Bryanpanduro6467

The pathogenesis of liver fibrosis involves liver damage, inflammation, oxidative stress, and intestinal dysfunction. Indole-3-propionic acid (IPA) has been demonstrated to have antioxidant, anti-inflammatory and anticancer activities, and a role in maintaining gut homeostasis. The current study aimed to investigate the role of IPA in carbon tetrachloride (CCl

)-induced liver fibrosis and explore the underlying mechanisms.

The liver fibrosis model was established in male C57BL/6 mice by intraperitoneal injection of CCl

twice weekly. IPA intervention was made orally (20 mg/kg daily). The degree of liver injury and fibrosis were assessed by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathology. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (qPCR) were used to detect the inflammatory cytokines. The malondialdehyde (MDA), glutathione, glutathione peroxidase, superoxide dismutase, and catalase were determined via commercial kits. Hepatocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression of mRNA and protein was assayed by qPCR, Western blotting, or immunohistochemical staining.

After IPA treatment, the ALT and AST, apoptotic cells, and pro-inflammatory factor levels were enhanced significantly. Moreover, IPA intervention up-regulated the expression of collagen I, α-smooth muscle actin, tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase-2, transforming growth factor-β1 (TGF-β1), Smad3, and phosphorylated-Smad2/3. Additionally, IPA intervention did not affect the MDA level. Attractively, the administration of IPA remodeled the gut flora structure.

IPA aggravated CCl

-induced liver damage and fibrosis by activating HSCs via the TGF-β1/Smads signaling pathway.

IPA aggravated CCl4-induced liver damage and fibrosis by activating HSCs via the TGF-β1/Smads signaling pathway.

Fibroblast growth factor (FGF)19 has been implicated in the pathogenesis of murine hepatocellular carcinoma. Whether it plays a role in the development or course of human cholangiocarcinoma remains to be determined. The aim of this study was to determine whether prolonged exposure to FGF19 results in the transformation of non-malignant human cholangiocytes into cells with malignant features.

Human SV-40 transfected non-malignant H69 cholangiocytes were cultured with FGF19 (0-50 ng/mL) for 6 weeks, followed by 6 weeks with medium alone. Cell proliferation, invasion, stem cell surface markers, oncofetoprotein expression, state of differentiation, epithelial-mesenchymal transition (EMT) and interleukin (IL)-6 expression were documented at various time intervals throughout the 12-week period.

FGF19 exposure was associated with significant increases in cell proliferation, de-differentiation, EMT and IL-6 expression. However, each of these effects returned to baseline or control values during the 6-week FGF19 free follow-up period. Galunisertib The remaining cell properties remained unaltered.

Six weeks of FGF19 exposure did not result in the acquisition of permanent malignant features in non-malignant, human cholangiocytes.

Six weeks of FGF19 exposure did not result in the acquisition of permanent malignant features in non-malignant, human cholangiocytes.

The overall survival (OS) of hepatocellular carcinoma (HCC) remains dismal. Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical decision. This study aimed to develop a prognostic gene model for HCC.

GSE14520 was retrieved as a training set to identify differential expressed genes (DEGs) between tumor and adjacent liver tissues in HCC patients with different OS. A DEG-based prognostic model was then constructed and the TCGA-LIHC and ICGC-LIRI datasets were used to validate the model. The area under the receiver operating characteristic curve (AUC) and hazard ratio (HR) of the model for OS were calculated. A model-based nomogram was established and verified.

In the training set, differential expression analysis identified 80 genes dysregulated in oxidation-reduction and metabolism regulation. After univariate Cox and LASSO regression, eight genes (LPCAT1, DHRS1, SORBS2, ALDH5A1, SULT1C2, SPP1, HEY1 and GOLM1) were selected to build the prognostic model. The AUC for 1-, 3- and 5-year OS were 0.779, 0.736, 0.754 in training set and 0.693, 0.689, 0.693 in the TCGA-LIHC validation set, respectively. The AUC for 1- and 3-year OS were 0.767 and 0.705 in the ICGC-LIRI validation set. Multivariate analysis confirmed the model was an independent prognostic factor (training set HR=4.422,

<0.001; TCGA-LIHC validation set HR=2.561,

<0.001; ICGC-LIRI validation set HR=3.931,

<0.001). Furthermore, a nomogram combining the model and AJCC stage was established and validated, showing increased OS predictive efficacy compared with the prognostic model (

0.035) or AJCC stage (

<0.001).

Our eight-gene prognostic model and the related nomogram represent as reliable prognostic tools for OS prediction in HCC patients.

Our eight-gene prognostic model and the related nomogram represent as reliable prognostic tools for OS prediction in HCC patients.

The efficacy of targeted programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) has been confirmed in many solid malignant tumors. The overexpression of PD-1/PD-L1 serves as a biomarker to predict prognosis and clinical progression. However, the role of PD-1 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) remains indeterminate. Given that HBV is the most important cause for HCC, this study aimed to investigate the prognostic and clinicopathological value of PD-1 in HBV-HCC via a meta-analysis.

We searched PubMed, Embase, Scopus, the Cochrane Library, Web of Science and Google Scholar up to January 2021 for studies on the correlation between clinicopathology/prognosis and PD-1 in patients with HBV-HCC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the prognostic significance of PD-1 expression. The odds ratios (ORs) and 95% CIs were determined to explore the association between PD-1 expressificantly predicted a poor prognosis of HBV-HCC, which suggests that anti-PD-1 therapy for HBV-HCC patients is plausible.

The impact of coronavirus disease-2019 (COVID-19) on liver function remains to be fully elucidated. This study was designed to investigate such and determine the clinical significance in determining mortality risk.

A retrospective study was conducted in patients with COVID-19 from March 2020 to July 2020. Clinical details were retrieved from electronic medical records to obtain clinical characteristics, medical history, laboratory tests, therapeutic intervention, and outcome data.

A total of 184 patients with COVID-19 were included (median age 45.5 years), comprised of 62.5% men. In total, 22 (12.0%) patients had severe infection and 162 (88.0%) had mild to moderate infection. Overall, 95 (51.6%) showed abnormal liver function test (LFT) and 17 (9.2%) showed normal LFT at admission. The median age, hospital stay, and LFT were significantly higher in severe vs. non-severe infection (

<0.001). Out of 12 deaths, the majority were due to severe infection (

=11). Deaths were also due to acute respiratord with prolonged hospital stay; mortality was associated with severity of COVID-19. For ruling out the risk of liver injury, it is crucial to vigilantly monitor the liver function parameters in patients with COVID-19 admitted to hospital.

In the last decade, several second-line therapies followed by sorafenib in patients with advanced hepatocellular carcinoma (HCC) have been reported. But the outcomes were different from each other. This meta-analysis aimed to evaluate the efficacy and safety of the second-line therapies followed by sorafenib in patients with advanced HCC.

Embase (1974 to October 2019) and Ovid MEDLINE (1946 to October 2019) were searched for randomized clinical trials on second-line therapies followed by sorafenib in patients with advanced HCC. The quality of each study was assessed by the modified Jadad scale. Statistical analysis was carried out by RevMan5.3 software. Efficacy and safety were analyzed. Efficacy included overall survival (OS), disease control rate, time to progression, and progression-free survival.

Eight studies involving 3,173 patients were eligible. No difference in OS was found between the second-line treatment group and the control group (HR=0.87, 95% CI 0.74-1.01,

=0.06). Disease control rate (relative risk (RR)=1.36, 95% CI 1.16-1.60,

=0.0002), time to progression (HR=0.64, 95% CI 0.51-0.81,

=0.0002) and progression-free survival (HR=0.60, 95% CI 0.46-0.77,

<0.0001) were significantly improved by the second-line therapies. There was a slight difference in adverse events of any grade (RR=1.07, 95% CI 1.00-1.14,

=0.03) between the two groups.

These second-line therapies followed by sorafenib may potentially improve the prognosis in patients with advanced HCC. Compared with other second-line therapies, regorafenib seemed to be more effective.

These second-line therapies followed by sorafenib may potentially improve the prognosis in patients with advanced HCC. Compared with other second-line therapies, regorafenib seemed to be more effective.

Primary biliary cholangitis (PBC) is a chronic liver disease that negatively affects the health-related quality of life (HRQoL) of patients. Furthermore, the HRQoL of Chinese patients has been neglected for a long time. The present study aimed to assess the HRQoL of Chinese patients with PBC and explore the clinical variables correlating to the improvement of itch and fatigue.

This was an observational, cross-sectional study. The PBC-40 and itch numerical rating scales were used to evaluate the symptoms and HRQoL of patients.

A total of 383 patients were recruited, and 86.4% were female, with a median age of 55 years (range 49-63 years). We found that females had significantly higher scores than males in symptoms (

=0.033) and cognitive domains (

=0.021), and the fatigue domain was higher in elderly patients (

=0.007). Meanwhile, patients whose body mass index was <18.5 had the highest scores in the symptoms (

=0.009), fatigue (

=0.010), and cognitive (

=0.019) domains. Age at participation (odds ratio [OR]=1.068,

=0.015) and albumin level at 12 months after ursodeoxycholic acid treatment (OR=208.807,

0.025) were independent factors that affected the improvement of the itch and fatigue domains, respectively.

The HRQoL of Chinese patients with PBC was significantly impaired depending on sex, age, and body mass index. Age and albumin level were significantly associated with the improvement of itch and fatigue, respectively. Therefore, treatment and support aimed at these two factors can be provided to improve the HRQoL of patients.

The HRQoL of Chinese patients with PBC was significantly impaired depending on sex, age, and body mass index. Age and albumin level were significantly associated with the improvement of itch and fatigue, respectively. Therefore, treatment and support aimed at these two factors can be provided to improve the HRQoL of patients.