw from each, once a day for 21 days, respectively. Tau-fluvalinate elevated MDA and NO levels while diminishing the activities of antioxidant enzymes (SOD, CAT, GSH-Px, GR, GST, G6PD) and GSH levels in the majority of the analyzed blood and tissues, statistically significant. Serum triglyceride, cholesterol, total protein and albumin levels as well as LDH and PChE activities decreased. Conversely, serum creatinine, AST, ALT and ALP levels/activities increased. Elevated protein levels of caspase 3, caspase 9, p53 and Bax and decreased protein levels of Bcl-2 were observed in the liver. There were negative changes in body/some organ weights. Diosmin and chrysin administration resulted in a marked recovery in tau-fluvalinate-induced toxic effects, but this improvement was not complete. These flavonoids may be considered as promising potential therapeutic options to alleviate the adverse effects associated with tau-fluvalinate intoxication.

Efficacy of Beetroot Juice Supplementation on Lowering Blood Pressure in Hypertensive Patients – A Single Centre Study

I Background : Quasi -interventional pretest posttest research design was adopted to investigate beetroot juice supplementation on reduction of blood pressure and serum cholesterol levels among 60 hypertensive clients with hyperlipidemia using non probability purposive sampling technique Methodology: On Day-1: The demographic and clinical information was gathered by using a self-structured questionnaire . On Day -2, the pretest level of hyperlipidemia was estimated and also, the pretest blood pressure level was assessed using sphygmomanometer. From Day-3, 200ml of beetroot juice was administered once a day for 30 days. On Day- 34 study participants were re-assessed to estimate the levels hyperlipidemia and blood pressure. Results: The study results concluded that, the pretest and posttest mean score with mean difference score of SBP and DBP in the Interventional Group was141.46±10.43,88.60±5.48 and 128.40±7.13 ,83.20±4.65 with mean difference score was13.06, 5.40 The calculated paired ‘t’ test value of SDP and DBP t =12.558 , 5.964 was statistically significant at p<0.001 Level. The pretest and posttest with mean difference score of total cholesterol,LDL,HDL, triglyceride , cholesterol/HDLratio in the interventional group was 176.86±14.26,103.60±9.68,36.96±4.73,156.53±32.48, 4.45±0.82 and 170.10±15.37,92.96±9.20,41.96±6.08,138.83±26.48,4.00±0.75with mean difference score was 6.76,10.64,5.0,17.70, 0.45.The calculated Paired ‘t’ test value of t =10.329,15.804, 7.816,10.652,14.879 was statistically significant at p<0.001 level.this clearly shows that after administered beetroot juice the blood pressure and serum cholesterol levels was significantly reduced in the Interventional group. Conclusion: administered Beetroot juice proved to be an effective intervention in reducing the blood pressure and serum cholesterol level among hypertensive patients with hyperlipidemia

A prospective study on prognostic value of hypocholestrolemia in sepsis

Background: Sepsis is a major cause of mortality in adult, non-coronary intensive care units (ICUs) and holds significant clinical importance. Multicentre prospective surveys have shown that 1% of hospitalized patients experience bacteraemia, with 0.3% suffering from bacteraemia with severe sepsis. These rates increase eightfold and thirtyfold, respectively, when ICU admissions are considered. Approximately 10% of ICU patients have sepsis, 6% have severe sepsis, and 2-3% experience septic shock. Aim: This study aimed to assess the dynamic changes in serum cholesterol levels in sepsis patients and evaluate whether these cholesterol levels correlate with prognosis using the Sequential Organ Failure Assessment (SOFA) score. Materials and methods: A comprehensive analysis was conducted over 18 months on 115 patients with sepsis. SOFA scores and lipid profiles were collected at ICU admission (day 0) and day 3. Patients were categorized into two groups based on their total cholesterol: Group A (<160 mg/dl) and Group B (>160 mg/dl). Statistical analysis was performed to examine differences. Results: The study found that 56.5% of patients had cholesterol <160 mg/dl (Group A) and 43.5% had >160 mg/dl (Group B). Significant differences in cholesterol and SOFA scores between groups were observed on days 0 and 3 (p < 0.001). Mortality was higher in Group B, indicating that hypocholesterolaemia is associated with increased mortality risk. Conclusion: This study suggests that monitoring cholesterol levels can serve as a prognostic tool in sepsis. An increasing cholesterol trend may indicate a better disease outcome.

Impact of nutrition-related laboratory tests on mortality of patients who are critically ill using artificial intelligence: A focus on trace elements, vitamins, and cholesterol.

This study aimed to understand the collective impact of trace elements, vitamins, cholesterol, and prealbumin on patient outcomes in the intensive care unit (ICU) using an advanced artificial intelligence (AI) model for mortality prediction. Data from ICU patients (December 2016 to December 2021), including serum levels of trace elements, vitamins, cholesterol, and prealbumin, were retrospectively analyzed using AI models. Models employed included category boosting (CatBoost), extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), and multilayer perceptron (MLP). Performance was evaluated using area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, and F1-score. The performance was evaluated using 10-fold crossvalidation. The SHapley Additive exPlanations (SHAP) method provided interpretability. CatBoost emerged as the top-performing individual AI model with an AUROC of 0.756, closely followed by LGBM, MLP, and XGBoost. Furthermore, the ensemble model combining these four models achieved the highest AUROC of 0.776 and more balanced metrics, outperforming all models. SHAP analysis indicated significant influences of prealbumin, Acute Physiology and Chronic Health Evaluation II score, and age on predictions. Notably, the ratios of selenium to age and low-density lipoprotein to total cholesterol also had a notable impact on the models' output. The study underscores the critical role of nutrition-related parameters in ICU patient outcomes. Advanced AI models, particularly in an ensemble approach, demonstrated improved predictive accuracy. SHAP analysis offered insights into specific factors influencing patient survival, highlighting the need for broader consideration of these biomarkers in critical care management.

Quercetin supplementation in metabolic syndrome: nutrigenetic interactions with the Zbtb16 gene variant in rodent models

BackgroundQuercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16).ResultsQuercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q.ConclusionQuercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene.

Study of antidiabetic activity of Aegle marmelos in streptozotocin-induced hyperglycemic Wistar rats in a tertiary care hospital

Background: Diabetes has become a major metabolic disorder disease that is increasingly becoming a killer disease worldwide. The aim of this study was to evaluate (bael tree) Aegle marmelos whole plant extract has the potential efficiency to control hyperglycemia, that affects kidney and lipid profile, in streptozotocin induced rats. This study aimed to evaluate the Antidiabetic activity of, Aegle marmelos in streptozotocin-induced hyperglycemic Wistar rats. Methods: Wistar rats of either sex were used grouped into six groups of six rats each. The first group was used as control, the second group was induced diabetes by inducting streptozotocin 70 mg/kg i.p., The 3rd,4th, 5th and 6th group was induced diabetes and treated with Metformin 600 mg/kg, A. marmelos methanol whole plant extract in the increasing dosage of 100 mg/kg, 200 mg/kg and 400 mg/kg body weight from the 7th to 28th day respectively. The blood samples were collected at day 0,7 and 28th day for estimation of fasting blood sugar, serum cholesterol, triglycerides and creatinine. Results was presented as the mean standard deviation (SD). A one-way analysis variance was performed using SPSS-17 and Graphpad Prism 5 statistical software. Results: After administration of Aegle marmelos extract in increasing level, fasting glucose level was significantly (p < 0.05) reduced. Also, there is significant reduction in serum cholesterol level, triglyceride level and creatinine level. The effect was more after 28 days of treatment. Conclusions: The study results indicate the active compounds in the Aegle marmelos whole plant methanol extract has antidiabetic and antilipidemic activity. It can also protect kidney to some extent.