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Molecular hybridization method was applied to design and synthesize a series of target compounds paeonol-based fibrate derivatives. The target compound was screened using a Triton WR-1339 induced hyperlipidemia mouse model, and compound T9 was found to have good lipid-lowering activity. The dose-dependent study of its lipid-lowering activity was also conducted. To further evaluate the lipid-lowering activity of compound T9, a hyperlipidemic mouse model induced by high fat emulsion can be used. The findings of the research illustrate that T9 is capable of significantly decreasing blood lipid levels, including TG, TC, LDL-C, and increasing HDL-C. The results of liver tissue oil red O staining and HE staining demonstrated that T9 improved the hepatic lipid accumulation, thus decreasing AST and ALT levels and protecting against hyperlipidemic liver injury. Studies into the lipid-lowering effect of T9 have indicated that it can upregulate PPAR-α protein expression in liver tissue, while simultaneously decreasing the expression of HMG-CoA protein. T9 was further demonstrated to possess antioxidant properties, as evidenced by an increase in SOD and a decrease in MDA, as well as anti-inflammatory effects, demonstrated by a decrease in TNF-α, IL-1β, and IL-6, thus confirming its potential as a hypolipidemia and hepatoprotective agent. [ABSTRACT FROM AUTHOR]

Obesity is a condition where excessive fat is accumulated, which poses a health risk. Several treatments for obesity have been carried out, ranging from lifestyle adjustments to medication to surgery. Corrosolic Acid (CA) is a natural compound that has the potential to act as an obesity agent through many mechanisms, including through reactive oxygen species (ROS). This study aims to prove that CA can reduce MDA levels and HMG-CoA reductase levels and increase leptin levels and GLP-1 levels in male Wistar rats with obesity. Wistar obese rats were orally treated with CA compound induction at a dose of 10 mg/Kg BW. MDA, HMG-CoA reductase, leptin and GLP-1 levels were examined using serum and plasma from mice in both groups of mice before and after treatment, using the ELISA method. CA to the treatment group can reduce the body weight of rat MDA levels significantly at p<0.0001, HMG-CoA reductase levels significantly at p<0.0001 and increase leptin and GLP-1 levels significantly at p<0.0001. CA's mechanism for treating obesity is through the ROS mechanism because CA has antioxidant levels that can capture free radicals in the body.CA has been proven to be an alternative drug in treating obesity by reducing body weight, MDA, and HMGCoA levels and increasing leptin and GLP-1 levels in obese Wistar rats. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). Recent Findings: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = − 0.06, 95% CI = − 0.19; 0.06 and SMD = 0.26, 95% CI = − 0.66; 1.19), but significantly different (p-value = 0.04). Meta-regression and subgroup analyses did not show any significant differences in pooled estimates across covariates. Summary: The effect of statins on CAC differs across study designs. OSs demonstrate associations between statin use and higher CAC scores and presence while being prone to confounding by indication. Effects from RCTs do not reach statistical significance and vary depending on the quantification method, hampering drawing conclusions. Further investigations are required to address the limitations inherent in each approach. [ABSTRACT FROM AUTHOR]

Introduction- Chronic Kidney Failure (CKF) causes various problems over a period of time which includes cardiovascular diseases. Cardiovascular complications are major cause of deaths inpatients of CKF than various other cause. In this complication’s dyslipidemia is commonly observed features of CKF. Since various study shows that there is relation between CRF and cardiovascular disease and dyslipidemia is constant feature we decided to study to understand the risk involved in cardiovascular morbidity in patients of CRF by studying lipid profile Aim and Objective-To assess cardiovascular risk in cases of chronic renal failure by studying Lipid profile Material and Methodology: This study was done in Medical College, Hospital and research Centre Study population: Total 100 subjects participated in this study 50 Chronic kidney failure (CRF) cases and 50 Controls. Collection of blood samples: 8-10 ml of blood samples after fasting was collected before and after hemodialysis in a plain bulb taking all aseptic precautions. Serum was used after centrifugation. Parameters Lipid profile which includes 1. Serum Total Cholesterol-Dynamic extended stability CHOD-PAP Method (With LCF-Lipid Clearing Factor), End Point by Roeshlaus 2. Serum HDL-Cholesterol-Liquid stable reagent by Trinder reaction. 3.Serum LDL- Cholesterol-Liquid stable reagent by Trinder reaction. 4.Serum Triglyceride-Dynamic extended stability (With LCF)GPO-Trinder Method End Point Observations and Results In our study Low Density Lipoprotein-Cholesterol, Total Cholesterol and Triglyceride levels increased in cases of chronic kidney failure patients in comparison with control whereas HDL-Cholesterol decreased in cases of chronic kidney failure patients in comparison with control. Conclusion: In our study there is altered lipid profile found in our study in CRF there is increased cardio-vascular risk patients. Alteration in concentration of lipoproteins which causes acceleration of process of atherosclerosis in cases of CRF patients. These complications can be prevented by lipid lowering diet and drugs such as the HMG-CoA reductase inhibitors (statins). So, to prevent these cardiovascular complication proper diet advice and drug treatment should be given to the CRF patients. [ABSTRACT FROM AUTHOR]

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin’s mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders.

The aim of this study was the modification of lovastatin by microbes to improve its potential. Actinobacteria exhibit staggering diversity in terms of their biosynthetic capability for specialized metabolites which has been traced back to the presence of specialized gene clusters. The objective of the study is to exploit the potential of Actinobacteria strain(s), which can biotransform lovastatin to simvastatin, which might be a more potent therapeutic agent than lovastatin. We have screened 40 Actinobacteria strains and assessed their biotransformation potential primarily through thin layer chromatography (TLC) analysis, followed by high performance thin layer chromatography and high performance liquid chromatography analysis. One strain C7 (CTL S12) has been identified as a potential Actinobacteria that favored the simvastatin biotransformation. The morphological and biochemical analysis together with 16S rRNA sequencing coupled with phylogenetic analysis confirmed the ideal strain (C7) as Streptomyces carpaticus. Successively, the purified simvastatin from S. carpaticus was characterized by liquid chromatography–mass spectrometry (LC–MS), infrared spectrometry, nuclear magnetic resonance, and HMG‐CoA assay. In the LC–MS analysis, a peak at 419.24 m/z confirmed the elemental composition of simvastatin (C25H39O5). In HMG‐CoA assay, the IC50 of simvastatin was 50 μg/ml, and the inhibitory potential was 1.36 times higher compared to that of lovastatin. Thus, the biotransformation of simvastatin from lovastatin by S. carpaticus is reported for the first time. [ABSTRACT FROM AUTHOR]

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin's mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders. [ABSTRACT FROM AUTHOR]

Aim: To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. Materials & methods: A systematic review and metaanalysis was conducted to summarize the effect sizes in randomized controlled trials and cohort studies that compared high-intensity statins. Results: Based on 44 articles, similar effectiveness was observed across the statins in reducing LDL levels from baseline. All statins were observed to have similar adverse drug reactions (ADRs), although higher dosages were associated with more ADRs. Based on a pooled quantitative analysis of atorvastatin 80 mg versus rosuvastatin 40 mg, rosuvastatin was statistically more effective in reducing LDL. Conclusion: This review further confirms that high-intensity statins reduce LDL by ≥50%, favoring rosuvastatin over atorvastatin. Additional data are needed to confirm the clinical significance on cardiovascular outcomes using real-world studies.

In recent years, many studies have demonstrated that the system of orexin plays a pivotal role in regulating lipogenesis enzymes. However, its effect on the mammary glands is not entirely known. This study answers the question of whether intra-ductal injection of orexin antagonists (OX1RA and OX2RA) into the mammary glands can result in the expression of fatty acid synthase (Fas) and HMG-CoA reductase (Hmgcr) genes and the secretion of cholesterol in lactating female rats or not. To this end, 42 Lactating rats were randomly divided into experimental groups including a control group and groups receiving OX1RA and OX2RA intraductal (with doses of 5, 10, and 20 µg/kg, i.duc). Milk samples were collected for cholesterol testing. Using specific primers for each gene, the target genes were measured via real-time PCR. Data differences were considered significant with P <0.05. PCR exhibited that the injection of orexin antagonists significantly reduced Fas and Hmgcr gene expression. Moreover, the injection of antagonists significantly reduced milk cholesterol. Intra-mammary injection of orexin antagonists reduces milk cholesterol levels by affecting the expression of Fas and Hmgcr genes. [ABSTRACT FROM AUTHOR]

Abstract Background Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [18F]Atorvastatin, the 18F-labeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. Results [18F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [18F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol−1. Incubation of [18F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [18F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [18F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. Conclusions The improved ruthenium-mediated 18F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [18F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [18F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients.

BackgroundBlepharitis is a common eye disorder that may be overlooked by patients and clinical practitioners. The symptoms of blepharitis often manifest as irritation, a burning sensation, grittiness, and itchiness and may decrease visual acuity if not treated promptly. Meibomian gland dysfunction (MGD), a common cause of blepharitis, is believed to be associated with increased inflammatory marker levels that may disrupt the composition of lipids produced by the sebaceous glands in the eyelids and ultimately cause tear film instability.MethodsThis is a retrospective, population-based study using National Health Insurance Research Database (NHIRD) data from a 14-year period (2000–2015). Pearson chi-squared and Student's t-tests were used to assess the differences in categorical and continuous variables, respectively, between statin users and non-statin users. Univariate and multivariate Cox regression analyses were performed to calculate the hazard ratios (HRs) after adjusting for confounders. Kaplan-Meier analysis was used to assess the cumulative risk of blepharitis between the two cohorts.ResultsA total of 67,014 patients who used statins were enrolled as the study cohort, and 268,056 patients who did not use statins were enrolled as the comparison cohort. The incidence of blepharitis was 3.04% with statin treatment and 3.72% without statin treatment (p < 0.001). Patients who used statins had a lower risk of developing blepharitis [adjusted hazard ratio (aHR): 0.746, p < 0.001] than those who did not. In addition, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), stroke, chalazion, rosacea, Sjogren syndrome, psoriasis and atopy were found to be possible risk factors for blepharitis.ConclusionStatin use can decrease the risk of developing blepharitis. However, further prospective studies are needed to evaluate statin treatment for various subtypes of blepharitis and to identify the associated mechanism.

Background: Elevated brain cholesterol increases the risk of Alzheimer's disease. Production of 24-hydroxycholesterol (24s-OHC) by neurons prevents cholesterol accumulation in the brain. In this study, we investigated the effect of 24s-OHC on the HMG-COA reductase and ABCA1 which are involved in the brain cholesterol homeostasis with or without β-amyloid in astrocytes. Methods and Materials: Astrocytes were treated with 24s-OHC with or without Aβ. Western blot and real-time polymerase chain reaction were done to detect protein and gene expression of β-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and ABCA1, respectively. Cholesterol release was determined using a quantitation kit. Results: Protein levels of HMGCR and ABCA1 were significantly increased by Aβ; however, the 24s-OHC was able to restore their levels and diminish the effect of amyloid-β. Aβ did not have a significant effect on HMGCR expression, while 24s-OHC reduced it by 68%. Aβ-induced ABCA1 expression did not increase cholesterol efflux as the lower levels of cholesterol in conditioned medium of Aβ-treated cells were found. Conclusion: Our novel findings show that Aβ affects two key elements in the brain cholesterol homeostasis, HMGCR and ABCA1, which are crucial in cholesterol synthesis and efflux. Since 24s-OHC could suppress the Aβ effects on enhancement of HMGCR and ABCA1, therefore the cytochrome P450 46A1 (Cyp46A1), which is exclusively expressed in the central nervous system and responsible for producing of 24s-OHC, could consider as a therapeutic target in the cholesterol-related neurodegenerative diseases such as Alzheimer's disease.

Statins is widely used in clinical practice as lipid-lowering drugs and has been proven to be effective in the treatment of cardiovascular, endocrine, metabolic syndrome and other diseases. The latest preclinical evidence shows that statins have anti-proliferation, pro-apoptotic, anti-invasion and radiotherapy sensitization effects on tumor cells, suggesting that statins may become a new type of anti-tumor drugs. For a long time, mevalonate pathway has been proved to play a supporting role in the development of tumor cells. As an effective inhibitor of mevalonate pathway, statins have been proved to have a direct auxiliary anti-tumor effect in a large number of studies. In addition, anti-tumor effects of statins through ferroptosis, pyroptosis, autophagy and tumor microenvironment (TME) have also been gradually discovered. However, the specific mechanism of the antitumor effect of statins in the tumor microenvironment has not been clearly elucidated. Herein, we reviewed the antitumor effects of statins in tumor microenvironment, focusing on hypoxia microenvironment, immune microenvironment, metabolic microenvironment, acid microenvironment and mechanical microenvironment.

Statins is widely used in clinical practice as lipid-lowering drugs and has been proven to be effective in the treatment of cardiovascular, endocrine, metabolic syndrome and other diseases. The latest preclinical evidence shows that statins have anti-proliferation, pro-apoptotic, anti-invasion and radiotherapy sensitization effects on tumor cells, suggesting that statins may become a new type of anti-tumor drugs. For a long time, mevalonate pathway has been proved to play a supporting role in the development of tumor cells. As an effective inhibitor of mevalonate pathway, statins have been proved to have a direct auxiliary anti-tumor effect in a large number of studies. In addition, anti-tumor effects of statins through ferroptosis, pyroptosis, autophagy and tumor microenvironment (TME) have also been gradually discovered. However, the specific mechanism of the antitumor effect of statins in the tumor microenvironment has not been clearly elucidated. Herein, we reviewed the antitumor effects of statins in tumor microenvironment, focusing on hypoxia microenvironment, immune microenvironment, metabolic microenvironment, acid microenvironment and mechanical microenvironment. [ABSTRACT FROM AUTHOR]

BackgroundThe coronary artery calcium (CAC) score predicts future coronary heart disease (CHD) events and could be used to guide primary prevention interventions, but CAC measurement has costs and exposes patients to low-dose radiation.Methods and resultsWe estimated the cost-effectiveness of measuring CAC and prescribing statin therapy based on the resulting score under a range of assumptions using an established model enhanced with CAC distribution and risk estimates from the Multi-Ethnic Study of Atherosclerosis. Ten years of statin treatment for 10,000 55-year-old women with high cholesterol (10-year CHD risk, 7.5%) was projected to prevent 32 myocardial infarctions, cause 70 cases of statin-induced myopathy, and add 1108 years to total life expectancy. Measuring CAC and targeting statin treatment to the 2500 women with CAC>0 would provide 45% of the benefit (+501 life-years), but CAC measurement would cost $2.25 million and cause 9 radiation-induced cancers. Treat all was preferable to CAC screening in this scenario and across a broad range of other scenarios (CHD risk, 2.5%-15%) when statin assumptions were favorable ($0.13 per pill and no quality of life penalty). When statin assumptions were less favorable ($1.00 per pill and disutility=0.00384), CAC screening with statin treatment for persons with CAC>0 was cost-effective (100 or >300) were generally not cost-effective.ConclusionsCAC testing in intermediate risk patients can be cost-effective but only if statins are costly or significantly affect quality of life.

The cellular control of cholesterol metabolism mediated by lipoproteins was first appreciated in pioneering work published in a 1974 PNAS Classic by Michael Brown and Joseph Goldstein. We know from this paper that the LDL binds to a cell surface receptor and dampens the activity of a key enzyme in cholesterol biosynthesis and that a receptor deficiency is responsible for a major genetic cause of hypercholesterolemia and premature atherosclerosis.

Hyperlipidemia is a metabolic abnormality in both young and aged populations across the world. Withaferin-A (WT) present in Withania somnifera (Indian ginseng) has been studied by many investigators for their therapeutic potentials. However, their effects on bile acid (BA) metabolism, that play a significant role in lipid homeostasis under hyperlipidemia has not been studied. This study explores the modulatory potential of WT on BA metabolism in young and aged hyperlipidemic rats. Hyperlipidemia was induced by feeding lard fat (35g/100g diet, HF) for 60 days. Withaferin-A (2.5 mg/kg diet) was fed to assess its effect on lipid metabolism and enterohepatic circulation of BA. In both models, compared to HF, WT had significantly (p

Objectives: To observe the variations in lipid profile in patients with secondary hyperlipidemia using HMG-CoA reductase inhibitor. Methods: This study was done at private hospital in patients predominantly suffering from secondary hyperlipidemia. The duration of study was about 4 months. Body weight, height and blood pressure of subjects were assessed. The subjects were asked to answer the related question on cigarette smoking, health related complaints, detailed history of family, drug usage, and nutritional habits. Subjects were requested to make up a permission form before starting the research study. This case control study was performed at local private Hospital, located at Karachi from 1st April 2017 to 30th July 2017. The aim of research was to analyze the effects of HMG-CoA reductase inhibitor on lipid profile in patients of secondary hyperlipidemia. Age between 35 to 65 years and secondary hyperlipidemic patients were included in the inclusion criteria. Lactating/pregnant women, renal, liver and established coronary artery diseases were included in exclusion criteria. Results: Sixty patients having deteriorated lipid profile were included in this research (age 30-60 years). Subjects were prescribed simvastatin orally 20 mg/day (international product) for 04 months. The total cholesterol, triacylglycerol, LDL and HDL were analysed using simvastatin (20mg/day) of international standard in the serum of secondary hyperlipidemic patients. Conclusion: During this study it is observed that Simvastatin raises the HDL level and reduces LDL level and cholesterol level.

As a valuable carotenoid, β-carotene is commercially used in food, cosmetics, animal feeds, and other industries. Metabolic engineering of microorganisms has been widely explored to improve the production of β-carotene. Compared with the traditional genetic modifications mainly focused on the pathways of mevalonate (MVA) and β-carotene biosynthesis, this study aims to increase the β-carotene production through promoting the synthesis of precursor substances by overexpressing hexokinase and hydroxymethylglutaryl-CoA synthase in an engineered Yarrowia lipolytica. In this study, we investigated the effect of the unique hexokinase gene (Hxk) overexpression on β-carotene accumulation and glucose consumption. The Hxk gene was introduced into a β-carotene producing strain Y.L-1 to generate strain Y.L-2, and this increased the β-carotene content by 98%. Overexpression of the Hxk gene led to increasing in hexokinase activity (329% higher), glucose-6-phosphate content (92% higher), and improvement of the transcriptional level of Hxk (315% higher) compared to the control Y.L-1 strain. Moreover, Hxk overexpression accelerated the utilization rate of glucose. The gene erg13 encoding hydroxymethylglutaryl-CoA synthase was also overexpressed to increase the precursor supply for β-carotene biosynthesis. Recombinant Y.L-4 harboring two copies of erg13 produced 8.41 mg/g dry cell weight (DCW) of β-carotene, which was 259% higher than Y.L-1. The β-carotene content of 9.56 mg/g DCW was achieved in strain Y.L-6 by integrating erg13 into the chromosome and Hxk overexpression. The 3-Hydroxy-3-Methylglutaryl-CoA content in the cells was increased by overexpressing two copies of the erg13 gene. Finally, the titer of β-carotene reached 2.4 g/L using a 50 L bioreactor by the engineered strain, and the fermentation cycle was shortened from 144 to 120 h. Overall, overexpression of Hxk and erg13 could improve β-carotene production and successfully overcoming the bottleneck of precursor generation to support a more efficient pathway for the production of the target product. Our results revealed a novel strategy to engineer the pathway of β-carotene synthesis.

Abstract Background Medical therapeutic options remain quite limited for uterine fibroids treatment. Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have anti-tumoral effects on multiple cancer types, however, little is known about their effects on uterine fibroids. Methods Initially, we conducted a retrospective study of 120 patients with uterine fibroids and hyperlipidemia from the Second Affiliated Hospital of Wenzhou Medical University. Then, we evaluated the effect of atorvastatin on proliferation and apoptosis both in immortalized uterine fibroids cells and primary uterine fibroids cells. Furthermore, the molecular mechanism by which atorvastatin suppressed uterine fibroids cell growth was explored. Results Our results showed that atorvastatin use for 1 or 2 years significantly suppressed growth of uterine fibroids. Atorvastatin inhibited the proliferation of immortalized and primary uterine fibroids cells in a dose and time-dependent manner and stimulated apoptosis of uterine fibroids cells by inducing caspase-3 activation, up-regulating Bim and down-regulating Bcl-2. Additionally, atorvastatin treatment suppressed phosphorylation of ERK1/2 and JNK. Furthermore, GGPP, a downstream lipid isoprenoid intermediate, significantly rescued the effect of atorvastatin. Conclusions These results suggest that atorvastatin exerts anti-tumoral effects on uterine fibroids through inhibition of cell proliferation and induction of apoptosis in HMG-CoA-dependent pathway. Our results provide the first clinical and preclinical data on the use of atorvastatin as a promising nonsurgical treatment option for uterine fibroids.

Purpose: A growing body of preclinical and observational research suggests that statins have potential as a therapeutic strategy in patients with cancer. This systematic review of randomised controlled trials (RCTs) in patients with solid tumours aimed to determine the efficacy of statin therapy on mortality outcomes, their safety profile and the risk of bias of included studies. Methods: Full-text articles comparing statin therapy versus control in solid tumours and reporting mortality outcomes were identified from Medline and Embase from conception to February 2020. A systematic review with qualitative (primarily) and quantitative synthesis was conducted. This systematic review was prospectively registered (Prospero registration CRD42018116364). Results: Eleven trials of 2165 patients were included. Primary tumour sites investigated included lung, colorectal, gastro-oesophageal, pancreatic and liver. Most trials recruited patients with advanced malignancy and used sub-maximal statin doses for relatively short durations. Aside from one trial which demonstrated benefit with allocation to pravastatin 40 mg in hepatocellular carcinoma, the remaining ten trials did not demonstrate efficacy with statins. The pooled hazard ratio for all-cause mortality with allocation to pravastatin in patients with hepatocellular carcinoma in two trials was 0.69 (95% confidence interval CI 0.30–1.61). Study estimates were imprecise. There were no clinically important differences in statin-related adverse events between groups. Overall, included trials were deemed low risk of bias. Conclusion: The trial evidence is not sufficiently robust to confirm or refute the efficacy and safety of statins in patients with solid malignant tumours. Study and patient characteristics may explain this uncertainty. The potential role of high-dose statins in adjuvant settings deserves further research. [ABSTRACT FROM AUTHOR]

As a valuable carotenoid, β-carotene is commercially used in food, cosmetics, animal feeds, and other industries. Metabolic engineering of microorganisms has been widely explored to improve the production of β-carotene. Compared with the traditional genetic modifications mainly focused on the pathways of mevalonate (MVA) and β-carotene biosynthesis, this study aims to increase the β-carotene production through promoting the synthesis of precursor substances by overexpressing hexokinase and hydroxymethylglutaryl-CoA synthase in an engineered Yarrowia lipolytica. In this study, we investigated the effect of the unique hexokinase gene (Hxk) overexpression on β-carotene accumulation and glucose consumption. The Hxk gene was introduced into a β-carotene producing strain Y.L-1 to generate strain Y.L-2, and this increased the β-carotene content by 98%. Overexpression of the Hxk gene led to increasing in hexokinase activity (329% higher), glucose-6-phosphate content (92% higher), and improvement of the transcriptional level of Hxk (315% higher) compared to the control Y.L-1 strain. Moreover, Hxk overexpression accelerated the utilization rate of glucose. The gene erg13 encoding hydroxymethylglutaryl-CoA synthase was also overexpressed to increase the precursor supply for β-carotene biosynthesis. Recombinant Y.L-4 harboring two copies of erg13 produced 8.41 mg/g dry cell weight (DCW) of β-carotene, which was 259% higher than Y.L-1. The β-carotene content of 9.56 mg/g DCW was achieved in strain Y.L-6 by integrating erg13 into the chromosome and Hxk overexpression. The 3-Hydroxy-3-Methylglutaryl-CoA content in the cells was increased by overexpressing two copies of the erg13 gene. Finally, the titer of β-carotene reached 2.4 g/L using a 50 L bioreactor by the engineered strain, and the fermentation cycle was shortened from 144 to 120 h. Overall, overexpression of Hxk and erg13 could improve β-carotene production and successfully overcoming the bottleneck of precursor generation to support a more efficient pathway for the production of the target product. Our results revealed a novel strategy to engineer the pathway of β-carotene synthesis. [ABSTRACT FROM AUTHOR]

Background: Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [18F]Atorvastatin, the 18F-labeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. Results: [18F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [18F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol−1. Incubation of [18F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [18F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [18F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. Conclusions: The improved ruthenium-mediated 18F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [18F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [18F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients. [ABSTRACT FROM AUTHOR]

Vitexin, a flavone is known for its anti-oxidative and anti-inflammatory activities. The aim of this study was to investigate the effect of vitexin in HFAD induced atherosclerosis risks in rats. Atherosclerosis risks were induced in Albino Wistar rats by administering HFAD for 45 days. Vitexin (three dose levels) and pravastatin were administered to HFAD animals for 30 days, starting day 16 onwards. Serum lipids (TC, LDL, HDL, Atherogenic index- (AI), HDL/TC-ratio-%HTR), adhesion molecules-inflammatory mediators (MCP-1, VCAM-1, ICAM-1, IL-1β, IL-6, TNF-α), anti-atherogenic markers (PON1 and HT activities) aortic nitrative-oxidative stress (nitrotyrosine, SOD, GPx, CAT), liver HMG-CoA-reductase activity and endothelial function (using thoracic aorta in organ chamber) were assessed. Administration of Vitexin and pravastatin (selective HMG-CoA reductase inhibitor) both alone and in-combination have corrected HFAD-induced increase in serum TC, LDL, AI, MCP-1, VCAM-1, ICAM-1, IL-1β, IL-6, TNF-α, aortic nitro tyrosine and liver HMG-CoA-reductase activity. Vitexin and pravastatin have also amended HFAD-induced reduction in serum HDL, %HTR, PON1, HT, aortic SOD, GPx, CAT and endothelial function. Vitexin and pravastatin may be considered as a possible anti-atherogenic agents, which may reduce the risk of atherosclerosis and its associated conditions, like ischemic-cerebrovascular disease, coronary Heart Disease and peripheral vascular disease. [ABSTRACT FROM AUTHOR]

Statins, the most prescribed class of drugs for the treatment of hypercholesterolemia, can cause muscle‐related adverse effects. It has been shown that the glucocorticoid‐induced leucine zipper (GILZ) plays a key role in the anti‐myogenic action of dexamethasone. In the present study, we aimed to evaluate the role of GILZ in statin‐induced myopathy. Statins induced GILZ expression in C2C12 cells, primary murine myoblasts/myotubes, primary human myoblasts, and in vivo in zebrafish embryos and human quadriceps femoris muscle. Gilz induction was mediated by FOXO3 activation and binding to the Gilz promoter, and could be reversed by the addition of geranylgeranyl, but not farnesyl, pyrophosphate. Atorvastatin decreased Akt phosphorylation and increased cleaved caspase‐3 levels in myoblasts. This effect was reversed in myoblasts from GILZ knockout mice. Similarly, myofibers isolated from knockout animals were more resistant toward statin‐induced cell death than their wild‐type counterparts. Statins also impaired myoblast differentiation, and this effect was accompanied by GILZ induction. The in vivo relevance of our findings was supported by the observation that gilz overexpression in zebrafish embryos led to impaired embryonic muscle development. Taken together, our data point toward GILZ as an essential mediator of the molecular mechanisms leading to statin‐induced muscle damage. [ABSTRACT FROM AUTHOR]

Functional staple food is the trend of industrialization of staple food in our country. It is an important way to make staple food with some specific functions.The physicochemical properties and HMG-CoA inhibition of extruded rice with red yeast rice flour (RYRF) addition were investigated. Results showed that RYRF addition was beneficial to produce hypolipidemic functional staple foods from extruded rice, involving in color, short-range order, HMG-CoA inhibition, porosity, crystallinity, and mass loss. These were mainly attributed to the biochemical reaction of RYRF which could inhibit the recrystallization of amylopectin and HMG-CoA reductase activity. Among the five concentrations of RYRF additives (0.5%, 1.0%, 2.0%, 3.0%, 4.0% w/w), the extruded rice with 3% RYRF addition achieved the best data in terms of porosity, crystallinity, mass loss and HMG-CoA inhibition rate. [Display omitted] • The red yeast rice flour (RYRF) improved the quality and function of extruded rice. • The RYRF inhibited recrystallization of amylopectin and HMG-Co A reductase activity. • The study provides a new idea for the application of red yeast in functional food. [ABSTRACT FROM AUTHOR]

Objective: In the proposed studies, we aimed to establish the in vitro–in vivo correlation (IVIVC) of antihyperlipidemic activity. We developed new in vitro chicken liver assay method for the evaluation of antihyperlipidemic activity and by using this method also evaluated atorvastatin antihyperlipidemic activity. In the proposed study, we aimed to correlate the in vivo response (serum total cholesterol) with an in vitro response (concentration of an extract of liver homogenate in isopropyl alcohol). Materials and Methods: Then, we hypothesized that chicken liver could be tried as an alternative to rat liver to avoid ethical issues. Moreover, chicken liver is widely available. Thus, we decided to include chicken liver homogenate as the source of enzymes for the in vitro biosynthesis of cholesterol homogenate with and without atorvastatin. We were selected n-hexane:isopropyl alcohol organic mixture to extract the lipid content from chicken liver. Isopropyl alcohol was used to make up the final volume before testing cholesterol content in residue. Results: Both in vitro and in vivo method results showed antihyperlipidemic activity and found that new apparatus is worth for screening activities. Conclusions: A good correlation was obtained between in vitro and in vivo data. Thus, it was concluded that an IVIVC was established for antihyperlipidemic activity. [ABSTRACT FROM AUTHOR]

Introduction: Statin drugs have become the most highly prescribed drugs for cardiovascular disease. However, there is disagreement as to the existence of adverse effects of statin administration on cognitive function. Therefore, it is important to better understand the effects of statins on cognition and possible mechanisms of these effects. Areas covered: We analyzed relevant studies of the relationship between cognitive performance and statin and usage. We included articles published between 2018 and 1992. We identified three randomized trials, one observational study and 66 case reports that provided credible evidence of statin-induced cognitive impairment. We also identified seven randomized trials and two observational studies reporting no significant evidence of statin-induced cognitive impairment. Expert opinion: We found methodological differences that may have contributed to the divergence of these results. Evaluation of all these studies indicated that statin-associated cognitive decline is a real entity. Likely mechanisms to explain the adverse effects include 1. Reduction of synthesis of coenzyme Q10 with consequent increasing oxidative stress and reduction of cerebral energy production; 2. Depletion of central nervous system myelin by inhibition of cholesterol synthesis. We conclude that statin-induced cognitive decline does exist, needs to be better recognized and requires more studies of prevention and treatment. [ABSTRACT FROM AUTHOR]

• The designed model of lipid rafts serves as a platform hosting a transmembrane protein. • Activity of immobilized HMG-CoA reductase was confirmed by the electroreduction of NADP generated in the process. • Inhibition of HMG-CoA reductase by statin is demonstrated on the example of fluvastatin. Electrochemical methods are used to characterize transport phenomena in the presence of membrane proteins to monitor changes in their catalytic properties or activity in the presence of activators or inhibitors. Because membrane proteins are fully active in their natural environment, the lipid membrane, electrochemical investigations of enzymes should be carried out when they are present in an appropriate lipid bilayer deposited on an electrode surface. Here, HMG-CoA reductase (HMGR), the membrane protein responsible for cholesterol synthesis, and its related coenzyme (HMG-CoA) were incorporated into a lipid bilayer obtained by spreading proteoliposomes on the surface of a gold electrode modified with a thioglucose. Nicotinamide adenine dinucleotide phosphate, NADPH was oxidized to NADP+ during the enzymatic reaction when HMG-CoA was reduced to the product, mevalonate, which is further transformed into cholesterol. The reconstitution of HMG-CoA reductase and its mechanism were investigated by following the NADP+ reduction on the electrode using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The activity of HMGR was studied over time and in the presence of fluvastatin, an exemplary HMGR reductase inhibitor commonly used to treat hypercholesterolemia. The inhibitory effect of the statin was electrochemically evaluated by monitoring the decrease of NADP+ reduction current and changes in the impedance parameters of the HMGR-proteoliposome-derived bilayer. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To determine the potential protective effect of prior statin use on the subsequent diagnosis of chronic rhinosinusitis (CRS). Study Design: Retrospective, case‐control. Methods: Electronic medical records for all patients seen in the otolaryngology clinic in 2019 and receiving a diagnosis of CRS were reviewed for the presence or absence of active prior statin use within 365 days of the visit. Similarly, prior statin use in a control group of patients without any diagnosis of CRS was also determined. Statin exposure in CRS patients was compared to statin exposure in control patients with 1:2 matching on age and sex with chi‐square and odds ratios were computed. Results: In 2019, 3655 patients (mean age, 52.9 years, 56.4% female) were identified with a diagnosis of chronic rhinosinusitis versus 41,636 patients without any diagnosis of CRS. All chronic rhinosinusitis patients were successfully matched to 7310 controls. 6.3% of CRS patients (229 patients) had prior statin use, versus 8.5% (624 patients) of control patients. The average mean duration of statin use prior to visit was not significantly different between CRS and control patients (mean days, 202.3 days versus 205.6 days, respectively; P =.697). The presence of a statin medication in use was associated with a significant protective effect against a subsequent diagnosis of CRS with and odds ratio for CRS diagnosis of 0.716 (95% confidence interval, 0.612–0.838) in those patients taking a statin medication (P <.001). Conclusions: The use of a statin medication was associated with a significant reduction in subsequent diagnosis of chronic rhinosinusitis. Level of Evidence: 3 Laryngoscope, 131:E1431–E1433, 2021 [ABSTRACT FROM AUTHOR]

Statins are HMG-CoA reductase inhibitors and decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. They are well tolerated, and because of their LDL-C-lowering effect, they are utilized to decrease the risk of atherosclerosis and cardiovascular disease. However, statins have pleiotropic effects, including immunomodulatory, anti-inflammatory, antioxidant, and anticancer. Currently, oral administration is the only Food and Drug Administration (FDA)-approved route of administration for statins. However, other administration routes have demonstrated promising results in different pre-clinical and clinical studies. For instance, statins also seem beneficial in dermatitis, psoriasis, vitiligo, hirsutism, uremic pruritus, and graft-versus-host disease. Topically applied statins have been studied to treat seborrhea, acne, rhinophyma, and rosacea. They also have beneficial effects in contact dermatitis and wound healing in animal studies, (HIV) infection, osseointegration, porokeratosis, and some ophthalmologic diseases. Topical and transdermal application of statins is a non-invasive drug administration method that has shown significant results in bypassing the first-pass metabolism in the liver, thereby reducing possible adverse effects. This study reviews the multifaceted molecular and cellular impacts of statins, their topical and transdermal application, novel delivery systems, such as nanosystems for topical and transdermal administration and the challenges concerning this approach., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atorvastatin, a lipid-lowering drug that is widely used in the treatment of cardiovascular diseases, has significant clinical significance. This article focuses on the synthetic procedures of atorvastatin, including Paal-Knorr synthesis and several new synthetic strategies. It also outlines chemical and chemo-enzymatic methods for synthesizing optically active side chain of atorvastatin. In addition, a comprehensive overview of the analytical monitoring techniques for atorvastatin and its metabolites and impurities is reported, alongside a discussion of their strengths and limitations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Ionizing radiation, such as gamma irradiation, serves as a useful approach to inhibit spore germination and to control pathogens in postharvest seeds. Recently, its application on phytochemical sources and its influence on antioxidant activity of various phytochemical compounds has become an interesting topic to be explored. Objective: The objectives of this study were to determine the effect of gamma irradiation as sterilization method on the resveratrol content and its antioxidant, HMG-CoA reductase inhibitory and dipeptidyl peptidase-4 (DPP-4) inhibitory activities of Melinjo (Gnetum gnemon) seeds. Methods: In this research, melinjo seeds were irradiated by 0.0; 2.5; 5.0; 7.5; and 10.0 kGy with gamma irradiation and then extracted with ethanol. The extracts were tested for resveratrol content with HPLC, antioxidant activities by DPPH assay, HMG-CoA inhibitory activity using HMGCoA reductase assay kit and DPP-4 inhibitory activity using DPP-4 Inhibitor Screening Assay Kit. Gamma irradiation has effect on resveratrol content, antioxidant activity, HMG-CoA reductase inhibition and DPP-4 inhibitory activity. Results: From the research, the highest value of resveratrol content is 0.18±0.004 mg/g seeds powder found in 5.0 kGy gamma irradiation treatment with IC50 94.64±0.236 μg/mL, while the highest HMG-CoA reductase inhibition is shown in 2.5 kGy irradiation dose. Melinjo seeds irradiated by 2.5 kGy gamma irradiation also shown a significant increase of DPP-4 inhibition activity. Conclusion: This study suggests that 2.5-5 kGy radiation is the effective gamma irradiation dose to improve the quality of melinjo seeds. [ABSTRACT FROM AUTHOR]

Statins are HMG-CoA reductase inhibitors with lipid-lowering effect and commonly used to reduce cardiovascular risk in diabetic patients. The present study investigates the ameliorative effect of simvastatin (SIM) on diabetic nephropathy in rats, pointing to its anti-apoptotic and anti-oxidative stress efficacies. Diabetes was induced by a single intraperitoneal injection of 55 mg/kg body weight streptozotocin (STZ) and both control and diabetic rats received 10 mg/kg SIM for 90 days. Treatment with SIM diminished the body weight loss, blood glucose and, serum creatinine, urea and uric acid in diabetic rats. SIM improved the creatinine clearance rate and urinary levels of creatinine, urea and albumin in STZ-induced rats. Lipid peroxidation and nitric oxide (NO) were significantly increased in the diabetic kidney whereas reduced glutathione, SOD and catalase were declined. Bax and caspase-3 showed a significant increase and Bcl-2 was decreased in the kidney of diabetic rats. SIM administration reduced lipid peroxidation and NO, and improved antioxidants and the expression of apoptotic markers. Diabetic rats showed increased collagen deposition in the kidney, atrophied irregular renal corpuscles with collapsed glomeruli and tubules with degenerated epithelial lining, an effect that was reversed following treatment with SIM. In conclusion, SIM can protect against diabetic nephropathy by attenuating oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSP or stress proteins) are intracellular molecules that participate in physiological cell metabolism and growth, although they are known to be involved in many stress conditions. Statins inhibit the action of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), which is important in the synthesis of cholesterol and essential isoprenoid intermediates, thereby lowering circulating low-density lipoprotein cholesterol (LDL), a major risk factor for cardiovascular disease (CVD). This review provides new insights into the mechanisms of action of statins in the regulation of HSPs. A better understanding of this involvement can help in development of new and more effective treatment strategies for CVD. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are considered to be the leading cause of disability and deaths in the whole world. The major cause behind this disease is the formation of lipid plagues in the form of thrombus. The statins (HMG-CoA reductase inhibitors) are used for the treatment and prevention of hyperlipidemia. Myopathy is the major side effect caused by statins. The purpose of this study was to determine the prevalence of statin induced myopathy. A cross- sectional study design was adopted using convenient random sampling technique at Punjab Institute of Cardiology, Lahore Pakistan from November 2016 to February 2017. A total of 300 male and female patients were included having age range of 40-80 years. Data was collected directly from the patients and prevalence of myalgia was determined by the symptoms of the patients. Creatine Phospho Kinase levels were obtained of those patients showing symptoms. Data was analyzed by using SPSS version 21. The results showed that 51% patients were myalgic with mean±SEM, 1.49±0.29. Myalgia was more prevalent in age range 40-50, with females 57% and males 47%. Significant relation was found between myalgia and type of statin (p=0.05), duration of use of statin (p=0.036) and dose of statin (p=0.031). The study concludes that the prevalence of myalgia was not significant but females were more prone to myalgic symptoms as compared to males. It was further concluded that myalgic symptoms were directly related to dose and duration & type of statin use. [ABSTRACT FROM AUTHOR]

The present study explored the antihyperlipidemic potential of a standardized methanolic extract of Averrhoa carambola (A. carambola) leaf (MEACL) in high-fat diet (HFD)-fed rats. The standardized MEACL was orally administered at different doses (250, 500, and 1000 mg/kg) to HFD-induced hyperlipidemic rats for five weeks. Serum lipid profile, body weight changes, body mass index (BMI), daily food intake, relative organ weight, and histology of the liver were evaluated. In addition, the effect of MEACL on HMG-CoA reductase and pancreatic lipase activities as well as hepatic and fecal lipids was demonstrated. MEACL supplementation reduced serum lipids in HFD-fed rats in a dose-dependent manner. Histopathological scores revealed that 1000 mg/kg MEACL restored the damage to liver tissue in hyperlipidemic rats. MEACL decreased the body mass index (BMI), atherogenic index, and hepatic cholesterol and triglycerides and increased fecal cholesterol and bile acids in HFD-fed rats. Also, MEACL ameliorated lipid peroxidation and improved antioxidant defenses in the liver of HFD-fed rats. Furthermore, HMG-CoA reductase and lipase were suppressed by MEACL. In conclusion, this study shows the potential effect of MEACL to ameliorate hyperlipidemia and oxidative stress in HFD-fed rats. It prevented hepatic lipid accumulation and exerted an inhibitory effect on HMG-CoA reductase and lipase.

Lohmann Brown hens (n = 420), at 28 weeks of age, were divided into five dietary treatments, and each treatment included six replicates of 14 laying hens. Dietary crude protein (14%) was presented as the control diet. Dietary L-Thr was added to the control diet for 12 weeks. Dietary Thr levels are 0.43%, 0.49%, 0.57%, 0.66%, and 0.74%, based on digestible base. From 28 to 40 weeks, hen-day egg production presented a quadratic trend to supplementing dietary Thr (R2 = 0.96, p = 0.02), and reached a maximum level at 0.58%. Serum uric acid demonstrated a quadratic trend (R2 = 0.62, p = 0.02) at 0.59%. Both serum total cholesterol and 3-hydroxy-3-methylglutaryl (HMG-CoA) reductase showed lower levels (p < 0.05) at 0.66% Thr. Serum CuZn-SOD elevated (p < 0.05) at 0.49%, 0.57%, and 0.66% Thr, as compared to the control group, and showed a quadratic trend (R2 = 0.87, p = 0.003) at 0.56%. Supplemental L-Thr decreased (p < 0.05) the expression of ileal HSP70 at 0.66% Thr. In summary, the optimal dietary Thr requirements to optimize egg production, serum uric acid, and serum CuZn-SOD were 0.58%, 0.59%, and 0.56%, respectively, by regression analysis.

The existence of genetic traits might explain the susceptibility to develop hypercholesterolemia and the inter-individual differences in statin response. This study was performed to evaluate whether individuals' polymorphisms in HMG-CoA and KIF6 genes are independently associated with hypercholesterolemia, other lipid-associated traits, and statin response in unselected individuals enrolled in the Brisighella heart study (Survey 2012). A total of 1622 individuals, of which 183 under statin medication, were genotyped for a total of five polymorphisms (KIF6 rs20455, rs9471077, rs9462535; HMG-CoA rs3761740, rs3846662). The relationships between the five loci and clinical characteristics were analyzed. The principal basic parameters calculated on 12 h fasting blood included total cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low-Density Lipoprotein Cholesterol (LDL-C), and triglycerides (TG). Hypercholesterolemia was defined as a TC >200 mg/dL or use of lipid-lowering medication. 965 individuals were characterized by hypercholesterolemia; these subjects were significantly older (p < 0.001), with body mass index (BMI) and waist circumference significantly higher (p < 0.001) compared to the others. HMG-CoA rs3846662 GG genotype was significantly over-represented in the hypercholesterolemic group (p = 0.030). HMG-CoA rs3846662 genotype was associated with the level of TC and LDL-C. Furthermore, in the same subset of untreated subjects, we observed a significant correlation between the KIF6 rs20455 and HDL-C. KIF6 variants were associated with a significantly lower (rs20455) or higher (rs9471077 and rs9462535) risk of obesity, in males only. No association between responsiveness to statins and the polymorphisms under investigation were observed. Our results showed associations between HMG-CoA rs3846662 and KIF6 rs20455 and lipid phenotypes, which may have an influence on dyslipidemia-related events. Moreover, this represents the first study implicating KIF6 variants with obesity in men, and point to the possible involvement of this genetic locus in the known gender-related differences in coronary artery disease. [ABSTRACT FROM AUTHOR]

Background Hyperlipidemia causes arteriosclerosis, a risk factor for coronary heart disease. Prevention of hyperlipidemia by improving dietary habits has recently attracted attention. In this regard, we investigated whether Aralia elata (Miq.) Seem (AE) extract inhibits hepatic cholesterol accumulation and modulate the cellular signaling pathway. Methods To determine AE's cholesterol regulating mechanism, we measured cholesterol level, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and cholesterol regulating-related gene expression in HepG2 cells and in high-fat diet (HFD)-induced mice using ELISA and RT-PCR assay. Results The AE extract reduced cholesterol levels and HMG-CoA reductase activity in hepatocellular carcinoma HepG2 cells. In addition, it also reduced the plasma cholesterol concentrations in HFD-induced mice. Furthermore, the AE extract increased the gene expression of the LDL-receptor (LDL-R); sterol-regulatory-element binding protein-2 (SREBP-2); ATP-binding cassette, sub-family A, member 1 (ABCA1); and scavenger receptor class B member 1 (SR-B1) in a dose-dependent manner. However, the AE extract did not affect the gene expression of acetyl-coenzyme A acetyltransferase (ACAT) in either the HepG2 cells or mice. Conclusion We demonstrated that the AE extract activated genes related to cholesterol metabolism, such as SREBP-2 and LDL-R, which resulted in hypocholesterolemic activities. [ABSTRACT FROM AUTHOR]

Introduction: HMG-CoA (3-hydroxy-3- methylglutary lcoenzyme A) reductase inhibitors (statins) have anti-inflammatory properties which may be particularly useful in rheumatoid arthritis to suppress disease activity and inflammatory factors. Aim: The purpose of this clinical trial was to determine antiinflammatory properties of statins in rheumatoid arthritis. Materials and Methods: Eighty Iranian patients with rheumatoid arthritis, aged between 19 to 75 years were recruited to take part in this randomized, double-blind placebo-controlled trial. Subjects were randomly allocated to two groups to take atorvastatin or placebo 40 mg daily as an adjunct to current disease-modifying anti-rheumatic drugs (DMARDs) treatment. Disease Activity Score-28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) & tender joint count (TJC) were assessed before and after three months intervention. Results: Analysis was based on intention to treat. DAS28 significantly declined in the atorvastatin group in comparison with placebo (p< 0.001). SJC, TJC, CRP and ESR also were significantly dropped in the atorvastatin group in comparison with placebo. Conclusion: It can be concluded that atorvastatin can suppress RA activity and inflmmatory factors in RA patients for high to moderate grade of inflmmation.