miR-3606-3p alleviates skin fibrosis by integratively suppressing the integrin/FAK, p-AKT/p-ERK, and TGF-β signaling cascades.

Introduction: Fibroblast abnormalities are crucial causes of skin fibrosis, including systemic sclerosis (SSc) and keloids. However, their mechanisms, including underlying microRNA regulatory mechanisms, remain elusive.

Objectives: This study aimed to evaluate the roles, mechanisms, and therapeutic potential of miR-3606-3p in regulating multiple fibroblast abnormalities.

Atypical chemokine receptor 1-positive endothelial cells mediate leucocyte infiltration and synergize with secreted frizzled-related protein 2/asporin-positive fibroblasts to promote skin fibrosis in systemic sclerosis.

Background: Skin fibrosis is the typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS); it has an unclear aetiology and few effective treatments. Although excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, evidence has suggested that vascular damage is the initiating event and that various cell types, including fibroblasts, work together to contribute to the pathogenesis of skin fibrosis.

Objectives: To explore the relationship between vascular endothelial cell lesions and immune cell infiltration, along with the interactions between various cell types within the fibrotic skin ecosystem.

TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis.

Objectives: Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear.

Care patterns and Traditional Chinese Medicine constitution as factors of depression and anxiety in patients with systemic sclerosis: A cross-sectional study during the COVID-19 pandemic.

Objective: Care patterns and Traditional Chinese Medicine (TCM) constitution affects the emotion and health of patients with systemic sclerosis (SSc) while the prevalence of COVID-19 may aggravate such patients' emotion and health. We investigated the depression and anxiety levels of patients with SSc during the pandemic to identify the correlation between care patterns, TCM constitution, and patients' emotion.

Materials And Methods: This was a cross-sectional study.

Testing the validity and reliability of the Chinese version of the Staden schizophrenia anxiety rating scale.

Accurate assessment of anxiety disorders and their symptomatology in schizophrenic patients is important for prognosis and treatment. Measuring anxiety on the traditional anxiety assessment scales such as the Hamilton Anxiety Rating (HAMA) Scale or the self-rating depression scale (SAS) is challenging and often considered unsuitable for assessing anxiety symptoms in patients with schizophrenia. The Staden schizophrenia anxiety rating scale (S-SARS) has been shown to reliably measure specified and undifferentiated anxiety in schizophrenia.

Paliperidone Extended Release Versus Olanzapine in Treatment-Resistant Schizophrenia: A Randomized, Double-Blind, Multicenter Study.

Purpose: Paliperidone is an atypical antipsychotic as effective as other atypical antipsychotics for schizophrenia. However, few studies have explored the efficacy of paliperidone for treatment-resistant schizophrenia. This study aimed to compare the efficacy and safety of paliperidone extended release (ER) versus olanzapine in schizophrenia patients with either poor treatment response or intolerable adverse effects due to standardized antipsychotic therapy.

LDLR dysfunction induces LDL accumulation and promotes pulmonary fibrosis.

Treatments for pulmonary fibrosis (PF) are ineffective because its molecular pathogenesis and therapeutic targets are unclear. Here, we show that the expression of low-density lipoprotein receptor (LDLR) was significantly decreased in alveolar type II (ATII) and fibroblast cells, whereas it was increased in endothelial cells from systemic sclerosis-related PF (SSc-PF) patients and idiopathic PF (IPF) patients compared with healthy controls. However, the plasma levels of low-density lipoprotein (LDL) increased in SSc-PF and IPF patients.

Left Cerebral Cortex Complexity in Patients with Major Depression Disorder: A Small-Sample Pilot Study.

Objective: To investigate cerebral cortical complexity (CCC) in patients with first-episode, drug-naive major depressive disorder (MDD) with source-based morphometry (SBM) analyses.

Methods: We used the SBM parameters gyrification index (GI) and fractal dimension (FD) to evaluate CCC in 14 first-episode, drug-naive patients diagnosed with MDD. The severity of depression symptoms was assessed with the 17-item Hamilton Depression Scale (HAMD-17).

Exome-Wide Association Analysis Suggests LRP2BP as a Susceptibility Gene for Endothelial Injury in Systemic Sclerosis in the Han Chinese Population.

Genetic factors play a key role in the pathogenesis of autoimmune diseases, whereas the disease-causing variants remain largely unknown. Herein, we performed an exome-wide association study of systemic sclerosis in a Han Chinese population. In the discovery stage, 527 patients with systemic sclerosis and 5,024 controls were recruited and genotyped.

Involvement of Disabled-2 on skin fibrosis in systemic sclerosis.

Background: Systemic sclerosis (SSc) is a connective tissue disease characterized by inflammation and fibrosis. Our previous research found Disabled-2 (DAB2) expression was significantly downregulated by salvianolic acid B, a small molecular medicine which attenuated experimental skin fibrosis of SSc. These suggest that DAB2 plays an important role in SSc skin fibrosis, but the role of DAB2 in SSc remains unclear.

Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2-associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)-induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear.

MiR-3606-3p inhibits systemic sclerosis through targeting TGF-β type II receptor.

Systemic sclerosis (SSc) is a multisystemic fibrotic disease characterized by excessive collagen deposition and extracellular matrix synthesis. Though transforming growth factor-β (TGF-β) plays a fundamental role in the pathogenesis of SSc, the mechanism by which TGF-β signaling acts in SSc remains largely unclear. Here, we showed that TGF-β type II receptor (TGFBR2) was significantly upregulated in both human SSc dermal tissues and primary fibroblasts.

Genome-Wide DNA Methylation Analysis in Systemic Sclerosis Reveals Hypomethylation of IFN-Associated Genes in CD4 and CD8 T Cells.

Epigenetic modifications, including DNA methylation, play an important role in the pathogenesis of autoimmune diseases. In this study, we characterized the DNA methylome in primary T cells of patients with systemic sclerosis. Genome-wide DNA methylation assays of CD4 and CD8 T cells from 24 systemic sclerosis patients and 24 matched controls were conducted and differentially methylated regions were validated.

Beneficial effect of fluoxetine treatment aganist psychological stress is mediated by increasing BDNF expression in selected brain areas.

SSRI antidepressant fluoxetine is widely used to treat psychological stress related disorders, however the underlying working mechanisms is not fully understood, as SSRIs can rapidly increase the extracellular serotonin levels but it normally takes weeks to reveal their therapeutic effect in the stress-related psychological disorders. Our previous study demonstrated that purely psychological stress without any physic stimuli induces a biphasic change in the expression of brain-derived neurotrophic factor (BDNF), which immediately decrease and then gradually increase after the stress; and that the latter BDNF increase in response to the psychological stress involves the activation of serotonin system. To investigate the role of BDNF in the fluoxetine treatment for stress-related psychological disorders, we examined the mRNA and protein levels of BDNF in the brain of Sprague-Dawley (SD) rats, which were pretreated with fluoxetine at 10 mg/kg or vehicle solution for 14 days, over 24 hour after an acute psychological stress exposure.

Increased expression of latent TGF-β-binding protein 4 affects the fibrotic process in scleroderma by TGF-β/SMAD signaling.

This corrects the article DOI: 10.1038/labinvest.2017.

Increased expression of latent TGF-β-binding protein 4 affects the fibrotic process in scleroderma by TGF-β/SMAD signaling.

Scleroderma is a fibrosis-related disorder characterized by cutaneous and internal organ fibrosis, and excessive collagen deposition in extracellular matrix (ECM) is a major cause of fibrosis. Transforming growth factor-β (TGF-β)/SMAD signaling has a central role in the pathogenesis of fibrosis by inducing abnormal collagen accumulation in ECM, and latent TGF-β-binding protein 4 (LTBP-4) affects the secretion of latent TGF-β to ECM. A previous study indicated that bleomycin (BLM) treatment increased LTBP-4 expression in lung fibroblasts of Thy-1 knockout mice with lung fibrosis, and LTBP-4 further promoted TGF-β bioavailability as well as SMAD3 phosphorylation.

Salvianolic Acid B Attenuates Experimental Pulmonary Fibrosis through Inhibition of the TGF-β Signaling Pathway.

Pulmonary fibrosis is a progressive and fatal disorder. In our previous study, we found that the Yiqihuoxue formula (YQHX), a prescription of Traditional Chinese Medicine, had a curative effect on scleroderma, a typical fibrotic disease. The aim of this study was to determine the key ingredient mediating the therapeutic effects of YQHX and to examine its effect on pulmonary fibrosis, including its mechanism.

Copy Number Variation of HLA-DQA1 and APOBEC3A/3B Contribute to the Susceptibility of Systemic Sclerosis in the Chinese Han Population.

Objective: Systemic sclerosis (SSc) is a systemic connective tissue disease caused by a genetic aberrant. The involvement of the copy number variations (CNV) in the pathogenesis of SSc is unclear. We tried to identify some CNV that are involved with the susceptibility to SSc.

Involvement of collagen-binding heat shock protein 47 in scleroderma-associated fibrosis.

Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 (HSP47) is closely related with the development of fibrosis. To explore the potential function of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed.

Lack of Association of the CD247 SNP rs2056626 with Systemic Sclerosis in Han Chinese.

Systemic sclerosis (SSc) is a complex disease involving multiple genetic factors. A recent genome-wide association study (GWAS) indicated that CD247 was strongly associated with SSc, which was subsequently confirmed in a SSc cohort of European population. However, genetic heterogeneity in different ethnic populations may significantly impact the complex trait of SSc.

Association of the HLA-DRB1 with scleroderma in Chinese population.

Multiple alleles of the Human leukocyte antigen (HLA) DRB1 have been strongly associated with systemic sclerosis (SSc) and its clinical or serological subsets. However, the associations vary in different ethnic populations. To define SSc-risk and/or -protective alleles of HLA-DRB1 in Chinese population, we studied a Han Chinese cohort containing 585 patients with SSc and 458 gender-matched, unrelated controls.

Dissection of the mechanism of traditional Chinese medical prescription-Yiqihuoxue formula as an effective anti-fibrotic treatment for systemic sclerosis.

Background: Systemic sclerosis (SSc) is a connective tissue fibrotic disease for which there is no effective treatment. Traditional Chinese Medicine (TCM), such as the Yiqihuoxue formula used in Shanghai TCM-integrated Hospital, has shown the efficacy of anti-fibrosis in clinical applications. This study was aiming to dissect the anti-fibrotic mechanism of Yiqihuoxue treatment for SSc.

Association of HLA-DPB1 with scleroderma and its clinical features in Chinese population.

Human leukocyte antigen DPB1 was reported to contain singly nucleotide polymorphisms conferring the strongest susceptibility to systemic sclerosis in Korean population. However, associations of specific DPB1 alleles with SSc vary in different ethnic populations. The aim of this study was to profile DPB1 alleles in Chinese population and to identify specific DPB1 alleles in association with SSc and clinical and serological features of SSc in Han Chinese.