Reduction In Cholesterol Levels Research Articles

Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.

A significant presence in atherosclerotic cardiovascular disease: Remnant cholesterol: A review.

The current first-line treatment for atherosclerotic cardiovascular disease (ASCVD) involves the reduction of a patient's low-density lipoprotein cholesterol (LDL-C) levels through the use of lipid-lowering drugs. However, even when other risk factors such as hypertension and diabetes are effectively managed, there remains a residual cardiovascular risk in these patients despite achieving target LDL-C levels with statins and new lipid-lowering medications. This risk was previously believed to be associated with lipid components other than LDL, such as triglycerides. However, recent studies have unveiled the crucial role of remnant cholesterol (RC) in atherosclerosis, not just triglycerides. The metabolized product of triglyceride-rich lipoproteins is referred to as triglyceride-rich remnant lipoprotein particles, and its cholesterol component is known as RC. Numerous pieces of evidence from epidemiological investigations and genetic studies demonstrate that RC plays a significant role in predicting the incidence of ASCVD. As a novel marker for atherosclerosis prediction, when LDL-C is appropriately controlled, RC should be prioritized for attention and intervention among individuals at high risk of ASCVD. Therefore, reducing RC levels through the use of various lipid-lowering drugs may yield long-term benefits. Nevertheless, routine testing of RC in clinical practice remains controversial, necessitating further research on the treatment of elevated RC levels to evaluate the advantages of reducing RC in patients at high risk of ASCVD.

The Effect of a Vegan Diet on the Health Indicators and Outcomes of P atients with Type 2 Diabetes Mellitus.

Recently, there has been a notable increase in interest in various forms of vegetarianism, which may be due to the growing prevalence of health issues, such as Type 2 Diabetes Mellitus (T2DM). Adhering to a vegan diet may have positive health outcomes. As a result, we conducted a review article to gather data from previous research studies on the effects of a vegan diet on different aspects of managing patients with T2DM. We searched the PubMed website for research studies on how a vegan diet affects the outcomes of patients with T2DM. The research studies were categorized according to the type of data collected, such as prevalence, incidence, body weight, insulin resistance, glycemic control, and lipid profile. It was found that following a vegetarian diet can significantly reduce the risk of mortality from heart disease. Additionally, studies have demonstrated that a vegetarian diet is linked to several improvements in T2DM. However, long-term weight loss plans and managing T2DM is a comprehensive intervention that includes caloric restriction, exercise, and behavioral modification. Incorporating a vegan diet can be a valuable factor to consider in managing T2DM, as it can offer numerous benefits, such as increased insulin sensitivity, weight loss, and reduced blood sugar levels. It helps to reduce cholesterol levels, LDL, and triglyceride levels, which are all risk factors associated with T2DM. By reducing these risk factors, the vegan diet can improve the overall health of T2DM patients. </p>.

Cyanidin‐3‐O‐glucoside ameliorates hydrogen peroxide‐induced oxidative stress by regulating HMGCR‐mediated cholesterol anabolism in HEK‐293T cells

AbstractCyanidin‐3‐O‐glucoside (C3G), as a typical anthocyanin, exhibits excellent antioxidant effects. This study aimed to demonstrate the role and mechanism of C3G in regulating 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR)‐mediated cholesterol anabolism on H2O2‐induced oxidative stress in HEK‐293T cells. Firstly, the inhibitory effect of C3G on oxidative stress was confirmed by CCK‐8, ROS, and mitochondrial membrane potential (MMP) experiments. Then, proteomics was used to investigate and screen differentially expressed proteins in inhibiting cellular oxidative stress by C3G. HMGCR was screened as a key differentially expressed protein by proteomic analysis. The results verified that C3G could reduce cholesterol levels by inhibiting sterol regulatory element‐binding protein (SREBP2)/HMGCR pathway, increasing ATP, and reducing acetyl‐CoA. Finally, HMGCR had been shown to positively increase ROS accumulation and decrease MMP, which were reversed by intervention of C3G through a series of knockdown and overexpression experiments. In conclusion, the results demonstrated that C3G could inhibit the disorder of cholesterol synthesis in oxidative stress cells by regulating the ROS/SREBP2/HMGCR pathway.

Efficacy of single-dose evolocumab injection in early-phase acute myocardial infarction: a retrospective single-center study.

Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with statins alone. This single-center, retrospective study aimed to assess the impact of single-dose injection of evolocumab 140 mg on LDL-C levels during the peri-percutaneous coronary intervention (PCI) period in patients with AMI. A total of 95 patients with AMI who underwent PCI were divided into the evolocumab (n = 50) and non-evolocumab (n = 45) groups. The percentage change of LDL-C level at 1-3 weeks from baseline was 78.4 ± 13.4% reduction in the evolocumab group versus 45.6 ± 22.6% in the non-evolocumab group, with a mean difference of -33.5% between the groups (95% CI: -42.6 to -24.5%; p < 0.001). The achievement rate of LDL-C levels below 55 mg/dL at 1-3 weeks was significantly higher in the evolocumab group than in the non-evolocumab group (97.7% vs. 60.0%, p < 0.001). Patients with AMI who received single-dose injection of evolocumab 140 mg during the peri-PCI period had a significantly greater LDL-C reduction and higher proportion of patients achieved the target LDL-C level in the early phase AMI than those who did not receive evolocumab.

Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

β-Cyclodextrin-based nanoassemblies for the treatment of atherosclerosis.

Atherosclerosis, a chronic and progressive condition characterized by the accumulation of inflammatory cells and lipids within artery walls, remains a leading cause of cardiovascular diseases globally. Despite considerable advancements in drug therapeutic strategies aimed at managing atherosclerosis, more effective treatment options for atherosclerosis are still warranted. In this pursuit, the emergence of β-cyclodextrin (β-CD) as a promising therapeutic agent offers a novel therapeutic approach to drug delivery targeting atherosclerosis. The hydrophobic cavity of β-CD facilitates its role as a carrier, enabling the encapsulation and delivery of various therapeutic compounds to affected sites within the vasculature. Notably, β-CD-based nanoassemblies possess the ability to reduce cholesterol levels, mitigate inflammation, solubilize hydrophobic drugs and deliver drugs to affected tissues, making these nanocomponents promising candidates for atherosclerosis management. This review focuses on three major classes of β-CD-based nanoassemblies, including β-CD derivatives-based, β-CD/polymer conjugates-based and polymer β-CD-based nanoassemblies, highlighting a variety of formulations and assembly methods to improve drug delivery and therapeutic efficacy. These β-CD-based nanoassemblies exhibit a variety of therapeutic mechanisms for atherosclerosis and offer systematic strategies for overcoming barriers to drug delivery. Finally, we discuss the present obstacles and potential opportunities in the development and application of β-CD-based nanoassemblies as novel therapeutics for managing atherosclerosis and addressing cardiovascular diseases.

Sugary snack restriction enhances body composition improvement in overweight women engaging in non-face-to-face walking during COVID-19.

This study assesses the impact of dietary modification, specifically sugary snack restriction, in conjunction with a brisk walking program on overweight management in young overweight women, with a focus on changes in body composition and glucose metabolism. An 8-week randomized controlled trial was conducted amidst the COVID-19 pandemic, utilizing a remote intervention approach to comply with health guidelines and ensure participant safety. The study's remote nature highlights adaptability in health interventions during challenging periods, such as the COVID-19 pandemic. Twenty-one overweight Korean women aged 20-39, with an average BMI of 24.6, were selected for the study. They were divided into two groups: one engaging in brisk walking and the other combining this exercise with a sugary snack restriction, demonstrating the study's focus on comparative intervention efficacy. The exercise-only group showed notable reductions in glucose, insulin, HOMA-IR (p < 0.05), and total cholesterol levels (p < 0.01). In contrast, the group that combined exercise with dietary modification displayed more pronounced improvements in body weight, fat mass, and waist circumference (p < 0.05). This differential outcome emphasizes the added benefit of integrating dietary control with physical activity. The findings suggest that adding a dietary component, particularly a sugary snack restriction, to an exercise regimen can significantly enhance the effectiveness of overweight management in young women. This study underscores the importance of holistic lifestyle interventions that combine dietary and physical activity modifications for improved health outcomes.

Monoglucosyl rutin, a flavonoid glycoside, improves low-density lipoprotein-cholesterol levels in healthy adults: A randomized controlled trial

Background: Atherosclerotic cardiovascular disease (ASCVD) continues to be a significant contributor to global mortality, impacting over 523 million individuals worldwide. Dyslipidemia stands as one of the foremost risk factors for ASCVD. Thus, prioritizing the reduction of low-density lipoprotein cholesterol (LDL-C) levels is essential in mitigating cardiovascular complications. Objective: This study aimed to evaluate the lipid-lowering activity of a dietary supplement containing monoglucosyl rutin (MR) in individuals with low to mild hypercholesterolemia. Methods: This was a randomized, placebo-controlled, double-blind, parallel-group study conducted from April 20 to December 24, 2022. The study population included 56 healthy Japanese adult participants with LDL-C levels between 120–139 mg/dL who were randomly allocated to either the MR or placebo groups (n = 28/group) using a computerized random number generator. 200 mg of MR or placebo divided into 3 tablets was given daily; participants were instructed to take 1 tablet with water after each meal for 12 weeks. The main focus was on measuring the serum LDL-C level as the primary outcome, with additional attention given to secondary outcomes such as serum high-density lipoprotein cholesterol (HDL-C), total cholesterol, and nonHDL-C levels. The study also evaluated the percentage of participants achieving serum LDL-C levels below 120 mg/dL after the 12-week intervention. Assessments were conducted after 4, 8, and 12 weeks of intervention. Results: There were 54 (27 in each group) participants in the per-protocol set (PPS) and 53 (placebo group, 26; MR group, 27) participants in the modified PPS (mPPS). A statistically significant group difference in serum LDL-C levels was observed (P &lt; 0.05), with a 5.0% decrease from preintervention to after 12 weeks. The reduction in LDL-C levels coincided with (statistically significant?) decreases in total cholesterol levels, nonHDL-C levels, and the LDL-C/HDL-C ratio. During the study period, there was no adverse event or concern about the safety of MR. Conclusions: MR has potential as a preventive or therapeutic tool for improving improve long-term health and reducing cardiovascular morbidity. Keywords: monoglucosyl rutin, flavonoid glycoside, low-density lipoprotein cholesterol, hyperlipidemia, lipid profile Trial registration number: UMIN000047790

Dual-Targeting EGCG/NO-Supplying protein assembled nanoparticles with Multi-Synergistic effects against atherosclerosis

Limited therapeutic options are available to effectively preventing atherosclerosis. Inflammatory endothelial cells, foamy macrophages, and high protease levels contribute to atherosclerotic plaque formation. Studies have shown that catechins effectively scavenge reactive oxygen species (ROS), inhibit monocyte adhesion and reduce cholesterol levels, while nitric oxide (NO) enhances endothelial function. However, due to the poor stability and bioavailability of catechins and the toxicity from the burst release of current synthetic small molecules NO donor, effective deliveryof these bioactive compounds to treat atherosclerosis is still a challenge. Herein, a catechin/protein-based NO donor co-delivery nanosystem was designed for combinatorial anti-atherosclerotic therapy. We engineered a (−)-epigallocatechin-3-gallate (EGCG)/NO-releasing protein co-assembled nanocomplex based on specific catechin-protein interactions. Furthermore, the nanocomplex was surface modified with fucoidan (Fu), a sulfated polysaccharide with anti-inflammatory activity. This nanocomplex exhibits sensitivity to ROS, pH, and enzymes. The Fu-functionalized nanoparticles specifically accumulates in atherosclerotic plaques mediated by P-selectin on inflamed endothelial cells and scavenger receptor A (SR-A) on foamy macrophages. Under environmental stimuli that simulate the condition of plaque, the nanoparticles are readily activated to release EGCG and NO in response to excess ROS and high protease levels, exerting the multi-synergistic anti-atherosclerosic effects on reducing monocyte adhesion, promoting NO production to proliferate endothelial cells, lowering ROS levels, and decreasing the foam cell formation in vitro, and reducing lipid accumulation, plaque size, and inflammatory cytokines release in high-fat diet-induced atherosclerosis model in ApoE−/− mice. The integration of plaques targeting ability and multiple therapeutic functions can provide an advanced therapeutic strategy foratherosclerosistreatment.

Apple cider vinegar for weight management in Lebanese adolescents and young adults with overweight and obesity: a randomised, double-blind, placebo-controlled study

Background and aimsObesity and overweight have become significant health concerns worldwide, leading to an increased interest in finding natural remedies for weight reduction. One such remedy that has gained popularity...

Simvastatin, Its Antimicrobial Activity and Its Prevention of Alzheimer's Disease.

Simvastatin, a blockbuster drug for treating hypercholesterolemia, has multifactorial benefits as an antimicrobial agent and plays a preventative role in reducing the incidence of Alzheimer's Disease (AD). Although most of the beneficial effects of simvastatin have been attributed to its ability to reduce cholesterol levels, recent scientific studies have suggested that its benefits are largely due to its pleiotropic effects in targeting other pathways, e.g., by inhibiting protein lipidation. There are certain pleiotropic effects that can be predicted from the inhibition of the mevalonate pathway; however, some of the effects of simvastatin in proteostasis lead to reduced levels of amyloid beta, the key contributor to AD. This review discusses the use of simvastatin as an antimicrobial agent and anti-AD drug.

Impact of in ovo feeding of grape pomace extract on the growth performance, antioxidant status, and immune response of hatched broilers

Delivering natural antioxidants via in ovo feeding holds promise for enhancing the antioxidant status and performance of chickens. Therefore, The objective of this study was to evaluate the impacts of in ovo feeding during early embryonic development using grape pomace extract as a natural antioxidant on hatchability, productive performance, immune response, and antioxidant status broilers.. A total of 900 fertile broiler eggs from the Arbor Acres strain were utilized. Each egg was individually weighed, with egg weights ranging from 61.88±3 g. On the 17.5th day of incubation (DOI), the fertile eggs were divided into six groups. The first treatment group was untreated and designated as the control (C). The second group was the sham group (Sh), receiving a simulated injection. The third group, designated as the vehicle group (V), was injected with 100 µl of dimethyl sulfoxide (DMSO). The fourth group received an injection of 100 µl of grape pomace dissolved in DMSO at a concentration of 2 mg (T2). Similarly, the fifth and sixth groups were injected with 100 µl of grape pomace dissolved in DMSO at concentrations of 4 mg and 6 mg, (T4), (T6) respectively. Subsequently, all groups were raised under uniform conditions in terms of management, environment, and nutrition till five weeks of age. The grape pomace extract (GPE), obtained is rich in total phenolic content (16.07 mg/g), total flavonoid content (7.42 mg/g), and total anthocyanin (8.37 mg/g). GPE has exhibited significant antioxidant properties as evidenced by its effectiveness in DPPH scavenging and reducing power assays. Significant improvements in body weight at hatch were observed with in ovo feeding of grape pomace extract, particularly at the 4 mg level, surpassing the effectiveness of the 2 mg and 6 mg grape pomace levels, and this enhancement in body weight continued until the age of five weeks. GPE injection also led to a significant reduction in cholesterol levels, with the lowest levels recorded for the T4 group. Plasma total Antioxidant Capacity (TAC) levels were significantly elevated in groups treated with T4, T6, and T2 compared to the control group. Conversely, the control group showed a significant increase (P<0.01) in plasma malondialdehyde (MDA) levels. The immune response of hatched chicks from grape pomace extract-injected groups, especially the T4 group, exhibited improvement through increased IgM and IgG. These findings demonstrate that in ovo feeding of GPE, particularly at a dosage of 4 mg, enhances growth performance, immune response, and antioxidant status in hatched chicks. Thus, administering natural antioxidants, such as grape pomace extract, to developing broiler embryos via in ovo feeding could serve as a valuable strategy for enhancing the subsequent post-hatch productive performance, as well as bolstering the antioxidant and immunological status of broiler chicks.

Exploring the sex difference in cardiovascular risk during growth hormone therapy in adults.

Given the previously identified sex differences in cardiovascular (CV) morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex-specific differences in the efficacy of (long-term) GHRT on CV risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men. Retrospective nationwide cohort study. We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to CV risk profile and morbidity at baseline and during follow-up. Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol, and triglyceride levels was greater in men than in women (all P < .05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardiovascular or cerebrovascular diseases during GHRT. Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing CV and cerebrovascular morbidity during GHRT.

#1294 The impact of plant-based diet on renal function and metabolic profile in kidney transplant recipients

Abstract Background and Aims Controlling and reducing protein intake is the most used approach to preserve renal function in CKD patients. Compared to protein restriction alone, plant-based diets have received particular attention. However, data on the potential risks and benefits of a plant-based diet in kidney transplant patients remains sparse, and evidence in this population is indirect. The primary purpose of this study was to evaluate if a plant-based diet affects proteinuria and eGFR in renal transplant patients. Establishing whether it influences acid load, glycolipid profile, nutritional status, and performance status were secondary objectives. Method 26 renal transplant recipients with eGFR &amp;gt;20 ml/min/1.73 m², urinary protein excretion &amp;gt;0.5 g/day, and transplant age &amp;gt;1 year were considered eligible for the study. Enrolled subjects underwent dietary assessment and biochemical tests at baseline, three and six months after starting the plant-based diet. All subjects underwent performance tests: sit-to-stand and handgrip tests. Results Only 18 patients were included in the statistical analysis. After six months, no significant changes in levels of proteinuria, urinary anion gap, triglycerides, and grip strength were detected. However, there was a statistically significant reduction in total cholesterol (p=0.03), LDL (p=0.04), and fasting blood sugar levels (p=0.001). A statistically significant reduction in eGFR (p=0.033) was observed, likely the regression of the previous hyperfiltration caused by the animal protein diet. A significant improvement was found in sit-to-stand test performance (p=0.037). Finally, a direct relationship between azoturia and urinary anion gap was observed. Conclusions The work carried out has highlighted how some of the potential benefits of the plant-based diet may also be relevant among kidney transplant patients. The plant-based diet is also associated with improved performance tests.

POSSIBILITIES OF OBTAINING AND VALORIZING DIETARY FIBERS IN THE CONTEXT OF THE CIRCULAR BIOECONOMY

This article aimed to review the recent literature on the characterization of dietary fibers and their role in the human body, focusing on the methods of extraction of dietary fibers from agro-food waste as well as their use in various areas of the food industry. Dietary fibers are biologically active substances with beneficial effects on human health. Soluble dietary fiber is involved in reducing cholesterol levels and blood sugar levels, while insoluble dietary fiber helps regulate intestinal transit and maintain colon health. It would be useful to identify the extraction procedures and characterization of dietary fibers from agro-food waste. Fruit waste contains relevant amounts of bioactive compounds, such as: phenolic acids, flavonoids, lignins, carotenoids, etc. In addition, fruit waste contains significant amounts of dietary fiber with nutraceutical important activities, such as modulating the intestinal microbiota, lowering cholesterol, triglycerides and glycemic load in the blood. Hence, obtaining dietary fiber from agro-industrial waste can solve a number of economic and environmental problems that aim reducing waste, increasing the sustainability and profitability of companies in the Republic of Moldova. Dietary fiber can be used in various types of food, such as products of bakery and confectionery, meat, dairy products, and pasta. They can be used as stabilizers with an impact on food texture or ingredients with low caloric value, partially replacing caloric constituents such as fats, starch or sugars. Another important property is the prebiotic effect of dietary fibers. This property is determined by the fact that dietary fibers are indigestible or poorly digestible and are fermented selectively by intestinal microbiota, conferring health benefits to the host.

Dietary Oryzanol (Ory) Improved the Survival and Growth of Large Yellow Croaker (Larimichthys crocea) Larvae via Promoting Activities of Digestive Enzymes, Antioxidant Capacity, and Lipid Metabolism

Dietary Oryzanol (Ory) Improved the Survival and Growth of Large Yellow Croaker (Larimichthys crocea) Larvae via Promoting Activities of Digestive Enzymes, Antioxidant Capacity, and Lipid Metabolism

Predictors of cardiovascular risk in familial hypercholesterolemia.

Familial Hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that all people with familial hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies. In the last year, several studies have been published focusing on the contribution of diabetes to familial hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia. It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.

Cholesterol uptake in the intestine is regulated by the LASP1-AKT-NPC1L1 signaling pathway.

Cholesterol is essential for the stability and architecture of the plasma membrane and a precursor of bile acids and steroid hormones in mammals. Excess dietary cholesterol uptake leads to hypercholesterolemia and atherosclerosis and plays a role in cancer development. The role of actin-binding scaffolding protein LIM and SH3 protein 1 (LASP1) in cholesterol trafficking has not been investigated previously. Cholesterol levels, its uptake, and excretion were studied in mice deficient for low-density lipoprotein receptor and Lasp1 (Ldlr-/-Lasp1-/- mice) upon feeding a high-fat diet, and in LASP1-knockdown, differentiated human intestinal epithelial CaCo-2 cells. When compared with diet-fed Ldlr-/- control mice, Ldlr-/-Lasp1-/- mice displayed a reduction in serum cholesterol levels. Mechanistically, we identified a new role of LASP1 in controlling the translocation of the intestinal cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) to the apical cell surface, which was limited in LASP1-knockdown human CaCo-2 enterocytes and in the intestine of Ldlr-/- Lasp1-/- compared with Ldlr-/- mice, linked to LASP1-pAKT signaling but not CDC42 activation. In line, a reduction in cholesterol reabsorption was noted in LASP1-knockdown CaCo-2 cells in vitro, and an enhanced cholesterol excretion via the feces was observed in Ldlr-/- Lasp1-/- mice. These data uncover a novel function of Lasp1 in cholesterol trafficking, promoting cholesterol reabsorption in the intestine. Targeting LASP1 locally could thus represent a novel targeting strategy to ameliorate hypercholesterolemia and associated diseases.NEW & NOTEWORTHY We here uncovered LASP1 as a novel regulator of the shuttling of the sterol transporter NPC1L1 to the cell surface in enterocytes to control cholesterol absorption. Accordingly, LASP1-deficient mice displayed lowered serum cholesterol levels under dietary cholesterol supplementation.

The Effectiveness of Clinician-Led Community-Based Group Exercise Interventions on Health Outcomes in Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the combined effects of clinician-led and community-based group exercise interventions on a range of health outcomes in adults with type 2 diabetes mellitus. Our literature search spanned Medline, Scopus, PubMed, Embase, and CINAHL databases, focusing on peer-reviewed studies published between January 2003 and January 2023. We included studies involving participants aged 18 years and older and articles published in English, resulting in a dataset of eight studies with 938 participants. Spanning eight peer-reviewed studies with 938 participants, the analysis focused on the interventions' impact on glycemic control, physical fitness, and anthropometric and hematological measurements. Outcomes related to physical fitness, assessed through the six-minute walk test, the 30 s sit-to-stand test, and the chair sit-and-reach test, were extracted from five studies, all of which reported improvements. Anthropometric outcomes from seven studies highlighted positive changes in waist circumference and diastolic blood pressure; however, measures such as body mass index, systolic blood pressure, weight, and resting heart rate did not exhibit significant changes. Hematological outcomes, reviewed in four studies, showed significant improvements in fasting blood glucose, triglycerides, and total cholesterol, with glycemic control evidenced by reductions in HbA1c levels, yet LDL and HDL cholesterol levels remained unaffected. Ten of the fifteen outcome measures assessed showed significant enhancement, indicating that the intervention strategies implemented may offer substantial health benefits for managing key type 2 diabetes mellitus-related health parameters. These findings in combination with further research, could inform the refinement of physical activity guidelines for individuals with type 2 diabetes mellitus, advocating for supervised group exercise in community settings.