HDAC9 inhibition reduces skeletal muscle atrophy and enhances regeneration in mice with cigarette smoke-induced COPD.

Cigarette smoke (CS) is the major risk factor for chronic obstructive pulmonary disease (COPD), and sarcopenia is one of the significant comorbidities of COPD. However, the pathogenesis of CS-related deficient skeletal muscle regeneration has yet to be clarified. The impact of CS on myoblast differentiation was examined, and then we determined which HDAC influenced the myogenic process and muscle atrophy in vitro and in vivo. Finally, we further investigated the potential mechanisms via RNA sequencing. Long-term CS exposure activated skeletal muscle primary satellite cells (SCs) while inhibiting differentiation, and defective myogenesis was also observed in C2C12 cells treated with CS extract (CSE). The level of HDAC9 changed in vitro and in vivo in CS exposure models as well as COPD patients, as detected by bioinformatics analysis. Our data showed that CSE impaired myogenic capacity and myotube formation in C2C12 cells via HDAC9. Moreover, inhibition of HDAC9 in mice exposed to CS prevented skeletal muscle dysfunction and promoted SC differentiation. The results of RNA-Seq analysis and verification indicated that HDAC9 knockout improved muscle differentiation in CS-exposed mice, probably by acting on the AKT/mTOR pathway and inhibiting the P53/P21 pathway. More importantly, the serum of HDAC9 KO mice exposed to CS alleviated the differentiation impairment of C2C12 cells caused by serum intervention in CS-exposed mice, and this effect was inhibited by LY294002 (an AKT/mTOR pathway inhibitor). These results suggest that HDAC9 plays an essential role in the defective regeneration induced by chronic exposure to CS.

Is There a Relationship Between Online Health Information Seeking and Health Anxiety? A Systematic Review and Meta-Analysis.

The internet has revolutionized how we live, providing unprecedented convenience and up-to-date information. Consequently, an increasing number of individuals are turning to the internet for health-related information, despite research suggesting a correlation between this behavior and health anxiety. Therefore, drawing on cognitive - behavioral theory, we explore the link between online health information seeking and health anxiety via a systematic review and meta-analysis of cross-sectional studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis, we ran searches in multiple databases, including PubMed, Web of Science, Embase, Elsevier/Science Direct, Cochrane Database, China National Knowledge Infrastructure, VIP Chinese Database, and Wanfang Data. Our searches identified 16 studies eligible for review, involving 4,920 participants across seven countries. The random-effects meta-analysis revealed a significant positive correlation between online health information seeking and health anxiety (r = 0.28, 95% confidence interval [0.16, 0.41], p < .0001), despite considerable heterogeneity. Furthermore, meta-regression analysis demonstrated that the identity characteristics of the sample, female percentage, sample size, and country all contributed to the heterogeneity across studies. Overall, this meta-analysis provides support for the association between online health information seeking and health anxiety, and helps to elucidate the cognitive - behavioral theory underpinning this phenomenon.

Prognostic significance of circulating Epstein-Barr virus DNA in pulmonary lymphoepithelioma-like carcinoma: A meta-analysis and validation study.

In small-scale studies, circulating Epstein-Barr virus (EBV) DNA levels have prognostic value in patients with pulmonary lymphoepithelioma-like carcinoma (LELC). Therefore, we performed a comprehensive meta-analysis to evaluate the prognostic significance of circulating EBV DNA levels in patients with pulmonary LELC. Studies that discussed the prognostic significance of circulating EBV DNA detection in pulmonary LELC were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Pooled hazard ratio (HR), 95% confidence intervals (CIs), and p value were calculated to estimate the prognostic significance of EBV DNA levels. Additionally, we conducted a further observation using an independent cohort. The pooled HR and 95% CI of pretreatment EBV DNA levels for OS and PFS were 3.63 (95% CI: 2.90-4.55) and 2.88 (95% CI: 1.90-4.38), respectively. The pooled HR and 95% CI for Posttreatment EBV DNA levels for OS and PFS were 3.77 (95% CI: 2.96-4.80) and 3.52 (95% CI: 1.91-6.51, p < 0.001), respectively. The independent cohort showed similar results that patients with high pretreatment EBV DNA or positive posttreatment EBV DNA had significantly inferior PFS. Circulating EBV DNA levels provide prognostic values of survival and treatment response in pulmonary LELC patients.

Resveratrol Prevents Skeletal Muscle Atrophy and Senescence via Regulation of Histone Deacetylase 2 in Cigarette Smoke-Induced Mice with Emphysema.

Objective: The aim of this study was to investigate the effects of resveratrol (RSV) on cigarette smoke (CS)-induced skeletal muscle atrophy and senescence in mice with emphysema and to explore the underlying mechanisms. Methods: Gastrocnemius muscle weight and lung and muscular morphology were observed in CS-exposed mice with or without RSV treatment. The expression of atrophy-related markers (MURF1 and MAFbx), senescence-related markers (P53, P21 and SMP30) and NF-κB inflammatory pathways was detected by Western blotting and real-time PCR. The levels of IL-1ß and TNF-α were also determined by ELISA, and the number of senescent cells was determined by SA-ß gal staining. In addition, the expression of HDAC2 and the effect of HDAC2 on CSE-induced skeletal muscle atrophy and senescence by RSV treatment were investigated. Results: RSV prevented emphysema and skeletal muscle atrophy in long-term CS-exposed mice. RSV decreased the expression of MURF1, MAFbx, P53, and P21 and inhibited the NF-κB pathway both in vivo and in vitro. Moreover, RSV reversed CS-induced downregulation of HDAC2 expression both in gastrocnemius and in C2C12 cells. Moreover, knockdown of HDAC2 significantly abolished the inhibitory effect of RSV on the expression of MURF1, MAFbx, P53, P21 and inflammatory factors (IL-1ß and TNF-α) in C2C12 cells. Conclusion: RSV prevents CS-induced skeletal muscle atrophy and senescence, and upregulation of HDAC2 expression and suppression of inflammation are involved.

Histone Deacetylase 2 Suppresses Skeletal Muscle Atrophy and Senescence via NF-κB Signaling Pathway in Cigarette Smoke-Induced Mice with Emphysema.

Background: Exposure to cigarette smoke (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD). CS not only causes chronic airway inflammation and lung damage but also is involved in skeletal muscle dysfunction (SMD). Previous studies have shown that histone deacetylase 2 (HDAC2) plays an important role in the progression of COPD. The aim of this study was to determine the role of HDAC2 in CS-induced skeletal muscle atrophy and senescence. Methods: Gastrocnemius muscle weight and cross-sectional area (CSA) were measured in mice with CS-induced emphysema, and changes in the expression of atrophy-related markers and senescence-related markers were detected. In addition, the relationship between HDAC2 expression and skeletal muscle atrophy and senescence was also investigated. Results: Mice exposed to CS for 24 weeks developed emphysema and gastrocnemius atrophy and exhibited a decrease in gastrocnemius weight and skeletal muscle cross-sectional area. In addition, the HDAC2 protein levels were significantly decreased while the levels of atrophy-associated markers, including MURF1 and MAFbx, and senescence-associated markers, including P53 and P21, were significantly increased in the gastrocnemius muscle. In vitro, the exposure of C2C12 cells to cigarette smoke extract (CSE) significantly increased the MAFbx and MURF1 protein levels and decreased the HDAC2 protein levels. Moreover, overexpression of HDAC2 significantly ameliorated CSE-induced atrophy and senescence and reversed the increased MURF1, MAFbx, P53, and P21 expression in C2C12 cells. In addition, CSE treatment significantly increased the IKK and NF-κB p65 protein levels, and PTDC (an NF-kB inhibitor) ameliorated atrophy and senescence. Conclusion: Our findings suggest that HDAC2 plays an important role in CS-induced skeletal muscle atrophy and senescence, possibly through the NF-κB pathway.

A gene missense mutation in diffuse pulmonary lymphangiomatosis with thrombocytopenia: A case report.

INTRODUCTION: Diffuse pulmonary lymphangiomatosis (DPL) is a rare condition. Most patients with DPL present dyspnea, cough, expectoration, and hemoptysis. There are few reports of DPL accompanied by thrombocytopenia, whose cause remains unknown. PATIENT CONCERNS: An 18-year-old male patient presented with recurrent cough, expectoration, and dyspnea for 5 years, and thrombocytopenia was observed during a 2-month follow-up. DIAGNOSIS: Chest computed tomography showed diffuse patchy shadows in both lungs, and pleural and pericardial effusions. Immunohistochemical lung tissue staining showed lymphatic and vascular endothelial cells positive for D2-40, CD31 and CD34. Routine blood test revealed platelets at 62 × 10 cells/L during follow-up. Bone marrow biopsy was normal. Ultrasound revealed no hepatosplenomegaly. Finally, the patient was diagnosed with DPL accompanied by thrombocytopenia. INTERVENTIONS: He was treated by subtotal pericardial resection, thoracocentesis, and anti-infective therapy. Oral prednisone was administered for 2 months. OUTCOMES: The symptoms of cough and shortness of breath were improved, but thrombocytopenia persisted. We investigated the cause of thrombocytopenia. Whole-exome sequencing identified a mutation in exon 3 of the TNFRSF13B gene in this patient. CONCLUSION: DPL may present with thrombocytopenia and DIC. Patients with thrombocytopenia but not DIC and splenomegaly should be screened for gene mutations.

Clinical characteristics of pulmonary cryptococcosis coexisting with lung adenocarcinoma: Three case reports.

BACKGROUND: Pulmonary cryptococcosis (PC) is an invasive fungal disease caused mainly by Cryptococcus (C.) neoformans or C. gattii. It may be present in immunocompetent or immunocompromised patients. The radiographic features of PC vary, and the most common computed tomography manifestation is the presence of solitary or multiple pulmonary nodules or masses distributed in the outer zone of the lung field. The appearance of nodular or mass-like PC on computed tomography scans resembles that of primary or metastatic lung cancers, and differential diagnosis is sometimes difficult. The coexistence of PC and malignant tumors is rarely observed. CASE SUMMARY: This paper reports three cases of PC combined with lung adenocarcinoma diagnosed by video-assisted thoracic surgery lung biopsy, which were successfully managed by early diagnosis and treatment. CONCLUSION: The present case report might serve as a reminder not to neglect PC coexisting with adenocarcinoma. Early diagnosis and treatment lead to a better prognosis.

The Neuropilin-1 Ligand, Sema3A, Acts as a Tumor Suppressor in the Pathogenesis of Acute Leukemia.

Semaphorin-3A (Sema3A) and vascular endothelial growth factor (VEGF165) are ligands of neuropilin-1 (NRP-1 or CD304) and are related to immunoregulation and tumor angiogenesis, respectively. However, possible interactions between NRP-1 and Sema3A and VEGF165 in acute leukemia remain unclear, especially whether Sema3A plays a role in acute leukemia. In this study, both of the proportion of regulatory T cells (Tregs) and their expression of NRP-1 were found to increase in acute leukemia patients compared with healthy controls. In contrast, lower mRNA and plasma levels of Sema3A were detected in the acute leukemia patients. In vitro, the addition of exogenous Sema3A inhibited the expression of NRP-1 on Tregs and it promoted apoptosis of leukemia cells. However, in the presence of anti-Sema3A antibody, the effect of rhSema3A on NRP-1 expression was reversed. These results suggest that Sema3A promotes apoptosis in leukemia cells by inhibiting expression of NRP-1, and thus, represents a tumor suppressor protein with a role in the pathogenesis of acute leukemia. Consequently, NRP-1/Sema3A signaling may represent a novel target for the treatment of acute leukemia and should be further studied. Anat Rec, 302:1127-1135, 2019. © 2018 Wiley Periodicals, Inc.

NS3 Protein from Rice stripe virus affects the expression of endogenous genes in Nicotiana benthamiana.

BACKGROUND: Rice stripe virus (RSV) belongs to the genus Tenuivirus. It is transmitted by small brown planthoppers in a persistent and circulative-propagative manner and causes rice stripe disease (RSD). The NS3 protein of RSV, encoded by the viral strand of RNA3, is a viral suppressor of RNA silencing (VSR). NS3 plays a significant role in viral infection, and NS3-transgenic plants manifest resistance to the virus. METHODS: The stability and availability of NS3 produced by transgenic Nicotiana benthamiana was investigated by northern blot analysis. The accumulation of virus was detected by western blot analysis. Transcriptome sequencing was used to identify differentially expressed genes (DEGs) in NS3-transgenic N. benthamiana. RESULTS: When the host plants were inoculated with RSV, symptoms and viral accumulation in NS3-transgenic N. benthamiana were reduced compared with the wild type. Transcriptome analysis identified 2533 differentially expressed genes (DEGs) in the NS3-transgenic N. benthamiana, including 597 upregulated genes and 1936 downregulated genes. These DEGs were classified into three Gene Ontology (GO) categories and were associated with 43 GO terms. KEGG pathway analysis revealed that these DEGs were involved in pathways associated with ribosomes (ko03010), photosynthesis (ko00195), photosynthesis-antenna proteins (ko00196), and carbon metabolism (ko01200). More than 70 DEGs were in these four pathways. Twelve DEGs were selected for RT-qPCR verification and subsequent analysis. The results showed that NS3 induced host resistance by affecting host gene expression. CONCLUSION: NS3, which plays dual roles in the process of infection, may act as a VSR during RSV infection, and enable viral resistance in transgenic host plants. NS3 from RSV affects the expression of genes associated with ribosomes, photosynthesis, and carbon metabolism in N. benthamiana. This study enhances our understanding of the interactions between VSRs and host plants.