Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and ...Wilson's disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.
A water‐soluble saponin, Esculentoside H (EsH), 3‐O‐(O‐β‐d‐glucopyranosyl‐(1→4)‐β‐d‐xylopyranosyl)‐28‐β‐d‐glucopyranosylphytolaccagenin has been isolated and purified from the root extract of ...perennial plant Phytolacca esculenta. EsH is known to be an anticancer compound, having a capacity for TNF‐α release. However, the effects of EsH on migration and growth in tumor cells have not yet been reported. In the current study, the suppressive effects of EsH on phorbol 12‐myristate 13‐acetate (PMA)‐induced cell migration were examined in murine colon cancer CT26 cells and human colon cancer HCT116 cells. Interestingly, the transwell assay and wound healing show that EsH suppresses the PMA‐induced migration and growth potential of HCT116 and CT26 colon cancer cells, respectively. EsH dose‐dependently suppressed matrix metalloproteinases‐9 (MMP‐9) expression that was upregulated upon PMA treatment in messenger RNA levels and protein secretion. Since the expression of MMP‐9 is correlated with nuclear factor‐κB (NF‐κB) signaling, it has been examined whether EsH inhibits PMA‐induced IκB phosphorylation that leads to the suppression of NK‐κB nuclear translocation. EsH repressed the phosphorylation level of JNK, but not extracellular signal‐regulated kinase and p38 signaling when the cells were treated with PMA. Overall, these results demonstrated that EsH could suppress cancer migration through blockage of the JNK1/2 and NF‐κB signaling‐mediated MMP‐9 expression.
Esculentoside H (EsH) has been isolated and purified from the root extract of perennial plant Phytolacca esculenta. In the current study, the suppressive effects of EsH on PMA‐induced cell migration were examined in murine colon cancer CT26 cells and human colon cancer HCT116 cells. The results demonstrated that EsH could suppress matrix metalloproteinases‐9 (MMP‐9) mediated cancer migration through blockage of the JNK1/2 and NF‐κB signaling‐mediated MMP‐9 expression.
Introduction: Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide with a prevalence of 20-33%. NAFLD may progress to fibrosis, compensated ...cirrhosis, advanced cirrhosis, or hepatocellular carcinoma. Despite the increasing prevalence of NAFLD, definitive medical treatment has not been established, with the exception of lifestyle modification with exercise. Because of the direct connection via portal vein between the intestines and the liver (gut-gut microbiota-liver axis), gut microbiota and associated dysbiosis have been known as regulators in the pathophysiology of NAFLD.
Area covered: New therapeutic approaches for modulation of gut microbiota have been proposed and the effectiveness of new therapies including probiotics, prebiotics, synbiotics, bile acid regulation, absorbent, and fecal microbiota transplantation have been demonstrated in recent several studies. This review focuses on the available evidences for new therapies modulating gut microbiota in the management and the prevention of NAFLD.
Expert commentary: Gut-gut microbiota-liver axis may play an important role in the etiology of many liver diseases, including NAFLD. It is logical to seek the manipulation of this axis, and further studies are required to understand the underlying precise mechanisms of microbiota-modulation on NAFLD.
Portal hypertension is a severe consequence of chronic liver diseases and is responsible for the main clinical complications of liver cirrhosis. Hepatic venous pressure gradient (HVPG) measurement is ...the best available method to evaluate the presence and severity of portal hypertension. Clinically significant portal hypertension is defined as an increase in HVPG to >10 mmHg. In this condition, the complications of portal hypertension might begin to appear. HVPG measurement is increasingly used in the clinical fields, and the HVPG is a robust surrogate marker in many clinical applications such as diagnosis, risk stratification, identification of patients with hepatocellular carcinoma who are candidates for liver resection, monitoring of the efficacy of medical treatment, and assessment of progression of portal hypertension. Patients who had a reduction in HVPG of ≥ 20% or to ≤ 12 mmHg in response to drug therapy are defined as responders. Responders have a markedly decreased risk of bleeding/rebleeding, ascites, and spontaneous bacterial peritonitis, which results in improved survival. This review provides clinical use of HVPG measurement in the field of liver disease.
Primary liver cancer is a heterogeneous disease. Liver cancer metabolism includes both the reprogramming of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to ...the tumor microenvironment and fluctuations in regular tissue metabolism. Currently, metabolomics and metabolite profiling in liver cirrhosis, liver cancer, and hepatocellular carcinoma (HCC) have been in the spotlight in terms of cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecules, chemicals, and metabolites. Metabolomics technologies can provide critical information about the liver cancer state. Here, we review how liver cirrhosis, liver cancer, and HCC therapies interact with metabolism at the cellular and systemic levels. An overview of liver metabolomics is provided, with a focus on currently available technologies and how they have been used in clinical and translational research. We also list scalable methods, including chemometrics, followed by pathway processing in liver cancer. We conclude that important drivers of metabolomics science and scientific technologies are novel therapeutic tools and liver cancer biomarker analysis.
The development of a high‐performance oxygen evolution reaction (OER) catalyst is pivotal for the practical realization of a water‐splitting system. Although an extensive search for OER catalysts has ...been performed in the past decades, cost‐effective catalysts remain elusive. Herein, an amorphous cobalt phyllosilicate (ACP) with layered crystalline motif prepared by a room‐temperature precipitation is introduced as a new OER catalyst; this material exhibits a remarkably low overpotential (η ≈ 367 mV for a current density of 10 mA cm−2). A structural investigation using X‐ray absorption spectroscopy reveals that the amorphous structure contains layered motifs similar to the structure of CoOOH, which is demonstrated to be responsible for the OER catalysis based on density functional theory calculations. However, the calculations also reveal that the local environment of the active site in the layered crystalline motif in the ACP is significantly modulated by the silicate, leading to a substantial reduction of η of the OER compared with that of CoOOH. This work proposes amorphous phyllosilicates as a new group of efficient OER catalysts and suggests that tuning of the catalytic activity by introducing redox‐inert groups may be a new unexplored avenue for the design of novel high‐performance catalysts.
The amorphous cobalt phyllosilicate introduced in this study exhibits the basic nature of a phyllosilicate as well as superior oxygen evolution reaction (OER) catalytic activity. Density functional theory calculations on the OER mechanism suggest that the silicate component aids in substantially reducing the η of the catalytic active sites by modulating the local structure.
Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic ...disorders, including obesity (OB). In another aspect, this study was focused on the anti‐OB efficacy of the non‐fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein–protein interaction (PPI), PAF‐signaling pathways‐targets‐compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti‐OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1‐gamma‐tocopherol, PPARA‐fucosterol, PPARD‐stigmasterol, (PPARG)‐fucosterol, (NR1H3)‐campesterol, and ILK‐alpha‐tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB.
Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by impaired or abnormal social interaction and communication and by restricted and repetitive behaviour. ASD is ...highly prevalent in Asia, Europe, and the United States, and the frequency of ASD is growing each year. Recent epidemiological studies have indicated that ASD may be caused or triggered by exposure to chemicals in the environment, such as those in the air or water. Thus, toxicological studies are needed to examine chemicals that might be implicated. However, the experimental efficiency of existing experimental models is limited, and many models represent challenges in terms of animal welfare. Thus, alternative ASD animal models are necessary. To address this, we examined the efficacy of the zebrafish embryo/larva as an alternative model of ASD. Specifically, we exposed zebrafish to valproic acid (0, 12.5, 25, 50, or 100 μM), which is a chemical known to induce autism-like effects. We then analysed subsequent developmental, behavioural, and transcriptomic changes. We found that 100 μM and 50 μM valproic acid decreased the hatching rate and locomotor activity of zebrafish embryos/larvae. Transcriptomic analysis revealed significant alterations in a number of genes associated with autism, such as adsl, mbd5, shank3, and tsc1b. Additionally, we found changes in gene ontology that were also reported in previous studies. Our findings indicate that zebrafish embryos/larvae and humans with ASD might have common physiological pathways, indicating that this animal model may represent an alternative tool for examining the causes of and potential treatments for this illness.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Prominin-1 (PROM1), also known as CD133, is expressed in hepatic progenitor cells (HPCs) and cholangiocytes of the fibrotic liver. In this study, we show that PROM1 is upregulated in the ...plasma membrane of fibrotic hepatocytes. Hepatocellular expression of PROM1 was also demonstrated in mice (
Prom1
CreER
; R26
TdTom
) in which cells expressed TdTom under control of the
Prom1
promoter. To understand the role of hepatocellular PROM1 in liver fibrosis, global and liver-specific
Prom1
-deficient mice were analyzed after bile duct ligation (BDL). BDL-induced liver fibrosis was aggravated with increased phosphorylation of SMAD2/3 and decreased levels of SMAD7 by global or liver-specific
Prom1
deficiency but not by cholangiocyte-specific
Prom1
deficiency. Indeed, PROM1 prevented SMURF2-induced SMAD7 ubiquitination and degradation by interfering with the molecular association of SMAD7 with SMURF2. We also demonstrated that hepatocyte-specific overexpression of SMAD7 ameliorated BDL-induced liver fibrosis in liver-specific
Prom1-
deficient mice. Thus, we conclude that PROM1 is necessary for the negative regulation of TGFβ signaling during liver fibrosis.
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