RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS), a traditional Chinese medicinal formula derived from Treatise on Febrile Diseases, is considered effective in the treatment of inflammatory bowel diseases based upon thousands of years of clinical practice. However, the bioactive ingredients and underlying mechanisms are still unclear and need further investigation. AIM OF THE STUDY: This study aimed to evaluate the effect, explore the bioactive ingredients and the underlying mechanisms of SNS in ameliorating ulcerative colitis (UC) and associated liver injury in dextran sodium sulphate (DSS)-induced mouse colitis models. MATERIALS AND METHODS: The effect of SNS (1.5, 3, 6 g/kg) on 3% DSS-induced acute murine colitis was evaluated by disease activity index (DAI), colon length, inflammatory cytokines, hematoxylin-eosin (H&E) staining, tight junction proteins expression, ALT, AST, and oxidative stress indicators. HPLC-ESI-IT/TOF MS was used to analyze the chemical components of SNS and the main xenobiotics in the colon of UC mice after oral administration of SNS. Network pharmacological study was then conducted based on the main xenobiotics. Flow cytometry and immunohistochemistry techniques were used to demonstrate the inhibitory effect of SNS on Th17 cells differentiation and the amelioration of Th17/Treg cell imbalance. LC-MS/MS, Real-time quantitative polymerase chain reaction (RT-qPCR), and western blotting techniques were performed to investigate the oxysterol-Liver X receptor (LXRs) signaling activity in colon. Targeted bile acids metabolomics was conducted to reveal the change of the two major pathways of bile acid synthesis in the liver, and the expression of key metabolic enzymes of bile acids synthesis was characterized by RT-qPCR and western blotting techniques. RESULTS: SNS (1.5, 3, 6 g/kg) decreased the DAI scores, protected intestinal mucosa barrier, suppressed the production of pro-inflammatory cytokines, improved hepatic and splenic enlargement and alleviated liver injury in a dose-dependent manner. A total of 22 components were identified in the colon of SNS (6 g/kg) treated colitis mice, and the top 10 components ranked by relative content were regarded as the potential effective chemical components of SNS, and used to conduct network pharmacology research. The efficacy of SNS was mediated by a reduction of Th17 cell differentiation, restoration of Th17/Treg cell homeostasis in the colon and spleen, and the experimental results were consistent with our hypothesis and the biological mechanism predicted by network pharmacology. Mechanistically, SNS regulated the concentration of 25-OHC and 27-OHC by up-regulated CH25H, CYP27A1 protein expression in colon, thus affected the expression and activity of LXR, ultimately impacted Th17 differentiation and Th17/Treg balance. It was also found that SNS repressed the increase of hepatic cholesterol and reversed the shift of BA synthesis to the acidic pathway in UC mice, which decreased the proportion of non-12-OH BAs in total bile acids (TBAs) and further ameliorated colitis and concomitant liver injury. CONCLUSIONS: This study set the stage for considering SNS as a multi-organ benefited anti-colitis prescription based on the significant effect of ameliorating intestinal and liver damage, and revealed that derivatives of cholesterol, namely oxysterols and bile acids, were closely involved in the mechanism of SNS anti-colitis effect.
Assuntos
Colesterol , Colite Ulcerativa , Sulfato de Dextrana , Medicamentos de Ervas Chinesas , Animais , Medicamentos de Ervas Chinesas/farmacologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Camundongos , Masculino , Colesterol/sangue , Células Th17/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Farmacologia em Rede , Citocinas/metabolismo , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
BACKGROUND: Older adults in the USA have worse health and wider socioeconomic inequalities in health compared with those in Britain. Less is known about how health in the two countries compares in mid-life, a time of emerging health decline, including inequalities in health. METHODS: We compare measures of current regular smoking status, obesity, self-rated health, cholesterol, blood pressure and glycated haemoglobin using population-weighted modified Poisson regression in the 1970 British Cohort Study (BCS70) in Britain (N = 9665) and the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the USA (N = 12â300), when cohort members were aged 34-46 and 33-43, respectively. We test whether associations vary by early- and mid-life socioeconomic position. RESULTS: US adults had higher levels of obesity, high blood pressure and high cholesterol. Prevalence of poor self-rated health and current regular smoking was worse in Britain. We found smaller socioeconomic inequalities in mid-life health in Britain compared with the USA. For some outcomes (e.g. smoking), the most socioeconomically advantaged group in the USA was healthier than the equivalent group in Britain. For other outcomes (hypertension and cholesterol), the most advantaged US group fared equal to or worse than the most disadvantaged groups in Britain. CONCLUSIONS: US adults have worse cardiometabolic health than British counterparts, even in early mid-life. The smaller socioeconomic inequalities and better overall health in Britain may reflect differences in access to health care, welfare systems or other environmental risk factors.
Assuntos
Disparidades nos Níveis de Saúde , Hipertensão , Obesidade , Fumar , Fatores Socioeconômicos , Humanos , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fumar/epidemiologia , Obesidade/epidemiologia , Hipertensão/epidemiologia , Estudos Longitudinais , Pressão Sanguínea , Colesterol/sangue , Nível de Saúde , Hemoglobinas Glicadas/análise , Estudos de CoortesRESUMO
Background: Remnant cholesterol (RC) predicts cardiovascular risk and is associated with a range of diseases, including asthma, hypertension, depression, periodontitis, and alcoholic fatty liver disease. However, its correlation with abdominal aortic calcification (AAC) has not been reported. Methods: Using a cross-sectional approach, this study examined data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) cycle. Multiple logistic regression, generalized summation models, and subgroup analyses were used in examining the correlation between RC and the prevalence of severe AAC. Results: The mean age of participants in this study was 57.70 ± 11.73 years, with 142 individuals (9.67%) suffering from severe AAC. The median RC was 0.52 mmol/L (Q1-Q3, 0.36-0.75 mmol/L). Among female participants, a significant positive correlation was observed between RC and severe AAC (per natural log [RC] increment: 2.14; 95% CI, 1.07-4.27). Smooth curve fitting and threshold effect analysis revealed a saturation effect at an RC level of 0.57 mmol/L. Conversely, in male participants, no significant correlation was found between RC and the prevalence of severe AAC (per natural log [RC] increment: 0.88; 95% CI, 0.43-1.78). Our findings suggest a significant interaction between gender and RC in relation to severe AAC (P for interaction = 0.0042). Conclusions: Higher RC levels were significantly associated with an increased prevalence of severe AAC in women.
Assuntos
Aorta Abdominal , Colesterol , Inquéritos Nutricionais , Calcificação Vascular , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Aorta Abdominal/patologia , Aorta Abdominal/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Colesterol/sangue , Idoso , Adulto , Estados Unidos/epidemiologia , Fatores Sexuais , Doenças da Aorta/epidemiologia , Doenças da Aorta/sangue , Prevalência , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Dyslipidemia is prominently associated with adverse outcomes in patients with coronary artery disease (CAD). The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel comprehensive lipid index. However, limited evidence exists on the relationship of the NHHR with the risk of adverse outcomes in patients with CAD. This study aimed to explore the associations between the NHHR and adverse outcomes and identify the optimal NHHR ranges linked to the lowest adverse outcome risk in patients with CAD undergoing percutaneous coronary intervention (PCI). METHODS: Among 2253 patients with CAD undergoing PCI, 2251 with available total cholesterol and HDL-C levels were analyzed. Furthermore, all patients were classified into quintiles based on the NHHR. The primary outcome was the incidence of MACCEs, comprising cardiac mortality, acute myocardial infarction, stroke, and repeat revascularization. Multivariable logistic regression analysis was used to assess the relationship between the NHHR and MACCEs. Moreover, restricted cubic spline (RCS) analysis was performed to quantify nonlinearity. Lastly, the consistency between these associations was confirmed by conducting subgroup and interaction analyses. RESULTS: A total of 270 patients experienced MACCEs over a median follow-up of 29.8 months (interquartile range, 25.6-34 months). After adjustment for confounding variables, the adjusted ORs (95% CIs) of the patients in quintiles 2, 3, 4, and 5 were 0.79 (0.52-1.20), 0.64 (0.42-0.99), 1.00 (0.67-1.48), and 1.17 (0.74-1.64), respectively (reference group: quintile 1). Additionally, RCS analysis demonstrated a U-shaped relationship between the NHHR and MACCEs, with an inflection point at an NHHR of 3.119 using a two-piecewise regression model. This relationship was consistent across the various subgroups, while significant interactions were not observed in these associations.The ORs and 95% CIs to the left and right of the inflection point were 0.734 (0.551-0.978) and 1.231 (1.038-1.460), respectively. CONCLUSIONS: This study reveals a U-shaped association between baseline NHHR and MACCE incidence in patients with CAD undergoing PCI.
Assuntos
HDL-Colesterol , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Masculino , Feminino , HDL-Colesterol/sangue , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Fatores de Risco , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , LDL-Colesterol/sangue , Colesterol/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Blood lipid profiles are associated with various nutritional elements and dietary factors. This study aimed to explore the association between total dietary vitamin E intake and remnant cholesterol (RC), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: A cross-sectional analysis was conducted using NHANES 2007-2018 data. A total of 8,639 eligible participants (45.58% men and 54.42% women) with an average age of 46.12 ± 16.65 years were included in this study. Weighted multivariate linear regression and subgroup analyses were used to examine the association between vitamin E intake and RC, TC, HDL-C, and LDL-C. Smooth curve fitting was used to explore potential non-linear associations. RESULTS: After adjusting for other covariates, multivariate linear regression analysis showed that higher vitamin E intake was negatively associated with plasma RC (ß = -0.22, 95% CI: -0.27, -0.16), TC (ß = -0.33, 95% CI: -0.51, -0.16), LDL-C (ß = -0.25, 95% [confidence interval] CI: -0.40, -0.10) and positively associated with HDL-C (ß = 0.13, 95% CI: 0.07, 0.20) in US adults. Subgroup analysis indicated that age may influence the association between vitamin E intake and RC. At the same time, gender may also affect the association between vitamin E intake and HDL-C. CONCLUSION: Higher vitamin E intake was negatively associated with plasma RC, TC, LDL-C and positively associated with HDL-C.
Assuntos
HDL-Colesterol , LDL-Colesterol , Colesterol , Inquéritos Nutricionais , Vitamina E , Humanos , Vitamina E/sangue , Vitamina E/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , HDL-Colesterol/sangue , Estudos Transversais , LDL-Colesterol/sangue , Adulto , Colesterol/sangue , Estados Unidos/epidemiologia , Modelos Lineares , Triglicerídeos/sangueRESUMO
Sedentary behavior has significant deleterious effects on human health. Sedentary behaviors associated with cardiovascular and metabolic disorders by decreasing lipoprotein lipase activities, impaired lipid and carbohydrate metabolism. This cross sectional study was done to see the association between fasting serum glucose and serum total cholesterol in sedentary male. This study was conducted in the Department of Physiology, Mymensingh Medical College, Bangladesh from Octy 2021 to June 2022. A total number of 100 subjects were included in this study. Among them, fifty (50) sedentary males were taken as study group (Group II) and fifty (50) active males were taken as control group (Group I). Age of both control and study group ranged from 25-60 years. Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test & Pearson's correlation coefficient test. Both of these biochemical parameters showed statistically significant difference in study group. The mean±SD of fasting serum glucose of control group (Group I) and study group (Group II) were 4.45±0.51 mmol/L and 5.91±0.60 mmol/L; and the mean±SD of serum total cholesterol level of control group (Group I) and study group (Group II) were 176.14±27.16 mg/dl and 252.58±18.97 mg/dl respectively. Fasting serum glucose and serum total cholesterol shows positive correlation in study group in comparison to control group. From this finding it can be concluded that there was significant correlation of fasting serum glucose and serum total cholesterol in sedentary males.
Assuntos
Glicemia , Colesterol , Jejum , Comportamento Sedentário , Humanos , Masculino , Adulto , Glicemia/análise , Glicemia/metabolismo , Estudos Transversais , Colesterol/sangue , Pessoa de Meia-Idade , Jejum/sangue , BangladeshRESUMO
BACKGROUND AND AIM: Remnant cholesterol (RC) is substantially related to negative outcomes in cardiac patients. Patients with coexisting hypertension and heart failure (HF) often develop left ventricular hypertrophy (LVH) and have poor prognoses. This study investigated baseline RC levels and LV remodelling and patients' prognoses. METHODS AND RESULTS: Six hundred thirty consecutive individuals with hypertension and HF participated in this prospective trial from October 2018 to August 2020. Based on left ventricular mass index (LVMI), 560 those eligible were separated into LVH and non-LVH groups. Multiple linear regression and receiver operating characteristic (ROC) curves examined the RC and LV relationship. A Cox regression analysis was conducted to examine the predictive value of RC for clinical outcomes. The LVH group presented significantly elevated values of RC, triglyceride, and cholesterol and decreased high-density lipoprotein cholesterol (HDLC). The optimal cutoff value for RC to predict LV remodelling was 0.49. The subjects were observed for a median of 58 months, and 104 participants met the primary endpoint. The risk models involving the two Cox models were adjusted to incorporate confounding factors, which revealed that those with elevated baseline levels of RC were more susceptible to cardiovascular mortality, as shown by an increased hazard ratio. (HR: 1.91, 95% CI: 1.62-2.26 vs. HR: 1.75, 95% CI: 1.43-2.16, P < 0.001). CONCLUSIONS: RC is linked to LV remodelling in patients with hypertensive HF, with LVH having greater RC values. Moreover, patients with hypertensive HF who had a higher RC suffered from an increased risk of cardiovascular mortality. TRIAL REGISTRATION: NCT03727828, 21 Oct 2018.
Assuntos
Colesterol , Insuficiência Cardíaca , Hipertensão , Hipertrofia Ventricular Esquerda , Triglicerídeos , Humanos , Hipertrofia Ventricular Esquerda/sangue , Masculino , Feminino , Hipertensão/complicações , Hipertensão/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/complicações , Colesterol/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Prognóstico , Triglicerídeos/sangue , Remodelação Ventricular , Curva ROC , Modelos de Riscos Proporcionais , HDL-Colesterol/sangue , Fatores de RiscoRESUMO
BACKGROUND: Point-of-care testing (POCT) is commonly used in epidemiological surveys due to its various advantages, such as portability and immediate test results. The CardioChek® PA analyser 3-in-1 lipid panel measures total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. This study tested the reliability and diagnostic accuracy of the CardioChek® PA analyser using a 3-in-1 lipid panel. METHODS: A cross-sectional study design with quota sampling was used. A total of 203 respondents aged 18 years and above from a research centre in the Ministry of Health, Malaysia, were recruited. Venous blood was sent to the laboratory and tested with Siemens Atellica CH, while a POCT analyser was used for capillary blood measurements. Intraclass coefficient correlation (ICC) analysis was employed to determine the agreement between capillary and venous blood parameters. The diagnostic performance of the evaluated tests was evaluated using STATA version 12. RESULTS: The agreement between capillary and laboratory venous blood was moderate (0.64-0.67) for TC and HDL, good (0.75) for LDL and excellent (0.91) for TG). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were as follows: TC, 57.1%, 94.3%, 92.3% and 64.8%; TG, 76.0%, 100%, 100%, and 96.6%; HDL, 96.2%, 83.2%, 47.2% and 99.3%; and LDL, 81.0%, 100%, 100% and 68.3%, respectively. CONCLUSIONS: The CardioChek® PA analyser showed acceptable diagnostic accuracy for screening high-risk individuals more often in places where laboratories are inaccessible. It could also be used in clinical settings where patients would benefit from swift treatment decisions.
Assuntos
HDL-Colesterol , LDL-Colesterol , Testes Imediatos , Triglicerídeos , Humanos , Testes Imediatos/normas , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Triglicerídeos/sangue , Estudos Transversais , LDL-Colesterol/sangue , HDL-Colesterol/sangue , Malásia/epidemiologia , Reprodutibilidade dos Testes , Idoso , Colesterol/sangue , Adulto Jovem , Lipídeos/sangue , Sensibilidade e Especificidade , AdolescenteRESUMO
BACKGROUND: Remnant cholesterol (RC), a potent atherogenic lipid, has been shown to be strongly correlated with insulin resistance and the pathogenesis of diabetes mellitus. However, the relationship between RC and normoglycemia reversal in individuals with impaired fasting glucose (IFG) is crucial and remains unclear. This investigation, which aimed to clarify this association, is important for understanding and potentially improving the management of diabetes. METHOD: This study, which included 15,019 IFG participants from 11 Chinese cities between 2010 and 2016, was conducted with a rigorous research process. Cox regression analysis revealed intriguing findings regarding the relationship between RC and normoglycemia reversal in individuals with IFG. Potential nonlinear associations were further explored via smooth curve-fitting techniques and 4-knot restricted cubic spline functions, ensuring a comprehensive analysis. To examine the validity of the results, an array of subgroup and sensitivity analyses were conducted, further bolstering the robustness of the findings. RESULTS: By the end of the 2.89-year median follow-up period, 6,483 of the 15,019 IFG participants (43.17%) had reverted to normoglycemia. The findings, which reveal that increased RC levels are inversely associated with the likelihood of normoglycemia reversal, are novel and significant. According to the fully adjusted Cox proportional hazards model analysis, an increase of one standard deviation in RC was associated with a 20% decrease in the likelihood of normoglycemia reversal among IFG participants (HR: 0.80, 95% CI: 0.77-0.82). A nonlinear association between RC and normoglycemia reversal was observed, with an inflection point at 41.37 mg/dL. This suggests that the growth rate of the likelihood of reversion decreased and stabilized after the inflection point was reached. Moreover, significant interactions were observed between the age groups, providing a more nuanced understanding of this complex relationship. CONCLUSION: Among Chinese adults with IFG, RC exhibited a negative nonlinear relationship with the probability of normoglycemia reversal. When RC levels reached or exceeded 41.38 mg/dL, the probability of achieving normoglycemia progressively diminished and subsequently stabilized. Maintaining RC levels below 41.38 mg/dL can significantly improve the probability of normoglycemia reversal among individuals with IFG, especially those aged 60 years or older.
Assuntos
Glicemia , Colesterol , Jejum , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Glicemia/metabolismo , Colesterol/sangue , Jejum/sangue , Modelos de Riscos Proporcionais , Adulto , Idoso , Estudos de Coortes , Triglicerídeos/sangue , China/epidemiologia , Resistência à Insulina , Intolerância à Glucose/sangueRESUMO
Bananas are one of the most extensively cultivated fruits globally, yielding substantial amounts of greenery, including their leaves. Banana leaves (BL) have notable protein content, bioactive compounds, and a significant fiber component. This study aimed to investigate the impact of incorporating dried and nutrient-determined BL along with a multienzyme complex into the diet of quails. The experiment lasted 35 days, a total of 280 one-day-old quail chicks (Coturnix coturnix japonica) were allocated into four groups with seven replicates. Experimental diets were formulated with the addition of dried BL at levels of 0% (C), 3% (BL3), 6% (BL6), and 9% (BL9), with the inclusion of 1,000 mg/kg multienzyme complex to the basal diet. The total fiber content of diets was determined at 2.77%, 4.28%, 5.77%, and 7.28%, respectively. The inclusion of BL in the diet did not significantly affect growth performance. However, the addition of 3% and 6% BL to the diet resulted in a significant reduction in meat oxidation. A 6% BL inclusion led to the lowest serum low-density lipoprotein and the highest high-density lipoprotein concentrations (p < 0.05). Meat yellowness (b*) increased with all three levels of BL in the diet compared to the basal diet (p < 0.05), while L* and a* values remained unaffected. A 6% BL addition to quail diets may lead to improved meat quality and higher serum HDL concentration without detrimental effects on growth performance.
Assuntos
Ração Animal , Colesterol , Coturnix , Dieta , Fibras na Dieta , Suplementos Nutricionais , Carne , Musa , Folhas de Planta , Animais , Musa/química , Ração Animal/análise , Folhas de Planta/química , Coturnix/crescimento & desenvolvimento , Coturnix/fisiologia , Dieta/veterinária , Fibras na Dieta/análise , Fibras na Dieta/administração & dosagem , Carne/análise , Suplementos Nutricionais/análise , Colesterol/sangue , Colesterol/análise , Fenômenos Fisiológicos da Nutrição Animal , MasculinoRESUMO
BACKGROUND: Hypocholesterolemia hallmarks critical illness though the underlying pathophysiology is incompletely understood. As low circulating cholesterol levels could partly be due to an increased conversion to cortisol/corticosterone, we hypothesized that glucocorticoid treatment, via reduced de novo adrenal cortisol/corticosterone synthesis, might improve cholesterol availability and as such affect adrenal gland and skeletal muscle function. METHODS: In a matched set of prolonged critically ill patients (n = 324) included in the EPaNIC RCT, a secondary analysis was performed to assess the association between glucocorticoid treatment and plasma cholesterol from ICU admission to day five. Next, in a mouse model of cecal ligation and puncture-induced sepsis, septic mice were randomized to receive either hydrocortisone (1.2 mg/day) (n = 17) or placebo (n = 15) for 5 days, as compared with healthy mice (n = 18). Plasma corticosterone, cholesterol, and adrenocortical and myofiber cholesterol were quantified. Adrenal structure and steroidogenic capacity were evaluated. Muscle force and markers of atrophy, fibrosis and regeneration were quantified. In a consecutive mouse study with identical design (n = 24), whole body composition was assessed by EchoMRI to investigate impact on lean mass, fat mass, total and free water. RESULTS: In human patients, glucocorticoid treatment was associated with higher plasma HDL- and LDL-cholesterol from respectively ICU day two and day three, up to day five (P < 0.05). Plasma corticosterone was no longer elevated in hydrocortisone-treated septic mice compared to placebo, whereas the sepsis-induced reduction in plasma HDL- and LDL-cholesterol and in adrenocortical cholesterol was attenuated (P < 0.05), but without improving the adrenocortical ACTH-induced CORT response and with increased adrenocortical inflammation and apoptosis (P < 0.05). Total body mass was further decreased in hydrocortisone-treated septic mice (P < 0.01) compared to placebo, with no additional effect on muscle mass, force or myofiber size. The sepsis-induced rise in markers of muscle atrophy and fibrosis was unaffected by hydrocortisone treatment, whereas markers of muscle regeneration were suppressed compared to placebo (P < 0.05). An increased loss of lean body mass and total and free water was observed in hydrocortisone-treated septic mice compared to placebo (P < 0.05). CONCLUSIONS: Glucocorticoid treatment partially attenuated critical illness-induced hypocholesterolemia, but at a cost of impaired adrenal function, suppressed muscle regeneration and exacerbated loss of body mass.
Assuntos
Glândulas Suprarrenais , Colesterol , Estado Terminal , Glucocorticoides , Músculo Esquelético , Animais , Estado Terminal/terapia , Humanos , Camundongos , Glucocorticoides/uso terapêutico , Glucocorticoides/farmacologia , Colesterol/sangue , Colesterol/análise , Masculino , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/fisiopatologia , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Feminino , Idoso , Hidrocortisona/análise , Hidrocortisona/uso terapêutico , Hidrocortisona/sangue , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Sepse/complicações , Modelos Animais de DoençasRESUMO
BACKGROUND: Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. METHODS: A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). RESULTS: In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P < 0.001). After TAF treatment, a significant elevation was observed in triglyceride (TG) levels (from 0.83 mmol/L to 1.02 mmol/L, P < 0.001) and total cholesterol (TC) levels (from 4.16 mmol/L to 4.32 mmol/L, P < 0.001). Similar changes in TG and TC levels were observed in the TAF group after propensity score matching (PSM). The TG levels (from 0.83 mmol/L to 1.04 mmol/L, P < 0.001) and TC levels (from 4.16 mmol/L to 4.38 mmol/L, P < 0.001) were both increased significantly compared to the baseline levels in the PSM cohort of patients treated with TAF. TAF treatment was independently associated with elevated TG levels (HR = 2.800, 95% CI: 1.334-5.876, P = 0.006) and TC levels (HR = 9.045, 95% CI: 3.836-21.328, P < 0.001). CONCLUSIONS: Compared with TDF treatment, TAF treatment was associated with dyslipidemia in patients with CHB. Close monitoring of lipid profiles is needed in patients with CHB who received TAF treatment.
Assuntos
Alanina , Antivirais , Hepatite B Crônica , Lipídeos , Tenofovir , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Masculino , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Antivirais/uso terapêutico , Alanina/uso terapêutico , Lipídeos/sangue , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/induzido quimicamente , Adenina/análogos & derivados , Adenina/uso terapêutico , Triglicerídeos/sangue , Colesterol/sangueRESUMO
BACKGROUND: Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP). METHODS: The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG. RESULTS: After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; ß = -0.75, 95% confidence interval [CI]: -1.38 - -0.12) and HDL levels (P < 0.001; ß = -2.91, 95% CI: -4.58 - -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; ß = -0.0039, 95% CI: -0.0073 - -0.006) and night peak (P = 0.027; ß = -0.0061, 95% CI: -0.0113 - -0.0008) in patients with POAG. CONCLUSIONS: Significantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk.
Assuntos
Glaucoma de Ângulo Aberto , Pressão Intraocular , Humanos , Glaucoma de Ângulo Aberto/sangue , Glaucoma de Ângulo Aberto/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Triglicerídeos/sangue , Lipídeos/sangue , China , Lipoproteínas/sangue , Glaucoma de Ângulo Fechado/sangue , Glaucoma de Ângulo Fechado/fisiopatologia , Povo Asiático , Apolipoproteínas E/sangue , Apolipoproteínas E/genética , Adulto , Colesterol/sangue , Apolipoproteínas A/sangue , População do Leste AsiáticoRESUMO
OBJECTIVE: Some observational studies have unexpectedly reported the association of cholesterol metabolism with mental and psychological disorders, but a firm conclusion has not been drawn. The aim of this study was to further investigate the effects of peripheral cholesterol traits and cholesterol-lowering therapy on depression and schizophrenia using a Mendelian randomisation approach. METHODS: Instrumental variables meeting the correlation, independence and exclusivity assumptions were extracted from one genome-wide association study for predicting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and nonHDL cholesterol. Instrumental variables for total cholesterol and LDL cholesterol were also adopted to predict statin use (a type of cholesterol-lowering drug); these instrumental variables should not only satisfy the above assumptions but also be close to 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR, the target gene of statins) on the chromosome. Three methods (including inverse variance weighted) were used to conduct causal inference of the above exposures with depression and schizophrenia. Sensitivity analyses were performed to assess horizontal pleiotropy. RESULTS: Higher levels of peripheral nonHDL cholesterol were nominally associated with a decreased risk of depression (P = 0.039), and higher levels of HMGCR-mediated total cholesterol and LDL cholesterol were nominally related to a decreased risk of depression (P = 0.013 and P = 0.028, respectively). Moreover, these cholesterol traits cannot affect the risk of schizophrenia. Sensitivity analysis did not reveal any horizontal pleiotropy. CONCLUSION: The study provided some interesting, but less sufficient, evidence that nonHDL cholesterol may have a protective effect on depression, and lowering cholesterol using statins might increase the risk of the disease.
Assuntos
Colesterol , Estudo de Associação Genômica Ampla , Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/metabolismo , Colesterol/sangue , Colesterol/metabolismo , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Depressão/genética , Depressão/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Polimorfismo de Nucleotídeo Único , Feminino , Masculino , Predisposição Genética para DoençaRESUMO
BACKGROUND: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. METHODS: Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. RESULTS: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. CONCLUSIONS: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.
Assuntos
Aterosclerose , Capsaicina , Células Espumosas , Inflamação , PPAR gama , Canais de Cátion TRPV , Animais , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Aterosclerose/prevenção & controle , Aterosclerose/tratamento farmacológico , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Capsaicina/farmacologia , Colesterol/sangue , Colesterol/metabolismo , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Knockout para ApoE , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPV/metabolismoRESUMO
AIM: To examine the long-term results and treatment effectiveness of liver transplantation (LT) in the treatment of homozygous familial hypercholesterolemia (HoFH) in children and adolescents. METHOD: Patients who underwent LT due to HoFH between 2007 and 2023 were included in the study. The patients' demographic data, clinical findings, preoperative and postoperative laboratory examinations, transplantation complications, and postoperative disease courses were evaluated. RESULTS: There were five boys with an average age of 6.2 (median: 6, range 4-10) years in the study. The average total cholesterol level of the patients before transplantation was 923 (median: 950, range: 780-1002) mg/dL and the average LDL-cholesterol level was 864 (median: 852, range: 770-957) mg/dL. No patients died of transplant-related complications. After an average follow-up of 9.2 (median: 9, range: 1.5-16) years, the average total cholesterol level of the patients was 197 (median: 164, range: 137-359) mg/dL, and the average LDL-cholesterol level was 138 (median: 92, range: 85-313) mg/dL. Four (80%) patients developed atherosclerotic cardiovascular disease during follow-up, and two (40%) died of this cause. CONCLUSION: LT in the treatment of HoFH did not help our patients reach the target LDL-cholesterol level after transplantation and did not prevent the development of cardiovascular disease. Therefore, LT alone is not curative in the treatment of HoFH.
Assuntos
LDL-Colesterol , Hiperlipoproteinemia Tipo II , Transplante de Fígado , Humanos , Masculino , Criança , Hiperlipoproteinemia Tipo II/cirurgia , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/terapia , Pré-Escolar , Resultado do Tratamento , LDL-Colesterol/sangue , Feminino , Seguimentos , Homozigoto , Adolescente , Estudos Retrospectivos , Colesterol/sangueRESUMO
Changes in dietary patterns and living habits have led to an increasing number of individuals with elevated cholesterol levels. Excessive consumption of high-cholesterol foods can disrupt the body's lipid metabolism. Numerous studies have firmly established the cholesterol-lowering effects of probiotics and prebiotics, with evidence showing that the synergistic use of synbiotics is functionally more potent than using probiotics or prebiotics alone. Currently, the screening strategy involves screening prebiotics for synbiotic development with probiotics as the core. However, in comparison to probiotics, there are fewer types of prebiotics available, leading to limited resources. Consequently, the combinations of synbiotics obtained are restricted, and probiotics and prebiotics are only relatively suitable. Therefore, in this study, a novel synbiotic screening strategy with prebiotics as the core was developed. The synbiotic combination of Lactobacillus rhamnosus S_82 and xylo-oligosaccharides was screened from the intestinal tract of young people through five generations of xylo-oligosaccharides. Subsequently, the cholesterol-lowering ability of the medium was simulated, and the two carbon sources of glucose and xylo-oligosaccharides were screened out. The results showed that synbiotics may participate in cholesterol-lowering regulation by down-regulating the expression of NPC1L1 gene, down-regulating ACAT2 and increasing the expression of ABCG8 gene in vitro through cell adsorption and cell absorption in vitro, and regulating the intestinal microbiota. Synbiotics hold promise as potential candidates for the prevention of hypercholesterolemia in humans and animals, and this study providing a theoretical foundation for the development of new synbiotic products.
Assuntos
Lacticaseibacillus rhamnosus , Oligossacarídeos , Prebióticos , Simbióticos , Lacticaseibacillus rhamnosus/metabolismo , Oligossacarídeos/farmacologia , Humanos , Hipolipemiantes/farmacologia , Colesterol/metabolismo , Colesterol/sangue , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos , GlucuronatosRESUMO
BACKGROUND: The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. METHODS AND RESULTS: We studied 1791 MESA (Multi-Ethnic Study of Atherosclerosis) participants who took part in an ancillary study on body composition with adipokine levels measured (leptin, adiponectin, and resistin) at either visit 2 or visit 3. RC was calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol, measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed-effects models were used to assess the cross-sectional and longitudinal associations between adipokines and log-transformed levels of RC. Mean±SD age was 64.5±9.6 years; mean±SD body mass index was 29.9±5.0 kg/m2; and 52.0% were women. In fully adjusted cross-sectional models that included body mass index, diabetes, low-density lipoprotein cholesterol, and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.6% (95% CI, 12.2-16.9) lower RC. With each 1-unit increment in leptin and resistin, there was 4.8% (95% CI, 2.7-7.0) and 4.0% (95% CI, 0.2-8.1) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5 (interquartile range, 4-8) years. CONCLUSIONS: Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for body mass index and low-density lipoprotein cholesterol.
Assuntos
Adipocinas , Adiponectina , Aterosclerose , Colesterol , Leptina , Resistina , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Aterosclerose/sangue , Aterosclerose/etnologia , Aterosclerose/epidemiologia , Leptina/sangue , Adipocinas/sangue , Adiponectina/sangue , Colesterol/sangue , Resistina/sangue , Estados Unidos/epidemiologia , Biomarcadores/sangue , Estudos Transversais , Idoso de 80 Anos ou mais , Triglicerídeos/sangue , Obesidade/sangue , Obesidade/etnologia , Obesidade/epidemiologia , Estudos Longitudinais , Fatores de Risco , Estudos ProspectivosRESUMO
BACKGROUND: Triglyceride-rich lipoproteins and remnants (TRL/remnants) have a causal, but not yet quantified, relationship with coronary heart disease (CHD): myocardial infarction plus revascularization. OBJECTIVES: The authors sought to estimate TRL/remnant per-particle atherogenicity, investigate causal relationships with inflammation, and determine whether differences in the atherogenicity of TRL/remnants and low-density lipoprotein (LDL) impact the causal association of non-high-density lipoprotein cholesterol (non-HDL-C) with CHD. METHODS: Single nucleotide polymorphisms (SNPs) (N = 1,357) identified by genome-wide association in the UK Biobank were ranked into 10 clusters according to the effect on TRL/remnant-C vs LDL-C. Mendelian randomization analysis was used to estimate for each SNP cluster CHD ORs per 10 mg/dL apolipoprotein B (apoB) and per 0.33 mmol/L non-HDL-cholesterol, and to evaluate association of TRL/remnants with biomarkers of systemic inflammation. RESULTS: SNPs in cluster 1 predominantly affected LDL-C, whereas SNPs in cluster 10 predominantly affected TRL/remnant-C. CHD risk per genetically predicted increase in apoB and in non-HDL-C rose across clusters. ORs per 10 mg/dL higher apoB was 1.15 (95% CI: 1.11-1.19) in cluster 1 vs 1.70 (95% CI: 1.52-1.90) in cluster 10. Comparing ORs between these TRL/remnant-predominant and LDL-predominant clusters, we estimated that TRL/remnants were at least 3.9 (95% CI: 2.8-5.4) times more atherogenic than LDL on a per-particle basis. For non-HDL-C, CHD ORs per 0.33 mmol/L rose from 1.15 (95% CI: 1.11-1.19) for cluster 1 to 1.40 (95% CI: 1.30-1.50) for cluster 10. TRL/remnants exhibited causal relationships with inflammation, but this did not explain their greater atherogenicity. CONCLUSIONS: TRL/remnants are about 4 times more atherogenic than LDL. Variation in the causal association of non-HDL-C with CHD indicates that adjustment for percentage TRL/remnant-C may be needed for accurate risk prediction.
Assuntos
Inflamação , Polimorfismo de Nucleotídeo Único , Triglicerídeos , Humanos , Triglicerídeos/sangue , Inflamação/sangue , Inflamação/genética , Masculino , Medição de Risco/métodos , Feminino , Pessoa de Meia-Idade , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/genética , Lipoproteínas/sangue , Colesterol/sangue , Doença das Coronárias/sangue , Doença das Coronárias/genética , Doença das Coronárias/epidemiologia , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Idoso , LDL-Colesterol/sangue , Biomarcadores/sangue , HDL-Colesterol/sangue , Reino Unido/epidemiologiaRESUMO
How cardiovascular activity interacts with lipid homeostasis is incompletely understood. We postulated a role for blood flow acting at endothelium in lipid regulatory organs. Transcriptome analysis was performed on livers from mice engineered for deletion of the flow-sensing PIEZO1 channel in endothelium. This revealed unique up-regulation of Cyp7a1, which encodes the rate-limiting enzyme for bile synthesis from cholesterol in hepatocytes. Consistent with this effect were increased gallbladder and plasma bile acids and lowered hepatic and plasma cholesterol. Elevated portal fluid flow acting via endothelial PIEZO1 and genetically enhanced PIEZO1 conversely suppressed Cyp7a1. Activation of hepatic endothelial PIEZO1 channels promoted phosphorylation of nitric oxide synthase 3, and portal flow-mediated suppression of Cyp7a1 depended on nitric oxide synthesis, suggesting endothelium-to-hepatocyte coupling via nitric oxide. PIEZO1 variants in people were associated with hepatobiliary disease and dyslipidemia. The data suggest an endothelial force sensing mechanism that controls lipid regulation in parenchymal cells to modulate whole-body lipid homeostasis.