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International Journal of Molecular... Oct 2022Increased cholesterol absorption and reduced synthesis are processes that have been associated with cardiovascular disease risk in a controversial way. However, most of...
BACKGROUND
Increased cholesterol absorption and reduced synthesis are processes that have been associated with cardiovascular disease risk in a controversial way. However, most of the studies involving markers of cholesterol synthesis and absorption include conditions, such as obesity, diabetes, dyslipidemia, which can be confounding factors. The present study aimed at investigating the relationships of plasma cholesterol synthesis and absorption markers with cardiovascular disease (CVD) risk factors, cIMT (carotid intima-media thickness), and the presence of carotid plaques in asymptomatic subjects.
METHODS
A cross-sectional study was carried out in 270 asymptomatic individuals and anthropometrical parameters, fasting plasma lipids, glucometabolic profiles, high-sensitivity C-reactive protein (hs-CRP), markers of cholesterol synthesis (desmosterol and lathosterol), absorption (campesterol and sitosterol), cIMT, and the presence of atherosclerotic plaques were analyzed.
RESULTS
Among the selected subjects aged between 19 and 75 years, 51% were females. Age, body mass index, systolic and diastolic blood pressure, total cholesterol, non-HDL-C, triglycerides, glucose, and lathosterol/sitosterol ratios correlated positively with cIMT ( ≤ 0.05). Atherosclerotic plaques were present in 19% of the subjects. A direct association of carotid plaques with campesterol, OR = 1.71 (95% CI = 1.04-2.82, ≤ 0.05) and inverse associations with both ratios lathosterol/campesterol, OR = 0.29 (CI = 0.11-0.80, ≤ 0.05) and lathosterol/sitosterol, OR = 0.45 (CI = 0.22-0.95, ≤ 0.05) were observed in univariate logistic regression analysis.
CONCLUSIONS
The findings suggested that campesterol may be associated with atherosclerotic plaques and the lathosterol/campesterol or sitosterol ratios suggested an inverse association. Furthermore, synthesis and absorption of cholesterol are inverse processes, and the absorption marker, campesterol, may reflect changes in body cholesterol homeostasis with atherogenic potential.
Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cholesterol; Cross-Sectional Studies; Desmosterol; Female; Glucose; Humans; Male; Middle Aged; Phytosterols; Plaque, Atherosclerotic; Sitosterols; Triglycerides; Young Adult
PubMed: 36233298
DOI: 10.3390/ijms231911997 -
Orthodontics & Craniofacial Research Feb 2022The aim of this systematic review was (i) to determine the role of muscular traction in the occurrence of skeletal relapse after advancement BSSO and (ii) to investigate... (Review)
Review
The aim of this systematic review was (i) to determine the role of muscular traction in the occurrence of skeletal relapse after advancement BSSO and (ii) to investigate the effect of advancement BSSO on the perimandibular muscles. This systematic review reports in accordance with the recommendations proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Electronic database searches were performed in the databases MEDLINE, Embase and Cochrane Library. Inclusion criteria were as follows: assessment of relapse after advancement BSSO; assessment of morphological and functional change of the muscles after advancement BSSO; and clinical studies on human subjects. Exclusion criteria were as follows: surgery other than advancement BSSO; studies in which muscle activity/traction was not investigated; and case reports with a sample of five cases or fewer, review articles, meta-analyses, letters, congress abstracts or commentaries. Of the initial 1006 unique articles, 11 studies were finally included. In four studies, an intervention involving the musculature was performed with subsequent assessment of skeletal relapse. The changes in the morphological and functional properties of the muscles after BSSO were studied in seven studies. The findings of this review demonstrate that the perimandibular musculature plays a role in skeletal relapse after advancement BSSO and may serve as a target for preventive strategies to reduce this complication. However, further research is necessary to (i) develop a better understanding of the role of each muscle group, (ii) to develop new therapeutic strategies and (iii) to define criteria that allow identification of patients at risk.
Topics: Humans; Mandible; Mandibular Advancement; Osteotomy; Recurrence; Sitosterols; Traction
PubMed: 33938136
DOI: 10.1111/ocr.12488 -
Archivum Immunologiae Et Therapiae... Feb 2014The ability of plant polyisoprenoids (polyprenols and polyprenyl phosphates) to diminish the levels of serum cholesterol affecting its biosynthetic pathway are... (Review)
Review
The ability of plant polyisoprenoids (polyprenols and polyprenyl phosphates) to diminish the levels of serum cholesterol affecting its biosynthetic pathway are highlighted here. Possible mechanism of such process is discussed. It is also noted that polyisoprenoids can prevent toxic injuries of the liver and restore disturbed hepatic functions. The possibility of polyprenyl phosphates to reveal at the same time anti-inflammatory action suppressing lipoxygenase activity and lowering the levels of proinflammatory cytokines will be illustrated. Attention will be focused on the potential usefulness of plant polyisoprenoids in the course of prevention and treatment of hypercholesterolemia. High efficiency for combined use of polyprenyl phosphate and β-sitosterol, which leads to substantial enhancement of the ability to overcome hypercholesterolemia versus the individual constituents will be demonstrated.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Cholesterol; Humans; Hypercholesterolemia; Lipoxygenase; Phytotherapy; Plants; Sitosterols; Terpenes
PubMed: 23995915
DOI: 10.1007/s00005-013-0253-y -
Scientific Reports Nov 2018Vitamin D is a secosterol hormone critical for bone growth and calcium homeostasis, produced in vertebrate skin by photolytic conversion of the cholesterol biosynthetic...
Vitamin D is a secosterol hormone critical for bone growth and calcium homeostasis, produced in vertebrate skin by photolytic conversion of the cholesterol biosynthetic intermediate provitamin D. Insufficient levels of vitamin D especially in the case of low solar UV-B irradiation is often compensated by an intake of a dietary source of vitamin D of animal origin. Small amounts of vitamin D were described in a few plant species and considered as a peculiar feature of their phytochemical diversity. In this report we show the presence of vitamin D in the model plant Arabidopsis thaliana. This plant secosterol is a UV-B mediated derivative of provitamin D, the precursor of sitosterol. The present work will allow a further survey of vitamin D distribution in plant species.
Topics: Arabidopsis; Sitosterols; Vitamin D
PubMed: 30397227
DOI: 10.1038/s41598-018-34775-z -
Clinical and Applied... Nov 2012Phytosterolemia is a rare autosomal recessive disease of plant sterol metabolism, the pathophysiological features of which are high plasma levels of plant sterols and...
Phytosterolemia is a rare autosomal recessive disease of plant sterol metabolism, the pathophysiological features of which are high plasma levels of plant sterols and xanthomatosis caused by mutations of ABCG5 and ABCG8 genes, and the combination of hemolysis and macrothrombocytopenia is an unusual clinical manifestation. All the patients of the 3 unrelated phytosterolemia first presented with prominent macrothrombocytopenia and stomatocytosis. They were either homozygous or compound heterozygous for ABCG5/ABCG8 gene mutations and had significantly elevated serum plant sterols levels quantified using high-performance liquid chromatography. The in vitro study demonstrated that sitosterol can cause changes in shape and osmotic fragility of red blood cells. These findings suggest that macrothrombocytopenia and stomatocytosis could be initial and main features in some patients with phytosterolemia and that serum phytosterols and relevant genes should be analyzed in patients whose macrothrombocytopenia and/or stomatocytosis are unexplained, especially whose parents are of consanguineous marriage.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Erythrocytes, Abnormal; Female; Heterozygote; Homozygote; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mutation; Osmotic Fragility; Pedigree; Phytosterols; Sitosterols; Xanthomatosis
PubMed: 22297561
DOI: 10.1177/1076029611435090 -
Circulation. Genomic and Precision... Oct 2020Familial sitosterolemia is a rare Mendelian disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols. Affected individuals typically...
BACKGROUND
Familial sitosterolemia is a rare Mendelian disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols. Affected individuals typically have complete genetic deficiency-homozygous loss-of-function (LoF) variants-in the or genes and have substantially elevated plasma sitosterol and LDL (low-density lipoprotein) cholesterol (LDL-C) levels. The impact of partial genetic deficiency of or -as occurs in heterozygous carriers of LoF variants-on LDL-C and risk of coronary artery disease (CAD) has remained uncertain.
METHODS
We first recruited 9 sitosterolemia families, identified causative LoF variants in or , and evaluated the associations of these or LoF variants with plasma phytosterols and lipid levels. We next assessed for LoF variants in or in CAD cases (n=29 321) versus controls (n=357 326). We tested the association of rare LoF variants in or with blood lipids and risk for CAD. Rare LoF variants were defined as protein-truncating variants with minor allele frequency <0.1% in or .
RESULTS
In sitosterolemia families, 7 pedigrees harbored causative LoF variants in and 2 pedigrees in . Homozygous LoF variants in either or led to marked elevations in sitosterol and LDL-C. Of those sitosterolemia families, heterozygous carriers of LoF variants exhibited increased sitosterol and LDL-C levels compared with noncarriers. Within large-scale CAD case-control cohorts, prevalence of rare LoF variants in and in was ≈0.1% each. heterozygous LoF variant carriers had significantly elevated LDL-C levels (25 mg/dL [95% CI, 14-35]; =1.1×10) and were at 2-fold increased risk of CAD (odds ratio, 2.06 [95% CI, 1.27-3.35]; =0.004). By contrast, heterozygous LoF carrier status was not associated with increased LDL-C or risk of CAD.
CONCLUSIONS
Although familial sitosterolemia is traditionally considered as a recessive disorder, we observed that heterozygous carriers of an LoF variant in had significantly increased sitosterol and LDL-C levels and a 2-fold increase in risk of CAD.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Adult; Case-Control Studies; Cholesterol, LDL; Coronary Artery Disease; Female; Heterozygote; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Loss of Function Mutation; Male; Middle Aged; Odds Ratio; Phytosterols; Risk Factors; Sitosterols
PubMed: 32862661
DOI: 10.1161/CIRCGEN.119.002871 -
The Cochrane Database of Systematic... Jul 2013Patients undergoing vascular surgery are a high-risk population with widespread atherosclerosis, an adverse cardiovascular risk profile and often multiple... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients undergoing vascular surgery are a high-risk population with widespread atherosclerosis, an adverse cardiovascular risk profile and often multiple co-morbidities. Postoperative cardiovascular complications, including myocardial infarct (MI), are common. Statins are the medical treatment of choice to reduce high cholesterol levels. Evidence is accumulating that patients taking statins at the time of surgery are protected against a range of perioperative complications, but the specific benefits for patients undergoing noncardiac vascular surgery are not clear.
OBJECTIVES
We examined whether short-term statin therapy, commenced before or on the day of noncardiac vascular surgery and continuing for at least 48 hours afterwards, improves patient outcomes including the risk of complications, pain, quality of life and length of hospital stay. We also examined whether the effect of statin therapy on these outcomes changes depending on the dose of statin received.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE via Ovid SP (1966 to August 2012), EMBASE via Ovid SP (1966 to August 2012), CINAHL via EBSCO host (1966 to August 2012) and ISI Web of Science (1946 to July 2012) without any language restriction. We used a combination of free text search and controlled vocabulary search. The results were limited to randomized controlled clinical trials (RCTs). We conducted forwards and backwards citation of key articles and searched two clinical trial Websites for ongoing trials (www.clinicaltrials.gov and http://www.controlled-trials.com).
SELECTION CRITERIA
We included RCTs that had compared short-term statin therapy, either commenced de novo or with existing users randomly assigned to different dosages, in adult participants undergoing elective and emergency noncardiac arterial surgery, including both open and endovascular procedures. We defined short-term as commencing before or on the day of surgery and continuing for at least 48 hours afterwards.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data, including information on adverse events. We contacted study authors for additional information. We performed separate analyses for the comparisons of statin with placebo/no treatment and between different doses of statin. We presented results as pooled risk ratios (RRs) with 95% confidence intervals (CIs) based on random-effects models (inverse variance method). We employed the Chi(2) test and calculated the I(2) statistic to investigate study heterogeneity.
MAIN RESULTS
We identified six eligible studies in total. The six Included studies were generally of high quality, but the largest eligible study was excluded because of concerns about its validity. Study populations were statin naive, which led to a considerable loss of eligible participants.Five RCTs compared statin use with placebo or standard care. We pooled results from three studies, with a total of 178 participants, for mortality and non-fatal event outcomes. In the statin group, 7/105 (6.7%) participants died within 30 days of surgery, as did 10/73 (13.7%) participants in the control group. Only one death in each group was from cardiovascular causes, with an incidence of 0.95% in statin participants and 1.4% in control participants, respectively. All deaths occurred in a single study population, and so effect estimates were derived from one study only. The risk ratio (RR) of all-cause mortality in statin users showed a non-significant decrease in risk (RR 0.73, 95% CI 0.31 to 1.75). For cardiovascular death, the risk ratio was 1.05 (95% CI 0.07 to 16.20). Non-fatal MI within 30 days of surgery was reported in three studies and occurred in 4/105 (3.8%) participants in the statin group and 8/73 (11.0%) participants receiving placebo, for a non-significant decrease in risk (RR 0.47, 95% CI 0.15 to 1.52). Several studies reported muscle enzyme levels as safety measures, but only three (with a total of 188 participants) reported explicitly on clinical muscle syndromes, with seven events reported and no significant difference found between statin users and controls (RR 0.94, 95% CI 0.24 to 3.63). The only participant-reported outcome was nausea in one small study,with no significant difference in risk between groups.Two studies compared different doses of atorvastatin, with a total of 145 participants, but reported data were not sufficient to allow us to determine the effect of higher doses on any outcome.
AUTHORS' CONCLUSIONS
Evidence was insufficient to allow review authors to conclude that statin use resulted in either a reduction or an increase in any of the outcomes examined. The existing body of evidence leaves questions about the benefits of perioperative use of statins for vascular surgery unanswered. Widespread use of statins in the target population means that it may now be difficult for researchers to undertake the large RCTs needed to demonstrate any effect on the incidence of postoperative cardiovascular events. However, participant-reported outcomes have been neglected and warrant further study.
Topics: Adult; Angioplasty; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Cause of Death; Cholestyramine Resin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Perioperative Care; Postoperative Complications; Pyrroles; Randomized Controlled Trials as Topic; Sitosterols; Vascular Surgical Procedures
PubMed: 23824754
DOI: 10.1002/14651858.CD009971.pub2 -
Medical Science Monitor : International... Jan 2022BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action...
BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.
Topics: Alkaloids; Caspase 3; Coronavirus; Coronavirus Infections; Cyclooxygenase 2; Databases, Pharmaceutical; Drugs, Chinese Herbal; Flavanones; Humans; Indoles; Interleukin-6; Lignin; Luteolin; Mitogen-Activated Protein Kinase 14; Mitogen-Activated Protein Kinase 8; Molecular Docking Simulation; NF-kappa B p50 Subunit; Naphthols; Nitric Oxide Synthase Type III; Protein Interaction Maps; Quercetin; SARS-CoV-2; Signal Transduction; Sitosterols; Transcriptome; COVID-19 Drug Treatment
PubMed: 35075100
DOI: 10.12659/MSM.934102 -
Journal of Agricultural and Food... Jan 2021The recombinant lipase of (OPEr) is characterized by its prominent sterol esterase activity. The protein was immobilized on magnetic nanoparticles, giving four enzyme...
The recombinant lipase of (OPEr) is characterized by its prominent sterol esterase activity. The protein was immobilized on magnetic nanoparticles, giving four enzyme variants that have been tested in solvent-free transesterification of methyl oleate and sitostanol. The yields of stanol esters reached 85%, and the catalysts can be reused. Stanol esters were also obtained in a two-step cascade reaction; a mixture of fatty acid methyl esters was enzymatically synthesized from cooking oil wastes and then used for stanol transesterification. An 85% conversion was achieved in 2 h from the second cycle onward, maintaining the activity over 5 cycles. The biocatalysts can be safely used since they don't release toxic compounds for HeLa and A549 cell lines. These procedures comply with the principles of green chemistry and contribute to the sustainable production of these nutraceuticals from secondary raw materials, like the lipid fraction from industrial or agricultural residues.
Topics: Biocatalysis; Cell Line; Enzymes, Immobilized; Fungal Proteins; Green Chemistry Technology; Humans; Lipase; Oleic Acids; Ophiostoma; Plant Oils; Sitosterols; Waste Products
PubMed: 33375783
DOI: 10.1021/acs.jafc.0c06581 -
Free Radical Biology & Medicine Mar 2024The exploration of drugs derived from natural sources holds significant promise in addressing current limitations in ovarian cancer (OC) treatments. While previous...
The exploration of drugs derived from natural sources holds significant promise in addressing current limitations in ovarian cancer (OC) treatments. While previous studies have highlighted the remarkable anti-cancer properties of the natural compound β-sitosterol (SIT) across various tumors, its specific role in OC treatment remains unexplored. This study aims to investigate the anti-tumor activity of SIT in OC using in vitro and in vivo models, delineate potential mechanisms, and establish a preclinical theoretical foundation for future clinical trials, thus fostering further research. Utilizing network pharmacology, we pinpoint SIT as a promising candidate for OC treatment and predict its potential targets and pathways. Through a series of in vitro and in vivo experiments, we unveil a novel mechanism through which SIT mitigates the malignant biological behaviors of OC cells by modulating redox status. Specifically, SIT selectively targets argininosuccinate synthetase 1 (ASS1), a protein markedly overexpressed in OC tissues and cells. Inhibiting ASS1, SIT enhances the interaction between Nrf2 and Keap1, instigating the ubiquitin-dependent degradation of Nrf2, subsequently diminishing the transcriptional activation of downstream antioxidant genes HO-1 and NQO1. The interruption of the antioxidant program by SIT results in the substantial accumulation of reactive oxygen species (ROS) in OC cells. This, in turn, upregulates PTEN, exerting negative regulation on the phosphorylation activation of AKT. The suppression of AKT signaling disrupted downstream pathways associated with cell cycle, cell survival, apoptosis, migration, and invasion, ultimately culminating in the death of OC cells. Our research uncovers new targets and mechanisms of SIT against OC, contributing to the existing knowledge on the anti-tumor effects of natural products in the context of OC. Additionally, this research unveils a novel role of ASS1 in regulating the Nrf2-mediated antioxidant program and governing redox homeostasis in OC, providing a deeper understanding of this complex disease.
Topics: Female; Humans; Antioxidants; Apoptosis; Argininosuccinate Synthase; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Reactive Oxygen Species; Signal Transduction; Sitosterols; Ubiquitins
PubMed: 38364944
DOI: 10.1016/j.freeradbiomed.2024.02.004