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Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction as well as MMP-2 Activity throughout Nicotine gum Fibroblasts.
Therefore, our results suggested that TEAD4 is a key regulatory factor in progression of psoriasis, and the crosstalk between keratinocytes and T cells mediated by TEAD4 plays a critical role in the psoriasis pathogenesis.Monosomy 7 is generally considered as an acquired cytogenetic abnormality within hematopoietic cells, and indicates an especially high risk of progression to bone marrow failure, myelodysplastic syndrome (MDS) or juvenile myelomonocytic leukemia (JMML). We report a case of a 6-month-old female infant with mosaic monosomy 7 who presented with clinical and laboratory evidences of immunodeficiency. The patient had suffered from recurrent respiratory infections since she was born. Peripheral blood lymphocyte subsets revealed an extremely low level of CD19+ B lymphocytes (0.3∼0.8%, normal range 6.4∼22.6%) and a decreased CD4/CD8 ratio (0.67∼1.12, normal range 1.4∼2.0). Decreased serum levels of IgG (1.53 g/L, normal range 4.09∼7.03 g/L), IgA (0.10 g/L, normal range 0.21∼0.47 g/L) and IgM (0.26 g/L, normal range 0.33∼0.73 g/L) were detected, while complements were normal. Tofacitinib JAK inhibitor Excepting transient neutropenia, routine blood tests were within normal limits. Clinical exome sequencing identified a de novo mosaic monosomy 7, while no pathogenic mutation associated with immunodeficiency was detected. However, peripheral blood cytogenetic analysis was failure to detect monosomy 7 due to the very few cell mitosis. Subsequent fluorescence in situ hybridization (FISH) identified a mosaic monosomy 7 in 58 cells within a total number of 100 cells, which was consistent with clinical exome sequencing. Therefore, the patient was diagnosed with primary immunodeficiency disease (PID) due to mosaic monosomy 7. Intravenous treatment with multiple antibiotic agents and infusion of gamma globulin could control the patient's respiratory infections effectively. A better understanding of PIDs will enable effective treatments and prevention of infections in these patients.Complement (C) system is a double edge sword acting as the first line of defense on the one hand and causing aggravation of disease on the other. C activation when unregulated affects different organs including muscle regeneration. However, the effect of factor H (FH), a critical regulator of the alternative C pathway in muscle remains to be studied. FH deficiency results in excessive C activation and generates proinflammatory fragments C5a and C3a as byproducts. C3a and C5a signal through their respective receptors, C5aR and C3aR. In this study, we investigated the role of FH and downstream C5a/C5aR signaling in muscle architecture and function. Using the FH knockout (fh-/-) and fh-/-/C5aR-/double knockout mice we explored the role of C, specifically the alternative C pathway in muscle dysfunction. Substantial C3 and C9 deposits occur along the walls of the fh-/- muscle fibers indicative of unrestricted C activation. Physical performance assessments of the fh-/- mice show reduced grip endurance (76 %), grip strength (14 %) and rotarod balance (36 %) compared to controls. Histological analysis revealed a shift in muscle fiber populations indicated by an increase in glycolytic MHC IIB fibers and reduction in oxidative MHC IIA fibers. Consistent with this finding, mitochondrial DNA (mtDNA) and citrate synthase (CS) expression were both reduced indicating possible reduction in mitochondrial biomass. In addition, our results showed a significant increase in TGFβ expression and altered TGFβ localization in this setting. The architecture of cytoskeletal proteins actin and vimentin in the fh-/- muscle was changed that could lead to contractile weakness and loss of skeletal muscle elasticity. The muscle pathology in fh-/- mice was reduced in fh-/-/C5aR-/- double knockout (DKO) mice, highlighting partial C5aR dependence. Our results for the first time demonstrate an important role of FH in physical performance and skeletal muscle health.The IFN-γ and TGF-β1 cytokines perform antagonistic activities in the immune response, and polymorphisms in these genes may induce changes in their plasma levels and influence the course of chronic Hepacivirus C (HCV) infection. The present study evaluated the IFNG +874A/T and TGFB1 -509 C/T polymorphisms in 99 samples from patients with chronic hepatitis C and in 300 samples from healthy donors, and the present study also investigated the association of cytokine plasma level with disease stage. Polymorphisms were identified by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of the IFNG +874A/T polymorphic allele was not associated with susceptibility to HCV infection, but it was associated with lower inflammatory activity (p = 0.0432). The frequency of the TGFB1 -509C/T polymorphic (TT) genotype was associated with HCV infection (p = 0.0062) and a higher risk of infection (OR = 2.0465; p = 0.0091). Plasma levels of IFN-γ were higher in TT genotype carriers among the control (p = 0.0012) and HCV groups (p = 0.0064) as well as in patients with fibrosis (p = 0.0346) and patients with a high degree of inflammatory activity (p = 0.0381). The highest TGF-β1 levels were found in HCV-infected (p = 0.0329) individuals and in TT genotype carriers. Patients with cirrhosis had higher TGF-β1 (p = 0.0400). IFN-γ and TGF-β1 levels showed a negative correlation (p = 0.0001). In conclusion, the TGFB1 -509C > T polymorphism is associated with a risk of developing chronic hepatitis C, leading to increased TGF-β1, which inhibits IFN-γ production, contributing to the progression to cirrhosis.Atypical hemolytic uremic syndrome (aHUS) is caused mainly by complement dysregulation. Although various defects in the complement system explaining pathophysiology have been described in recent years, the etiology still remains unclear in about thirty percent of cases. In exploring other causes, similar to anti- complement factor H (anti-CFH) antibody associated HUS, we hypothesized that anti-complement factor I (anti-CFI) antibody could play a role in aHUS. Further, we tried to describe the clinical profile and outcome of those with high anti CFI antibody titers. Eleven of thirty five children (31 %) diagnosed with aHUS from July 2017 to December 2018 had high IgG anti-CFI antibody titers. Median age was 10 months (6, 33) with no sex difference. Thirty-six percent (4/11) had nephrotic-range proteinuria. C3 was low in 8 children (72.7 %) with mean C3 (68.1 ± 14.7 mg/dL). Plasmapheresis was done in 2 children who promptly responded, suggesting the possible role of anti-CFI antibody in pathogenesis of aHUS in these patients.
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