GRIM-19-mediated induction of mitochondrial STAT3 alleviates systemic sclerosis by inhibiting fibrosis and Th2/Th17 cells.

The gene associated with the retinoid-IFN-induced mortality-19 (GRIM-19) protein is a regulator of a cell death regulatory protein that inhibits STAT3, which is a critical transcription factor for interleukin (IL)-17-producing T (Th17) cells and a key integrator of extracellular matrix accumulation in systemic sclerosis (SSc). This protein is also a component of mitochondrial complex I, where it directly binds to STAT3 and recruits STAT3 to the mitochondria via the mitochondrial importer Tom20. In this study, the role of GRIM19 and its relationship with STAT3 in SSc development was investigated using a murine model of SSc.

Aberrant overexpression of the autoantigen protein vimentin promotes Th17 cell differentiation and autoimmune arthritis via activation of STAT3 signaling.

Vimentin contributes to the positioning and function of organelles, cell migration, adhesion, and division. However, secreted vimentin accumulates on the cell surface (Mor-Vaknin et al., 2003; Ramos et al.

Fingolimod, an antagonist of sphingosine 1-phosphate, ameliorates Sjögren's syndrome by reducing the number of STAT3-induced germinal center B cells and increasing the number of Breg cells.

Background: Sjögren's syndrome (SS) is an autoimmune disease caused by infiltrating lymphocytes. FTY720 affects the S1P signaling pathway, which plays a role in T and B cell migration from secondary lymphoid tissues to target organs. In this study, we investigate the regulatory mechanism of FTY720 in the context of SS.

Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection.

Hepatitis B virus (HBV) is a sex-specific pathogen that is more severe in males than in females. Sex disparities in HBV infection have been attributed to hormonal differences between males and females. However, whether HBV infection affects the metabolic signatures of steroid hormones and how these influences viral replication remains unclear.

IL-21 drives skin and lung inflammation and fibrosis in a model for systemic sclerosis.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, abnormal inflammation, and fibrosis of the skin and internal organs, notably the skin and lungs, significantly impairing quality of life. There is currently no cure for SSc, and its etiology remains largely unknown, presenting a primary barrier to effective treatment. We investigated the role of interleukin-21 (IL-21) in the pathogenesis of SSc.

Electron-Transport-Chain-Mediated Selective Growth of Gold Nanocrystals in the Intermembrane Space of Live Microbial Cells.

Hybridization of microbial cells with inorganic nanoparticles that could dramatically improve cellular functions such as electron transfer has been realized by the random attachment or stochastic entry of the nanoparticles. Clearly, the selective growth of inorganic nanoparticles on target functional organelles is ideal for such hybridization. Here, we report the selective growth of gold nanocrystals in the intermembrane space (IMS) of by exploiting the electron transport chain (ETC).

Bisphenol A is more potent than bisphenol S in influencing the physiological and pathological functions of lungs via inducing lung fibrosis and stimulating metastasis.

Bisphenol A (BPA) is widely used in the production of plastics, food containers, and receipt ink globally. However, research has identified it as an endocrine disruptor, affecting the hormonal balance in living organisms. Bisphenol S (BPS), one of the alternative substances, was developed, but its effects on human health and the underlying mechanisms remain unclarified.

Establishment of a humanized mouse model of keloid diseases following the migration of patient immune cells to the lesion: Patient-derived keloid xenograft (PDKX) model.

Keloid disorder is an abnormal fibroproliferative reaction that can occur on any area of skin, and it can impair the quality of life of affected individuals. To investigate the pathogenesis and develop a treatment strategy, a preclinical animal model of keloid disorder is needed. However, keloid disorder is unique to humans, and the development of an animal model of keloid disorder is highly problematic.

Faecalibacterium prausnitzii alleviates inflammatory arthritis and regulates IL-17 production, short chain fatty acids, and the intestinal microbial flora in experimental mouse model for rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease that leads to joint destruction and functional disability due to the targeting of self-antigens present in the synovium, cartilage, and bone. RA is caused by a number of complex factors, including genetics, environment, dietary habits, and altered intestinal microbial flora. Microorganisms in the gut bind to nod-like receptors and Toll-like receptors to regulate the immune system and produce various metabolites, such as short-chain fatty acids (SCFAs) that interact directly with the host.

SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis.

Background: Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood.

Methods: This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model.

(LA-1) and butyrate inhibit osteoarthritis by controlling autophagy and inflammatory cell death of chondrocytes.

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA.

Soluble CCR2 gene therapy controls joint inflammation, cartilage damage, and the progression of osteoarthritis by targeting MCP-1 in a monosodium iodoacetate (MIA)-induced OA rat model.

Background: Osteoarthritis (OA) is the most common type of degenerative arthritis and affects the entire joint, causing pain, joint inflammation, and cartilage damage. Various risk factors are implicated in causing OA, and in recent years, a lot of research and interest have been directed toward chronic low-grade inflammation in OA. Monocyte chemoattractant protein-1 (MCP-1; also called CCL2) acts through C-C chemokine receptor type 2 (CCR2) in monocytes and is a chemotactic factor of monocytes that plays an important role in the initiation of inflammation.

Inner-Membrane-Bound Gold Nanoparticles as Efficient Electron Transfer Mediators for Enhanced Mitochondrial Electron Transport Chain Activity.

Electron transfer through the mitochondrial electron transport chain (ETC) can be critically blocked by the dysfunction of protein complexes. Redox-active molecules have been used to mediate the electron transfer in place of the dysfunctional complexes; however, they are limited to replacing complex I and are known to be toxic. Here we report artificial mitochondrial electron transfer pathways that enhance ETC activity by exploiting inner-membrane-bound gold nanoparticles (GNPs) as efficient electron transfer mediators.

Ezetimibe ameliorates clinical symptoms in a mouse model of ankylosing spondylitis associated with suppression of Th17 differentiation.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes spinal inflammation and fusion. Although the cause of AS is unknown, genetic factors (e.g.

Dysregulation of Liver Regeneration by Hepatitis B Virus Infection: Impact on Development of Hepatocellular Carcinoma.

The liver is unique in its ability to regenerate in response to damage. The complex process of liver regeneration consists of multiple interactive pathways. About 2 billion people worldwide have been infected with hepatitis B virus (HBV), and HBV causes 686,000 deaths each year due to its complications.

Susceptibility of Drug Resistant Hepatitis B Virus Mutants to Besifovir.

Currently, interferon alpha and nucleos(t)ide analogues (NAs) are clinically available to treat hepatitis B virus (HBV) infection. Several NAs, including lamivudine (LMV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF or TAF) have been approved and administered to chronic hepatitis B (CHB) patients. NAs inhibit HBV DNA synthesis by targeting the reverse transcriptase (RT) domain of HBV polymerase.

IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts the STAT3 and HIF-1α Dependent Signaling Pathways.

Keloid is an abnormal fibrotic disease after cutaneous injury characterized by exaggerated scar tissue formation, which often extends beyond the boundaries of the original wound. Although chronic inflammation is known to be associated with the excessive inflammation in keloid tissue, there are few studies on the role of autophagy in the pathogenesis of keloid. In this study, we evaluated the pattern of autophagy in keloid fibroblasts (KF) and normal fibroblasts (NF).

Characteristics of Extracellular Vesicles and Preclinical Testing Considerations Prior to Clinical Applications.

Cell therapy products have significant limitations, such as storage instability, difficulties with transportation, and toxicity issues such as tumorigenicity and immunogenicity. Extracellular vesicles (EVs) secreted from cells show potential for therapeutic agent development. EVs have not been widely examined as investigational drugs, and non-clinical studies for the clinical approval of EV therapeutic agents are challenging.

Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System.

During viral evolution and adaptation, many viruses have utilized host cellular factors and machinery as their partners. HBx, as a multifunctional viral protein encoded by the hepatitis B virus (HBV), promotes HBV replication and greatly contributes to the development of HBV-associated hepatocellular carcinoma (HCC). HBx interacts with several host factors in order to regulate HBV replication and evolve carcinogenesis.