RESUMEN
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.
Asunto(s)
Colesterol , Colitis Ulcerosa , Sulfato de Dextran , Medicamentos Herbarios Chinos , Animales , Medicamentos Herbarios Chinos/farmacología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Colitis Ulcerosa/metabolismo , Ratones , Masculino , Colesterol/sangre , Células Th17/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Farmacología en Red , Citocinas/metabolismo , Linfocitos T Reguladores/efectos de los fármacosRESUMEN
Background: Mounting evidence indicates the importance of the interplay between skeletal muscles and lipid metabolism. Remnant cholesterol (remnant-C) is considered one of the principal residual risk factors for cardiovascular disease and metabolic disorders; however, there are limited studies on the impact of remnant-C on sarcopenia. Methods: Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) between 2008 and 2011 were used in this nationwide population-based study. In total, 17,408 participants were enrolled in this study. The subjects were categorized into four groups according to the quartile of remnant-C values. We conducted multivariable logistic regression analysis to evaluate the association between remnant-C and muscle mass measured using dual-energy X-ray absorptiometry. Results: A total of 1,791 participants (10.3%) presented low muscle mass, and there was a sequential increase in the percentage of low muscle mass across remnant-C quartiles (Q1, 5.2%; Q2, 8.7%; Q3, 11.5%; Q4, 15.7%). In the full adjusted model, those in the highest remnant-C quartile group showed significantly increased odds ratio (OR) for low muscle mass compared with those in the lowest remnant-C group after adjusting for various confounding factors (OR = 1.33, 95% confidence interval (CI) = 1.06-1.68, P <0.05). A wide range of subgroups and sensitivity analyses showed consistent results, supporting the robustness of our findings. Conclusions: Increased remnant-C value was associated with a high risk of low muscle mass in the Korean population. Remnant-C may be a novel marker for the prediction and management of sarcopenia in aging societies.
Asunto(s)
Colesterol , Encuestas Nutricionales , Sarcopenia , Humanos , Sarcopenia/epidemiología , Femenino , Masculino , República de Corea/epidemiología , Persona de Mediana Edad , Colesterol/sangre , Adulto , Anciano , Factores de Riesgo , Estudios Transversales , Músculo Esquelético/metabolismo , Absorciometría de FotónRESUMEN
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.
Asunto(s)
LDL-Colesterol , Hiperlipoproteinemia Tipo II , Trasplante de Hígado , Humanos , Masculino , Niño , Hiperlipoproteinemia Tipo II/cirugía , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/terapia , Preescolar , Resultado del Tratamiento , LDL-Colesterol/sangre , Femenino , Estudios de Seguimiento , Homocigoto , Adolescente , Estudios Retrospectivos , Colesterol/sangreRESUMEN
INTRODUCTION: Metabolic syndrome (MetS) and hypothyroidism are well-established forerunners of atherogenic cardiovascular disease (CVD). It is possible that patients suffering from both these disease entities may have a compounded risk. This study aimed at determining the prevalence of hypothyroidism in MetS. MATERIALS AND METHODS: This cross-sectional study was conducted from September 2017 to August 2018 in the department of medicine at a tertiary care hospital in Northern India. Ethical approval was obtained from the institutional ethical committee. The study subjects consisted of 157 patients with MetS, the diagnosis of which was based on the International Diabetes Federation criteria. After a detailed history and physical examination, relevant investigations including complete thyroid profile were done. The data were analyzed using appropriate statistical tests (P < 0.05). RESULTS: In our study, the age of subjects ranged between 14 and 92 years, with a mean ± standard deviation of 48.1 ± 17.01 years. There were more females than males with a male-to-female ratio of 1:1.3. The prevalence of hypothyroidism was 46.5%. Hypothyroidism was more common in females (58.9%) as compared to males (41.1%). Patients with hypothyroidism had significantly higher body weight and body mass index (BMI) in comparison to euthyroid patients. The rest of the anthropometric parameters were comparable. Waist circumference and BMI of overt hypothyroid patients were found to be higher as compared to subclinical hypothyroid patients. Total cholesterol and triglyceride were significantly higher (P = 0.001 and P < 0.001, respectively), while high-density lipoprotein levels were significantly lower in patients with hypothyroidism than the euthyroid group (P < 0.001). CONCLUSION: Hypothyroidism, especially subclinical hypothyroidism, is a common endocrine disorder in patients with MetS. As MetS and hypothyroidism are independent risk factors for CVD, hence there is a need for screening for hypothyroidism and the treatment of the same can be beneficial in reducing the cardiovascular morbidity and mortality in patients with MetS.
Résumé Introduction:Le syndrome métabolique (METS) et l'hypothyroïdie sont des précurseurs bien établis d'une maladie cardiovasculaire athérogène (MCV). Il est possible que les patients souffrant de ces deux entités maladie puissent avoir un risque composé. Cette étude visait à déterminer la prévalence de l'hypothyroïdie dans les Mets.Matériaux et méthodes:Cette étude transversale a été menée de septembre 2017 à août 2018 dans le Département de médecine dans un hôpital de soins tertiaires du nord de l'Inde. L'approbation éthique a été obtenue auprès du Comité éthique institutionnel. Les sujets de l'étude étaient composés de 157 patients atteints de MetS, dont le diagnostic était basé sur les critères internationaux de la Fédération du diabète. Après un historique détaillé et un examen physique, des enquêtes pertinentes, y compris un profil thyroïdien complet, ont été effectuées. Les données ont été analysées en utilisant des tests statistiques appropriés (P <0,05).Résultats:Dans notre étude, l'âge des sujets variait entre 14 et 92 ans, avec une moyenne ± standard déviation de 48,1 ± 17,01 ans. Il y avait plus de femelles que les hommes avec un rapport masculin à féminin de 1: 1,3. La prévalence de l'hypothyroïdie était de 46,5%. L'hypothyroïdie était plus fréquente chez les femmes (58,9%) par rapport aux hommes (41,1%). Les patients atteints d'hypothyroïdie avaient Indice de poids corporel et de masse corporelle significativement plus élevé (IMC) par rapport aux patients euthyroïdiens. Le reste des paramètres anthropométriques étaient comparables. Le tour de taille et l'IMC des patients hypothyroïdiens manifestes se sont révélés plus élevés par rapport à l'hypothyroïde subclinique patients. Le cholestérol total et les triglycérides étaient significativement plus élevés (P = 0,001 et P <0,001, respectivement), tandis que les lipoprotéines à haute densité Les niveaux étaient significativement plus faibles chez les patients atteints d'hypothyroïdie que le groupe euthyroïdien (P <0,001).Conclusion:hypothyroïdie, en particulier L'hypothyroïdie subclinique est un trouble endocrinien commun chez les patients atteints de Metts. Comme les Mets et l'hypothyroïdie sont des facteurs de risque indépendants Pour les MCV, il y a donc un besoin de dépistage pour l'hypothyroïdie et le traitement de la même chose peut être bénéfique pour réduire le cardiovasculaire morbidité et mortalité chez les patients atteints de MetS.
Asunto(s)
Índice de Masa Corporal , Hipotiroidismo , Síndrome Metabólico , Humanos , Hipotiroidismo/epidemiología , Hipotiroidismo/complicaciones , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adulto , Prevalencia , India/epidemiología , Anciano , Factores de Riesgo , Adulto Joven , Adolescente , Triglicéridos/sangre , Circunferencia de la Cintura , Anciano de 80 o más Años , Colesterol/sangreRESUMEN
BACKGROUND: Pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae can vary in severity, and several risk factors for the development of organ dysfunction in PLA have been implicated. However, few studies to date have explored the most common risk factors for clinical severity. METHODS: We conducted a study on patients with PLA caused by Klebsiella pneumoniae between February 2013 and December 2022.Using logistic regression analysis, we sought to identify factors associated with positive blood culture, septic shock, and intensive care unit (ICU) admission. RESULTS: After included 200 patients, we found that an elevated procalcitonin (PCT) level (p = 0.03), higher glucose level (p = 0.03), and lower total cholesterol (TC) level (p = 0.01) were associated with a higher likelihood of positive blood bacteriological culture. Additionally, an increased PCT level (p = 0.02) and lower TC level (p < 0.01) were associated with an elevated risk of septic shock. Furthermore, a higher PCT level (p < 0.01) was associated with a higher probability of ICU admission. CONCLUSION: In patients with PLA caused by Klebsiella pneumoniae, the PCT, glucose, and TC levels were found to be associated with positive blood culture, septic shock, and ICU admission.
Asunto(s)
Colesterol , Unidades de Cuidados Intensivos , Infecciones por Klebsiella , Klebsiella pneumoniae , Absceso Piógeno Hepático , Choque Séptico , Humanos , Absceso Piógeno Hepático/microbiología , Absceso Piógeno Hepático/sangre , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Factores de Riesgo , Femenino , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/epidemiología , Persona de Mediana Edad , Choque Séptico/microbiología , Choque Séptico/sangre , Pronóstico , Anciano , Unidades de Cuidados Intensivos/estadística & datos numéricos , Colesterol/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre , Glucemia/metabolismo , Glucemia/análisis , Estudios Retrospectivos , Modelos Logísticos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND AND OBJECTIVE: The value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) assessment in the context of metabolic abnormalities is growing in importance. Nevertheless, the relationship between NHHR and hyperuricemia (HUA) is unknown. This study seeks to investigate the relationship between NHHR and HUA. METHODS: The data derived from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) included 7,876 adult participants. The multivariable logistic regression model, subgroup analysis and smooth fitting curve were utilized in order to investigate the association between NHHR and HUA. RESULTS: In the fully adjusted model 3, NHHR was significantly associated with HUA. Specifically, participants in the highest quartile of NHHR had 1.95 times higher odds of HUA prevalence compared to those in the lowest quartile [2.95 (2.39, 3.64), P < 0.0001]. Although the overall trend suggested a positive association, further analysis using smooth fitting curves and threshold effect analysis indicated that this association was nonlinear, with an inflection point at 5.8. The positive association persisted across different HUA definitions and after removing outliers. Subgroup analysis showed significant interactions between NHHR and HUA in different races and diabetes statuses. The odds of HUA prevalence were higher among non-diabetic participants [1.40 (1.32, 1.49), P < 0.0001] compared to diabetic participants [1.18 (1.06, 1.32), P = 0.0031]. Mexican Americans had the lowest odds of HUA prevalence [1.09 (0.92, 1.27), P = 0.2413] compared to other races. CONCLUSIONS: There is a significant positive association between NHHR and HUA, indicating that NHHR may serve as a potential risk assessment maker for HUA, although further prospective studies are needed for validation.
Asunto(s)
HDL-Colesterol , Hiperuricemia , Encuestas Nutricionales , Humanos , Hiperuricemia/sangre , Hiperuricemia/epidemiología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , HDL-Colesterol/sangre , Adulto , Prevalencia , Factores de Riesgo , Modelos Logísticos , Anciano , Colesterol/sangre , LDL-Colesterol/sangreRESUMEN
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.
Asunto(s)
Adipoquinas , Adiponectina , Aterosclerosis , Colesterol , Leptina , Resistina , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Aterosclerosis/sangre , Aterosclerosis/etnología , Aterosclerosis/epidemiología , Leptina/sangre , Adipoquinas/sangre , Adiponectina/sangre , Colesterol/sangre , Resistina/sangre , Estados Unidos/epidemiología , Biomarcadores/sangre , Estudios Transversales , Anciano de 80 o más Años , Triglicéridos/sangre , Obesidad/sangre , Obesidad/etnología , Obesidad/epidemiología , Estudios Longitudinales , Factores de Riesgo , Estudios ProspectivosRESUMEN
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.
Asunto(s)
Lacticaseibacillus rhamnosus , Oligosacáridos , Prebióticos , Simbióticos , Lacticaseibacillus rhamnosus/metabolismo , Oligosacáridos/farmacología , Humanos , Hipolipemiantes/farmacología , Colesterol/metabolismo , Colesterol/sangre , Microbioma Gastrointestinal/efectos de los fármacos , Probióticos , GlucuronatosRESUMEN
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.
Asunto(s)
Colesterol , Insuficiencia Cardíaca , Hipertensión , Hipertrofia Ventricular Izquierda , Triglicéridos , Humanos , Hipertrofia Ventricular Izquierda/sangre , Masculino , Femenino , Hipertensión/complicaciones , Hipertensión/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/complicaciones , Colesterol/sangre , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Pronóstico , Triglicéridos/sangre , Remodelación Ventricular , Curva ROC , Modelos de Riesgos Proporcionales , HDL-Colesterol/sangre , Factores de RiesgoRESUMEN
Grape seed proanthocyanidin extract (GSPE) is a natural polyphenolic compound, which plays an important role in anti-inflammatory and antioxidant. The present study aimed to investigate the effects of GSPE supplementation on the cholesterol metabolism and antioxidant status of finishing pigs. In longissimus dorse (LD) muscle, the data showed that GSPE significantly decreased the contents of total cholesterol (T-CHO) and triglyceride (TG), and decreased the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and Fatty acid synthase (FAS), while increased the mRNA expression of carnitine palmitoyl transferase-1b (CPT1b), peroxisome proliferator-activated receptors (PPARα) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). GSPE also reduced the enzyme activities of HMG-CoAR and FAS, and meanwhile amplified the activity of CPT1b in LD muscle of finishing pigs. Furthermore, dietary GSPE supplementation increased the serum catalase (CAT) and total antioxidant capacity (T-AOC), serum and liver total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) levels, while reduced serum and liver malondialdehyde (MDA) level in finishing pigs. In the liver, Superoxide Dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1), Nuclear Factor erythroid 2-Related Factor 2 (NRF2) mRNA levels were increased by GSPE. In conclusion, this study showed that GSPE might be an effective dietary supplement for improving cholesterol metabolism and antioxidant status in finishing pigs.
Asunto(s)
Antioxidantes , Colesterol , Extracto de Semillas de Uva , Proantocianidinas , Animales , Proantocianidinas/farmacología , Extracto de Semillas de Uva/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Colesterol/sangre , Colesterol/metabolismo , Porcinos , Suplementos Dietéticos , Hígado/metabolismo , Hígado/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Carnitina O-Palmitoiltransferasa/metabolismo , Carnitina O-Palmitoiltransferasa/genéticaRESUMEN
Investigate the impact of remnant cholesterol (RC) levels on carotid artery intima thickness (CIT) in type 2 diabetes mellitus (T2DM) patients. From September 2021 to September 2023, a prospective multicenter study involved 158 T2DM patients. They were divided into a higher RC group (n = 80) and a lower RC group (n = 78) based on median RC levels. Additionally, 92 healthy volunteers served as the control group. CIT, carotid media thickness (CMT), and carotid intima-media thickness (CIMT) were measured. General clinical data, lab results, CIMT, CIT, and CMT differences among the three groups were compared. Multiple regression analysis explored CIT factors in T2DM patients. 1. No significant sex, age, BMI, high-density lipoprotein cholesterol (HDL-C), T2DM duration, fasting blood glucose, or glycated hemoglobin differences were found among the groups (p > 0.05). 2. CIMT and CIT were significantly higher in T2DM than the control group (p < 0.05). 3. The higher RC group had thicker CIT than the lower RC group (p < 0.05), while CIMT differences were not significant (p > 0.05). Multiple linear regression analysis showed RC as an influencing CIT factor in T2DM patients (ß = 0.473, p = 0.005). CIT is significantly thicker in T2DM patients with higher RC than in those with lower RC, and RC is the influence factor of CIT, which suggests that more attention should be paid to the detection of RC in T2DM patients.
Asunto(s)
Grosor Intima-Media Carotídeo , Colesterol , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/patología , Masculino , Femenino , Persona de Mediana Edad , Colesterol/sangre , Estudios Prospectivos , Anciano , Estudios de Casos y Controles , Adulto , Factores de RiesgoRESUMEN
BACKGROUND: Lipid levels have been suggset to be correlated with multiple myeloma (MM) risk, though causality remains unconfirmed. To explore this further, a detailed study combining meta-analysis and Mendelian randomization (MR) was conducted. METHODS: Literature searches were performed on PubMed and Embase; summary data for plasma lipid traits were extracted from the IEU and MM data from the FinnGen database. Meta-analysis and MR were utilized to analyze the link of lipids with MM risk, including mediator MR to identify potential mediators. The study was conducted in accordance with PRISMA and STROBE-MR guidelines. RESULTS: Observational studies analyzed through meta-analysis showed that elevated levels of LDL, HDL, total cholesterol (TC), and triglycerides correlate with a lower risk of MM, with HRs of 0.73, 0.59, 0.60, and 0.84, respectively. MR analysis confirmed a potential causal link of triglyceride with a reduced MM risk (OR: 0.67, 95% CI: 0.46-0.98), independent of BMI. Mediation analysis pointed to X-11,423-O-sulfo-L-tyrosine and neuropilin-2 as potential mediators. CONCLUSIONS: The findings suggest that higher lipid levels (LDL, HDL, TC, and triglycerides) are linked with a reduced MM risk, and higher triglyceride levels are causally associated with a reduced MM risk. This suggests new avenues for therapeutic interventions targeting MM.
Asunto(s)
Análisis de la Aleatorización Mendeliana , Mieloma Múltiple , Triglicéridos , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/sangre , Triglicéridos/sangre , Factores de Riesgo , LDL-Colesterol/sangre , HDL-Colesterol/sangre , Colesterol/sangre , Lípidos/sangreRESUMEN
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.
Asunto(s)
HDL-Colesterol , LDL-Colesterol , Pruebas en el Punto de Atención , Triglicéridos , Humanos , Pruebas en el Punto de Atención/normas , Masculino , Femenino , Adulto , Persona de Mediana Edad , Triglicéridos/sangre , Estudios Transversales , LDL-Colesterol/sangre , HDL-Colesterol/sangre , Malasia/epidemiología , Reproducibilidad de los Resultados , Anciano , Colesterol/sangre , Adulto Joven , Lípidos/sangre , Sensibilidad y Especificidad , AdolescenteRESUMEN
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.
Asunto(s)
Glándulas Suprarrenales , Colesterol , Enfermedad Crítica , Glucocorticoides , Músculo Esquelético , Animales , Enfermedad Crítica/terapia , Humanos , Ratones , Glucocorticoides/uso terapéutico , Glucocorticoides/farmacología , Colesterol/sangre , Colesterol/análisis , Masculino , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/fisiopatología , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Femenino , Anciano , Hidrocortisona/análisis , Hidrocortisona/uso terapéutico , Hidrocortisona/sangre , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Sepsis/complicaciones , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: The role of dietary fat quality in promotion of cardiovascular diseases is studies before. However, the results are inconsistent. Recently, cholesterol to saturated fatty acid index (CSI) is suggested as a novel indicator of the atherogenicity and thrombogenicity potential of a diet. However, due to limited number of studies, in the current cross-sectional study, we aimed to evaluate the role of CSI in metabolic and inflammatory response among obese individuals. METHODS: In the current cross-sectional study 488 obese individuals aged 18-50 years old were involved in volunteer based invitation from outpatient obesity clinics. Subjects underwent anthropometric assays including weight, height, waist circumference (WC) and body composition and their fasting blood sample were obtained for biochemical assessments including blood sugar, serum lipids, hs-CRP and IL-6 concentrations by commercial kits. Physical activity was also assessed by short form of international physical activity questionnaire (IPAQ). RESULTS: According to our results, being at the top tetile of CSI was associated with higher anthropometric indices including weight, height, WC, FFM, and basal metabolic rate (BMR) compared with those at the lowest tertile (P < 0.05). Similarly, those at the highest category of CSI had significantly higher levels of serum glucose and hs-CRP both in crude and adjusted models in ANCOVA and in multinomial logistic regression models (P < 0.05). CONCLUSION: In the current study, for the first time, we identified the possible triggering role of dietary cholesterol to saturated fat index in increasing serum glucose and hs-CRP levels. due to cross-sectional design of the current study, causal inference is impossible. Further studies will help for better scientific justification.
Asunto(s)
Colesterol , Ácidos Grasos , Obesidad , Humanos , Masculino , Estudios Transversales , Femenino , Adulto , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Obesidad/metabolismo , Adolescente , Adulto Joven , Ácidos Grasos/sangre , Ácidos Grasos/metabolismo , Colesterol/sangre , Inflamación/sangre , Biomarcadores/sangre , Grasas de la Dieta , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismoRESUMEN
There is scarce information about the effect of sperm morphology and seminal plasma composition on cat semen freezability. Thus, this study aims to assess the effect of cat sperm morphology and seminal plasma cholesterol (CHOL) and triacylglyceride (TAG) concentrations on sperm post-thaw survival. Ejaculates (n = 49) were evaluated, and seminal plasma was separated and frozen until CHOL and TAG concentrations were measured. The sperm pellet was diluted in a tris-based egg yolk extender, frozen (n = 38), or processed for sperm ultrastructure study (n = 11). Abnormalities recorded were abnormal head shape and size, detached heads, knobbed or ruffled acrosomes, eccentric mid-piece insertion, proximal and distal cytoplasmic droplets, folded and coiled tails, and Dag defect. Ultramicroscopic evaluation detected several sperm abnormalities in fresh semen and some sperm damage in frozen semen. Seminal plasma lipids components were positively correlated with post-thaw motility and acrosome integrity. Higher freezability indices for motility and acrosome integrity were observed in frozen-thawed semen with high seminal plasma CHOL and TAG concentrations. No freezability differences were observed between teratozoospermic and normozoospermic ejaculates. Our results showed that even when seminal plasma was removed before cryopreservation, sperm survival after thawing was significantly higher in samples with high seminal plasma CHOL and TAG concentrations, indicating a rapid adherence to these compounds to the sperm plasma membrane, protecting sperm cells from temperature changes. Nevertheless, there were no differences in sperm freezability by sperm morphology.
Asunto(s)
Colesterol , Criopreservación , Preservación de Semen , Semen , Espermatozoides , Triglicéridos , Animales , Masculino , Gatos , Semen/química , Colesterol/sangre , Preservación de Semen/veterinaria , Triglicéridos/sangre , Criopreservación/veterinaria , Análisis de Semen/veterinaria , Motilidad EspermáticaRESUMEN
OBJECTIVE: Cerebral infarction treatments are most effective if used early after stroke symptoms occur. Also, early detection is crucial for delaying and improving cognitive impairment. This study investigated the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (Non-HDL-C/HDL-C), which reflects the entire burden of the cholesterol transported in atherogenic lipoproteins, and the level of ß-amyloid 1-42 (Aß-1-42), a major component of cerebrovascular amyloid deposits, in peripheral blood and cognitive dysfunction secondary to cerebral infarction. METHODS: A total of 83 patients with cerebral infarction admitted to Bozhou People's Hospital between June 2019 and June 2022 were assessed. The patients were divided into two groups based on their Mini-Mental State Scale (MMSE) scores: cognitive dysfunction group (n = 30) and non-cognitive dysfunction group (n = 53). In addition, a control group comprising 34 patients with transient cerebral insufficiency or cerebrovascular stenosis was selected. The groups were compared in terms of various clinical factors, including gender, age, hypertension, hyperlipidemia, lipid indexes, Non-HDL-C/HDL-C, and Aß1-42 levels. Logistic regression analysis was used to identify the risk factors associated with cognitive dysfunction. RESULTS: The results showed that hypertensive patients with cognitive dysfunction secondary to cerebral infarction had a higher proportion of frontal lobe, temporal lobe, and thalamus involvement and lower scores on the MMSE compared to the non-cognitive impairment group and control group (p < 0.05). Additionally, the levels of homocysteine (HCY), Non-HDL-C/HDL-C, and Aß1-42 in peripheral blood were significantly higher in hypertensive patients with cognitive dysfunction compared to the other two groups (all p < 0.05) and were identified as risk factors for cognitive dysfunction secondary to cerebral infarction. Peripheral blood levels of Non-HDL-C/HDL-C and Aß1-42 are risk factors for secondary cognitive dysfunction following a cerebral infarction. CONCLUSION: These data have important clinical implications for understanding the mechanisms underlying cognitive dysfunction in individuals with cerebrovascular disorders, potentially leading to new early interventions for preventing or treating such diseases.
Asunto(s)
Péptidos beta-Amiloides , Infarto Cerebral , Disfunción Cognitiva , Fragmentos de Péptidos , Humanos , Masculino , Femenino , Péptidos beta-Amiloides/sangre , Infarto Cerebral/sangre , Infarto Cerebral/complicaciones , Anciano , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Disfunción Cognitiva/etiología , Disfunción Cognitiva/sangre , HDL-Colesterol/sangre , Factores de Riesgo , Anciano de 80 o más Años , Colesterol/sangre , Biomarcadores/sangreRESUMEN
BACKGROUND: Remnant cholesterol (RC) exert a significant influence on atherosclerotic cardiovascular disease development. However, the prognostic implications of RC in menopausal women received percutaneous coronary intervention (PCI) who experiencing acute coronary syndrome (ACS) remain uncertain. METHODS: RC was derived by subtracting the sum of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol from the total cholesterol. Kaplan-Meier survival and Cox regression analysis were employed for assessing the correlation between continuous RC levels and composite and individual adverse events in Q1-Q4 quartiles. Receiver operator characteristic (ROC) curves, derived from Cox regression, were employed for analyzing the relationship between RC and both composite and individual adverse events. RESULTS: 1505 consecutive menopausal women who underwent PCI and diagnosed with ACS were included. Kaplan-Meier survival analysis demonstrated a progressive reduction in composite adverse event survival rates across the four groups, observed in both the general population and among diabetic individuals, as RC values increased (Log-rank P < 0.001). The analysis of multivariate Cox regression indicated RC remained independently associated with both composite and individual adverse events. ROC analysis showed that RC enhanced the area under the curve both in total and diabetic populations for composite adverse events. CONCLUSION: Among menopausal women diagnosed with ACS who underwent PCI, heightened levels of RC were found to be independently correlated with an increased occurrence of adverse events.