Introduction: We performed a cross-sectional study to investigate the clinical usefulness of YKL-40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL-40 in patients with polymyositis (PM)/DM. Materials and methods: A cross-sectional study and a systematic review were performed to study the clinical value of YKL-40 in patients with PM/DM. In the cross-sectional study, a total of 65 DM patients with mean age 47.71 years and 30 healthy controls with mean age 47.73 years were included. Serum YKL-40 level was detected using enzyme-linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed by Spearman correlation analysis. The diagnostic value of serum YKL-40 in patients with DM was assessed by receiver operating characteristic (ROC) curve analysis. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL-40 in patients with PM/DM.Results: In the cross-sectional study, serum YKL-40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72-176.4] ng/mL vs 27. 37 [12.30-53.58] ng/mL, p<0.0001). Serum levels of YKL-40 were associated with the course of DM (r=-0.469, p<0.001), CRP (r=0.303, p=0.043), CK (r=0.263, p=0.037), and global disease activity (r=0.628, p<0.001). The area under the ROC curve was 0.835 (95% con dence interval 0.751-0.920). In the systematic review, a total of 4 studies were included with moderate to high quality. Serum level of YKL-40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death.Conclusion: Serum YKL-40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.
Idiopathic pulmonary fibrosis is a progressive lung disease with limited survival. The specific roles of Janus Kinases - tyrosine kinases that transduce cytokine-mediated signals - in lung fibrosis are not well defined. In this study, the interactions between JAK1/STAT3 signaling and TGF-β induced fibroblast responses were investigated using both pharmacological and siRNA approaches in human normal and IPF-derived lung fibroblasts. We found that JAK1 directly interacts with the TGF-β receptor I (TβRI), and silencing JAK1 promotes myofibroblast trans-differentiation. However, the suppression of JAK1 signaling in vitro and in vivo using an inhibitor (Upadacitinib) did not alter lung fibroblast activation or fibrosis development. STAT3 was constitutively active in cultured primary lung fibroblasts: this STAT3 activation was JAK1 dependent and repressed myofibroblast trans-differentiation. Loss of phosphorylated STAT3 following transcriptional JAK1 silencing promoted myofibroblast trans-differentiation. In contrast, transcriptional silencing of unphosphorylated STAT3 suppressed TGF-β signaling, decreased SMAD3 activation, and reduced myofibroblast trans-differentiation and ECM production. Taken together, these observations support a role for JAK1/STAT3 as a direct regulator of TGF-β signaling in lung fibroblasts. Modulation of JAK1/STAT3 signaling in lung fibroblasts represents a non-canonical approach to regulate TGF-β induced fibrosis and suggests the potential for a novel approach to treat pulmonary fibrosis.
Background The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir ( LPV/r ) in the treatment of COVID-19 infection, compared with that of using LPV/r alone. Methods Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b . Results A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16±9.7 vs 23±10.5 days; P =0.028). Moreover, the days of hospitalization in early intervention group decreased from 25±8.5 days to 10±2.9 days compared with delayed intervention group ( P =0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups. Conclusions Subcutaneous injection of IFN alpha-2b combined with LPV/r shortened the length of hospitalization and accelerated viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.
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