Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular ...carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
The prion hypothesis posits that a misfolded form of prion protein (PrP) is responsible for the infectivity of prion disease. Using recombinant murine PrP purified from Escherichia coli, we created a ...recombinant prion with the attributes of the pathogenic PrP isoform: aggregated, protease-resistant, and self-perpetuating. After intracerebral injection of the recombinant prion, wild-type mice developed neurological signs in approximately 130 days and reached the terminal stage of disease in approximately 150 days. Characterization of diseased mice revealed classic neuropathology of prion disease, the presence of protease-resistant PrP, and the capability of serially transmitting the disease; these findings confirmed that the mice succumbed to prion disease. Thus, as postulated by the prion hypothesis, the infectivity in mammalian prion disease results from an altered conformation of PrP.
Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells ...epithelial-mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells' EMT and explored their regulatory mechanisms and clinical significance in UCBs.
We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells' EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes,
and
, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).
We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.
CircPRMT5 exerts critical roles in promoting UCB cells' EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.
Background and Aims
Endoscopic radiofrequency ablation (RFA) is an emerging technique for the palliation of inoperable malignant biliary strictures (MBSs). We aimed to systemically investigate the ...long‐term outcome of RFA in a large cohort of patients.
Methods
We recruited 883 patients with various MBSs who underwent endoscopic interventions at two large‐volume centers; 124 patients underwent RFA and stenting, whereas 759 underwent stenting alone. To overcome selection bias, we performed 1:4 propensity score matching (PSM). The main outcome was overall survival (OS).
Results
Following PSM, patients in the RFA group showed significantly longer OS (9.5 months; 95% CI: 7.7‐11.3 months) than those in the stenting alone group (6.1 months; 95% CI: 5.6‐6.6 months; P < .001). In stratified analyses, the improved OS was only demonstrated in the subgroup of extrahepatic cholangiocarcinoma (11.3 months 95% CI: 10.2‐12.4 vs 6.9 months 95% CI: 6.0‐7.8; P < .001), but not in the subgroups of gallbladder cancer, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, pancreatic cancer, and other metastatic cancers (all P > .05). The survival benefits were noted only in the patients with non‐metastatic cholangiocarcinoma (11.5 vs 7.4 months, P < .001).
Conclusions
The survival benefits of endoscopic RFA appear to be limited to patients with extrahepatic cholangiocarcinoma without distant metastasis.
HighlightXia and colleagues investigated the outcomes of endoscopic interventions in a large cohort of 883 patients with inoperable malignant biliary strictures using propensity score matching. Compared with stenting alone, additional endobiliary radiofrequency ablation improved overall survival; however, the survival benefit was limited to patients with extrahepatic cholangiocarcinoma without distant metastasis.
Metal-organic frameworks (MOFs) have been widely applied for pollutants removal in water. However, the powdered MOFs are always suffered from aggregation during use and difficult collection after ...use. These problems discount their efficiency and inhibit their reusability. In this work, Zr-based MOF (UiO-66) was successfully imprisoned into a water-stable polyacrylonitrile (PAN) substrate by electrospinning. The containing UiO-66 hybrid membrane was confirmed by instrumental characterizations and its stability was also investigated by ICP-OES analysis. The obtained composite membrane can efficiently remove both arsenite (AsIII) and arsenate (AsV) from water under natural pH conditions. The adsorption kinetic fitted well with pseudo-second-order model and was dominated by chemisorption. Its adsorption isotherm can be described by Langmuir model. The maximal adsorption capacities of the hybrid membrane for As(V) and As(III) were 42.17 mg/g and 32.90 mg/g, respectively. Our results demonstrated that the MOFs-dispersed electrospun nanofiber membrane can greatly inherit the MOFs’ original adsorption properties and exhibits good regenerability without loss of MOFs. Electrospinning is an effective and practical method for the preparation of MOFs hybrid membrane, which makes the composite very easy to be collected after use.
Electrospun MOFs hybrid nanofibers remove arsenic efficiently. Display omitted
●A stable MOFs containing hybrid membrane was prepared by electrospinning.●The membrane exhibited efficient adsorption ability for both As(III) and As(V).●The inherit properties of the contained MOFs can be remained without loss from the fibers.●The hybrid membrane can be easily collected and environment-friendly recycled after use.
To directly compare traditional lipid ratios (total cholesterol TC/high density lipoprotein cholesterol HDL-C, non-HDL-C/HDL-C, low density lipoprotein cholesterol LDL-C/HDL-C, and triglycerides ...TG/HDL-C), apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio, visceral adiposity index (VAI), lipid accumulation product (LAP), and the product of TG and fasting glucose (TyG) for strength and independence as risk factors for insulin resistance (IR).
We conducted a cross-sectional analysis of 7629 Chinese adults using data from the China Health and Nutrition Survey 2009.
For all lipid ratios (traditional lipid ratios and apoB/apoA-I), among both sexes, TG/HDL-C explained the most additional percentage of variation in HOMA-IR (2.9% in men, and 2.3% in women); for all variables of interest, the variability in HOMA-IR explained by VAI and TG/HDL-C were comparable; TyG had the most significant association with HOMA-IR, which explained 9.1% for men and 7.8% for women of the variability in HOMA-IR. Logistic regression analysis showed the similar patterns. Receiver operating characteristic (ROC) curve analysis showed that, among both sexes, TG/HDL-C was a better discriminator of IR than apoB/apoA-I; the area under the ROC curve (AUC) for VAI (0.695 in men and 0.682 in women) was greater than that for TG/HDL-C (AUC 0.665 in men and 0.664 in women); TyG presented the greatest value of AUC (0.709 in men and 0.711 in women).
The apoB/apoA-I performs no better than any of the traditional lipid ratios in correlating with IR. The TG/HDL-C, VAI and TyG are better markers for early identification of IR individuals.
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•Tissue-specific profiling of primary and secondary metabolites in two different species of ginseng by using GC- and LC-MS.•Revealed a complex consecutive coordination of primary and ...secondary metabolism and corresponding pathways.•149 primary metabolites and 10 ginsenosides were identified from tissues-specific in P. ginseng and P. quinquefolius.•To investigate the contribution of tissue-specific C and N metabolism to the biosynthesis of ginsenosides.•Ginsenosides was dependent on main and lateral root energy metabolism and independent of leaf and petiole photosynthesis.
The traditional medicine Ginseng mainly including Panax ginseng and Panax quinquefolius is the most widely consumed herbal product in the world. Despite the extensive investigation of biosynthetic pathway of the active compounds ginsenosides, our current understanding of the metabolic interlink between ginsenosides synthesis and primary metabolism at the whole-plant level. In this study, the tissue-specific profiling of primary and the secondary metabolites in two different species of ginseng were investigated by gas chromatography- and liquid chromatography coupled to mass spectrometry. A complex continuous coordination of primary- and secondary-metabolic network was modulated by tissues and species factors during growth. The results showed that altogether 149 primary compounds and 10 ginsenosides were identified from main roots, lateral roots, stems, petioles and leaves in P. ginseng and P. quinquefolius. The partial least squares-discriminate analysis (PLS-DA) revealed obvious compounds distinction among tissue-specific districts relative to species. To survey the dedication of carbon and nitrogen metabolism in different tissues to the accumulation of ginsenosides, we inspected the tissue-specific metabolic changes. Our study testified that the ginsenosides content was dependent on main roots and lateral roots energy metabolism, whereas independent of leaves and petiole photosynthesis during ginsenosides accumulation. When tow species were compared, the results indicated that high rates of C assimilation to C accumulation are closely associated with ginsenosides accumulation in P. ginseng main roots and P. quinquefolius lateral roots, respectively. Taken together, our results suggest that tissue-specific metabolites profiling dynamically changed in process of ginsenosides biosynthesis, which may offer a new train of thoughts to the mechanisms of the ginsenosides biosynthesis at the metabolite level.
Accumulating evidence has demonstrated that endothelial progenitor cells (EPCs) could facilitate the reendothelialization of injured arteries by replacing the dysfunctional endothelial cells, thereby ...suppressing the formation of neointima. Meanwhile, other findings suggest that EPCs may be involved in the pathogenesis of age-related vascular remodeling. This review is presented to summarize the characteristics of EPCs and age-related vascular remodeling. In addition, the role of EPCs in age-related vascular remodeling and possible solutions for improving the therapeutic effects of EPCs in the treatment of age-related diseases are discussed.
Clinically, most of human urothelial carcinoma of the bladder (UCB)-related deaths result from tumor metastasis, but the underlying molecular mechanisms are largely unknown. Recently, a growing ...number of tripartite motif (TRIM) family members have been suggested to be important regulators for tumorigenesis. However, the impact of most TRIM members on UCB pathogenesis is unclear. In this study, TRIM65 was first screened as an important oncogenic factor of UCB from the Cancer Genome Atlas (TCGA) database and was validated by a large cohort of clinical UCB tissues. By in vitro and in vivo experiments, we demonstrated that TRIM65 promotes UCB cell invasive and metastatic capacities. Notably, we showed that TRIM65 modulates cytoskeleton rearrangement and induces UCB cells epithelial-mesenchymal transition by the ubiquitination of ANXA2, ultimately leading to an enhanced invasiveness of UCB cells. Importantly, UCBs with high expression of TRIM65 and low expression of ANXA2 showed the poorest outcome. Collectively, our results suggest that the overexpression of TRIM65 has an essential oncogenic role via ubiquitination of ANXA2 in UCB pathogenesis, and that such could be used as a novel prognostic marker and/or therapeutic target for UCB.
•TRIM65 is overexpressed in UCBs and is an independent prognostic biomarker.•TRIM65 promotes UCB cell invasive and metastatic capacities.•TRIM65 modulates cytoskeleton rearrangement and induces UCB cell EMT.•TRIM65 promotes ANXA2 ubiquitination and degradation in UCB cells.•ANXA2 is responsible for TRIM65-induced UCB cell EMT, morphological alteration and invasiveness.
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