RESUMO
The dysregulation of cholesterol metabolism is a high-risk factor for non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and atherosclerosis (AS). Cholesterol transport maintains whole-body cholesterol homeostasis. Low-density apolipoprotein receptor (LDLR) mediates cholesterol uptake in cells and plays an important role in the primary route of circulatory cholesterol clearance in liver cells. Caveolins 1 is an integral membrane protein and shuttle between the cytoplasm and cell membrane. Caveolins 1 not only plays a role in promoting cholesterol absorption in cells but also in the transport of cellular cholesterol efflux by interacting with the ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI). These proteins, which are associated with reverse cholesterol transport (RCT), are potential therapeutic targets for NAFLD and AS. Many studies have indicated that natural products have lipid-lowering effects. Moreover, natural molecules, derived from natural products, have the potential to be developed into novel drugs. However, the mechanisms underlying the regulation of cholesterol transport by natural molecules have not yet been adequately investigated. In this review, we briefly describe the process of cholesterol transport and summarize the mechanisms by which molecules regulate cholesterol transport. This article provides an overview of recent studies and focuses on the potential therapeutic effects of natural molecules; however, further high-quality studies are needed to firmly establish the clinical efficacies of natural molecules.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Aterosclerose , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Aterosclerose/tratamento farmacológico , Transporte Biológico , Colesterol , Humanos , Receptores Depuradores Classe B/metabolismoRESUMO
BACKGROUND: Metabolic syndrome (MetS) presents a notable public health challenge on a global scale, exerting a considerable impact on individuals' health and quality of life. There is mounting evidence indicating a robust association between MetS and levels of sex hormones. Therefore, the study aims to explore the relationship between sex hormone binding-globulin (SHBG) and MetS, and to provide evidence that could inform the development of effective prevention strategies for MetS. METHODS: Data for this cross-sectional investigation were collected during the 2013-2016 cycle of the National Health and Nutrition Examination Survey (NHANES), from which 5,499 adults were sampled. The criteria established by the Adult Treatment Program III of the National Cholesterol Education Program were utilized to define MetS. SHBG levels were measured using a standardized technique. Multivariate-adjusted logistic regression, multivariate restricted cubic spline, and threshold effect analyses were utilized to investigate the association between SHBG levels and MetS. Moreover, the stratified analyses and interaction tests of covariables were presented in a forest plot. Finally, sensitivity analysis was utilized to ensure the robustness of the results. RESULTS: Overall, 1822 participants had MetS. After adjusting for possible confounders, SHBG levels were associated with MetS (Odds ratio [OR], 0.984; 95% confidence interval [CI], 0.981-0.986; P < 0.01). The multivariate restricted cubic spline analysis demonstrated a non-linear association between SHBG and MetS (P < 0.001). With two piecewise regression models, the adjusted OR of developing MetS was 0.964 (95% CI, 0.959-0.969; P < 0.001) among people with SHBG < 76.653 nmol/L, but there was no correlation between SHBG and MetS in participants with SHBG ≥ 76.653 nmol/L. The stability of the association between SHBG levels and MetS was confirmed using subgroup analysis and sensitivity analyses. CONCLUSIONS: Our results suggest that reduced SHBG levels are associated with an increased prevalence of MetS in adults, particularly when SHBG levels are below 76.653 nmol/L. More investigation is required to understand comprehend the mechanisms underlying these results and to delve into their clinical implications.
RESUMO
BACKGROUND: The aim of this study was to determine the efficacy and safety of acupuncture treatment (AT) or acupuncture plus conventional medicine (CM) versus CM alone using a meta-analysis of all published randomized controlled trials (RCTs) for nonalcoholic fatty liver disease (NAFLD). METHODS: Eight databases were searched independently from inception to April 30, 2020. RCTs were included if they contained reports on the use acupuncture or the use of acupuncture combined with CM and compared with the use of CM. Summary odds ratio (OR) and 95% confidence intervals (CIs) were used to calculate the overall clinical efficacy. Secondary outcomes, namely aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index, were calculated by mean difference with 95% CIs. RESULTS: After the final screening, 8 RCTs with 939 patients were included. This meta-analysis showed that AT was superior to CM in improving overall clinical efficacy (ORâ=â3.19, 95% CI: 2.06-4.92, Pâ <â.00001). In addition, AT plus CM could significantly improve overall clinical efficacy compared to treatment with CM alone (ORâ=â5.11, 95% CI: 2.43-10.75, Pâ <â.0001). Moreover, the benefits were also demonstrated in other outcomes, including alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol indexes. However, AT plus CM could not decrease body mass index levels in comparison with CM. The safety profile of Acupuncture therapy was satisfactory. Taichong, Zusanli, Fenglong, and Sanyinjiao were major acupoints on NAFLD treatment. CONCLUSION: Acupuncture may be effective and safe for treatment of NAFLD. However, due to insufficient methodological quality and sample size, further high-quality studies are needed.
Assuntos
Terapia por Acupuntura , Hepatopatia Gordurosa não Alcoólica/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Many immune cells participate in the pathogenesis of ulcerative colitis (UC), and fatty acid metabolism (FAM) is reported to supporting their cell-specific functions and proliferation, but the underlying mechanism is unclear. This study aimed to investigate the relationship between FAM and inflammation in colon tissues and identify potential therapeutic targets for regulating immune response. A total of 870 different expression genes (DEGs), 304 immunity-related DEGs, and 11 FAM-related DEGs were obtained, gene ontology analysis results showed that immune DEGs were significantly enriched in neutrophil migration, positive regulation of T cell activation. Fifteen types of immune cells were identified in inflamed colon tissues. Five FAM-related DEGs (ACOX1, ACSL4, ELOVL5, FADS2, and SCD) were highly correlated with immunity-related DEGs, and ACSL4, ELOVL5, and FADS2 were significantly upregulated in immune cells, while SCD is downregulated. Five FAM-related DEGs were highly correlated with immune cells. The study promotes the understanding of the pathogenesis of FAM in UC immune cells.
Assuntos
Colite Ulcerativa/genética , Ácidos Graxos/metabolismo , Redes Reguladoras de Genes , Transcriptoma , Acil-CoA Oxidase/genética , Acil-CoA Oxidase/metabolismo , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Colite Ulcerativa/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Elongases de Ácidos Graxos/genética , Elongases de Ácidos Graxos/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Linfócitos/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismoRESUMO
The majority of Musashi 1 (Msi1)positive cells derived from mouse embryonic stem cells (mESCs) are prone to differentiate into neural epitheliallike cells, and only a small proportion of Msi1positive cells differentiate into intestinal epitheliallike cells. Whether inhibiting the phosphatidylinositol 3kinase (PI3K) signaling of mESCs can promote the differentiation of Msi1positive cells into intestinal epitheliallike cells remains to be fully elucidated. In the present study, to inhibit PI3K signaling, mESCs were treated with LY294002. A pMsi1green fluorescence protein reporter plasmid was used to sort the Msi1positive cells from mESCs treated and untreated with LY294002 (5 µmol/l). The Msi1positive cells were hypodermically engrafted into the backs of nonobese diabetic/severe combined immunodeficient mice. The presence of neural and intestinal epitheliallike cells in the grafts was detected by reverse transcriptionquantitative polymerase chain reaction analysis and immunohistochemistry. Compared with the Msi1positive cells derived from mESCs without LY294002 treatment, Msi1positive cells derived from mESCs treated with LY294002 expressed higher levels of leucinerich repeatcontaining Gprotein coupled receptor, a marker of intestinal epithelial stem cells, and lower levels of Nestin, a marker of neural epithelial stem cells. The grafts from Msi1positive cells treated with LY294002 contained more intestinal epitheliallike tissues and fewer neural epitheliallike tissues, compared with those from untreated Msi1positive cells. LY294002 had the ability to promote the differentiation of mESCs into intestinal epitheliallike tissues. The Msi1positive cells selected from the cell population derived from mESCs treated with LY294002 exhibited more characteristics of intestinal epithelial stem cells than those from the untreated group.