Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model.

Background: Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options. Recombinant adeno-associated virus (rAAV) provides a promising platform for gene therapy on such kinds of diseases. A microRNA (miRNA) let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.

Hepatitis B virus core protein stabilizes RANGAP1 to upregulate KDM2A and facilitate hepatocarcinogenesis.

Purpose: As a vital component of the hepatitis B virus (HBV) nucleocapsid, HBV core protein (HBC) contributes to hepatocarcinogenesis. Here, we aimed to assess the effects of RANGAP1 and KDM2A on tumorigenesis induced by HBC.

Methods: Co-immunoprecipitation (Co-IP) combined with mass spectrometry were utilized to identify the proteins with the capacity to interact with HBC.

The role of glutamate receptors in the regulation of the tumor microenvironment.

Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several factors can affect the expression of glutamate receptors, playing either a tumor-promoting or tumor-suppressor role in cancer. Thus, the activation of glutamate receptors by the ligand could play a role in tumor development as ample studies have demonstrated the expression of glutamate receptors in a broad range of tumor cells.

infection induces hepatobiliary injury disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2.

infection induces severe hepatobiliary injuries, which can cause inflammation, periductal fibrosis, and even cholangiocarcinoma. Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) and its receptor S1P receptors (S1PRs) have been implicated in many liver-related diseases. However, the role of S1PRs in -mediated biliary epithelial cells (BECs) proliferation and hepatobiliary injury has not been elucidated.

IL-10 regulates Th17 response to inhibit hepatobiliary injury caused by infection in C57BL/6J mice.

Clonorchiasis caused by is a mainly foodborne parasitic disease. It can lead to hepatobiliary duct inflammation, fibrosis, obstructive jaundice, liver cirrhosis, and even cholangiocarcinoma. Interleukin (IL)-10 is an immune-regulatory cytokine which plays an immunosuppressive role during infection.

Interleukin-33 deficiency prevents biliary injuries and repairments caused by Clonorchis sinensis via restraining type 2 cytokines.

Background: Clonorchiasis caused by Clonorchis sinensis is a zoonotic parasitic disease characterized by cholangitis, biliary proliferation, biliary fibrosis, and even cholangiocarcinoma. Our previous study showed that the expression of interleukin (IL)-33 is increased in both humans and mice infected by C. sinensis, suggesting that IL-33 is potentially involved in the pathogenesis of clonorchiasis.

FXR deficiency in hepatocytes disrupts the bile acid homeostasis and inhibits autophagy to promote liver injury in Schistosoma japonicum-infected mice.

Background: Schistosomiasis, with 250 million people affected, is characterized by its serious hepatic inflammatory response and fibrosis formation, which could lead to dangerous complications, such as portal hypertension, splenomegaly and even ascites. But until now, the pathogenesis of schistosomiasis remains largely unknown. Farnesoid X Receptor (FXR), a bile acid-activated nuclear transcription factor mainly expresses in hepatocytes in the liver, can regulate liver diseases by controlling bile acid metabolism.

Molecular Mechanisms of -Host Interactions and Implications for Vaccine Development.

Infections caused by remain a significant public health challenge for both humans and animals, causing pyogenic cholangitis, cholelithiasis, cholecystitis, biliary fibrosis, and even cholangiocarcinoma. However, the strategies used by the parasite and the immunological mechanisms used by the host have not yet been fully understood. With the advances in technologies and the accumulated knowledge of host-parasite interactions, many vaccine candidates against liver flukes have been investigated using different strategies.

Csi-let-7a-5p delivered by extracellular vesicles from a liver fluke activates M1-like macrophages and exacerbates biliary injuries.

Chronic infection with liver flukes (such as ) can induce severe biliary injuries, which can cause cholangitis, biliary fibrosis, and even cholangiocarcinoma. The release of extracellular vesicles by (CsEVs) is of importance in the long-distance communication between the hosts and worms. However, the biological effects of EVs from liver fluke on biliary injuries and the underlying molecular mechanisms remain poorly characterized.

β2-Adrenergic Receptor Enhances the Alternatively Activated Macrophages and Promotes Biliary Injuries Caused by Helminth Infection.

The autonomic nervous system has been studied for its involvement in the control of macrophages; however, the mechanisms underlying the interaction between the adrenergic receptors and alternatively activated macrophages (M2) remain obscure. Using FVB wild-type and beta 2 adrenergic receptors knockout, we found that β2-AR deficiency alleviates hepatobiliary damage in mice infected with . Moreover, β2-AR-deficient mice decrease the activation and infiltration of M2 macrophages and decrease the production of type 2 cytokines, which are associated with a significant decrease in liver fibrosis in infected mice.

Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity.

A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut microbiota. An important next step is to elucidate a human-relevant "map'' of microbiota-host interactions that regulate the metabolic health of the host. An improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat obesity.

MicroRNA-497 induced by Clonorchis sinensis enhances the TGF-β/Smad signaling pathway to promote hepatic fibrosis by targeting Smad7.

Background: Various stimuli, including Clonorchis sinensis infection, can cause liver fibrosis. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) with massive production of extracellular matrix (ECM). Our previous study showed that the TGF-β-induced Smad signaling pathway played a critical role in the activation of HSCs during liver fibrosis induced by worm infection; however, the mechanisms that modulate the TGF-β/Smad signaling pathway are still poorly understood.

TLR4 Deficiency Exacerbates Biliary Injuries and Peribiliary Fibrosis Caused by in a Resistant Mouse Strain.

Mice with different genetic backgrounds have various susceptibilities to infection with , although the mechanisms underlying are largely unknown. Toll-like receptor 4 (TLR4) as one of the most important pattern recognition receptors (PPRs) is essential for the invasion, survival, pathogenesis, and elimination of worms. The roles played by TLR4 in infection may vary due to the different genetic backgrounds of mice.

Recombinant CsHscB of carcinogenic liver fluke Clonorchis sinensis induces IL-10 production by binding with TLR2.

Background: Clonorchis sinensis, a fluke dwelling in the intrahepatic bile ducts causes clonorchiasis, which affect about 15 million people wide-distributed in eastern Asia. During C. sinensis infection, worm-host interaction results in activation of patterns recognition receptors (PRRs) such as Toll-like receptors (TLRs) and further triggers immune responses, which determines the outcome of the infection.

Evaluation of toxoplasmosis in pregnant women using dot-immunogold-silver staining with recombinant Toxoplasma gondii peroxiredoxin protein.

Background: Toxoplasma gondii infection endangers human health and affects animal husbandry. Serological detection is the main method used for epidemiological investigations and diagnosis of toxoplasmosis. The key to effective diagnosis of toxoplasmosis is the use of a standardized antigen and a specific and sensitive detection method.

Interleukin 3-induced GITR promotes the activation of human basophils.

Human basophils regulate allergic reactions by secreting histamine, interleukin 4 (IL-4) and IL-13 through key surface receptors FcεRI as well as IL-3R, which are constitutively expressed on basophils. IL-3/IL-3R signaling axis plays key roles in regulating the development and activation of basophils. We and others have shown that IL-3-induced surface receptors e.

Clonorchis sinensis ESPs enhance the activation of hepatic stellate cells by a cross-talk of TLR4 and TGF-β/Smads signaling pathway.

Excretory/Secretory products (ESPs) from Clonorchis sinensis-a fluke dwelling on the biliary ducts-promote the activation of hepatic stellate cells (HSCs) and lead to hepatic fibrosis ultimately, although the mechanisms that are responsible for CsESPs-induced activation of HSCs are largely unknown. In the present study, we investigated the underlying mechanism of TLR4 in the regulation of the activation of HSCs caused by CsESPs. We found that the expression of TLR4 was significantly increased in the HSCs with CsESPs for 24 h, compared to the control group.

[Effect of transfusing blood components containing on infection in BALB/c mice].

Objective: To evaluate the effects of intravenous injection of different blood components containing on infection in mice.

Methods: Healthy mice were infected with , and then blood samples were collected from the mouse orbit to prepare whole blood, serum-free blood components and pure red blood cells containing . Twenty seven BALB/c mice were divided into three groups, including the whole blood group, the serum-free blood component group and the pure red blood cell group, of 9 mice in each group, and then, each group was divided into three subgroups, of 3 mice in each subgroup, which were injected with 100 μL of blood components containing at concentrations of 9.

Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production.

Background: Inflammation-induced dysfunction of hepatic stellate cells (HSCs) is involved in schistosomiasis-associated liver fibrosis, and soluble egg antigen (SEA) is a crucial pathogen-associated molecular pattern associated with liver injury in schistosomiasis. In addition, numerous studies have shown that caspase-1-mediated pyroptosis participates in the development of multiple inflammation-related diseases. However, whether pyroptotic cell death of HSCs is involved in SEA-mediated liver damage is not well understood.

Membrane-bound IgE on B cells is increased during Clonorchis sinensis infection.

A high level of serum IgE is a hallmark of helminthic disease. Secretory IgE can bind FcεRI or FcεRII/CD23. The combination of IgE and FcεRI, a high-affinity interaction, has long received attention and is believed to facilitate helminth control, while the properties of CD23-bound IgE have long been unexplored.

The excretory-secretory products of Echinococcus granulosus protoscoleces stimulated IL-10 production in B cells via TLR-2 signaling.

Background: Excretory-secretory products released by Echinococcus granulosus protoscoleces (EgPSC-ESPs) are well-known to regulate T cell responses. However, their direct influence on the differentiation of B cell subsets remains largely elusive. This study investigated the effects of EgPSC-ESPs on the differentiation of IL-10-producing B cells (B10), and explored the possible role of Toll-like receptor 2 (TLR-2) signaling in this process.

Ischemic postconditioning confers cerebroprotection by stabilizing VDACs after brain ischemia.

Ischemic postconditioning provides robust neuroprotection, therefore, determining the molecular events may provide promising targets for stroke treatment. Here, we showed that the expression of functional mitochondrial voltage-dependent anion channel proteins (VDAC1, VDAC2, and VDAC3) reduced in rat vulnerable hippocampal CA1 subfield after global ischemia. Ischemic postconditioning restored VDACs to physiological levels.