Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 119.149
Filtrar
1.
Braz. j. biol ; 84: e253084, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345551

RESUMO

Abstract Repeatedly frying process of dietary edible oil has a potential role in the generation of free radicals. Therefore, questions have always been raised as to whether, there is an efficient and economical method to reduce the harmful effects of repeated use of frying edible oil. Since hibiscus has been stated to have a wide variety of therapeutic effects, it was important to investigate its properties against harmful effects of free radicals. The current study aspires to find out whether irradiated powder of hibiscus has a protective role against adverse effects of repeated use of frying edible oil. Thirty-five adult male albino rats were equally assigned into five groups. First group"G1" was fed with normal diet as control group, meanwhile, group"G2" the diet mixed with fresh oil, "G3" diet mixed with repeatedly frying oil only, "G4" diet mixed with frying oil treated with hibiscus and "G5" diet mixed with frying oil treated with irradiated hibiscus. Feeding duration was six weeks. Fatty acid analyses of oil as well as peroxide values were determined. Blood and liver samples were collected for biochemical analyses as well as histological study. Repeatedly heated cooked oil has significant increases in peroxide value, acid value, free fatty acid and both conjugated diene and triene compared with repeatedly frying oil treated with hibiscus. Also there are significant increases in cholesterol and triglyceride and impaired in liver functions in "G3"compared with others. In addition, relative to the hibiscus groups, there is a substantial reduction in oxygen consumption in "G3". Both hibiscus as well as irradiated hibiscus attract attention in order to play a vital and economical role against harmful effects of frequent use of frying edible oil on some biological functions but, irradiated hibiscus was more effective.


Resumo O processo de fritura repetida de óleo comestível da dieta tem papel potencial na geração de radicais livres que podem ter efeitos prejudiciais em algumas funções biológicas. Portanto, sempre se questionou se existe uma maneira eficiente e econômica de prevenir ou pelo menos reduzir os efeitos nocivos do uso repetido de óleo comestível para fritar. Como o hibisco tem ampla variedade de efeitos terapêuticos, foi importante investigar suas propriedades como agente antioxidante contra os efeitos nocivos dos radicais livres. O presente estudo pretende descobrir se o pó irradiado de hibisco tem papel protetor contra os efeitos adversos do uso repetido de óleo comestível para fritar. Trinta e cinco ratos albinos machos adultos foram divididos igualmente em cinco grupos. O primeiro grupo "G1" foi alimentado com dieta normal como grupo controle, enquanto o grupo "G2" dieta misturada com óleo fresco, dieta "G3" misturada com óleo de fritura repetida, dieta "G4" misturada com óleo de fritura tratada com hibisco e dieta "G5" misturada com óleo de fritura tratada com hibisco irradiado. A duração da alimentação foi de seis semanas. Foram determinadas as análises de ácidos graxos de óleo, bem como os valores de peróxidos. Amostras de sangue e fígado foram coletadas para análises bioquímicas e estudo histológico. O óleo cozido repetidamente aquecido tem aumentos significativos no valor de peróxido, valor de ácido, ácido graxo livre e dieno e trieno conjugados em comparação com óleo de fritura repetidamente tratado com hibisco. Também há aumentos significativos no colesterol e triglicérides e comprometimento das funções hepáticas no "G3" em comparação com outros. Além disso, em relação aos grupos de hibiscos, há uma redução substancial no consumo de oxigênio no "G3". Tanto o hibisco como o hibisco irradiado chamam atenção por desempenhar papel vital e econômico contra os efeitos nocivos do uso frequente de óleo comestível para fritar em algumas funções biológicas, mas o hibisco irradiado foi mais eficaz.


Assuntos
Animais , Ratos , Hibiscus , Óleos Vegetais/farmacologia , Colesterol , Culinária , Temperatura Alta
2.
Eur J Prev Cardiol ; 28(18): 2001-2009, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33624058

RESUMO

AIM: The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). METHODS AND RESULTS: Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. CONCLUSION: This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Colesterol , LDL-Colesterol , Ezetimiba/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Infarto do Miocárdio/prevenção & controle
3.
BMC Cardiovasc Disord ; 22(1): 357, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931987

RESUMO

BACKGROUND: There is limited evidence regarding the relationship between lipid parameters and vascular mechanical characteristics in the normotensive population without diabetes mellitus. The aim of this study was to identify an association between lipid parameters and changes in vascular mechanical characteristics between men and women, and in women before and after menopause. METHODS: Six hundred-seventy patients who underwent vascular functional testing and who fulfilled the inclusion and exclusion criteria were enrolled in our cross-sectional study. All participants were from the Qinghai-Tibet Plateau (Luhuo County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China; mean altitude: 3860 m). Trained clinical physicians assessed brachial-ankle pulse wave velocity (Ba-PWV) and augmentation index adjusted to a 75-beats-per-minute heart rate (AIx@75). To investigate the relationship between lipid parameters and vascular mechanical characteristics in different sexes and menstrual stages, partial correlation analysis and multiple linear regression were used. RESULTS: The 670 participants comprised 445 women (103 post-menopausal). Mean Ba-PWV and AIx@75 were 1315.56 ± 243.41 cm/s and 25.07% ± 15.84%, respectively. Men had greater Ba-PWV values compared with women (1341.61 ± 244.28 vs 1302.39 ± 242.17 cm/s, respectively; P < 0.05), while AIx@75 values were higher in women compared with men (27.83% ± 15.85% vs 19.64% ± 14.40%, respectively; p < 0.001). In the partial correlation analysis adjusted for age, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (HDL-C) were associated with Ba-PWV in both men and women (p < 0.05); however, the magnitude was larger in men. Statistical significance was not seen for AIx@75 among both men and women. Multiple linear regression analysis revealed that TC (ß = 0.165, p = 0.024) and non-HDL-C (ß = 0.151, p = 0.042) remained independent predictors of change in Ba-PWV in men after adjusting for age, mean arterial pressure, waist circumference, hemoglobin, platelet count, fasting blood glucose, estimated glomerular filtration rate, and uric acid. After adjusting for traditional cardiovascular risk factors, pre-menopausal women had a similar association to that of men between LDL-C (ß = 0.126, p = 0.030), non-HDL-C (ß = 0.144, p = 0.013), TC/HDL-C (ß = 0.162, p = 0.005), LDL-C/HDL-C (ß = 0.142, p = 0.013) and Ba-PWV; however, post-menopausal women had no association between the lipid parameters and vascular function. CONCLUSIONS: Overall, TC and non-HDL-C were independent associated factors for vascular compliance alterations evaluated through Ba-PWV in normotensive men. In pre-menopausal women, LDL-C, non-HDL-C, TC/HDL-C and LDL-C/HDL-C were independent associated factors for vascular compliance alterations. After controlling for traditional risk factors, lipid profiles were not associated with these metrics for AIx@75, which can measure the amplification of reflex flow, because of the high number of confounding factors that do not genuinely reflect changes in vascular characteristics. Lipid factors did not appear to be linked to vascular function in post-menopausal women.


Assuntos
Diabetes Mellitus , Rigidez Vascular , Índice Tornozelo-Braço , Colesterol , HDL-Colesterol , LDL-Colesterol , Estudos Transversais , Feminino , Humanos , Lipoproteínas , Masculino , Análise de Onda de Pulso , Fatores de Risco , Tibet , Rigidez Vascular/fisiologia
4.
Gen Physiol Biophys ; 41(4): 319-328, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35938965

RESUMO

This current work is aimed to make investigations for the action mechanism of aerobic exercise in rats with type 2 diabetes mellitus (T2DM) after myocardial ischemia/reperfusion injury (MI/RI). The high-fat diet was used to induce T2DM in male Wistar rats. After treatments, the rats in the exercise groups were underwent swimming training for 8 weeks. Two days later, all the rats were subjected to perform MI/RI experiments via left anterior descending artery ligation and reperfusion. The blood samples and myocardial tissues were collected for biochemistry analysis and histology assessment. The results demonstrated that aerobic exercise reduced the levels of serum glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and thrombosis in T2DM rats. In addition, aerobic exercise further decreased the levels of myocardial injury markers and also repressed inflammation responses. Furthermore, the AMP-activated protein kinase (AMPK)/silent information regulator factor 2-related enzyme 1 (Sirt1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway could be activated by aerobic exercise. In a word, aerobic exercise may attenuate myocardial ischemia/reperfusion injury and repress thrombosis via activation of the AMPK/Sirt1/PGC-1α pathway in DM rats.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Traumatismo por Reperfusão Miocárdica , Trombose , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Colesterol , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Masculino , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Sirtuína 1/metabolismo
5.
Proc Natl Acad Sci U S A ; 119(34): e2205475119, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35939716

RESUMO

We employed in a correlative manner an unconventional combination of methods, comprising cathodoluminescence, cryo-scanning electron microscopy (SEM), and cryo-focused ion beam (FIB)-SEM, to examine the volumes of thousands of cubed micrometers from rabbit atherosclerotic tissues, maintained in close-to-native conditions, with a resolution of tens of nanometers. Data from three different intralesional regions, at the media-lesion interface, in the core, and toward the lumen, were analyzed following segmentation and volume or surface representation. The media-lesion interface region is rich in cells and lipid droplets, whereas the core region is markedly richer in crystals and has lower cell density. In the three regions, thin crystals appear to be associated with intracellular or extracellular lipid droplets and multilamellar bodies. Large crystals are independently positioned in the tissue, not associated with specific cellular components. This extensive evidence strongly supports the idea that the lipid droplet surfaces and the outer membranes of multilamellar bodies play a role in cholesterol crystal nucleation and growth and that crystal formation occurs, in part, inside cells. The correlative combination of methods that allowed the direct examination of cholesterol crystals and lipid deposits in the atherosclerotic lesions may be similarly used for high-resolution examination of other tissues containing pathological or physiological cholesterol deposits.


Assuntos
Aterosclerose , Animais , Colesterol/metabolismo , Microscopia Eletrônica de Varredura , Coelhos
6.
BMC Med ; 20(1): 292, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35941608

RESUMO

BACKGROUND: Although cholesterol metabolism is a common pathway for the development of antitumor drugs, there are no specific targets and drugs for clinical use. Here, based on our previous study of sterol O-acyltransferase 1 (SOAT1) in hepatocelluar carcinoma, we sought to screen an effective targeted drug for precise treatment of hepatocelluar carcinoma and, from the perspective of cholesterol metabolism, clarify the relationship between cholesterol regulation and tumorigenesis and development. METHODS: In this study, we developed a virtual screening integrated affinity screening technology for target protein drug screening. A series of in vitro and in vivo experiments were used for drug activity verification. Multi-omics analysis and flow cytometry analysis were used to explore antitumor mechanisms. Comparative analysis of proteome and transcriptome combined with survival follow-up information of patients reveals the clinical therapeutic potential of screened drugs. RESULTS: We screened three compounds, nilotinib, ABT-737, and evacetrapib, that exhibited optimal binding with SOAT1. In particular, nilotinib displayed a high affinity for SOAT1 protein and significantly inhibited tumor activity both in vitro and in vivo. Multi-omics analysis and flow cytometry analysis indicated that SOAT1-targeting compounds reprogrammed the cholesterol metabolism in tumors and enhanced CD8+ T cells and neutrophils to suppress tumor growth. CONCLUSIONS: Taken together, we reported several high-affinity SOAT1 ligands and demonstrated their clinical potential in the precision therapy of liver cancer, and also reveal the potential antitumor mechanism of SOAT1-targeting compounds.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma , Colesterol/metabolismo , Humanos , Esterol O-Aciltransferase/química , Esterol O-Aciltransferase/metabolismo
7.
Front Endocrinol (Lausanne) ; 13: 939366, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909515

RESUMO

Objectives: Infants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants. Study Design: The Japan Environment and Children's Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight <-2 standard deviation [SD]) without congenital abnormalities from the original JECS cohort comprising a total of 104,062 fetal records. According to the distribution of maternal TC in the entire cohort, participants were classified into nine groups per each fifth percentile with the 20th-79th percentiles (204-260 mg/dl) as the reference group. No-CU was defined by a Z-score of height at 3 years <-2 SD according to the growth standard charts for Japanese children. Multivariable-adjusted logistic regression models were carried out using multiple imputations. Additionally, a multiple-adjusted restricted cubic spline model was performed in the complete dataset. Results: A total of 362 (16.3%) children were No-CU at 3 years. After adjusting for the Z-score of birth weight, age of mother, smoking status, weight gain during pregnancy, breastfeeding and meal frequency at 2 years, and parents' heights, the odds ratio (95% confidence intervals) of No-CU was 2.95 (1.28-6.80) for children whose maternal TC levels were in the highest category (≥294 mg/dl), compared to the reference group. A multiple-adjusted restricted cubic spline model showed a non-linear trend of the significant association between high maternal TC and No-CU (p for linear trend = 0.05, p for quadratic trend <0.05). Conclusion: High maternal TC at mid-pregnancy was associated with No-CU among SGA infants. Such infants should be carefully followed up to introduce appropriate growth hormonal treatment. The findings may support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. Future studies are required to elucidate the detailed mechanism.


Assuntos
Colesterol , Recém-Nascido Pequeno para a Idade Gestacional , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Japão/epidemiologia , Gravidez , Estudos Prospectivos
8.
Front Immunol ; 13: 946825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911688

RESUMO

Background: Guillain-Barré syndrome (GBS) is the most common severe acute paralytic neuropathy, with a mortality rate of 5% and permanent sequelae rate of 10%. Currently, the cause of GBS remains unclear. Therefore, we sought to determine potential predictors for GBS and its severity. Methods: A case-control study was performed at Tiantan Hospital in Beijing from January 2017 to December 2021. Laboratory and clinical characteristics were assessed in recruited GBS patients and healthy control individuals (matched by sex and age). The potential risk factors for GBS and severe GBS were assessed using a logistic regression analysis. The mRNA levels of toll-like receptor 4 (TLR4), toll-like receptor 2 (TLR2) and nuclear factor κB (NF-κB) in GBS patients and control PBMCs were detected by fluorescence quantitative PCR. THP-1 cells were costimulated with LPS and free cholesterol to demonstrate the effect of free cholesterol on monocyte activation. Results: A total of 147 GBS patients and 153 healthy individuals were included in the study. Logistic regression analyses showed that preceding infection, alcohol consumption, remnant cholesterol, homocysteine and the dyslipidemia index were correlated with a higher risk of GBS. In contrast, increased HDL cholesterol was correlated with a lower risk of GBS. Moreover, remnant cholesterol and the dyslipidemia index were significantly correlated with severe GBS. The mRNA levels of TLR4, TLR2 and NF-κB in the PBMCs of GBS patients were significantly higher than those of healthy individuals. LPS activated THP-1 cells, and free cholesterol treatment increased the expression of TLR4, TLR2, NF-κB and IL-1ß mRNA in LPS-activated THP-1 cells. Conclusion: Dyslipidemia was correlated with the risk of GBS and severe GBS. Remnant cholesterol may promote the activation of monocytes in GBS patients. It may be valuable to control lipid levels in the prevention of GBS and severe GBS.


Assuntos
Dislipidemias , Síndrome de Guillain-Barré , Estudos de Casos e Controles , Colesterol , Humanos , Lipopolissacarídeos , Monócitos , NF-kappa B , RNA Mensageiro , Fatores de Risco , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
9.
J Am Heart Assoc ; 11(15): e024531, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916348

RESUMO

Background Bempedoic acid (BA) inhibits ATP-citrate lyase in the cholesterol synthesis pathway and lowers low-density lipoprotein cholesterol (LDL-C). As with other lipid-lowering therapies, interindividual variation in response to BA was observed in clinical trials. We characterized LDL-C response to BA using guideline-defined statin intensity categories and identified clinical factors associated with enhanced LDL-C lowering with BA. Methods and Results This post hoc analysis used pooled data from 4 phase 3 studies. Patients were randomized 2:1 to once-daily BA 180 mg (n=2321) or placebo (n=1167) for 12 to 52 weeks and grouped based on percent change in LDL-C from baseline to week 12 according to guideline-established statin intensity categories. Factors associated with ≥30% reduction in LDL-C were identified using logistic regression analyses. From baseline to week 12, BA lowered LDL-C levels comparable to a moderate- or high-intensity statin (≥30%) in 28.9% of patients; this degree of LDL-C lowering was observed in 50.9% of patients not receiving background statin therapy. In a multivariable analysis, the absence of statins, female sex, a history of diabetes, ezetimibe use, and higher high-sensitivity C-reactive protein level were associated with increased rates of achieving ≥30% LDL-C reduction with BA (P<0.01 for each). Conclusions A large percentage of patients receiving BA achieved LDL-C reductions comparable to a moderate- or high-intensity statin. Factors including statin absence, female sex, diabetes history, ezetimibe use, and a higher high-sensitivity C-reactive protein level may be useful to identify patients who may have a greater LDL-C reduction with BA. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02666664, NCT02991118, NCT02988115, NCT03001076.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/uso terapêutico , Proteína C-Reativa , Colesterol , LDL-Colesterol , Ácidos Dicarboxílicos , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Ácidos Graxos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Resultado do Tratamento
10.
Contrast Media Mol Imaging ; 2022: 8639139, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35919501

RESUMO

Objective: To explore the effect and mechanism of epigallocatechin gallate (EGCG) in mice with coronary heart disease (CHD). Methods: Firstly, a CHD model of mouse was established by feeding mice high-fat diet and randomly divided into four groups, including Model group (0.5% sodium cholate) and 10 mg/kg EGCG, 20 mg/kg EGCG, and 40 mg/kg EGCG groups. After oral administration of sodium cholate or EGCG, HE staining was conducted to assess the pathological changes of mouse cardiac tissues in each group of mice, biochemical kits to measure the levels of blood lipid and oxidative stress substance activity, and western blot to detect matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGFA), as well as expression levels of protein related to Nrf2/HO-1/NQO1 pathway in cardiac tissues. Results: The mice in the CHD model appeared to have myocardial pathological damage with elevated serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Of note, administration of EGCG significantly attenuated myocardial injuries and improved blood lipid levels in mice in a concentration-dependent manner. The advent of EGCG significantly decreased the expression of VEGFA and MMP-2 and increased the activity of superoxide dismutase (SOD), when reducing the content of reactive oxygen species (ROS) in the myocardial tissue and upregulating the expression of HO-1, NQO1, and Nrf2. Conclusion: EGCG may reduce atherosclerotic plaque and alleviate pathological damage in the cardiac tissue of CHD mice as well as improve blood lipid levels with antioxidative effect. The mechanism of its effect may be related to the activation of the Nrf2/HO-1/NQO1 antioxidant pathway in vivo of the CHD mice.


Assuntos
Doença das Coronárias , Fator 2 Relacionado a NF-E2 , Animais , Antioxidantes/farmacologia , Catequina/análogos & derivados , Colesterol , Doença das Coronárias/tratamento farmacológico , Lipídeos , Metaloproteinase 2 da Matriz , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Colato de Sódio , Fator A de Crescimento do Endotélio Vascular
11.
Zhonghua Nei Ke Za Zhi ; 61(8): 921-927, 2022 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-35922217

RESUMO

Objective: To investigate the association between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation, and the independent risk factors affecting left atrial appendage function. Methods: Patients with non-valvular atrial fibrillation, who visited the Atrial Fibrillation Center of the First Affiliated Hospital of Xinjiang Medical University from June 1, 2019 to June 1, 2021, were selected. According to left atrial appendage flow velocity (LAAFV), they were divided into normal left atrial appendage function group (297 patients with LAAFV ≥ 40 cm/s) and abnormal left atrial appendage function group (85 patients with LAAFV<40 cm/s). Baseline data and transesophageal echocardiography images were collected from all the patients. The occurrence of thrombotic events was recorded. Univariate and multivariate unconditional logistic regression analyses were conducted to investigate the correlation between abnormal left atrial appendage function and the occurrence of thrombotic events. Results: There were significant differences in gender, type of atrial fibrillation, CHA2DS2-VASc score, anticoagulant therapy, total cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), left atrial diameter, proportion of patients with right atrial enlargement, left ventricular ejection fraction, inner diameter, sum of inner diameter, depth, and sum of depth of all angles of the left atrial appendage, and incidence of thrombotic events between the two groups (all P<0.05). After adjusting for confounders, multivariate unconditional logistic regression analyses showed that abnormal left atrial appendage function was closely associated with thrombotic events (ß=1.168 P=0.002), and left atrial diameter (OR=1.084, 95%CI 1.019-1.153, P=0.011) and persistent atrial fibrillation (OR=2.323, 95%CI 1.226-4.403, P=0.010) were independent risk factors affecting left atrial appendage function. Conclusions: Abnormal left atrial appendage function is closely associated with thrombosis. The left atrial diameter and persistent atrial fibrillation were independent risk factors affecting left atrial appendage function.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Trombose , Colesterol , Humanos , Fatores de Risco , Volume Sistólico , Função Ventricular Esquerda
12.
Physiol Rep ; 10(15): e15405, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35923133

RESUMO

Rats selectively bred for the high intrinsic aerobic capacity runner (HCR) or low aerobic capacity runner (LCR) show pronounced differences in susceptibility for high-fat/high sucrose (HFHS) diet-induced hepatic steatosis and insulin resistance, replicating the protective effect of high aerobic capacity in humans. We have previously shown multiple systemic differences in energy and substrate metabolism that impacts steatosis between HCR and LCR rats. This study aimed to investigate hepatic-specific mechanisms of action via changes in gene transcription. Livers of HCR rats had a greater number of genes that significantly changed in response to 3-day HFHS compared with LCR rats (171 vs. 75 genes: >1.5-fold, p < 0.05). HCR and LCR rats displayed numerous baseline differences in gene expression while on a low-fat control diet (CON). A 3-day HFHS diet resulted in greater expression of genes involved in the conversion of excess acetyl-CoA to cholesterol and bile acid (BA) synthesis compared with the CON diet in HCR, but not LCR rats. These results were associated with higher fecal BA loss and lower serum BA concentrations in HCR rats. Exercise studies in rats and mice also revealed higher hepatic expression of cholesterol and BA synthesis genes. Overall, these results suggest that high aerobic capacity and exercise are associated with upregulated BA synthesis paired with greater fecal excretion of cholesterol and BA, an effect that may play a role in protection against hepatic steatosis in rodents.


Assuntos
Dieta Hiperlipídica , Fígado Gorduroso , Animais , Ácidos e Sais Biliares , Colesterol , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/metabolismo , Humanos , Metabolismo dos Lipídeos/fisiologia , Camundongos , Ratos , Regulação para Cima
13.
Sci Rep ; 12(1): 13469, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931741

RESUMO

The insertion of an endogenous retroviral long terminal repeat (LTR) sequence into the bovine apolipoprotein B (APOB) gene is causal to the inherited genetic defect cholesterol deficiency (CD) observed in neonatal and young calves. Affected calves suffer from developmental abnormalities, symptoms of incurable diarrhoea and often die within weeks to a few months after birth. Neither the detailed effects of the LTR insertion on APOB expression profile nor the specific mode of inheritance nor detailed phenotypic consequences of the mutation are undisputed. In our study, we analysed German Holstein dairy heifers at the peak of hepatic metabolic load and exposed to an additional pathogen challenge for clinical, metabolic and hepatic transcriptome differences between wild type (CDF) and heterozygote carriers of the mutation (CDC). Our data revealed that a divergent allele-biased expression pattern of the APOB gene in heterozygous CDC animals leads to a tenfold higher expression of exons upstream and a decreased expression of exons downstream of the LTR insertion compared to expression levels of CDF animals. This expression pattern could be a result of enhancer activity induced by the LTR insertion, in addition to a previously reported artificial polyadenylation signal. Thus, our data support a regulatory potential of mobile element insertions. With regard to the phenotype generated by the LTR insertion, heterozygote CDC carriers display significantly differential hepatic expression of genes involved in cholesterol biosynthesis and lipid metabolism. Phenotypically, CDC carriers show a significantly affected lipomobilization compared to wild type animals. These results reject a completely recessive mode of inheritance for the CD defect, which should be considered for selection decisions in the affected population. Exemplarily, our results illustrate the regulatory impact of mobile element insertions not only on specific host target gene expression but also on global transcriptome profiles with subsequent biological, functional and phenotypic consequences in a natural in-vivo model of a non-model mammalian organism.


Assuntos
Retroelementos , Sequências Repetidas Terminais , Alelos , Animais , Apolipoproteínas B/genética , Bovinos , Colesterol , Feminino , Mamíferos/genética , Retroelementos/genética , Sequências Repetidas Terminais/genética
14.
Cell Mol Life Sci ; 79(9): 472, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933495

RESUMO

Cholesterol biosynthesis plays a critical role in rapidly proliferating tumor cells. X-box binding protein 1 (XBP1), which was first characterized as a basic leucine zipper-type transcription factor, exists in an unspliced (XBP1-u) and spliced (XBP1-s) form. Recent studies showed that unspliced XBP1 (XBP1-u) has unique biological functions independent from XBP1-s and could promote tumorigenesis; however, whether it is involved in tumor metabolic reprogramming remains unknown. Herein, we found that XBP1-u promotes tumor growth by enhancing cholesterol biosynthesis in hepatocellular carcinoma (HCC) cells. Specifically, XBP1-u colocalizes with sterol regulatory element-binding protein 2 (SREBP2) and inhibits its ubiquitination/proteasomal degradation. The ensuing stabilization of SREBP2 activates the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a rate-limiting enzyme in cholesterol biosynthesis. We subsequently show that the XBP1-u/SREBP2/HMGCR axis is crucial for enhancing cholesterol biosynthesis and lipid accumulation as well as tumorigenesis in HCC cells. Taken together, these findings reveal a novel function of XBP1-u in promoting tumorigenesis through increased cholesterol biosynthesis in hepatocarcinoma cells. Hence, XBP1-u might be a potential target for anti-tumor therapeutic strategies that focus on cholesterol metabolism in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Transformação Celular Neoplásica , Colesterol/metabolismo , Humanos , Neoplasias Hepáticas/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteína 1 de Ligação a X-Box/genética
15.
Klin Lab Diagn ; 67(7): 381-390, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35924768

RESUMO

The antiatherogenic role of high-density lipoproteins (HDL) is associated primarily with their participation in the reverse transport of excess cholesterol from peripheral tissues to the liver. The efficiency of this mechanism depends on the ability of apolipoprotein A-I (apoA-I), the main protein component of HDL, to capture cholesterol from cells. It is known that the acceptor properties of this protein can change under the influence of various factors. This review discusses modern approaches aimed both at increasing the plasma level of HDL and preserving their native functional properties. As one of the key criteria of HDL functionality it is proposed to determine the ability of HDL to accept labeled cholesterol from macrophages. Studies have shown that injection of recombinant HDL or apoA-I mimetic peptides accelerates cholesterol efflux from peripheral tissues, improves vascular endothelial state, and leads to regression of atherosclerotic plaque. Thus, therapy with recombinant HDL/apoA-I may become an effective way to treat cardiovascular diseases caused by cholesterol accumulation in the vascular wall.


Assuntos
Aterosclerose , Lipoproteínas HDL , Apolipoproteína A-I/metabolismo , Aterosclerose/tratamento farmacológico , Colesterol , Humanos , Macrófagos/metabolismo
16.
Front Endocrinol (Lausanne) ; 13: 913749, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909574

RESUMO

Background: Subclinical hypothyroidism (SCH) is usually treated with levothyroxine, but there is controversy as to whether SCH should be treated, especially for older patients. The aim of the systematic review and meta-analysis was to evaluate whether levothyroxine has a beneficial or harmful effect on older patients with SCH. Methods: Databases including PubMed, Embase, Cochrane Library, Web of Science, Wanfang, Weipu and China National Knowledge Infrastructure were searched from inception until December 21, 2021. Subjects must be diagnosed with SCH, and older than or equal to 60 years of age. Interventions should be thyroid hormone therapy (e.g. levothyroxine). The literature was independently screened by 2 researchers. Statistical analysis was performed using RevMan5.3 software. Results: A total of 13 articles were included. Meta-analysis results showed that in older SCH patients, levothyroxine can significantly reduce cholesterol (TC) (p < 0.00001), triglyceride (TG) (p < 0.00001), low-density lipoprotein cholesterol (LDL-C) (p = 0.03) and apolipoprotein B (ApoB) (p < 0.00001). In addition, levothyroxine had no significant effect on bone mineral density, fatigue, hypothyroidism symptoms, quality of life, BMI, cognitive function, depression, blood pressure, etc. in older SCH patients, and also did not significantly increase the incidence of adverse events. Conclusions: Among older SCH patients, levothyroxine treatment may reduce TC, TG, LDL-C, and ApoB.


Assuntos
Hipotireoidismo , Tiroxina , Idoso , Apolipoproteínas B , Colesterol , LDL-Colesterol , Humanos , Qualidade de Vida , Tiroxina/uso terapêutico , Triglicerídeos
17.
PLoS One ; 17(8): e0271514, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35925965

RESUMO

The purpose of this study was to identify molecular mechanisms by which the liver influences total lesion burden in a nonhuman primate model (NHP) of cardiovascular disease with acute and chronic feeding of a high cholesterol, high fat (HCHF) diet. Baboons (47 females, 64 males) were fed a HCHF diet for 2 years (y); liver biopsies were collected at baseline, 7 weeks (w) and 2y, and lesions were quantified in aortic arch, descending aorta, and common iliac at 2y. Unbiased weighted gene co-expression network analysis (WGCNA) revealed several modules of hepatic genes correlated with lesions at different time points of dietary challenge. Pathway and network analyses were performed to study the roles of hepatic module genes. More significant pathways were observed in males than females. In males, we found modules enriched for genes in oxidative phosphorylation at baseline, opioid signaling at 7w, and EIF2 signaling and HNF1A and HNF4A networks at baseline and 2y. One module enriched for fatty acid ß oxidation pathway genes was found in males and females at 2y. To our knowledge, this is the first study of a large NHP cohort to identify hepatic genes that correlate with lesion burden. Correlations of baseline and 7w module genes with lesions at 2y were observed in males but not in females. Pathway analyses of baseline and 7w module genes indicate EIF2 signaling, oxidative phosphorylation, and µ-opioid signaling are possible mechanisms that predict lesion formation induced by HCHF diet consumption in males. Our findings of coordinated hepatic transcriptional response in male baboons but not female baboons indicate underlying molecular mechanisms differ between female and male primate atherosclerosis.


Assuntos
Aterosclerose , Dieta Hiperlipídica , Analgésicos Opioides/metabolismo , Animais , Aterosclerose/patologia , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fator de Iniciação 2 em Eucariotos/metabolismo , Feminino , Humanos , Fígado/metabolismo , Masculino , Papio
18.
Ann Palliat Med ; 11(7): 2368-2381, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35927772

RESUMO

BACKGROUND: The related factors of diabetic retinopathy (DR) had attracted the attention of many scholars, and a large number of articles had been published, but the research results were not consistent. A meta-analysis was conducted to synthesize recent evidence, aiming at exploring the relationship between DR and multiple risk factors. METHODS: The China National Knowledge Infrastructure, VIP, Wanfang, PubMed, Embase, Medline, and Cochrane databases were searched. The English and Chinese keywords included diabetes mellitus, DM, diabetic retinopathy, DR, and risk factors. In case-control study, the subjects are DR patients and NDR patients. In the cohort study, the subjects were diabetic patients. Measures in the intervention and control groups were described in detail. The methodological quality of the included literature was assessed using the Newcastle-Ottawa Scale (NOS). Egger's test is used to identify publication bias. With odds ratio (OR) as the effect index, heterogeneity test was conducted, and fixed effect model or random effect model was selected to calculate the combined OR and 95% CI. RESULTS: The meta-analysis included 12 literatures and 13 related risk factors, of which 4 (33.33%) were cohort studies and 8 (66.66%) were case-control studies. NOS shows that there are 7 references with 8 points (58.33%), 4 references with 7 points (33.33%) and 1 reference with 6 points (8.33%). The risk factors associated with the occurrence of DR were: course of diabetes (OR =1.03, 95% CI: 1.02-1.03), systolic blood pressure (OR =1.01, 95% CI: 1.01-1.02), body mass index (OR =0.96, 95% CI: 0.94-0.99), HbA1c (OR =1.08, 95% CI: 1.06-1.10), total cholesterol (OR =1.20, 95% CI: 0.98-1.46), high-density lipoprotein cholesterol (OR =1.74, 95% CI: 1.19-2.56), fasting blood glucose (OR =1.19, 95% CI: 1.13-1.26), and hypertension (OR =1.25, 95% CI: 1.07-1.47), and the overall effect test results were statistically significant. Sensitivity analysis results show that the random effect model is used for meta-analysis of all Meta, and the combined OR is 1.10, and the 95% CI is (1.05, 1.15). DISCUSSION: The occurrence of DR was related to the course of diabetes, SBP, HbA1c, total cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, and hypertension which provided a more intuitive and comprehensive scientific basis for the prevention and treatment of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Hipertensão , Glicemia , Colesterol , Estudos de Coortes , Hemoglobina A Glicada , Humanos , Hipertensão/complicações , Lipoproteínas HDL , Fatores de Risco
19.
J Med Life ; 15(6): 751-756, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35928361

RESUMO

Inflammatory cytokines, cell adhesion molecules, and toll-like receptors (TLRs) play an important role in atherosclerosis. The aim of this study was to further evaluate the role of inflammatory cytokines, cell adhesion molecules, and toll-like receptors in atherosclerosis. Forty local breed domestic male rabbits were divided randomly into 4 groups, 10 rabbits each. Group I was the control group, group II received a high cholesterol diet, group III received the drug solvent dimethyl sulfoxide (DMSO), and group IV received Atorvastatin (3.5 mg/kg/day). Blood samples were collected at 0 times, 5 weeks, and at the end of 10 weeks. TLRs expression on monocyte was measured by flow cytometry, IL-10, IL-17, IL-1ß, intracellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) were measured by ELISA. In group II, a high cholesterol diet led to a statistically significant elevation of lipids profile (TC, TG, and LDL) at both 5 weeks and 10 weeks compared to the control. The expression of TLRs was also increased compared to the control (13.53±2.5 to 25.79±6.5). The intimal thickness increased from 103.46±13.85 to 248.43±11.11. IL-17 increased significantly from 3.4±0.4 to 7.7±1.00, and IL-1ß increased from 1.04±0.19 to 9.66±1.4 (P 0.05) at 10 weeks. ICAM and VCAM increased from 1.7±0.16 to 8.2±0.74 and from 0.89±0.07 to 5.2±0.45, respectively. Atorvastatin significantly reduced TLRs at 10 weeks to 21.98±3.4 and intimal thickness to 191.6±15.59. IL-17, IL-1ß, ICAM, and VCAM were significantly reduced by Atorvastatin. Cytokines, cellular adhesion molecules, and probably TLRs have a role in the pathogenesis of hyperlipidemia and atherosclerosis.


Assuntos
Aterosclerose , Citocinas , Animais , Aterosclerose/tratamento farmacológico , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Moléculas de Adesão Celular , Colesterol , Interleucina-17 , Masculino , Coelhos , Receptores Toll-Like , Molécula 1 de Adesão de Célula Vascular
20.
West Afr J Med ; 39(7): 761-768, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35929510

RESUMO

BACKGROUND: Accurate early biomarkers of oxidative stress, placenta perfusion and vascular resistance and endothelial platelet interaction for prediction of preeclampsia have not been shown to be beneficial for routine clinical use. The study of association between abnormal lipid levels in early pregnancy and preeclampsia is thus necessary in a bid to reduce the progression and severity of complications of preeclampsia. OBJECTIVE: To determine the association between abnormal lipid levels in early pregnancy and the development of preeclampsia. MATERIALS AND METHODS: A prospective longitudinal study involving 184 pregnant women with singleton pregnancy who met the inclusion criteria and recruited from the antenatal clinic at gestational age of < 20weeks. Their fasting blood samples were collected for the measurement serum lipid profile. They were monitored until delivery for the development of preeclampsia. The mean values of serum lipid profile were analyzed for association with pre-eclampsia using the statistical package for social sciences (SPSS) version 21.0 and P value of < 0.05 was considered statistically significant. RESULTS: Out of 184 participants, 3 had spontaneous miscarriage and were excluded while 5 were lost to follow up. This left a total of 176 participants who completed the study, 11 of which developed preeclampsia. There was a statistically significant increase in the levels of total cholesterol (TC) and low-density lipoprotein (LDL) in the preeclamptic group. The mean serum lipid levels were 4.8 mmol/L for total cholesterol, 1.87 mmol/L for total triglycerides, 1.3 mmol/L for high-density lipoprotein and 2.67 mmol/L for low-density lipoprotein. Age and parity also showed a causal association with development of preeclampsia. CONCLUSION: There was an association between elevated serum total cholesterol and low-density lipoprotein with development of preeclampsia later in pregnancy.


CONTEXTE: Les biomarqueurs précoces précis du stress oxydatif, de la perfusion et de la résistance vasculaire du placenta et de l'interaction endothéliale-plaquettaire pour la prédiction de la prééclampsie ne se sont pas révélés avantageux pour l'utilisation clinique courante. L'étude de l'association entre les taux anormaux de lipides en début de grossesse et la prééclampsie est donc nécessaire pour réduire la progression et la gravité des complications de la prééclampsie. OBJECTIF: Déterminer l'association entre des taux de lipides anormaux en début de grossesse et le développement de la pré- éclampsie. MATÉRIEL ET MÉTHODES: Une étude longitudinale prospective impliquant 184 femmes enceintes avec une grossesse unique qui répondaient aux critères d'inclusion et qui ont été recrutées à la clinique prénatale à l'âge gestationnel de < 20 semaines. Des échantillons de sang à jeun ont été prélevés pour mesurer le profil lipidique sérique. Elles ont été suivies jusqu'à l'accouchement pour le développement de la pré-éclampsie. Les valeurs moyennes du profil lipidique sérique ont été analysées pour leur association avec la pré-éclampsie à l'aide du progiciel statistique pour les sciences sociales (SPSS) version 21.0 et une valeur P de < 0,05 a été considérée comme statistiquement significative. RÉSULTATS: Sur les 184 participantes, 3 ont fait une fausse couche spontanée et ont été exclues, tandis que 5 ont été perdues de vue. Il restait donc un total de 176 participantes qui ont terminé l'étude, dont 11 ont développé une prééclampsie. On a constaté une augmentation statistiquement significative des taux de cholestérol total (CT) et de lipoprotéines de basse densité (LDL) dans le groupe prééclamptique. Les taux moyens de lipides sériques étaient de 4,8 mmol/L pour le cholestérol total, 1,87 mmol/L pour les triglycérides totaux, 1,3 mmol/L pour les lipoprotéines de haute densité et 2,67 mmol/L pour les lipoprotéines de basse densité. L'âge et la parité ont également montré une association causale avec le développement de la prééclampsie. CONCLUSION: Il y avait une association entre un taux élevé de cholestérol total sérique et de lipoprotéines de basse densité et le développement de la prééclampsie plus tard dans la grossesse. Mots clés: Association, Prééclampsie, Cholestérol sérique, Lipoprotéines de basse densité, Lipoprotéines de haute densité, Triglycérides, Lipides sériques.


Assuntos
Pré-Eclâmpsia , Adulto , Colesterol , Feminino , Humanos , Lipoproteínas LDL , Estudos Longitudinais , Pré-Eclâmpsia/epidemiologia , Gravidez , Estudos Prospectivos , Triglicerídeos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...