Inflamed Microglia like Macrophages in the Central Nervous System of Prodromal Parkinson's Disease.

We investigated the role of inflammation in the pathogenesis of prodromal Parkinson's Disease (PD), performing single-cell RNAseq analysis of cerebrospinal fluid (CSF) and blood from 111 individuals, comparing control subjects with early prodromal PD and later PD to patients with multiple sclerosis (MS). Surprisingly, we identified a pleocytosis in the CSF, most pronounced in patients with early PD. Single-cell RNAseq revealed increases in CSF-specific microglia-like macrophages expressing JAK-STAT and TNFα signaling signatures in prodromal PD, with a lack of T cell activation in the CSF.

Transcriptomic profiling after B cell depletion reveals central and peripheral immune cell changes in multiple sclerosis.

Multiple sclerosis (MS) is a complex, genetically mediated autoimmune disease of the CNS, in which anti-CD20-mediated B cell depletion is remarkably effective in the treatment of early disease. Although previous studies investigated the effect of B cell depletion on select immune cell subsets using flow cytometry-based methods, the therapeutic effect on the patient's immune landscape is unknown. In this study, we explored how B cell-depleting therapies modulate the immune landscape using single-cell RNA-Seq.

mtSTAT3 suppresses rheumatoid arthritis by regulating Th17 and synovial fibroblast inflammatory cell death with IL-17-mediated autophagy dysfunction.

Th17 cells are activated by STAT3 factors in the nucleus, and these factors are correlated with the pathologic progression of rheumatoid arthritis (RA). Recent studies have demonstrated the presence of STAT3 in mitochondria, but its function is unclear. We investigated the novel role of mitochondrial STAT3 (mitoSTAT3) in Th17 cells and fibroblast-like synoviocytes (FLSs) and analyzed the correlation of mitoSTAT3 with RA.

Small heterodimer partner-interacting leucine zipper protein suppresses pain and cartilage destruction in an osteoarthritis model by modulating the AMPK/STAT3 signaling pathway.

Objective: Osteoarthritis (OA) is a degenerative joint disease caused by the breakdown of joint cartilage and adjacent bone. Joint injury, being overweight, differences in leg length, high levels of joint stress, abnormal joint or limb development, and inherited factors have been implicated in the etiology of OA. In addition to physical damage to the joint, a role for inflammatory processes has been identified as well.

Systems Analysis of Immune Changes after B-cell Depletion in Autoimmune Multiple Sclerosis.

Multiple sclerosis (MS) is a complex genetically mediated autoimmune disease of the central nervous system where anti-CD20-mediated B cell depletion is remarkably effective in the treatment of early disease. While previous studies investigated the effect of B cell depletion on select immune cell subsets using flow cytometry-based methods, the therapeutic impact on patient immune landscape is unknown. In this study, we explored how a therapy-driven " " modulates the diverse immune landscape by measuring transcriptomic granularity with single-cell RNA sequencing (scRNAseq).

Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.

Unlabelled: Adding anti-programmed cell death protein 1 (anti-PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (n = 47) sequentially adding pembrolizumab to 5-FU/platinum in advanced GEA. Using serial biopsy of the primary tumor at baseline, after one cycle of 5-FU/platinum, and after the addition of pembrolizumab, we transcriptionally profiled 358,067 single cells to identify evolving multicellular tumor microenvironment (TME) networks.

Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer.

Early detection and surgical treatment are essential to achieve a good outcome in gastric cancer (GC). Stage IV and recurrent GC have a poor prognosis. Therefore, new treatments for GC are needed.

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.

Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation.

Rheumatoid arthritis (RA) is an autoimmune disease that causes joint swelling and inflammation and can involve the entire body. RA is characterized by the increase of pro-inflammatory cytokines such as interleukin (IL) and tumor necrosis factor, and the over-activation of T lymphocytes and B lymphocytes, which may lead to severe chronic inflammation of joints. However, despite numerous studies the pathogenesis and treatment of RA remain unresolved.

Rebamipide treatment ameliorates obesity phenotype by regulation of immune cells and adipocytes.

Obesity is a medical term used to describe an over-accumulation of adipose tissue. It causes abnormal physiological and pathological processes in the body. Obesity is associated with systemic inflammation and abnormalities in immune cell function.

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.

Expanded IL-22 Group 3 Innate Lymphoid Cells and Role of Oxidized LDL-C in the Pathogenesis of Axial Spondyloarthritis with Dyslipidaemia.

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis.

Early Tumor-Immune Microenvironmental Remodeling and Response to First-Line Fluoropyrimidine and Platinum Chemotherapy in Advanced Gastric Cancer.

Unlabelled: Chemotherapy is ubiquitous in first-line treatment of advanced gastric cancer, yet responses are heterogeneous, and little is known about mediators of chemotherapy response. To move forward, an understanding of the effects of standard chemotherapy on the tumor-immune microenvironment (TME) is needed. Coupling whole-exome sequencing, bulk RNA and single-cell transcriptomics from paired pretreatment and on-treatment samples in treatment-naïve patients with HER2-positive and HER2-negative gastric cancer, we define features associated with response to platinum-based chemotherapy.

IL-17 and CCR9α4β7 Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren's Syndrome.

Previous studies have evaluated the roles of T and B cells in the pathogenesis of Sjögren's syndrome (SS); however, their relationships with age-dependent and metabolic abnormalities remain unclear. We examined the impacts of changes associated with aging or metabolic abnormalities on populations of T and B cells and SS disease severity. We detected increased populations of IL-17-producing T and B cells, which regulate inflammation, in the salivary glands of NOD/ShiLtJ mice.

Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.

Scleroderma is an autoimmune disease that causes dermal fibrosis. It occurs when collagen accumulates in tissue as a result of persistent inflammation. Th17 cells and pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-α play important roles in the pathogenesis of scleroderma.

GRIM-19 Ameliorates Multiple Sclerosis in a Mouse Model of Experimental Autoimmune Encephalomyelitis with Reciprocal Regulation of IFNγ/Th1 and IL-17A/Th17 Cells.

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved.

Liposome/gold hybrid nanoparticle encoded with CoQ10 (LGNP-CoQ10) suppressed rheumatoid arthritis via STAT3/Th17 targeting.

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders.

Brown adipose tissue ameliorates autoimmune arthritis via inhibition of Th17 cells.

The functions of adipose tissue are associated with autoimmune diseases, such as rheumatoid arthritis (RA). Some studies have shown that the three compositions of adipose tissue (white, brown, and beige) have different functions. Brown adipose tissue (BAT) is known to secrete several factors that differ from those in white adipose tissue.

Inhibition of RIPK3 Pathway Attenuates Intestinal Inflammation and Cell Death of Inflammatory Bowel Disease and Suppresses Necroptosis in Peripheral Mononuclear Cells of Ulcerative Colitis Patients.

Receptor-interacting serine/threonine-protein kinase (RIPK) 3 is a member of the TNF receptor-I signaling complex and mediates necroptosis, an inflammatory cell death. Ulcerative colitis (UC) is an excessive inflammatory disease caused by uncontrolled T cell activation. The current study is aimed to determine whether RIPK3 inhibitor attenuates UC development inhibiting inflammation and necroptosis using experimental colitis mice model.

Robust pathway-based multi-omics data integration using directed random walks for survival prediction in multiple cancer studies.

Background: Integrating the rich information from multi-omics data has been a popular approach to survival prediction and bio-marker identification for several cancer studies. To facilitate the integrative analysis of multiple genomic profiles, several studies have suggested utilizing pathway information rather than using individual genomic profiles.

Methods: We have recently proposed an integrative directed random walk-based method utilizing pathway information (iDRW) for more robust and effective genomic feature extraction.

Expression of polo-like kinase 1 in pre-implantation stage murine somatic cell nuclear transfer embryos.

Somatic cell nuclear transfer (SCNT) has various applications in research, as well as in the medical field and animal husbandry. However, the efficiency of SCNT is low and the accurate mechanism of SCNT in murine embryo development is unreported. In general, the developmental rate of SCNT murine embryos is lower than counterparts.