Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.

Background & Aims: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH.

Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1α.

Tripartite motif 8 (TRIM8) is an E3 ligase that plays dual roles in various tumor types. The biological effects and underlying mechanism of TRIM8 in hepatocellular carcinoma (HCC) remain unknown. Hepatocyte nuclear factor 1α (HNF1α) is a key transcriptional factor that plays a significant role in regulating hepatocyte differentiation and liver function.

miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells.

Background: The activation of hepatic stellate cells (HSCs) has been emphasized as a leading event of the pathogenesis of liver cirrhosis, while the exact mechanism of its activation is largely unknown. Furthermore, the novel non-invasive predictors of prognosis in cirrhotic patients warrant more exploration. miR-541 has been identified as a tumor suppressor in hepatocellular carcinoma and a regulator of fibrotic disease, such as lung fibrosis and renal fibrosis.

TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4α stability.

Background & Aims: Endoplasmic reticulum (ER) stress of hepatocytes plays a causative role in non-alcoholic fatty liver disease (NAFLD). Reduced expression of hepatic nuclear factor 4α (HNF4α) is a critical event in the pathogenesis of NAFLD and other liver diseases. Whether ER stress regulates HNF4α expression remains unknown.

Comprehensive Analysis of PANoptosis-Related Gene Signature of Ulcerative Colitis.

Accumulating evidence shows that the abnormal increase in the mortality of intestinal epithelial cells (IECs) caused by apoptosis, pyroptosis, and necroptosis is closely related to the function of mucous membrane immunity and barrier function in patients with ulcerative colitis (UC). As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets.

PKM2 Nuclear Translocation Promotes Glial Cell Activation and Aggravates the Brain Injury of Intracerebral Hemorrhage.

Background: The purpose of this study was to investigate the potential involvement of pyruvate kinase M2 (PKM2), an enzyme acting as a rate-limiting enzyme in the final phase of glycolysis, in the regulation of glial activation and brain damage of intracerebral hemorrhage (ICH).

Methods: Western blotting and immunofluorescence were performed to investigate PKM2 expression, terminal deoxynucleotidyl transferase deoxyurinary triphosphate (dUTP) nick end labeling staining, hematoxylin and eosin staining, and behavioral tests were employed to evaluate the brain damage of ICH mice, and RNA-seq and bioinformatic analyses were performed to detect gene expression changes in ICH mice treated with TEPP-46.

Results: Increased PKM2 levels in perihematomal brain tissue were found starting from 3 days following ICH and peaked at 5 and 7 days post ICH.

Effect of acupuncture on arthritic pathological injury in rats with type Ⅱ collagen-induced rheumatoid arthritis.

Objectives: To observe the effect of acupuncture stimulation of "Yanglingquan"(GB34), "Zusanli"(ST36) and "Xuanzhong" (GB39) on arthritis index (AI), joint synovial membrane pathology, serum-related immunoinflammatory factors, and expressions of tumor suppressor gene mt-p53, nuclear factor kappa B (NF-κB) and peroxisome proliferator activated receptor gamma (PPARγ) in knee joint synovial tissue of rats with type Ⅱ collagen-induced arthritis (CIA), so as to explore its possible mechanisms underlying improvement of rheumatoid arthritis (RA).

Methods: Male SD rats were used in the present study. The CIA model was established by subcutaneous injection of collagen emulsion (200 μL/rat) in the tail root region on the first day and repeat (100 μL/rat) once on the 9 day.

Bardoxolone methyl inhibits the infection of rabies virus via Nrf2 pathway activation in vitro.

Background: Rabies is a widespread, fatal, infectious disease. Several antivirals against rabies virus (RABV) infection have been reported, but no approved, RABV-specific antiviral drugs that inhibit RABV infection in the clinic after symptom onset are available. Therefore, more effective drugs to reduce rabies fatalities are urgently needed.

BCX4430 inhibits the replication of rabies virus by suppressing mTOR-dependent autophagy invitro.

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV). However, no effective anti-RABV drugs for treatment during the symptomatic phase are available. The novel adenosine nucleoside analog galidesivir (BCX4430) has broad-spectrum activity against a wide variety of highly pathogenic RNA viruses.

Depletion of Tgfbr2 in hepatocytes alleviates liver fibrosis and restores hepatic function in fibrotic mice.

Objectives: Previous studies have demonstrated the pivotal role of transforming growth factor (TGF)-β signaling in activating hepatic stellate cells during liver fibrosis. In this study we aimed to demonstrate the effects and underlying mechanism of TGF-β signaling in hepatocytes on hepatic fibrogenesis.

Methods: Hepatocyte-specific Tgfbr2-knockout (Tgfbr2 ) mice were generated by AAV8-TBG-Cre injection via the tail vein of Tgfbr2 mice.

Sulodexide attenuates liver fibrosis in mice by restoration of differentiated liver sinusoidal endothelial cell.

Sulodexide is a heparinoid compound with wide-ranging pharmacological activities. However, the effect of sulodexide on liver fibrogenesis has not been reported. In this study, we aim to evaluate the therapeutic potential of sulodexide in mouse model of liver fibrosis and explore the underlying antifibrotic mechanisms.

Inhibition of protein arginine methyltransferase 1 alleviates liver fibrosis by attenuating the activation of hepatic stellate cells in mice.

Protein arginine methyltransferase 1 (PRMT1) has been reported to be involved in various diseases. The expression of PRMT1 was increased in cirrhotic livers from human patients. However, the role of PRMT1 in hepatic fibrogenesis remains largely unexplored.

Proteomic analysis of lysine acetylation reveals that metabolic enzymes and heat shock proteins may be potential targets for DSS-induced mice colitis.

Background: Research on acetylation modification and its modification sites will be of great significance for revealing the mechanism of disease and developing new targeted medicines. In this study, we aim to construct a complete atlas of acetylome in the DSS-induced ulcerative colitis mice model (UC model) METHODS: A high-resolution mass spectrometry-based quantitative approach was employed to identify lysine-acetylated proteins and acetylation sites. Bioinformatics analysis and in vitro experiments verified anti-inflammatory effects of HSP90B1-K142ac.

The Role of Bone Morphogenetic Protein 9 in Nonalcoholic Fatty Liver Disease in Mice.

It's reported that bone morphogenetic protein 9 (BMP9) played an important role in lipid and glucose metabolism, but the role of BMP9 in nonalcoholic fatty liver disease (NAFLD) is unclear. Here, we evaluated the therapeutic efficacy of recombined BMP9 in NAFLD mice and investigated the potential mechanism. The effects of recombinant BMP9 on NAFLD were assessed in HFD-induced NAFLD mice.

Targeting p300/CBP Attenuates Hepatocellular Carcinoma Progression through Epigenetic Regulation of Metabolism.

Targeting epigenetics in cancer has emerged as a promising anticancer strategy. p300/CBP is a central regulator of epigenetics and plays an important role in hepatocellular carcinoma (HCC) progression. Tumor-associated metabolic alterations contribute to the establishment and maintenance of the tumorigenic state.

Inflammatory response and MAPK and NF-κB pathway activation induced by natural street rabies virus infection in the brain tissues of dogs and humans.

Background: Street rabies virus (RABV) usually infects hosts at peripheral sites and migrates from motor or sensory nerves to the central nervous system. Several studies have found that inflammation is mild in a mouse model of street RABV infection. However, the pathogenetic mechanisms of street RABV in naturally infected dogs or humans are not well understood.

Rabies viruses of different virulence regulates inflammatory responses both in vivo and in vitro via MAPK and NF-κB pathway.

Immune responses and central nervous system dysfunction are two main factors to be considered during rabies virus (RABV) infection. However, the mechanisms by which RABV strains of different virulence regulate with chemokine expression and the signaling pathways responsible for the immune responses in the terminal stage of infection both in vivo and in vitro have not been fully elucidated. In this study, we found low expression levels of proinflammatory chemokines in the mouse brain upon infection with street RABV strains (CXZ17 and HN10) at the late stage of infection.

Human rabies in China: evidence-based suggestions for improved case detection and data gathering.

Background: China still suffers heavily from rabies, although reported human cases continue to decrease year over year. There are far fewer laboratory-confirmed human cases than clinically diagnosed cases, which is a big problem that needs to be addressed. In this report, we summarize analyses of all specimens from human cases tested in our laboratory over the past 15 years, in order to promote laboratory diagnosis of rabies.

Establishment of a Chinese street rabies virus library and its application for detecting neutralizing activity.

Background: The injection of rabies immune globulin (RIG) is of the utmost importance in the management of category III exposures to rabies-suspect animals. Because of the high cost and limited availability of existing RIG, one possible replacement for RIG is monoclonal antibodies (MAbs) against the rabies virus (RABV). Consequently, it is necessary to determine the neutralizing activity of the MAbs against rabies viruses, especially street rabies virus.

The Adverse Effect of the 2-1-1 Regimen for Rabies PEP in Preschool Children.

Post-exposure prophylaxis (PEP) has proved to be the most important measure for rabies prevention and control. There is little information regarding adverse reactions to the Essen and 2-1-1 regimens in preschool children (aged 0-6). We reexamined the outcomes of 1,109 preschool children who were vaccinated using SPEEDA under the Essen regimen between January 2011 and December 2012 and 1,267 preschool children under the 2-1-1 regimen between January 2013 and December 2014.

Matrine promotes oligodendrocyte development in CNS autoimmunity through the PI3K/Akt signaling pathway.

Aims: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, has been recently found to be beneficial in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly through its anti-inflammatory effect. In the present study, we tested the effect of MAT on ongoing EAE and defined possible mechanisms underlying its effects on myelination and oligodendrocytes.

Main Methods: EAE was induced in C57BL/6 mice and MAT treatment was started at disease onset.

Comparison among soil additives for enhancing Pteris vittata L.: Phytoremediation of As-contaminated soil.

Pot experiments were conducted to assess the effects of monoammonium phosphate (NHHPO) and citric acid (CA) on the arsenic uptake of Chinese brake fern (Pteris vittata L. in two typical arsenic-contaminated soils i.e.