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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, and the connection between dyslipidemia and remnant cholesterol (RC), a component of triglyceride-rich lipoproteins, remains enigmatic. METHODS: In this cross-sectional study, our primary aim was to investigate the role of RC in the progression of NAFLD and to provide robust evidence of RC's involvement in the pathogenesis of NAFLD. We enrolled 2800 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES). Logistic regression was employed to examine the relationship between serum RC levels and liver stiffness, while receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of RC. RESULTS: RC exhibited an independent correlation with the extent of liver stiffness, with odds ratios (OR) of 1.02 for liver steatosis (p = 0.014) and 1.02 for liver fibrosis (p = 0.014). To predict NAFLD, the optimal RC thresholds were 17.25 mg/dL for males and 15.25 mg/dL for females in the case of liver steatosis. For advanced liver fibrosis, the best thresholds were 17.25 mg/dL for males and 16.25 mg/dL for females. CONCLUSIONS: RC demonstrated a positive correlation with the degree of liver stiffness and exhibited superior diagnostic efficacy for liver steatosis and fibrosis compared to other cholesterol indicators.
Elevated serum remnant cholesterol (RC) levels may serve as a potential indicator of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD). The connection between serum RC and NAFLD has been previously undervalued. In our investigation, we examined 2800 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES). Our cross-sectional study has revealed a more distinct relationship between RC and the degree of liver stiffness, especially concerning liver steatosis when compared to other cholesterol indicators. Recognizing RC's significant role in metabolic disorders may lead to innovative approaches for diagnosing and treating NAFLD patients.
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Dislipidemias , Enfermedad del Hígado Graso no Alcohólico , Masculino , Femenino , Humanos , Encuestas Nutricionales , Estudios Transversales , Cirrosis Hepática , Dislipidemias/complicacionesRESUMEN
In the last two decades, human life expectancy has increased by about 10 years, but this has not been accompanied by a corresponding increase in healthy lifespan. Aging is associated with a wide range of human disorders, including cancer, diabetes, and cardiovascular and neurodegenerative diseases. Delaying the aging of organs or tissues and improving the physiological functions of the elderly can reduce the risk of aging-related diseases. Autophagy and apoptosis are crucial mechanisms for cell survival and tissue homeostasis, and may also be primary aging-regulatory pathways. Recent epidemiological studies have shown that eating more colorful plant foods could increase life expectancy. Several representative phytochemicals in dark-colored plant foods such as quercetin, catechin, curcumin, anthocyanins, and lycopene have apparent antiaging potential. Nevertheless, the antiaging signaling pathways of the phytochemicals from dark-colored plant foods remain elusive. In the present review, we summarized autophagy- and apoptosis-associated targeting pathways of those phytochemicals and discussed the core targets involved in the antiaging effects. Further clinical evaluation and exploitation of phytochemicals as antiaging agents are needed to develop novel antiaging therapeutics for preventing age-related diseases and improving a healthy lifespan.
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Catequina , Curcumina , Anciano , Antocianinas , Apoptosis , Autofagia , Humanos , Licopeno , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , QuercetinaRESUMEN
Weight regain subsequent to weight reduction resulting from dietary interventions represents a prevalent phenomenon recognized as "Yo-yo dieting." However, the impact of prolonged Yo-yo dieting on health, especially in relation to the aging process, remains poorly understood. This study aimed to investigate the influence of Yo-yo dieting on the aging process in male Drosophila melanogaster that have been exposed to a high-calorie (HC) diet. Fruit flies were fed with either a consistent HC diet or an alternating regimen of HC and low-calorie diets every 3 days (referred to as "Yo-yo dieting") for a total of 24 days. Biochemical assays were utilized to quantify levels of oxidative stress and activities of the mitochondrial respiratory chain complexes. The frozen section staining method was employed to assess the presence of lipid droplets, reactive oxygen species, cellular viability, and mitochondrial abundance in tissues. Additionally, we examined the expression of key regulators involved in mitochondrial dynamics and biogenic signaling pathways. Yo-yo dieting resulted in an extension of the fruit flies' lifespan, concomitant with reduced body weight, decreased body protein content, and lower triglyceride levels compared to continuous a HC diet feeding. Furthermore, Yo-yo dieting ameliorated impairments in motility and intestinal barrier function. Importantly, it improved mitochondrial function and upregulated the expression of essential mitochondrial fusion proteins, namely mitofusin 1 and mitofusin 2, optic atrophy 1, and peroxisome proliferator-activated receptor-γ coactivator-1α. Therefore, the practice of Yo-yo dieting extends the lifespan of fruit flies by modulating mitochondrial dynamics and the associated biogenic signaling pathways.
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Envejecimiento , Drosophila melanogaster , Animales , Masculino , Drosophila melanogaster/metabolismo , Estrés Oxidativo , Mitocondrias/metabolismo , Restricción CalóricaRESUMEN
The relationship between anthocyanin intake and obesity-related inflammatory markers remains unclear in existing research. To investigate this, we hypothesized that anthocyanin supplementation could reduce plasma concentrations of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1, and other cytokines in obesity. We conducted a systematic search of PubMed, Web of Science, Scopus, SinoMed, and other related literature and identified 16 randomized controlled trials that met our inclusion criteria. Our findings showed that anthocyanin intake was significantly associated with a reduction in vascular cell adhesion molecule-1 mean plasma concentrations (-53.56 ng/mL; 95% confidence interval [CI], -82.10 to -25.03). We also observed a modest decrease in CRP (-0.27 ng/mL; 95% CI, -0.58 to 0.05), TNF-α (-0.20 ng/mL; 95% CI, -0.54 to 0.15), and IL-6 (-0.53 ng/mL; 95% CI, -1.16 to 0.10) mean plasma concentrations. Subgroup analysis revealed that anthocyanin intake tended to decrease CRP and IL-6 concentrations in overweight or dyslipidemic individuals. Additionally, the intervention duration subgroup analysis showed that anthocyanin supplementation had a stronger effect on plasma IL-6 and TNF-α in participants after 8 to 12 weeks of intervention. In conclusion, our meta-analysis indicated that anthocyanin supplementation can effectively reduce obesity-related inflammatory markers associated with chronic low-grade inflammation.
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Antocianinas , Interleucina-6 , Humanos , Antocianinas/farmacología , Antocianinas/uso terapéutico , Factor de Necrosis Tumoral alfa , Molécula 1 de Adhesión Celular Vascular , Ensayos Clínicos Controlados Aleatorios como Asunto , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Proteína C-Reactiva , Inflamación/tratamiento farmacológico , Suplementos DietéticosRESUMEN
Nonalcoholic steatohepatitis (NASH) represents an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD). The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome triggers pyroptosis, thus propelling the progression from simple steatosis to NASH. Silibinin, a hepatoprotective compound derived from milk thistle, exerts diverse hepatoprotective effects. However, the direct impact of silibinin on NLRP3 inflammasome activation and its ability to mitigate pyroptosis remain uncertain. To address this, we utilized an in vitro model of NASH, employing HepG2 cells treated with deoxycholic acid (DCA) and free fatty acids. Subsequently, we treated these model cells with silibinin for 24 h. Our findings demonstrated that, although there were no significant changes in cellular lipid content, silibinin effectively ameliorated hepatocyte injuries. Silibinin treatment inhibited the activation of the NLRP3 inflammasome and suppressed DCA-induced pyroptosis. Additionally, molecular docking analysis revealed that silibinin exhibited a binding affinity to components of the NLRP3 inflammasome similar to that of MCC950, a selective NLRP3 inhibitor. These results suggest that silibinin may alleviate inflammation in DCA-exposed HepG2 cells by mitigating pyroptosis, possibly through its binding affinity and inhibition of the NLRP3 inflammasome. Overall, our study indicates that silibinin holds promise as a therapeutic agent for NASH by modulating pyroptosis and inhibiting NLRP3 inflammasome activation.
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Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), which can lead to liver fibrosis and cirrhosis. Bile acid levels are correlated with markers of hepatic injury in NASH, suggesting a possible role for bile acids in the progression of NAFLD. Here, we examined the role of deoxycholic acid (DCA) in driving steatotic hepatocytes to pyroptosis, a pro-inflammatory form of programmed cell death. HepG2 cells were stimulated with odium oleate and sodium palmitate for modeling steatotic hepatocytes and then treated with DCA alone or in combination with a specific mitophagy agonist, carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Our results showed that DCA dose-dependently induced a pro-inflammatory response in steatotic hepatocytes but had no significant effect on lipid accumulation. Moreover, activation of the NLRP3 inflammasome and pyroptosis were triggered by DCA. Expression levels of the mitophagy markers PTEN-induced kinase 1 (PINK1) and E3 ubiquitin ligase Parkin were significantly diminished by DCA, whereas induction of mitophagy by CCCP prevented DCA-induced inflammatory response and restored the pyroptosis. Collectively, our data showed that DCA-induced pyroptosis involves the inhibition of PINK1-mediated mitophagy and the activation of the NLRP3 inflammasome. These findings provide insight into the association of DCA with mitophagy, pyroptosis, and inflammation in NASH.
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Mitofagia , Piroptosis , Ácido Desoxicólico/farmacología , Ácidos Grasos no Esterificados/farmacología , Hepatocitos/metabolismo , Humanos , Proteínas Quinasas/metabolismo , Ubiquitina-Proteína LigasasRESUMEN
BACKGROUND: Previous studies have demonstrated that ursodeoxycholic acid (UDCA) possesses anti-inflammatory, antioxidant, and anti-fibrotic properties, and it may reduce the degree of liver damage caused by nonalcoholic steatohepatitis (NASH). However, the effectiveness of UDCA in improving liver function and histology in cases of NASH remains unclear. Therefore, we performed a meta-analysis to assess the efficacy of UDCA in the treatment of NASH. METHODS: PubMed, Web of Science, Embase, Cochrane, and other databases were searched for randomized controlled trials (RCTs) published before 1 January 2022, in which UDCA was used to treat patients with NASH. RESULTS: A total of 8 studies with 655 participantsmet the criteria for inclusion in this meta-analysis. The forest plot displayed that UDCA treatment significantly reduced blood concentrations of alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT). However, the pooled effect size results did not suggest any significant effect of UDCA on anthropometric characteristics or hepatic histology. CONCLUSION: UDCA therapy can effectively reduce serum levels of ALT and GGT in patients with NASH but has no significant effects on physical characteristics or liver histology. Further large-scale and dose-response clinical studies are needed to evaluate the clinical potential of UDCA in treating NASH.
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Enfermedad del Hígado Graso no Alcohólico , Ácido Ursodesoxicólico , Alanina Transaminasa , Colagogos y Coleréticos/efectos adversos , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Ácido Ursodesoxicólico/efectos adversosRESUMEN
OBJECTIVE: To investigate the effect of RbAp48 knockdown on the migration and invasion of human cervical cancer cells and explore the mechanism. METHODS: A small interference RNA (siRNA) was used to knock down the expression of RbAp48 in MS751 cells. The changes in cell migration and invasion were evaluated using wound healing assay and Transwell assay, respectively, and the expressions of RbAp48, vimentin, N-cadherin, E-cadherin, Snail, Twist, MMP-2 and TIMP-2 were determined with Western blotting. RESULTS: After siRNA-mediated RbAp48 knockdown, MS751 cells showed a significantly reduced expression of RbAp48 with significantly suppressed cell migration and invasion (P<0.01). RbAp48 knockdown induced obvious down-regulation of the expressions of interstitial cell phenotype proteins vimentin, N-cadherin, and MMP-2 and up-regulation of epithelial cell phenotype proteins E-cadherin and TIMP-2, suggesting the inhibition of epithelial- mesenchymal transition of the cells. The expressions of Snail and Twist were significantly down-regulated in the cells following RbAp48 knockdown. CONCLUSION: Knockdown of RbAp48 can significantly inhibit epithelial-mesenchymal transition and suppress the migration and invasion of cervical cancer cell line MS751, the mechanism of which may involve the down-regulation of Snail and Twist expressions.