A novel function of claudin-5 in maintaining the structural integrity of the heart and its implications in cardiac pathology.

This study aims to investigate the role of claudin-5 (Cldn5) in cardiac structural integrity. Proteomic analysis was performed to screen the protein profiles in enlarged left atrium from atrial fibrillation (AF) patients. Cldn5 shRNA adeno-associated virus (AAV) or siRNA was injected into the mouse left ventricle or added into HL1 cells respectively to knockdown Cldn5 in cardiomyocytes to observe whether the change of Cldn5 influences cardiac morphology and function, and affects those protein expressions stem from the proteomic analysis. Mitochondrial density and membrane potential were also measured by Mitotracker staining and JC-1 staining under the confocal microscope in HL1 cells. Cldn5 was reduced in cardiomyocytes from the left atrial appendage of AF patients compared to non-AF donors. Proteomic analysis showed 83 proteins were less abundant and 102 proteins were more abundant in AF patients. KEGG pathway analysis showed less abundant CACNA2D2, CACNB2, MYL2 and MAP6 were highly associated with dilated cardiomyopathy. Cldn5 shRNA AAV injection caused severe cardiac atrophy, dilation and myocardial dysfunction in mice. The decreases in mitochondrial numbers and mitochondrial membrane potentials in HL1 cells were observed after Cldn5 knockdown. We demonstrated for the first time the mechanism of Cldn5 downregulation-induced myocyte atrophy and myocardial dysfunction might be associated with the downregulation of CACNA2D2, CACNB2, MYL2 and MAP6, and mitochondrial dysfunction in cardiomyocytes.

Comparative analysis of clinical features of lower respiratory tract infection with respiratory syncytial virus and influenza virus in adults: a retrospective study.

BACKGROUND: Respiratory syncytial virus (RSV) infection in adults remains less recognized and understood, both socially and clinically, compared to influenza virus infection. This retrospective study aims to delineate and compare the clinical manifestations of adult RSV and influenza virus infections in the lower respiratory tract, thereby enhancing awareness of RSV lower respiratory tract infection and providing strategic insights for its prevention and treatment. METHODS: Clinical data from January 2019 to December 2020 were analyzed for 74 patients with RSV and 129 patients with influenza A/B virus lower respiratory tract infections who were admitted to respiratory or intensive care units. All patients had complete clinical data with positive IgM and negative IgG viral antibodies. Comparison parameters included onset timing, baseline data, clinical manifestations, supplementary examination results, treatment methods, and prognosis, while logistic regression was employed to ascertain the correlation of clinical features between the two patient groups. RESULTS: In comparison to the influenza group, the RSV group presented less frequently with fever at admission but exhibited a higher incidence of dyspnea and wheezing on pulmonary auscultation (P < 0.01). RSV infection was more prevalent among patients with underlying diseases, particularly chronic obstructive pulmonary disease (COPD) and demonstrated a higher probability of co-infections, most notably with Mycoplasma (P < 0.01). The RSV group had significantly higher lymphocyte counts (P < 0.01) and exhibited more incidences of pleural thickening, pulmonary fibrosis, and emphysema (P < 0.05). The use of non-invasive mechanical ventilation was more common, and hospital stays were longer in the RSV group compared to the influenza group (P < 0.05). Logistic multivariate regression analysis further revealed that age and tachypnea incidence were significantly higher in the RSV group (P < 0.05). CONCLUSION: Compared to influenza virus infection, adults with COPD are more susceptible to RSV infection. Moreover, RSV infection elevates the risk of co-infection with Mycoplasma and may lead to conditions such as pleural thickening, pulmonary fibrosis, and emphysema. The requirement for non-invasive mechanical ventilation is higher in RSV-infected patients, who also tend to have longer hospital stays. Therefore, greater awareness and preventive strategies against RSV infection are imperative.

N 6-methyladenosine modification contributes to respiratory syncytial virus infection.

Background: Respiratory syncytial virus (RSV) is the second leading cause of death due to lower respiratory tract infections. Effective prevention and treatment measures are lacking, posing a huge socioeconomic burden to the world. N 6-methyladenosine (m6A) is the most common internal modification in messenger RNA and noncoding RNA. Numerous recent studies have shown that the dysregulation of m6A modification is associated with diseases caused by pathogenic viruses. Methods: The changes in m6A modification were evaluated using m6A RNA methylation assay. The differences in gene expression levels of various m6A-modifying enzymes were observed using Quantitative Real-time PCR (qRT-PCR) during RSV infection. The autophagosomes were observed using transmission electron microscopy, and the expression of autophagy-associated protein Microtubule Associated Protein 1 Light Chain 3 Beta Ⅱ/Ⅰ (LC3B Ⅱ/Ⅰ) and Beclin1 in Human Normal Lung Epithelial Cells (BEAS-2B) cells using Western blot during RSV infection. The significantly differentially expressed genes were screened guided by bioinformatics. Their relationship with m6A-modifying enzymes was analyzed through protein-protein interaction network and expression correlation analysis. Results: The m6A abundance decreased and demethylase Fat Mass and Obesity- Associated Protein (FTO) significantly increased during RSV infection after 24 h. We also found that the DNA Damage-Inducible Transcript 3 Protein (DDIT3) level significantly increased during RSV infection after 24 h and observed autophagosomes in BEAS-2B cells. In addition, RSV infection could cause the upregulation of LC3B Ⅱ/Ⅰ and Beclin1. The expression correlation analysis showed that DDIT3 levels were positively correlated with the FTO level, and Methyltransferase Like 3 (METTL3), RNA Binding Motif Protein 15B (RBM15B), YTH Domain-Containing Family Protein 1 (YTHDF1), and levels were negatively correlated with the DDIT3 level. Conclusions: We uncovered a significant role for m6A modification during RSV infection. Also, a correlation was found between m6A and autophagy, providing new ideas for therapeutic advancements in RSV treatment.

Comprehensive analysis of an endoplasmic reticulum stress-related gene prediction model and immune infiltration in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease. This study aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in IPF and explore its correlation with immune infiltration. Methods: ERS-related differentially expressed genes (ERSRDEGs) were identified by intersecting differentially expressed genes (DEGs) from three Gene Expression Omnibus datasets with ERS-related gene sets. Gene Set Variation Analysis and Gene Ontology were used to explore the potential biological mechanisms underlying ERS. A nomogram was developed using the risk signature derived from the ERSRDEGs to perform risk assessment. The diagnostic value of the risk signature was evaluated using receiver operating characteristics, calibration, and decision curve analyses. The ERS score of patients with IPF was measured using a single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. Subsequently, a prognostic model based on the ERS scores was established. The proportion of immune cell infiltration was assessed using the ssGSEA and CIBERSORT algorithms. Finally, the expression of ERSRDEGs was validated in vivo and in vitro via RT-qPCR. Results: This study developed an 8-ERSRDEGs signature. Based on the expression of these genes, we constructed a diagnostic nomogram model in which agouti-related neuropeptide had a significantly greater impact on the model. The area under the curve values for the predictive value of the ERSRDEGs signature were 0.975 and 1.000 for GSE70866 and GSE110147, respectively. We developed a prognostic model based on the ERS scores of patients with IPF. Furthermore, we classified patients with IPF into two subtypes based on their signatures. The RT-qPCR validation results supported the reliability of most of our conclusions. Conclusion: We developed and verified a risk model using eight ERSRDEGs. These eight genes can potentially affect the progression of IPF by regulating ERS and immune responses.

Analysis of Clinical Characteristics of Connective Tissue Disease-Associated Interstitial Lung Disease in 161 Patients: A Retrospective Study.

Objective: This study was conducted to retrospectively analyze the clinical characteristics of CTD-ILD patients to provide strategies for clinical management. Methods: This study collected and analyzed the clinical data and relevant examination results of 161 patients diagnosed with CTD-ILD between 01 January 2018 and 01 January 2021. Results: A total of 161 CTD-ILD patients, 74.53% were females and 25.47% were males, 32.92% were elderly and 67.08% were non-elderly. The main clinical symptoms of CTD-ILD patients were cough (44.72%), decreased activity tolerance (40.37%). RA-ILD was the most common one in the non-elderly and the elderly CTD-ILD patients (48.15% and 50.94%, respectively). Compared with non-elderly, elderly patients with CTD-ILD had a longer duration of CTD (p=0.04). However, fatigue (p=0.005), activity tolerance (p=0.029), the incidence of pulmonary diffusion dysfunction (p=0.047), and systemic immunoinflammatory index (SII, p=0.014) (platelet × NLR) were all decreased. The standard deviation of red blood cell distribution width (RDW) (p=0.024) and immunoglobulin (IgA) (p=0.033) was significantly increased. The smoking index was significantly higher in men than in women with CTD-ILD (p=0.000), but symptoms of reduced activity tolerance were less pronounced than in women (p<0.05). Elderly CTD-ILD patients (p=0.003) and women from non-elderly patients were prone to lower hemoglobin (p=0.000). Among the elderly, the lymphocyte ratio was more significantly elevated in female CTD-ILD patients than in males (p=0.018). In contrast, neutrophil to lymphocyte ratio (NLR) and SII were lower in female (p=0.038) than in male CTD-ILD patients (p=0.043). Conclusion: CTD-ILD mainly affects non-elderly and women. Age may not be involved with decreased activity tolerance and increased lung function impairment in CTD-ILD patients. However, the elderly patients with CTD-ILD, especially the elderly female patients with low inflammation levels and high immune disorders, have a poor prognosis.

PPA1, an energy metabolism initiator, plays an important role in the progression of malignant tumors.

Inorganic pyrophosphatase (PPA1) encoded by PPA1 gene belongs to Soluble Pyrophosphatases (PPase) family and is expressed widely in various tissues of Homo sapiens, as well as significantly in a variety of malignancies. The hydrolysis of inorganic pyrophosphate (PPi) to produce orthophosphate (Pi) not only dissipates the negative effects of PPi accumulation, but the energy released by this process also serves as a substitute for ATP. PPA1 is highly expressed in a variety of tumors and is involved in proliferation, invasion, and metastasis during tumor development, through the JNK/p53, Wnt/ß-catenin, and PI3K/AKT/GSK-3ß signaling pathways. Because of its remarkable role in tumor development, PPA1 may serve as a biological target for adjuvant therapy of tumor malignancies. Further, PPA1 is a potential biomarker to predict survival in patients with cancer, where the assessment of its transcriptional regulation can provide an in-depth understanding. Herein, we describe the signaling pathways through which PPA1 regulates malignant tumor progression and provide new insights to establish PPA1 as a biomarker for tumor diagnosis.

Characterization of the fatty acid metabolism-related genes in lung adenocarcinoma to guide clinical therapy.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common cancer with a bad prognosis. Numerous investigations have indicated that the metabolism of fatty acids plays an important role in the occurrence, progression, and treatment of cancer. Consequently, the objective of the current investigation was to elucidate the role and prognostic significance of genes associated with fatty acid metabolism in patients diagnosed with LUAD. MATERIALS AND METHODS: The data files were acquired from The Cancer Genome Atlas database and GSE31210 dataset. Univariate Cox and least absolute shrinkage and selection operator regression analyses were conducted to establish a prognostic risk scoring model depending on fatty acid metabolism-associated genes to predict the prognosis of patients with LUAD. pRRophetic algorithm was utilized to evaluate the potential therapeutic agents. Gene set variation analysis combined with cell-type identification based on the estimation of relative subsets of RNA transcript and single-sample gene set enrichment analysis was used to determine the association between immune cell infiltration and risk score. Tumor immune dysfunction and exclusion algorithm was employed to predict immunotherapeutic sensitivity. RESULTS: To forecast the prognosis of patients with LUAD, a risk scoring model based on five genes associated with fatty acid metabolism was developed, including LDHA, ALDOA, CYP4B1, DPEP2, and HPGDS. Using the risk score algorithm, patients were divided into higher- and lower-risk categories. Patients classified as minimal risk showed superior prognosis than those with elevated risk. In addition, individuals in the higher-risk group had a proclivity toward chemoresistance and amenable to immunotherapy. CONCLUSION: The prognostic risk scoring model aids in estimating the prognosis of LUAD patients. It may also provide new insights into LUAD carcinogenesis and therapeutic strategies.

Pulmonary hypertension secondary to seronegative rheumatoid arthritis overlapping antisynthetase syndrome: A case report.

BACKGROUND: Polyarthritis is the most frequent clinical manifestation in antisynthetase syndrome (ASS) forms of idiopathic inflammatory myositis and may be misdiagnosed as rheumatoid arthritis (RA), particularly in patients with seronegative RA (SNRA). It is unclear whether there is an overlap between ASS and RA, or if ASS sometimes mimics RA. Pulmonary hypertension (PAH) is common in connective tissue diseases (CTDs). However, published reports on CTD-PAH do not include overlapping CTDs, and its incidence and impact on patient prognosis are unclear. CASE SUMMARY: We report the case of a 63-year-old woman who presented with a 3-mo history of symptom aggravation of recurrent symmetrical joint swelling and pain that had persisted for over 10 years. The patient was diagnosed with RA and interstitial lung disease. The patient repeatedly presented to the hospital's respiratory and rheumatology departments with arthralgia, plus shortness of breath after activity. Relevant tests indicated that anti-CCP and RF remained negative, while anti-J0-1 and anti-Ro-52 were strongly positive. It was not until recently that we recognized that this could be an unusual case of SNRA with concurrent ASS. Joint pain was relieved after regular anti-rheumatic treatment. Chest computed tomography scans showed that pulmonary interstitial changes did not progress significantly over several years; however, they showed gradual widening of the pulmonary artery, and cardiac ultrasound indicated elevated pulmonary artery systolic pressure. The prescribed treatment of PAH was not effective in improving shortness of breath. CONCLUSION: Overlap of RA and ASS may be missed. Further research is necessary to facilitate early diagnosis, effective evaluation, and prognosis.

Ultrasound imaging features of bronchial anthracofibrosis: A case-control study.

To determine the ultrasound imaging characteristics of patients with bronchial anthracofibrosis (BAF) and identify clinical markers for prevention and treatment. We randomly selected 1243 participants (113 with BAF) who underwent bronchoscopy and received treatment at our institution between April 2018 and October 2019. BAF was classified as flat, deep-seated retracted, or black mucosal protruding based on microscopic findings. Ultrasound probes were used to determine the maximum thickness of the tube walls and submucosa. The average values of the submucosal and bony tissue areas in the BAF subtypes were compared. The BAF group included 13 participants with a history of tuberculosis (11.5%) and 57 participants with biofuel exposure (50.4%). The average exposure time was 17.4 ± 6.2 years; BAF accounted for 10% of the bronchoscopies performed. The maximum tube-wall thicknesses of the deep-seated retracted (17.3 ± 5.7) and black mucosal protruding (19.3 ± 5.4) groups were significantly greater than those of the flat group (12.5 ± 5.0; P < .05). The maximum thicknesses of the submucosa in the deep-retracted (9.8 ± 3.0) and black mucosal protruding (14.5 ± 5.0) groups were significantly greater than that of the flat group (6.6 ± 3.5; P < .05). The ratios of bone tissue in the flat and black mucosal protruding groups were 33.3 ± 9.3% and 34.9% ± 12.1%, respectively. The ratio in the deep-seated retracted group (65.2% ± 8.7%) was significantly reduced (P < .05). The flat group showed no significant change (P > .05). Differences in BAF airway remodeling among different subtypes may lead to varying clinical symptoms. Analyzing the characteristics of BAF airway remodeling and the regulatory pathway may provide new clues for treatment.

Integrated Trinity Test With RPA-CRISPR/Cas12a-Fluorescence for Real-Time Detection of Respiratory Syncytial Virus A or B.

Respiratory syncytial virus (RSV) is a common virus that causes respiratory infection, especially severe respiratory infection in infants and young children, the elderly people over 65 years old, and people with weak immunity. Currently, RSV infection has no effective vaccine and antiviral treatment. The number of deaths due to RSV infection increases every year. Moreover, RSV A infection occurs in a large number and has severe clinical symptoms and complications than RSV B infection. Therefore, the development of a simple, rapid, and inexpensive detection method with high amplification efficiency, high sensitivity, and specificity is very important for the diagnosis of RSV A or RSV B infection, which can help in the early clinical medication and prevent the progress of the disease. Therefore, we developed an integrated trinity test with an RPA-CRISPR/Cas12a-fluorescence (termed IT-RAISE) assay system to detect RSV A or RSV B. The characteristic of the IT-RAISE system is that after target recognition, the reporter single-stranded DNA (ssDNA) is cleaved by Cas12a that is activated by different crRNAs to detect the generated fluorescent signal. This method is simple and helps in adding all reagents rapidly. It is a high-sensitive method that can detect 1.38 × 101 copies/µl of the target sequences, and it can distinguish RSV A or RSV B infection within 37 min. In addition, clinical specimens were detected for IT-RAISE system. It was found that the sensitivity and specificity of RSV A were 73.08 and 90%, respectively, and those of RSV B were 42.86 and 93.33%, respectively. The cost of ONE specimen for IT-RAISE system was approximately $ 2.6 (excluding rapid RNA extraction and reverse transcription costs). IT-RAISE system has good clinical application prospects for detecting RSV A or RSV B infection; it is a simple, rapid, and inexpensive method with high amplification efficiency, high sensitivity, and high specificity. The IT-RAISE system might also detect other viral or bacterial infections.

Using biological information to analyze potential miRNA-mRNA regulatory networks in the plasma of patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is the most common malignant tumor, and it has a high mortality rate. However, the study of miRNA-mRNA regulatory networks in the plasma of patients with non-small cell lung cancer (NSCLC) is insufficient. Therefore, this study explored the differential expression of mRNA and miRNA in the plasma of NSCLC patients. METHODS: The Gene Expression Omnibus (GEO) database was used to download microarray datasets, and the differentially expressed miRNAs (DEMs) were analyzed. We predicted transcription factors and target genes of the DEMs by using FunRich software and the TargetScanHuman database, respectively. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for GO annotation and KEGG enrichment analysis of downstream target genes. We constructed protein-protein interaction (PPI) and DEM-hub gene networks using the STRING database and Cytoscape software. The GSE20189 dataset was used to screen out the key hub gene. Using The Cancer Genome Atlas (TCGA) and UALCAN databases to analyze the expression and prognosis of the key hub gene and DEMs. Then, GSE17681 and GSE137140 datasets were used to validate DEMs expression. Finally, the receiver operating characteristic (ROC) curve was used to verify the ability of the DEMs to distinguish lung cancer patients from healthy patients. RESULTS: Four upregulated candidate DEMs (hsa-miR199a-5p, hsa-miR-186-5p, hsa-miR-328-3p, and hsa-let-7d-3p) were screened from 3 databases, and 6 upstream transcription factors and 2253 downstream target genes were predicted. These genes were mainly enriched in cancer pathways and PI3k-Akt pathways. Among the top 30 hub genes, the expression of KLHL3 was consistent with the GSE20189 dataset. Except for let-7d-3p, the expression of other DEMs and KLHL3 in tissues were consistent with those in plasma. LUSC patients with high let-7d-3p expression had poor overall survival rates (OS). External validation demonstrated that the expression of hsa-miR-199a-5p and hsa-miR-186-5p in peripheral blood of NSCLC patients was higher than the healthy controls. The ROC curve confirmed that the DEMs could better distinguish lung cancer patients from healthy people. CONCLUSION: The results showed that miR-199a-5p and miR-186-5p may be noninvasive diagnostic biomarkers for NSCLC patients. MiR-199a-5p-KLHL3 may be involved in the occurrence and development of NSCLC.

Bioinformatics Analysis of mRNAs and miRNAs for Identifying Potential Biomarkers in Lung Adenosquamous Carcinoma.

Background: Lung adenosquamous carcinoma (LASC) is a special type of lung cancer. LASC is a malignant tumor with strong aggressiveness and a poor prognosis. Previous studies have revealed that microRNAs (miRNAs) are widely involved in the development of tumors by targeting mRNA. This study is aimed at identifying the key mRNAs and miRNAs of LASC and constructing miRNA-mRNA networks for deeply comprehending the latent molecular mechanisms. Methods: mRNA dataset (GSE51852) and miRNA dataset (GSE51853) were extracted and downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were picked out by the GEO2R web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were conducted in the DAVID database. The protein-protein interaction (PPI) network was performed and analyzed by using the STRING database and Cytoscape software, respectively. TransmiR v2.0 was applied to predict potential transcription factors of miRNAs. The target genes of DEMs were predicted in the miRWalk database. Results: In comparison to normal tissues, a total of 1458 DEGs (511 upregulated and 947 downregulated) and 13 DEMs (5 upregulated and 8 downregulated) were screened out in LASC tissues. The PPI network of the DEGs displayed five key modules and seventeen hub genes. Six target genes of the DEMs were predicted, and five essential miRNA-mRNA regulatory pairs were established. Ensuingly, CENPF, one of the target genes, was also the hub genes of GSE51852, which was obtained from MCODE and cytoHubba and regulated by hsa-miR-205. Conclusions: We constructed the miRNA-mRNA regulatory pairs, which are helpful to study the potential regulatory mechanisms and find out promising diagnosis biomarkers and therapeutic targets for LASC.

Association between inflammatory biomarkers and acute respiratory distress syndrome or acute lung injury risk : A systematic review and meta-analysis.

BACKGROUND: The relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose of this meta-analysis was to summarize the available studies evaluating the association between levels of inflammatory factors and ARDS/ALI incidence. METHODS: We searched the PubMed, EmBase, and Cochrane databases for studies published up to July 2017. For each inflammatory factor, a random effects model was employed to pool results from different studies. RESULTS: We identified 63 studies that included 6243 patients in our meta-analysis. Overall, the results indicated that the levels of angiopoietin (ANG)-2 (standard mean difference, SMD: 1.34; P < 0.001), interleukin (IL)-1ß (SMD: 0.92; P = 0.012), IL­6 (SMD: 0.66; P = 0.005), and tumor necrosis factor (TNF)-α (SMD: 0.98; P = 0.001) were significantly higher in patients with ARDS/ALI than in unaffected individuals. No significant differences were observed between patients with ARDS/ALI and unaffected individuals in terms of the levels of IL­8 (SMD: 0.61; P = 0.159), IL-10 (SMD: 1.10; P = 0.231), and plasminogen activator inhibitor (PAI)-1 (SMD: 0.70; P = 0.060). CONCLUSIONS: ARDS/ALI is associated with a significantly elevated levels of ANG­2, IL-1ß, IL­6, and TNF­α, but not with IL­8, IL-10, and PAI­1 levels.

Mesenchymal stem cells after the proprocessing of tanshinone IIA attenuate cognitive deficits and oxidative stress injury in an amyloid ß-peptide (25-35)-induced rodent model of Alzheimer's disease.

OBJECTIVES: To verify whether mesenchymal stem cells cocultured with tanshinone IIA may ameliorate Alzheimer's disease by inhibiting oxidative stress. METHODS: Sixty male Sprague-Dawley rats were randomly divided into 4 groups named Sham, Aß25-35, mesenchymal stem cells, and mesenchymal stem cells (tanshinone IIA). The rats were treated according to different groups. The neurobehavioral performance of Sprague-Dawley rats was evaluated via Morris water maze test. Histological changes were checked via hematoxylin-eosin staining. The levels of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde in hippocampus were assayed by ELISA kit. The levels of Aß, p-tau/tau, and p-AMP-activated protein kinase/AMP-activated protein kinase in hippocampus were checked by Western blot. RESULTS: Our research showed that the injection of mesenchymal stem cells (tanshinone IIA) into the hippocampus alleviated learning and memory deficits and reduced hippocampal neuronal injury in the Alzheimer's disease rats. Moreover, mesenchymal stem cells (tanshinone IIA) treatment suppressed oxidative stress, attenuated Aß accumulation reduced Tau hyperphosphorylation, and enhanced the activity of AMP-activated protein kinase in the hippocampus of the Alzheimer's disease rats. However, there were almost no significant difference between the mesenchymal stem cells and Aß25-35 groups. CONCLUSIONS: Mesenchymal stem cells (tanshinone IIA) transplantation may be a potential treatment for curing Alzheimer's disease, which may be related to the inhibition of oxidative stress.

Association between peripheral blood WBCs C3aR mRNA level and plasma C3a, C3aR, IL-1ß concentrations and acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The relationship between C3a-C3aR, IL-1ß, and the acute exacerbation of chronic obstructive pulmonary disease is still unclear. This study aims to explore the expression levels of C3aR in peripheral blood WBCs and the concentrations of C3a, C3aR, and IL-1ß in plasma in healthy controls and patients with chronic obstructive pulmonary disease (COPD). METHODS: WBCs C3aR level in the peripheral blood, the concentrations of C3a, C3aR, and IL-1ß in plasma were measured in 60 patients with acute exacerbation of COPD (AECOPD), 30 patients with stable COPD (SCOPD), and 30 healthy controls. The baseline characteristics and clinical data collected from enrolled patients, including age, gender, laboratory indicators, and lung function. We analyzed the correlation between C3a, C3aR, IL-1ß, and lung function indicators (forced expiratory volume in the first second as a percentage of predicted value, FEV1%pred) in the AECOPD group. RESULTS: The white blood cell count (WBC), neutrophil/lymphocyte ratio (NLR), and C-reactive protein (CRP) of patients in COPD were higher than in healthy controls (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD were higher than in SCOPD and healthy controls (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3aR, and IL-1ß in AECOPD combined with respiratory failure were higher than in the non-respiratory failure group (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD with high-risk were higher than in the low-risk group (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD were negatively correlated with FEV1pred%. The peripheral blood WBCs C3aR mRNA, the plasma C3a and C3aR in AECOPD were positively correlated with IL-1ß. CONCLUSION: The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in COPD patients were significantly related to the risk of disease deterioration. The C3a-C3aR axis may be involved in airway inflammation in patients with COPD.

The prognostic relevance of 14-3-3ξ expression in cancers: A meta-analysis.

OBJECTIVE: To gain an enhanced understanding of the prognostic importance of 14-3-3ξ levels in cancer patients. METHODS: The meta-analysis and systematic review was conducted in October 2019. Two reviewers independently reviewed Web of Science, Embase and PubMed databases to identify published studies using relevant key words. The correlation between the level of 14-3-3ξ and cancer patient survival was assessed based upon pooled hazard ratios and 95% confidence intervals derived from the selected studies. Data was analysed using STATA 12. RESULTS: Of the 244 studies initially identified, 22(9%) were included, and they comprised 2,676 patients. Elevated 14-3-3ξ level correlated significantly with poorer overall survival (hazard ratio: 1.93; 95% confidence interval: 1.42-2.61) in cancer patients. With respect to disease-free survival, the pooled hazard ratio for cancer patients expressing high levels of 14-3-3ξ was 1.89 (95% confidence interval: 1.56-2.30). Patients with elevated 14-3-3ξ expression also exhibited reduced cancer-specific survival (hazard ratio: 3.47; 95% confidence interval: 2.12-5.69). CONCLUSIONS: Higher level of 14-3-3ξ correlated with poorer patient prognosis in a range of cancer types.

Downregulation of miR­483­5p inhibits TGF­ß1­induced EMT by targeting RhoGDI1 in pulmonary fibrosis.

Transforming growth factor­ß1 (TGF­ß1)­induced epithelial­mesenchymal transition (EMT) serves a significant role in pulmonary fibrosis (PF). Increasing evidence indicates that microRNAs (miRNAs or miRs) contribute to PF pathogenesis via EMT regulation. However, the role of miR­483­5p in PF remains unclear. Therefore, the present study investigated the potential effect of miR­483­5p on TGF­ß1­induced EMT in PF. It was found that the expression of miR­483­5p was upregulated in both PF tissue and A549 cells treated with TGF­ß1, whereas expression of Rho GDP dissociation inhibitor 1 (RhoGDI1) was downregulated. miR­483­5p mimic transfection promoted TGF­ß1­induced EMT; by contrast, miR­483­5p inhibitor inhibited TGF­ß1­induced EMT. Also, miR­483­5p mimic decreased RhoGDI1 expression, whereas miR­483­5p inhibitor increased RhoGDI1 expression. Furthermore, dual­luciferase reporter gene assay indicated that miR­483­5p directly regulated RhoGDI1. Moreover, RhoGDI1 knockdown eliminated the inhibitory effect of the miR­483­5p inhibitor on TGF­ß1­induced EMT via the Rac family small GTPase (Rac)1/PI3K/AKT pathway. In conclusion, these data indicated that miR­483­5p inhibition ameliorated TGF­ß1­induced EMT by targeting RhoGDI1 via the Rac1/PI3K/Akt signaling pathway in PF, suggesting a potential role of miR­483­5p in the prevention and treatment of PF.

A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma.

BACKGROUND: Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. METHODS: The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. RESULTS: Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. CONCLUSION: A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.

Analysis of Incidence and Clinical Characteristics of RSV Infection in Hospitalized Children: A Retrospective Study.

OBJECTIVE: To investigate the incidence and clinical characteristics of hospitalized children with respiratory syncytial virus (RSV) infection, and to provide evidence for the importance of preventive strategies and improvements in supportive care of RSV infection. METHODS: This retrospective study included children under 14 years who received throat swab test and were diagnosed with RSV infection from January 2019 to December 2020. Throat swabs and intravenous blood were the main sources of samples, which were obtained within 24 hours of hospitalization. Direct immunofluorescence assay was used to diagnose RSV infection. RESULTS: Among the 448 hospitalized children with RSV infection, males (71.9%) showed the highest proportion, the highest incidence was found in children<6 months old (45.3%), and 76.6% of them had pneumonia. Pharyngeal redness, cough, expectoration, and mental fatigue were the most common symptoms in hospitalized children of all ages. More than 60% of hospitalized children had increased lymphocyte count, aspartate aminotransferase, creatine kinase-MB form, lactate dehydrogenase, and α-HBDH levels. The rates of myocardial damage, respiratory failure, stay in the intensive care unit (ICU), use of mechanical ventilation, and absorption of oxygen were higher in children<6 months old. Except for children who were 37-60 months old, the percentage of length of hospital stay≥7 days in the other age groups was greater than 62.0%. Except for children who were 0-28 days old and>61 months old, the other age groups showed a re-hospitalization situation due to re-infection with RSV. In hospitalized children diagnosed with RSV infection from throat swabs, we also performed the RSV IgM test and found that 59.2% of them were positive, 8.0% of them were weakly positive, and 32.8% of them were negative. CONCLUSION: This study analyzes the incidence and clinical characteristics of hospitalized children with RSV infection, which provides evidence for the importance of preventive strategies and improvements in supportive care of RSV infection.

Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats.

Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke.