Reduction In Cholesterol Levels Research Articles

The Safety Profile of Inclisiran in Patients with Dyslipidemia: A Systematic Review and Meta-Analysis

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. It has demonstrated a significant reduction in LDL cholesterol levels compared to a placebo. We aim to comprehensively evaluate the safety of using Inclisiran in patients with dyslipidemia and ASCVD or an ASCVD risk equivalent. Methods: Four electronic databases, namely, Pubmed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, were searched from inception to June 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of Inclisiran and the control group. The outcomes investigated were all-cause mortality, major adverse cardiovascular events (MACEs), injection-site adverse events, new-onset or worsening type 2 diabetes mellitus (T2DM), and nasopharyngitis. The effect estimates of outcomes were assessed using the risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method. Subgroup analysis was performed based on different dosing regimens. Results: The study included 7 RCTs, enrolling 4790 patients (age 63.8 ± 9.7 years, 33.2% females) who received Inclisiran. Compared to the control group, Inclisiran use did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I2 = 0%), MACEs (RR, 0.98; 95% CI, 0.82 to 1.17; I2 = 0%), nasopharyngitis (RR, 1.10; 95% CI, 0.83 to 1.45; I2 = 0%), and T2DM (RR, 1.02; 95% CI, 0.85 to 1.21; I2 = 0%). However, Inclisiran use demonstrated a significant increase in injection-site adverse events (RR, 6.50; 95% CI, 3.20 to 13.20; I2 = 29%). Conclusions: Inclisiran use significantly increased injection-site reactions, with no increase in mortality, T2DM, or nasopharyngitis. It demonstrates a generally favorable safety profile, making it a promising option for lipid management in individuals at high cardiovascular risk, such as those with ASCVD or equivalent conditions. While it effectively improves dyslipidemia, decision-makers should be aware of an increased incidence of injection-site reactions, which, though typically mild, warrant consideration in clinical practice. Further trials are required to assess the safety of Inclisiran, particularly the association of the severity of injection-site adverse events over longer treatment durations.

LC-MS/MS-based proteomics and metabolomics of HCT-116 colorectal cancer cells: A potential anticancer activity of atorvastatin

Colorectal cancer (CRC) is the third most prevalent tumor in men, the second most common in women, and the fourth leading cause of mortality worldwide. Statins reduce cholesterol levels by hampering the function of 3-hydroxy-3-methyl-glutaryl-CoA reductase enzymes in cholesterol synthesis. Strains have shown anticancer effects against CRC. However, statins’ anticancer mechanism is yet unknown. Liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomics and proteomics were employed to study statins’ effects on CRC using the CRC cell line HCT-116. These approaches were utilized to identify potential underlying metabolic pathways and proteins altered in atorvastatin (a statin)-treated HCT-116 cells. Compared to the control, atorvastatin significantly altered numerous metabolites in HCT-116 cells, including a reduction in the levels of decanoylcarnitine and octanoyl-L-carnitine and in the biosynthesis and metabolism of amino acids like alanine and citrate cycle. Proteomic study showed that atorvastatin-treated HCT-116 cells expressed 127 proteins differently from controls. Novel findings were among them, such as centromere-associated protein E, cytochrome c oxidase subunit 6A1 mitochondrial, and hyaluronan synthase 1. The findings indicate that atorvastatin may have potential anticancer characteristics and highlight the essential role metabolomics and proteomics to understand complex metabolic pathways and proteins relevant to cancer and develop novel treatment targets.

Unraveling the Role of Quinoa in Managing Metabolic Disorders: A Comprehensive Review.

The review aims to address the knowledge gap and promote the widespread adoption of quinoa as a functional food for improving metabolic health. By presenting a comprehensive overview of its nutritional profile and bioactive components, the review aims to increase consumers' awareness of the potential therapeutic benefits of incorporating quinoa into diets. Recent studies have highlighted the diverse range of bioactive compounds in quinoa, such as phytosterols, saponins, phenolic acids, phytoecdysteroids, and betalains. These compounds exhibit various health-promoting properties, such as anti-inflammatory, antioxidant, antidiabetic, and gut microbiota-modulating effects. Furthermore, research indicates that regular quinoa consumption can improve metabolic parameters, including reduced cholesterol levels, blood sugar, fat accumulation, and blood pressure. These findings highlight the potential of quinoa as a dietary tool for preventing and managing metabolic disorders, such as obesity, cardiovascular diseases, diabetes, and gut dysbiosis. The article concludes that quinoa has emerged as a promising solution to food security challenges due to its adaptability to diverse environments and rich nutritional profile. However, some findings are not consistent in the mentioned studies, therefore, well-designed cohort randomized clinical trials with diverse populations are needed. While in vivo studies are necessary to elucidate the specific mechanisms behind the potential benefits of quinoa.

Asparagopsis taxiformis supplementation to mitigate enteric methane emissions in dairy cows - effects on performance and metabolism.

Methane emissions from ruminant digestion contribute significantly to global anthropogenic greenhouse gas emissions. Members of the phylum Rhodophyta (red algae), particularly Asparagopsis sp., have shown promising results in reducing methane emissions in ruminants, due to their high content of halogenated methane analog compounds. However, knowledge is lacking regarding the effects of red algae on animal performance and metabolism. This study investigated the effects of dairy cow diet supplementation with Asparagopsis taxiformis on enteric methane performance, metabolism of bromine and iodine, and health status of the cows. Thirty lactating Nordic Red dairy cows fed a total mixed ration, were blocked according to parity and days in milk, and randomly assigned to one of 3 diets: a control diet with no Asparagopsis taxiformis (CON), a diet with 0.15% Asparagopsis taxiformis on an organic matter (OM) basis (L-AT), and a diet with 0.3% Asparagopsis taxiformis on an OM basis (H-AT). The cows were fed the experimental diets continuously for 13 weeks, beginning with a baseline week (wk 0), which served as covariate by week where all cows received the basal diet. Individual feed intake and milk yield were recorded automatically throughout the experiment. Milk composition was determined by collecting milk samples during each milking session on 2 consecutive days every experimental week. While enteric methane and hydrogen levels were measured continuously by the GreenFeed system. Feces grab samples were collected as spot samples from a subset of 6 cows per treatment after milking during sampling wk 0, 2, 4, 8, and 12. Urine spot samples were collected from the same subset of cows during the same weeks as fecal samples. One urine sample was taken per day on 2 consecutive days, and the samples were analyzed for wk 12. Rumen fluid was collected after morning milking using a stomach tube in wk 0, 2, 4, and 12. We observed a 30% reduction in methane production in the H-AT group, with a concomitant increase in hydrogen production by 383%. However, the interaction between treatment and week showed that the AT effect on methane reduction began to diminish by wk 9 of the experiment. In the L-AT group, methane was reduced by 7.6% and hydrogen production was increased by 70%. However, dry matter intake (DMI) was 7% lower and energy-corrected milk (ECM) yield was 2% lower in the H-AT group compared with the other 2 groups. Total concentration of volatile fatty acids in rumen fluid was lower in the H-AT group compared with CON, with a reduction in acetate concentration and an increase in propionate, butyrate and valerate in the H-AT group. Bromine concentration was 5-fold higher and iodine concentration was 9-fold higher in milk from the H-AT group compared with CON. Bromine concentration in feces and urine samples from H-AT cows was approximately 4-fold and 9-fold higher, respectively, than in samples from CON cows. Metabolic profiling revealed a reduction in cholesterol levels and a decrease in the ferric-reducing ability of plasma in the H-AT treatment group compared with the CON group, as well as an increase in plasma magnesium concentration in the H-AT group. In conclusion, using 0.3% Asparagopsis taxiformis as an additive in dairy cow feed rations can mitigate enteric methane emissions, but this reduction was observed only during the first 8 weeks of the experiment, with no effect on methane emissions from wk 9 to 12. Additionally, it may have negative effects on DMI and ECM yield. Further long-term studies on red algae as methane inhibitor is needed to examine its sustained inhibitory effects over time and its impact on various metabolic processes. The effects appear to decline after wk 8 and influence several metabolic mechanisms.

Assessing the physicochemical and sensory attributes of yogurt enriched with mango and potato peel powders and their hypolipidemic effects on rats consuming a high-fat diet

Enhancing dairy products with bioactive functional foods and plant-derived compounds boosts their nutritional value and health benefits. The objective of the present study was to evaluate the physical, chemical, and sensory properties of yogurt that had been enriched with mango and potato peel powder at levels 1, 2, and 3%. The results demonstrated that fortifying yogurt with 3% potato and mango peel significantly enhanced its nutritional and functional qualities, as total solids increased from 13.34% in the control yogurt to 15.14 and 15.84% in the potato and mango peel-fortified versions, respectively. Protein content also rose from 3.78 to 3.94 and 4.05%, while ash levels improved from 0.78 to 0.90 and 0.98%. Additionally, fiber, which was absent in the control, reached 0.47 and 0.20% in the potato and mango peel-fortified yogurt, respectively. This fortification also led to a sharp increase in phenolic content, from 40.60 mg GAE/g in the control to 53.70 and 65.90 mg GAE/g, alongside a notable improvement in antioxidant activity, which increased from 20.60 to 33.50 and 40.80%. Together, these findings highlight the substantial positive impact of fortification on both nutritional composition and potential health benefits of yogurt. The strongest sensory features were seen in yogurt containing 2% mango and potato peel powder with a total score of 93.0 when compared to other treatments. In addition, the 2% mango and potato peel powder-fortified yogurt was tested as a hypercholesterolemia inhibitor in obese rats. Forty male Wistar rats were divided into five groups. The first group served as the healthy control group, while Groups 2 through 5 were fed a high-fat, high-cholesterol diet for the duration of the experiment and given 10 g/day of various types of yogurt: yogurt with 2% mango powder and 2% potato peel powder as a treatment. The findings revealed a considerable reduction in LDL, cholesterol, triglycerides, AST, ALT, creatinine, and urea levels as compared to the positive control group, combined with a marked rise in HDL and total protein levels. According to the findings, yogurt, mango, and potato peel powder help liver and kidney functions in hyperlipidemic rats. Collectively, these data showed that yogurt, mango, and potato peel powder shielded rats from oxidative stress and hyperlipidemia.

Virtual screening and evaluation of bioactive peptides from Haliotis discus hannai as potential HMGCR inhibitors for hyperlipidemia treatment.

Hyperlipidemia remains a major disease threatening global public health. The morbidity and mortality associated with cardiovascular diseases have been increasing. The inhibition of 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a key enzyme in the cholesterol synthesis pathway, can effectively reduce cholesterol levels. In this study, the most suitable protease for preparing HMGCR inhibitory peptides was screened using the evaluation indexes of peptide yield and HMGCR inhibition rate. Peptide sequences with molecular weights <1 kDa were identified, and peptide fragments were docked with HMGCR for virtual screening. The inhibitory effects of these peptides on HMGCR activity were evaluated in vitro using a high-fat Hep-G2 cell model. The screened peptides possessed significant HMGCR inhibitory activity and reduced cholesterol micelle solubility and total cholesterol and triglyceride levels in hyperlipidemic Hep-G2 cells. This study provides novel insights into developing natural drugs for hyperlipidemia; moreover, the results will facilitate the functional application of marine bioactive peptides.

Evaluating chia (Salvia hispanica L.) seed administration for cholesterol reduction in quail (Coturnix coturnix)

Chia (Salvia hispanica L.) seeds contain phenolic compounds such as flavonols and phenolic acids (myricetin, quercetin, kaempferol, caffeic acid) that act as primary and synergistic antioxidants. These antioxidants reduce cholesterol by inhibiting absorption in the intestine and enhancing bile acid formation, facilitating cholesterol excretion through feces. Additionally, the high protein and fiber content in S. hispanica L. seeds reduces appetite and promotes prolonged satiety. This study evaluates the effect of different administration patterns of S. hispanica L. seeds on cholesterol reduction in common quail (Coturnix coturnix). The research involved five groups: three treatment groups receiving S. hispanica L. seeds at varying frequencies (once, twice, three times daily) and two controls (positive, negative), with six C. coturnix in each group. The S. hispanica L. seed dose was 1.8 mg per 200 g body weight (BW) administered for 30 days. Cholesterol levels were measured at baseline and after treatment and analyzed using one-way ANOVA and Duncan’s Post Hoc Test. Results indicated that administering S. hispanica L. seeds three times daily significantly reduced cholesterol levels (p &lt; 0.05) compared to other frequencies. This research provides a foundation for further exploration into practical applications of S. hispanica L. seeds in cholesterol management, both in animals and potentially in humans.

Efek Pendidikan Kesehatan terhadap Pengetahuan Lansia dalam Pencegahan Kolestrol

Prevention of cholesterol can be carried out for all individuals with cholesterol issues. Several natural, safe, and effective ways to reduce cholesterol levels include consuming cholesterol-lowering foods, exercising regularly, reducing sugar intake, avoiding smoking, limiting alcohol consumption, managing stress, and taking additional cholesterol-lowering supplements. The purpose of this study is to determine the relationship between health education and elderly knowledge regarding cholesterol prevention. The research method used is a quasi-experimental design. The population in this study consisted of 40 elderly individuals in Karampuang Village, with a total sampling technique used to select all 40 participants. Data were analyzed using a paired test to determine the p-value. Before receiving health education, the majority of the elderly participants (57.5%) had poor knowledge, and none were categorized as having good knowledge. After health education, 85.0% of the participants reached the good knowledge category, while the moderate knowledge category decreased to 15.0%, and no participants remained in the poor knowledge category. Health education significantly improved the level of knowledge among the elderly regarding cholesterol prevention.

Консервы из скумбрии дальневосточной и их функциональное значение

Research has been conducted to establish the positive effect of canned Far Eastern mackerel on the human body. The composition of fatty acids in canned mackerel natural and with the addition of oil was studied and nutritional quality indices of lipids were determined. It has been established that the group of polyunsaturated fatty acids predominates in the lipids of canned food. Canned Far Eastern mackerel are sources of eicosapentaenoic and docosahexaenoic acids. Based on food lipid quality indices, the potential ability of canned food to reduce cholesterol levels in human blood, as well as the intensity of blood clot formation in blood vessels, is substantiated.

Phenolic and Flavonoids Contributions to the Antioxidant, Antidiabetic, and Anticholesterol Activities of Eriobotrya japonica Fruit Extract: An In Vitro Analysis

Eriobotrya japonica has been traditionally used for its medicinal properties. This study investigates its fruit ethanol extract's phenolic and flavonoids profiles and evaluates its antioxidant, antidiabetic, and anticholesterol activities. Eriobotrya japonica fruit ethanol extract was tested for total phenolic and flavonoid content using Folin-Ciocalteu and AlCl3 methods. The antioxidant capacity was assessed by DPPH and metal chelation assays. The antidiabetic action was assessed using α-glucosidase inhibition and the Nelson-Somogyi method, whereas the Liebermann-Burchard method was used to measure anticholesterol. The extract exhibited large quantities of phenolics (38.62 mg GAE/g) and flavonoids (4.23 mg QE/g), demonstrating robust antioxidant activity with IC50 of 55 μg/mL by DPPH method and substantial inhibition (71%) by metal ion chelation. In addition, it exhibited strong antidiabetic effects 2.42 μg/mL in the α-glucosidase inhibition test, and at 10 μg/mL using the Nelson-Somogyi method resulted in a 24.02% yield. The extract demonstrated a significant reduction in cholesterol levels during the process of cholesterol reduction, obtaining a maximum reduction of 47.31% at the highest concentration tested. Ethanol extract of Eriobotrya japonica can be used in treating oxidative stress and diabetes and introduce its potential to reduce cholesterol levels. The high content of phenolic and flavonoids total contributes to its bioactivities, indicating its potential as a functional food ingredient.

Impact of statin therapy on CD40:CD40L signaling: mechanistic insights and therapeutic opportunities.

Statins are widely utilized to reduce cholesterol levels, particularly in cardiovascular diseases. They interface with cholesterol synthesis by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase enzyme. Besides their primary effect, statins demonstrate anti-inflammatory and immune-modulating properties in various diseases, highlighting the pleiotropic effect of these drugs. The CD40:CD40L signaling pathway is considered a prominent inflammatory pathway in multiple diseases, including autoimmune, inflammatory, and cardiovascular diseases. The findings from clinical trials and in vitro and in vivo studies suggest the potential anti-inflammatory effect of statins in modulating the CD40 signaling pathway and downstream inflammatory mediator. Accordingly, as its classic ligand, statins can suppress immune responses in autoimmune diseases by inhibiting CD40 expression and blocking its interaction with CD40L. Additionally, statins affect intracellular signaling and inhibit inflammatory mediator secretion in chronic inflammatory diseases like asthma and autoimmune disorders such as myasthenia gravis, multiple sclerosis, systemic lupus erymanthus, and cardiovascular diseases like atherosclerosis. However, it is essential to note that the anti-inflammatory effect of statins may vary depending on the specific type of statin used. In this study, we aim to explore the potential anti-inflammatory effects of statins in treating inflammatory diseases by examining their role in regulating immune responses, particularly their impact on the CD40:CD40L signaling pathway, through a comprehensive review of existing literature.

Evaluation of the Hypoglycemic Activity of Methanolic Extract of Foeniculum Vulgare in Streptozotocin-induced Diabetic Wistar Rats.

This study aimed to assess the hypoglycemic effects of methanolic extract of Foeniculum vulgare in male Wistar rats that were diabetic due to streptozotocin. Experimental diabetes was initially induced in male Wistar rats by intravenous injection of streptozotocin (55 mg/kg). Subsequently, the rats received daily oral administration of the methanolic extract of Foeniculum vulgare (250 mg/kg) and the standard drug metformin (300 mg/kg) for 28 days. Furthermore, a tolerance test was carried out. The study findings suggest that the diabetic rats in the untreated control group showed hyperglycemia and significant weight loss, as well as polydipsia, polyphagia, and polyuria. However, rats treated with methanolic extract of Foeniculum vulgare for 28 days showed a significant reduction in blood glucose levels and a marked improvement in body weight. Additionally, there was a notable decrease in the daily rate of food consumption and water intake and a significant reduction in serum glucose level, triglycerides, total cholesterol, creatinine, urea, AST, and ALT levels compared to the untreated diabetic control group. Histopathological examination revealed that after 28 days of treatment with 250 mg/kg of methanolic extract of the Foeniculum vulgare, the size of the islets of Langerhans in the pancreas tissue was decreased. Moreover, liver tissue demonstrated normalization with a normal central lobular structure, and kidney tissue showed normalization with a normal Bowman's capsule. These findings suggest that the methanolic extract of Foeniculum vulgare can potentially treat diabetes and should be evaluated further for drug development.

Sleeve gastrectomy plus single anastomosis sleeve ileal bipartition versus sleeve gastrectomy alone: The role of bipartition.

Sleeve gastrectomy (SG) with single anastomosis sleeve ileal bipartition (SASI) is a novel procedure for increasing the anti-metabolic efficacy of SG in severely people with obesity. This study aimed to compare 1-year results between SASI and SG, thereby assessing the role of bipartition. The study was conducted at the Medical University hospital. Between November 2021 and December 2022, 39 patients received an SG + SASI surgery, a total of 35 patients completed 1-year follow-up after the surgery. They were matched with a group of 70 patients with SG that were equal in age, sex, and body mass index (BMI). Operative risk, weight loss, and remission of comorbidities were evaluated after 12 months. The operation time of the SASI group was significantly longer than the SG group (140.3 ± 22.8 vs. 114.9 ± 21.6 min; p < .001). At 12 months after surgery, the SASI group had better weight loss (total weight loss: 37.0% vs. 29.7%; p = .001) and achieved a lower BMI than SG (23.4 ± 2.6 kg/m2 vs. 24.6 ± 2.9 kg/m2; p = .046). Reduction of A1C and remission of T2D was greater in the SASI group. The SASI group had a higher reduction in uric acid, low-density lipoprotein, total cholesterol, and triglyceride levels after operation than the SG group. However, the SG group is superior to the SASI group in mean corpuscular volume, calcium, and iron levels. In this study, adding an ileum bipartition to SG increases the weight loss, glycemic, and blood lipid control of SG only.

Sex- and Metamorphosis-Related Changes in the Cuticular Lipid Profile of Galleria mellonella Pupae and Adults.

The majority of insects reproduce sexually. Among the many factors involved in controlling the reproductive process, cuticular lipids play an important role as unique chemical signatures of species, developmental stage, and sex, and participate in mate recognition. An understanding of the sex- and metamorphosis-related fluctuations in the cuticular lipid profiles of harmful insects is necessary to hamper their reproductive process. A GC/MS analysis of the cuticular lipids of the beehive pest Galleria mellonella Linnaeus (Lepidoptera: Pyralidae) revealed 11 FFAs in the male pupae (C8:0, C9:0, C14:0, C15:0, C16:1, C16:0, C17:0, C18:1, C18:0, C20:1, and C21:1) together with another two in the females (C10:0 and C17:1). As metamorphosis progressed, some FFAs disappeared from the pupal cuticle (C8:0 and C17:0 in both sexes, and C10:0, C17:1, and C20:1 only in female pupae) and the levels of the others changed. In adult virgin males and females, C8:0, C17:1, and C17:0 reappeared and two FFAs absent in pupae (C6:0 and C11:0) appeared. In virgin males, C13:0 also appeared (absent in pupae). Copulation resulted in the disappearance of C13:0 and C17:1, decreased the concentrations of C9:0, C11:0, C18:1, and C18:0, and elevated the amounts of C14:0, C16:1, and C16:0 in mated males. In mated females, the concentrations of C11:0, C14:0, C15:0, C16:0, C17:1, and C18:1 increased while C18:1 decreased. Copulation reduced cholesterol levels in mated females, and increased those in males.

Alternative LDL Cholesterol–Lowering Strategy vs High-Intensity Statins in Atherosclerotic Cardiovascular Disease

In patients with atherosclerotic cardiovascular disease (ASCVD), intensive lowering of low-density lipoprotein (LDL) cholesterol levels with high-intensity statins is generally recommended. However, alternative approaches considering statin-related adverse effects and intolerance are needed. To compare the long-term efficacy and safety of an alternative LDL cholesterol-lowering strategy vs high-intensity statin strategy in patients with ASCVD in randomized clinical trials. PubMed, Embase, and other websites (ClinicalTrials.gov, European Society of Cardiology, tctMD) were systematically searched from inception to April 19, 2024. Randomized clinical trials comparing an alternative LDL cholesterol-lowering strategy vs a high-intensity statin strategy in patients with ASCVD, with presence of cardiovascular events as end points. Individual patient data were obtained from randomized clinical trials that met the prespecified eligibility criteria: RACING (Randomized Comparison of Efficacy and Safety of Lipid-Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease) and LODESTAR (Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy vs Intensity-Based Statin Therapy in Patients With Coronary Artery Disease). The moderate-intensity statin with ezetimibe combination therapy in the RACING trial and the treat-to-target strategy in the LODESTAR trial were classified as alternative LDL cholesterol-lowering strategies. The primary analysis was based on a 1-stage approach. The primary end point was a 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. The secondary end points comprised clinical efficacy and safety end points. Individual patient data from 2 trials including 8180 patients with ASCVD (mean [SD] age, 64.5 [9.8] years; 2182 [26.7%] female; 5998 male [73.3%]) were analyzed. The rate of the primary end point did not differ between the alternative strategy and high-intensity statin strategy groups (7.5% [304 of 4094] vs 7.7% [310 of 4086]; hazard ratio, 0.98; 95% CI, 0.84-1.15; P = .82). The mean (SD) LDL cholesterol level during treatment was 64.8 (19.0) mg/dL in the alternative strategy group and 68.5 (20.7) mg/dL in the high-intensity statin strategy group (P < .001). The alternative strategy group had a lower rate of new-onset diabetes (10.2% [271 of 2658] vs 11.9% [316 of 2656]; P = .047), initiation of antidiabetic medication for new-onset diabetes (6.5% [173 of 2658] vs 8.2% [217 of 2656]; P = .02), and intolerance-related discontinuation or dose reduction of assigned therapy (4.0% [163 of 4094] vs 6.7% [273 of 4086]; P < .001). Results of this systematic review and individual patient data meta-analysis suggest that compared with a high-intensity statin strategy, the alternative LDL cholesterol-lowering strategy demonstrated comparable efficacy regarding 3-year death or cardiovascular events in patients with ASCVD, with an associated reduction in LDL cholesterol levels and risk for new-onset diabetes and intolerance. PROSPERO CRD42024532550.

Synergistic Effect and Mechanism of Combined Astaxanthin and Curcumin Administration on Ovarian Function in PCOS Mice.

To investigate the synergistic effect of astaxanthin and curcumin on ovarian function in polycystic ovary syndrome (PCOS) mice and to elucidate the underlying mechanisms, fifty 4-week-old female mice were randomly divided into five groups: (i) normal control group; (ii) PCOS model group; (iii) PCOS + astaxanthin group; (iv) PCOS + curcumin group; and (v) PCOS + astaxanthin-curcumin. Throughout the study, various parameters were meticulously evaluated, including serum levels of key reproductive hormones (testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH)), as well as monitoring alterations in the estrous cycle, follicle development, and ovulation rates. Additionally, markers of oxidative stress and inflammation were measured. Findings revealed that PCOS mice exhibited disordered estrous cycle, polycystic ovarian morphologies, abnormal serum reproductive hormones and lipid metabolism, heightened oxidative stress, and augmented inflammatory responses. Notably, upon administration of the combined astaxanthin and curcumin, PCOS mice exhibited significant improvements in their estrous cyclicity and ovarian histology. The treatment led to a significant reduction in serum total cholesterol (TC) levels and normalization of T, E2, FSH, LH, and AMH levels. Moreover, there was a marked decrease in the levels of serum reactive oxygen species (ROS) and malondialdehyde (MDA), indicating attenuation of oxidative stress. Concurrently, the activity of the antioxidant enzyme catalase (CAT) significantly increased, while proinflammatory cytokines interferon-γ (IFN-γ) and interleukin-6 (IL-6) in the ovarian tissue were notably decreased. The combined treatment also resulted in a substantial increase in the number of ova and a significant decline in the rate of abnormal ova, with these therapeutic effects proving more effective compared to either astaxanthin or curcumin alone. In conclusion, the co-administration of astaxanthin and curcumin demonstrated a remarkable effect in improving abnormal lipid metabolism and restoring reproductive endocrine functions in PCOS mice. Furthermore, it effectively mitigated systemic and local oxidative stress and chronic inflammatory injury, thereby promoting follicular growth and enhancing ovulatory function in the context of PCOS.

Interleukin-6: Cardiovascular Aspects of Long-Term Cytokine Suppression in Patients with Rheumatoid Arthritis.

In recent years, many atherogenesis researchers have focused on the role of inflammatory cytokines in the development of cardiovascular disease (CVD). Interleukin-6 (IL-6) cytokine is independently associated with higher CVD risk in patients with rheumatoid arthritis (RA). The effect of IL-6 inhibitors on the cardiovascular system in RA patients remains poorly understood, especially with its long-term use. This study investigates the effect of therapy with IL-6 receptor blocker tocilizumab (TCZ) on the dynamics of cardiovascular risk (CVR), modifiable risk factors (RFs), carotid artery (CA) structural changes, and the incidence of cardiovascular complications (CVCs) in RA patients during a 265-week follow-up period. Forty-five patients with active RA (DAS28-ESR 6.2 (5.5;6.8) with ineffectiveness and/or intolerance to disease-modifying antirheumatic drugs (DMARDs) were included in this study. During long-term therapy with TCZ in RA patients, no increase in CVR and no significant structural changes in CA were observed. No significant changes in the blood lipid spectrum were observed in patients without statin therapy. In the group of patients receiving statins, there was a 43% increase in high-density lipoprotein cholesterol (HDL-C), a 15% reduction in total cholesterol levels, and a 56% decrease in the atherogenicity index (p < 0.01 in all cases). Associations were found between ∆ total cholesterol and ∆ C-reactive protein (CRP) (R = 0.36, p = 0.04), ∆ low-density lipoprotein cholesterol (LDL-C), and ∆-CRP (R = 0.42, p = 0.03) in RA patients receiving statins. Initially, the thickness of the intima-media complex of carotid arteries (cIMT) positively moderately correlated with age (R = 0.7; p < 0.01), BMI (R = 0.37; p < 0.01), and systolic blood pressure (R = 0.64; p < 0.01); however, it weakly correlated with the lipid spectrum parameters: total cholesterol (R = 0.29; p < 0.01) and LDL-C (R = 0.33; p < 0.01). No new associations of cIMT by the end of the follow-up period, as well as the relationship of cIMT value with RA activity and therapy, were revealed. Patients with carotid ASPs showed an oppositely directed relationship between total cholesterol and sVCAM-1 at baseline (R = -0.25, p = 0.01) and at the end of this study (R = 0.29, p < 0.01). The incidence of cardiovascular events was 0.53 per 100 patient-years during the 265-week period of TCZ therapy.

Investigating the Antibacterial, Antioxidant, and Cholesterol-lowering Properties of Yogurt Fortified with Postbiotic of Lactobacillus acidophilus and Lactiplantibacillus plantarum in the Wistar Rat Model

Postbiotics have gained attention in the food industry due to their functional properties and ease of use compared to their live parent cells. Postbiotics are the metabolic byproducts of probiotic microorganisms, offering advantages such as antimicrobial and anti-diabetic effects. The study aimed to explore the potential antibacterial, antioxidant, and cholesterol-lowering effects of postbiotics from Lactobacillus acidophilus (LA) and Lactiplantibacillus plantarum (LbP) through in vitro and in vivo studies. Freeze-dried postbiotics from L. acidophilus BLAC 258 and L. plantarum were used in yogurt to inhibit foodborne pathogens over a 21-day storage period at 4 °C. The cholesterol-lowering effects of the postbiotic yogurt were assessed in Wistar rats fed with Normal Basal Diet (NBD) and High Cholesterol Diet (HCD). All experiments were performed in triplicate, and the collected data were analyzed with a one-way ANOVA using SPSS v.20 (2021) software. The Tukey Honestly Significant Difference (HSD) test was used for means differences at the 95% confidence interval. The results showed that postbiotic-fortified yogurt exhibited significant antioxidant and antibacterial effects. The antioxidant capacity of the yogurt increasingly peaked at 48.81% on day 14. Also, Listeria monocytogenes counts in the postbiotic yogurt decreased by approximately 2 Log10 on day 3. High-cholesterol-fed rats receiving postbiotic yogurt experienced significant reductions in total cholesterol, triglycerides, and LDL levels. Overall results indicate that postbiotics functional yogurt might be a safe and effective strategy for managing cholesterol levels and inhibiting foodborne pathogens.

The Emerging Potential of Apolipoprotein C-III Inhibition for ASCVD Prevention: A State-of-the-Art Review.

Multiple agents are being developed that inhibit apolipoprotein (apo) C-III. This state-of-the-art review examines their potential for atherosclerotic cardiovascular disease (ASCVD) risk reduction. Apo C-III, an apolipoprotein on the surface of triglyceride-rich lipoproteins (TRLs), impairs clearance of TRLs through both lipoprotein lipase dependent and independent pathways, thereby resulting in increased concentrations of triglycerides. Apo C-III has also been shown to have pro-atherogenic effects when bound to high-density lipoprotein (HDL) particles. Classical and genetic epidemiology studies provide support for the concept that apo C-III is associated with an increased risk of ASCVD events. Drug efficacy of agents that silence APOC3 mRNA has been studied in populations with varying hypertriglyceridemia severity, including those with familial chylomicronemia syndrome, multifactorial chylomicronemia syndrome/severe hypertriglyceridemia, and mixed hyperlipidemia. Randomized controlled trials have reported significant reductions in TG and non-HDL cholesterol levels among these patients treated with APOC3 inhibitors. Upcoming clinical outcomes trials seek to establish a role for APOC3 inhibitors to reduce risk of ASCVD.

Apolipoprotein A1-encoding recombinant adenovirus remodels cholesterol metabolism in tumors and the tumor microenvironment to inhibit hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor requiring effective treatments. Oncolytic viruses induce anti-tumor responses but have limited efficacy. Apolipoprotein A1 (ApoA1) inhibits inflammation, modulates immunity, and promotes anti-oxidation. This study aims to construct an oncolytic adenovirus (Ad5)-ApoA1 for superior anti-tumor effects. We analyzed ApoA1 expression in tumors and its prognostic significance using public databases. Subsequently, we engineered a recombinant oncolytic adenovirus Ad5-ApoA1 and assessed its replication and oncolytic efficacy in vitro and in nude mice. The impact of Ad5-ApoA1 on the tumor microenvironment of HCC was evaluated through flow cytometry, transcriptome sequencing, single-cell sequencing, and other methodologies. Additionally, mechanisms of immune microenvironment modulation by Ad5-ApoA1 were explored. ApoA1 expression was down-regulated with HCC progression and significantly positively correlated with the prognosis of HCC patients. Ad5-ApoA1 exhibited robust oncolytic activity but showed no therapeutic effect on nude mice. However, it significantly inhibited HCC growth and prolonged the survival period of both healthy-immune and humanized immune-reconstituted NCG mice. Furthermore, Ad5-ApoA1 significantly promoted the expression of IFN-γ and GzmB in CD8+ T cells while inhibiting the expression of PD-1 and LAG-3. Notably, the cholesterol content in the CD8+ T cells studied was significantly correlated with the expression of PD-1 and LAG-3, with ApoA1 promoting cholesterol efflux and reducing cholesterol levels. Ad5-ApoA1 activates CD8+ T cells by promoting large-scale viral replication. High levels of ApoA1 protein expression promote cholesterol efflux, inhibit CD8+ T cell depletion, and reduce inflammatory factors, ultimately leading to superior therapeutic effects on hepatocellular carcinoma.