Neutrophil-secreted S100A8/A9 participates in fatty liver injury and fibrosis by promoting myofibroblast migration.

Fatty liver, which is induced by abnormal lipid metabolism, is one of the most common causes of chronic liver disease globally and causes liver fibrosis. During this process, bone marrow-derived mesenchymal stromal cells (BMSCs) and hepatic stellate cells (HSCs) migrate toward the injured liver and participate in fibrogenesis by transdifferentiating into myofibroblasts. S100A8/A9 is a powerful inducer of cell migration and is involved in liver injury.

Adult spinal cord tissue transplantation combined with local tacrolimus sustained-release collagen hydrogel promotes complete spinal cord injury repair.

The strategy of replacing a completely damaged spinal cord with allogenic adult spinal cord tissues (aSCs) can potentially repair complete spinal cord injury (SCI) in combination with immunosuppressive drugs, such as tacrolimus (Tac), which suppress transplant rejection and improve graft survival. However, daily systemic administration of immunosuppressive agents may cause harsh side effects. Herein, a localized, sustained Tac-release collagen hydrogel (Col/Tac) was developed to maximize the immune regulatory efficacy but minimize the side effects of Tac after aSC transplantation in complete SCI recipients.

Multifunctional hydrogel modulates the immune microenvironment to improve allogeneic spinal cord tissue survival for complete spinal cord injury repair.

Transplantation of allogeneic adult spinal cord tissues (aSCTs) to replace the injured spinal cord, serves as a promising strategy in complete spinal cord injury (SCI) repair. However, in addition to allograft immune rejection, damage-associated molecular pattern (DAMP)-mediated inflammatory microenvironments greatly impair the survival and function of transplants. In this study, we aimed to regulate the immune microenvironment after aSCT implantation by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects.

Activated Neutrophils Secrete Chitinase-Like 1 and Attenuate Liver Inflammation by Inhibiting Pro-Inflammatory Macrophage Responses.

Excessive activation and recruitment of neutrophils are generally considered to be associated with pathological aggravation of multiple diseases. However, as the role of neutrophils in tissue injury repair is receiving increasing attention, it is necessary to further explore the beneficial role of activated neutrophils in promoting the resolution of inflammation after injury. In this study, we found that activated neutrophils have a crucial function in suppressing liver inflammation.

Recombinant porcine beta defensin 2 alleviates inflammatory responses induced by Escherichia coli in IPEC-J2 cells.

pBD2 is one of the porcine beta defensins with broad antimicrobial activity, and plays an important role in immune regulation. However, the activities and mechanisms of pBD2 regulating host resistance to Escherichia coli infection are unclear. In this study, the immunomodulatory activity and mechanisms of recombinant pBD2 against Escherichia coli infection were explored in IPEC-J2 cells.

Ethanol-Induced Flash Sintering of ZnO Ceramics at Room Temperature.

Ceramic flash sintering with a strong electric field at room temperature is the most attractive method. This paper presents the flash sintering of ZnO ceramics at room temperature by the application of a 3-kV/cm electric field after a dropwise addition of ethanol. This method is simple and easy to control.

Optimized, visible light-induced crosslinkable hybrid gelatin/hyaluronic acid scaffold promotes complete spinal cord injury repair.

Severe microenvironmental changes after spinal cord injury (SCI) present serious challenges in neural regeneration and tissue repair. Gelatin (GL)- and hyaluronic acid (HA)-based hydrogels are attractive scaffolds because they are major components of the extracellular matrix and can provide a favorable adjustable microenvironment for neurogenesis and motor function recovery. In this study, three-dimensional hybrid GL/HA hydrogel scaffolds were prepared and optimized.

NLRP3 inflammasome priming and activation in cholestatic liver injury via the sphingosine 1-phosphate/S1P receptor 2/Gα/MAPK signaling pathway.

NLRP3 inflammasome-driven inflammation represents a key trigger for hepatic fibrogenesis during cholestatic liver injury. However, whether sphingosine 1-phosphate (S1P) plays a role in NLRP3 inflammasome priming and activation remains unknown. Here, we found that the expression of NLRP3 in macrophages and NLRP3 inflammasome activation were significantly elevated in the liver injured by bile duct ligation (BDL).

Neutrophil recruitment mediated by sphingosine 1-phosphate (S1P)/S1P receptors during chronic liver injury.

Excessive neutrophils are recruited to damaged tissue and cause collateral injury under chronic inflammatory conditions. Sphingosine 1-phosphate (S1P) modulates kinds of physiological and pathological actions by inducing recruitment of various cell types through S1P receptors (S1PRs). This study aimed to detect the S1P/S1PRs-mediated effects on neutrophil recruitment during chronic liver inflammation.

Macrophage Sphingosine 1-Phosphate Receptor 2 Blockade Attenuates Liver Inflammation and Fibrogenesis Triggered by NLRP3 Inflammasome.

NLR family pyrin domain containing 3 (NLRP3) inflammasome accompanies chronic liver injury and is a critical mediator of inflammation-driven liver fibrosis. Sphingosine 1-phosphate (S1P)/S1P Receptor (S1PR) signaling participates in liver fibrogenesis by affecting bone marrow (BM)-derived monocytes/macrophage (BMM) activation. However, the relationship between S1P/S1PR signaling and NLRP3 inflammasome in BMMs remains unclear.

Neutrophils undergo switch of apoptosis to NETosis during murine fatty liver injury via S1P receptor 2 signaling.

Inappropriate neutrophil infiltration and subsequent neutrophil extracellular trap (NET) formation have been confirmed to be involved in chronic inflammatory conditions. Fatty liver disease is an increasingly severe health problem worldwide and currently considered the most common cause of chronic liver disease. Sphingosine 1-phosphate (S1P), a product of membrane sphingolipid metabolism, regulates vital physiological and pathological actions by inducing infiltration and activation of various cell types through S1P receptors (S1PRs).

Cannabinoid Receptor 1/miR-30b-5p Axis Governs Macrophage NLRP3 Expression and Inflammasome Activation in Liver Inflammatory Disease.

Nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) has been regarded as an important initiator or promoter in multiple inflammatory diseases. However, the relationship between cannabinoid receptor 1 (CB1) and macrophage NLRP3 inflammasome and the corresponding molecular mechanism in liver inflammation remain unclear. Mouse liver injury models were induced by carbon tetrachloride (CCl) or methionine-choline-deficient and high fat (MCDHF) diet.

Junctional and somatic hypermutation-induced CXC motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody.

Induction of broadly neutralizing monoclonal antibodies (bNAbs) that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus (HCV) vaccine research. The study of bNAbs arising in natural infection is essential in this endeavor. We generated a human antibody, 8D6, recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient.

TRIM34 attenuates colon inflammation and tumorigenesis by sustaining barrier integrity.

Loss of the colonic inner mucus layer leads to spontaneously severe colitis and colorectal cancer. However, key host factors that may control the generation of the inner mucus layer are rarely reported. Here, we identify a novel function of TRIM34 in goblet cells (GCs) in controlling inner mucus layer generation.

Neutrophil Chemotaxis and NETosis in Murine Chronic Liver Injury via Cannabinoid Receptor 1/ Gα/ ROS/ p38 MAPK Signaling Pathway.

Neutrophils play an essential role in the control of inflammatory diseases. However, whether cannabinoid receptors (CBs) play a role in neutrophil chemotaxis and NETosis in sterile liver inflammation remains unknown. The expression of marker genes on neutrophils was characterized by FACS, immunofluorescence, qRT-PCR, and Western blot.

Single-Cell Transcriptomes Reveal Characteristic Features of Mouse Hepatocytes with Liver Cholestatic Injury.

Hepatocytes are the main parenchymal cells of the liver and play important roles in liver homeostasis and disease process. The heterogeneity of normal hepatocytes has been reported, but there is little knowledge about hepatocyte subtype and distinctive functions during liver cholestatic injury. Bile duct ligation (BDL)-induced mouse liver injury model was employed, and single-cell RNA sequencing was performed.

ECM1 Prevents Activation of Transforming Growth Factor β, Hepatic Stellate Cells, and Fibrogenesis in Mice.

Background & Aims: Activation of TGFB (transforming growth factor β) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanisms of TGFB activation are not clear. We investigated the role of ECM1 (extracellular matrix protein 1), which interacts with extracellular and structural proteins, in TGFB activation in mouse livers.

Methods: We performed studies with C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1).

IFN-λ4 desensitizes the response to IFN-α treatment in chronic hepatitis C through long-term induction of USP18.

The recently discovered interferon lambda 4 (IFN-λ4) is a new member of the human type III interferons which could induce a strong antiviral effect through the JAK-STAT cascade. However, hepatitis C virus (HCV) patients who are capable of expressing IFN-λ4 usually have poor response to IFN-α treatment, and the mechanism behind this paradox remains unknown. Here, we reported that IFN-λ4 desensitized IFN-α-stimulated JAK-STAT signalling.

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A.

TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNα) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRIM22's targeting of the HCV NS5A protein.

Unusual architecture of the p7 channel from hepatitis C virus.

The hepatitis C virus (HCV) has developed a small membrane protein, p7, which remarkably can self-assemble into a large channel complex that selectively conducts cations. We wanted to examine the structural solution that the viroporin adopts in order to achieve selective cation conduction, because p7 has no homology with any of the known prokaryotic or eukaryotic channel proteins. The activity of p7 can be inhibited by amantadine and rimantadine, which are potent blockers of the influenza M2 channel and licensed drugs against influenza infections.