Beta cells AND statins

AIMS: We conducted a network meta-analysis (NMA) to determine the effects of low-dose (20 mg/day or less) conventional statin therapy (CST) and high-dose (40 mg/day or more) intensive statin therapy (IST) on the frequency of Tregs and their associated cytokines (IFN-γ, IL-10, TGF-β) compared to placebo. METHODS AND RESULTS: PubMed, Cochrane Library, and EMBASE databases were searched for randomized clinical trials (RCTs) to identify relevant articles published until June 2021...

Lipid rafts in cell plasma membranes play a critical role in the life cycle of many viruses. However, the involvement of membrane cholesterol-rich lipid rafts in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into target cells is not well known. In this study, we investigated whether the presence of cholesterol-rich microdomains is required for the entry of SARS-CoV-2 into host cells. Our results show that depletion of cholesterol in the rafts by methyl-beta-cyclodextrin (MβCD) treatment impaired the expression of the cell surface receptor angiotensin-converting enzyme 2 (ACE2), resulting in a significant increase in SARS-CoV-2 entry into cells...

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysregulation and is linked with various cardiovascular complications, which often lead to poor prognostic outcomes. To develop a standard therapy for NAFLD and to urgently address its complications, the current study aimed to investigate the mechanisms of NAFLD-related heart disease and the therapeutic effects of drugs targeting various metabolic pathways. METHODS: To explore the mechanism of NAFLD-related heart disease, a medaka model of high-fat diet-induced NAFLD was utilized...

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene ( kl/kl ). These mice have a shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary disease, cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of Klotho has opposite effects, extending lifespan. In humans, Klotho levels decline with age, chronic kidney disease, diabetes, Alzheimer's disease and other conditions...

Background: Mutations in the tumor suppressor gene Adenomatous Polyposis Coli ( APC ) are found in 80% of sporadic colorectal cancer (CRC) tumors and are also responsible for the inherited form of CRC, Familial adenomatous polyposis (FAP). Methods: To identify novel therapeutic strategies for the treatment of APC mutated CRC, we generated a drug screening platform that incorporates a human cellular model of APC mutant CRC using CRISPR-cas9 gene editing and performed an FDA-approved drug screen targeting over 1000 compounds...

OBJECTIVE: Recent evidence suggests that statins, among lipid-lowering drugs, can be used to lower serum cholesterol levels for reducing the risk of cardiovascular disease in individuals with high cholesterol, as well as reducing DNA damage and having anti-ageing and pleiotropic effects. Additionally, nuclear factor kappa B (NF-κB) is reported to be suppressed in statin-administered nucleus pulposus (NP) cells for the prevention of interleukin (IL) -1 beta (IL-1β)-induced apoptosis and extracellular matrix (ECM) degradation...

We report a patient's journey with a four-year history of hypertension (HTN) and hyperlipidemia (HLD), stable on beta-blocker and statin, monitored every six months by alternating visits between her cardiologist and primary care physician (PCP) in North Carolina (NC). Six months before relocating to New York (NY) she had been informed about incidental severe hyponatremia during her last outpatient visit, the need for repletion with sodium chloride tablets, and the critical importance of prompt follow-up to rule out malignancy by starting with a chest X-ray...

Statins have anti-inflammatory and antifibrotic effects in addition to cholesterol-lowering effect. We aimed to investigate the effect of atorvastatin (ATR) in fibrotic mouse lung and human lung fibroblasts (MRC5s). Pulmonary fibrosis was induced by a single dose of bleomycin by intratracheal instillation in adult mice. ATR was administered (20 mg/kg ip) to mice with healthy and pulmonary fibrosis for 10 days from Day 7 of the experiment. Mice were dissected on the 21st day. The levels of alpha-smooth muscle actin (α-SMA), pSMAD2/3, LOXL2, and p-Src were determined by Western blot analysis in the lungs...

Cachexia may be caused by congestive heart failure, and it is then called cardiac cachexia, which leads to increased morbidity and mortality. Cardiac cachexia also worsens skeletal muscle degradation. Cardiac cachexia is the loss of edema-free muscle mass with or without affecting fat tissue. It is mainly caused by a loss of balance between protein synthesis and degradation, or it may result from intestinal malabsorption. The loss of balance in protein synthesis and degradation may be the consequence of altered endocrine mediators such as insulin, insulin-like growth factor 1, leptin, ghrelin, melanocortin, growth hormone and neuropeptide Y...

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and affects around 24 million individuals worldwide. Several studies showed an association between high plasma low-density lipoprotein (LDL) levels and an increased risk of developing AD. To that effect, multiple drugs treating hypercholesterolaemia, such as statins, have been tested to prevent AD. In this study, we propose a new pharmacological target called Cholesteryl Ester Transfer Protein (CETP). In recent years, studies have shown an association between different genetic variants of CETP and the risk of developing AD...

There is increasing awareness that in those who develop early-onset (18-39 years) adult type 2 diabetes, the increases in insulin resistance, deterioration in beta-cell and clustering of cardiovascular risk factors are particularly pronounced. Pregnant women with type 2 diabetes have additional risk factors for serious adverse pregnancy outcomes as well as added barriers regarding healthcare access before, during and after pregnancy. Compared to pregnant women with type 1 diabetes, those with type 2 diabetes are older, have higher body mass index (BMI), with more metabolic comorbidities and concomitant medications and are more likely to belong to minority ethnic groups, and live in the highest areas of socio-economic deprivation...

The combat against the Corona virus disease of 2019 (COVID-19), has created a chaos among the healthcare institutions and researchers, in turn accelerating the dire need to curtail the infection spread. The already established entry mechanism, via ACE2 has not yet successfully aided in the development of a suitable and reliable therapy. Taking in account the constant progression and deterioration of the cases worldwide, a different perspective and mechanistic approach is required, which has thrown light onto the cluster of differentiation 147 (CD147) transmembrane protein, as a novel route for SARS-CoV-2 entry...

PURPOSE OF REVIEW: Chronic inflammation has been recognized as one of the most important pathophysiological mechanisms' initiation and progression of atherosclerosis. Statins belong to most successful therapeutic agents in the prevention and treatment of atherothrombotic vascular disease. Their non-lipid related effects including suppression of inflammation have been repeatedly proven in both experimental and clinical settings. RECENT FINDINGS: Recently, the importance of inflammation in the process of atherosclerosis has been confirmed by interventions targeting inflammation selectively...

Acute respiratory distress syndrome is a heterogenous syndrome with many etiologies for which there are no definitive pharmacologic treatments, despite decades of research. We explore some adjunctive pharmacologic therapies, including neuromuscular blockade, corticosteroids, and inhaled pulmonary vasodilators. Additionally, we explore some investigative therapies, including Vitamin C, beta-agonists, statins, mesenchymal stromal cells, and granulocyte-macrophage colony stimulating factor. We do discuss the potential role of steroids in acute respiratory distress syndrome with severe acute respiratory syndrome coronavirus 2 as a trigger...

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes...

BACKGROUND: Hematopoietic cell transplantation (HCT) offers long-term cure against early morbidity and mortality of hemoglobinopathies such as sickle cell disease (SCD) and beta-thalassemia. Following transplant, sirolimus is one immunosuppressant used to prevent graft vs host disease (GVHD), while receiving trimethoprim-sulfamethoxazole (TMP-SMX) for pneumocystis jiroveci (PCP) prophylaxis and other antimicrobial agents (including acyclovir). One rare adverse event associated with both drugs is rhabdomyolysis, defined as creatine kinase (CK) elevation at least 5-10 times the upper limit of normal (ULN)...

Portal hypertension, defined as increased pressure in the portal vein, develops as a consequence of increased intrahepatic vascular resistance due to the dysregulation of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), frequently arising from chronic liver diseases. Extrahepatic haemodynamic changes contribute to the aggravation of portal hypertension. The pathogenic complexity of portal hypertension and the unsuccessful translation of preclinical studies have impeded the development of effective therapeutics for patients with cirrhosis, while counteracting hepatic and extrahepatic mechanisms also pose a major obstacle to effective treatment...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits an interferon (IFN) deficiency state, which aggravates the type I interferon deficiency and slow IFN responses, which associate with e.g. aging and obesity. Additionally, SARS-CoV-2 may also elicit a cytokine storm, which accounts for disease progression and ultimately the urgent need of ventilator support. Based upon several reports, it has been argued that early treatment with IFN-alpha2 or IFN-beta, preferentially in the early disease stage, may prohibit disease progression...

Statins are a group of lipid-lowering drugs that inhibit cholesterol biosynthesis and have anti-inflammatory, anti-tumor, and immunomodulatory properties. Several lines of evidence indicate that statins regulate multiple proteins associated with the regulation of differing cellular pathways. The 5'-adenosine monophosphate-activated protein kinase (AMPK) pathway plays an important role in metabolism homeostasis with effects on cellular processes including apoptosis and the inflammatory responses through several pathways...

BACKGROUND AND AIMS: Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) is an endogenous inhibitor of the LDL receptor (LDLR). Mendelian randomization studies suggest that PCSK9 deficiency increases diabetes risk, but the underlying mechanisms remain unknown. The aim of our study was to investigate whether PCSK9 or its inhibition may modulate beta cell function. METHODS: We assessed PCSK9 and insulin colocalization in human pancreatic sections by epifluorescent and confocal microscopy...