Objective The incidence of metabolic syndrome (MS) increases after liver transplantation. This study was performed to evaluate the impact of MS on patients' quality of life after liver transplantation. Methods We collected the medical records of 152 patients during their post-liver transplantation outpatient follow-up. Quality of life was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey. Data on the patients' general condition as well as MS-related indicators were assessed in all patients. Based on the MS diagnostic criteria proposed by the International Diabetes Federation in 2005, the patients were divided into two groups: those with and without MS. We then analyzed the factors influencing MS and their impact on the patients' quality of life. Results After liver transplantation, age and underlying liver disease were significantly associated with MS and diabetes, and sex and body mass index were associated with central obesity. Central obesity affected the patients' general health (GH) score and health transition (HT) score, and hypertension affected their GH score and physical component score (PCS). Conclusions After liver transplantation, central obesity had a negative impact on patients' GH score and HT score, and hypertension affected their GH score and PCS.
The purpose of this study was to develop and evaluate a scoring system for assessing reperfusion status based on arterial spin labeled (ASL) perfusion MRI in acute ischemic stroke (AIS) patients receiving thrombolysis and/or endovascular treatment. Pseudo-continuous ASL with background suppressed 3D GRASE was acquired along with DWI in 90 patients within 24 h post-treatment. An automatic reperfusion scoring system (auto-RPS) was devised based on the Alberta Stroke Program Early CT Score (ASPECTS) template, and compared with manual RPS and DWI-ASPECTS. TICI (thrombolysis in cerebral infarction) scores were graded in 48 patients who received endovascular treatment. Favorable outcomes were defined by a modified Rankin Scale score of 0-2 at three months. Auto-RPS was positively correlated with DWI-ASPECTS (ρ = 0.6, P < 0.001) and was on average 1 point lower than DWI-ASPECTS ( P < 0.001). The area under the receiver operating characteristic curve for discriminating poor functional outcome (n = 90) was 0.75 (95% CI, 0.64-0.86) for manual RPS, 0.85 (95% CI, 0.76-0.94) for auto-RPS, and 0.81 (95% CI, 0.71-0.90) for DWI-ASPECTS. Multiple logistic regression analysis in the TICI-graded patients (n = 48) showed that auto-RPS is highly associated with functional outcome (OR = 25.2, 95% CI 4.02-496, P < 0.01). Post treatment auto-RPS within 24 h provides a useful tool to predict functional outcome in AIS patients.
The hepatic SLC13A5/SLC25A1-ACLY signaling pathway, responsible for maintaining the citrate homeostasis, plays a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Bempedoic acid (BA), an ACLY inhibitor commonly used for managing hypercholesterolemia, has shown promising results in addressing hepatic steatosis. This study aimed to elucidate the intricate relationships in processes of hepatic lipogenesis among SLC13A5, SLC25A1 and ACLY, and to examine the therapeutic potential of BA in NAFLD, providing insights into its underlying mechanism. In murine primary hepatocytes and HepG2 cells, the silencing or pharmacological inhibition of SLC25A1/ACLY resulted in significant upregulation of SLC13A5 transcription and activity. This increase in SLC13A5 activity subsequently led to enhanced lipogenesis, indicating a compensatory role of SLC13A5 when the SLC25A1/ACLY pathway was inhibited. However, BA effectively counteracted this upregulation, reduced lipid accumulation, and ameliorated various biomarkers of NAFLD. The disease-modifying effects of BA were further confirmed in NAFLD mice. Mechanistic investigations revealed that BA could reverse the elevated transcription levels of SLC13A5 and ACLY, and the subsequent lipogenesis induced by PXR activation in vitro and in vivo. Importantly, this effect was diminished when PXR was knocked down, suggesting the involvement of the hepatic PXR-SLC13A5/ACLY signaling axis in the mechanism of BA action. In conclusions, SLC13A5-mediated extracellular citrate influx emerges as an alternative pathway to SLC25A1/ACLY in the regulation of lipogenesis in hepatocytes, BA exhibits therapeutic potential in NAFLD by suppressing the hepatic PXR-SLC13A5/ACLY signaling axis, while PXR, a key regulator in drug metabolism may be involved in the pathogenesis of NAFLD. Significance Statement This work describes that bempedoic acid, an ACLY inhibitor, ameliorates hepatic lipid accumulation and various hallmarks of NAFLD. Suppression of hepatic SLC25A1-ACLY pathway upregulates SLC13A5 transcription, which in turn activates extracellular citrate influx and the subsequent DNL. Whereas in hepatocytes or the liver tissue challenged with high energy intake, bempedoic acid reverses compensatory activation of SLC13A5 via modulating the hepatic PXR-SLC13A5/ACLY axis, thereby simultaneously downregulating SLC13A5 and ACLY.
Abstract Both pathogenesis and detection of liver fibrosis and early cirrhosis are elusive. Our study focused on role of microRNAs (miRNAs) as predictive biomarkers of liver fibrosis and early cirrhosis. Methods: We recruited patients with chronic hepatitis B background and divided them into three subgroups according to the pathological staging results: no liver fibrosis group (CHB 11, 12.0%), liver fibrosis group but without liver cirrhosis (LF 41, 44.6%), and early liver cirrhosis group (LC 40, 43.4%). Results: Levels of miR-122 in the CHB and LF group were significantly elevated compared with the LC group. Meanwhile, upregulation levels of miR-146a-5p, miR-29c-3p, miR-223 were seen in the CHB group versus LC. MiR-122-5p was best able to differentiate between patients with LC and without LC (area under the curve (AUC) 0.734). It can also distinguish patients with LF from those without LF (AUC 0.681). Panel including miR-122-5p miR-29c-3p and miR-381-3p resulted in an AUC of 0.700 in detection of LF. Meanwhile panel including miR-122-5p, miR-29c-3p, MiR-223 turned out to be good predictors, resulted in an AUC of 0.752 to discriminate LC in HBV-associated disease. HBV load, ALT and AST showed significant positive correlation with miR-122-5p and miR-381-3p. Conclusions: Our study explored changes of plasm miRNA levels in HBV-associated disease patients, constructed diagnostic miRNAs panel to predict liver fibrosis and early cirrhosis. Meanwhile In the process of liver fibrosis and cirrhosis, there are involving not only common pathway molecules, but also its specific pathway molecules.
Liver fibrosis has a high incidence worldwide and is the common pathological basis of many chronic liver diseases. Liver fibrosis is caused by the excessive deposition of extracellular matrix and concomitant collagen accumulation in livers and can lead to the development of liver cirrhosis and even liver cancer. A large number of studies have provided evidence that liver fibrosis can be blocked or even reversed by appropriate medical interventions. However, the antifibrosis drugs with ideal clinical efficacy are still insufficient. The edible plant-derived natural compounds have been reported to exert effective antifibrotic effects with few side-effects, representing a kind of promising source for the treatment of liver fibrosis. In this article, we reviewed the current progress of the natural compounds derived from dietary plants in the treatment of liver fibrosis, including phenolic compounds (capsaicin, chlorogenic acid, curcumin, ellagic acid, epigallocatechin-3-gallate, resveratrol, sinapic acid, syringic acid, vanillic acid and vitamin E), flavonoid compounds (genistein, hesperidin, hesperetin, naringenin, naringin and quercetin), sulfur-containing compounds (S-allylcysteine, ergothioneine, lipoic acid and sulforaphane) and other compounds (betaine, caffeine, cucurbitacin B, lycopene, α-mangostin, γ-mangostin, ursolic acid, vitamin C and yangonin). The pharmacological effects and related mechanisms of these compounds in in-vivo and in-vitro models of liver fibrosis are focused.
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