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Pulmonary arterial hypertension (PAH) is a complex and serious cardiopulmonary disease; it is characterised by increased pulmonary arterial pressure and pulmonary vascular remodelling accompanied by disordered endothelial and smooth muscle cell proliferation within pulmonary arterioles and arteries. Although recent reports have suggested that dysregulated immunity and inflammation are key players in PAH pathogenesis, their roles in PAH progression remain unclear. Intriguingly, altered host immune cell distribution, number, and polarisation within the lung arterial vasculature have been linked to disease development. This review mainly focusses on the roles of different immune cells in PAH and discusses the underlying mechanisms.

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Cytokine storm is a phenomenon characterized by strong elevated circulating cytokines that most often occur after an overreactive immune system is activated by an acute systemic infection. A variety of cells participate in cytokine storm induction and progression, with profiles of cytokines released during cytokine storm varying from disease to disease. This review focuses on pathophysiological mechanisms underlying cytokine storm induction and progression induced by pathogenic invasive infectious diseases. Strategies for targeted treatment of various types of infection-induced cytokine storms are described from both host and pathogen perspectives. In summary, current studies indicate that cytokine storm-targeted therapies can effectively alleviate tissue damage while promoting the clearance of invading pathogens. Based on this premise, "multi-omics" immune system profiling should facilitate the development of more effective therapeutic strategies to alleviate cytokine storms caused by various diseases.

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Background: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there are limited studies reflecting the available biomarkers from separate gene expression profiles in PAH. This study explored two microarray datasets by an integrative analysis to estimate the molecular signatures in PAH. Methods: Two microarray datasets (GSE53408 and GSE113439) were exploited to compare lung tissue transcriptomes of patients and controls with PAH and to estimate differentially expressed genes (DEGs). According to common DEGs of datasets, gene and protein overrepresentation analyses, protein-protein interactions (PPIs), DEG-transcription factor (TF) interactions, DEG-microRNA (miRNA) interactions, drug-target protein interactions, and protein subcellular localizations were conducted in this study. Results: We obtained 38 common DEGs for these two datasets. Integration of the genome transcriptome datasets with biomolecular interactions revealed hub genes (HSP90AA1, ANGPT2, HSPD1, HSPH1, TTN, SPP1, SMC4, EEA1, and DKC1), TFs (FOXC1, FOXL1, GATA2, YY1, and SRF), and miRNAs (hsa-mir-17-5p, hsa-mir-26b-5p, hsa-mir-122-5p, hsa-mir-20a-5p, and hsa-mir-106b-5p). Protein-drug interactions indicated that two compounds, namely, nedocromil and SNX-5422, affect the identification of PAH candidate biomolecules. Moreover, the molecular signatures were mostly localized in the extracellular and nuclear areas. Conclusions: In conclusion, several lung tissue-derived molecular signatures, highlighted in this study, might serve as novel evidence for elucidating the essential mechanisms of PAH. The potential drugs associated with these molecules could thus contribute to the development of diagnostic and therapeutic strategies to ameliorate PAH.

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Orf is an epithelial zoonotic infectious disease caused by orf virus (ORFV). Mounting studies have shown that IL-17-driven neutrophil inflammation plays a central role in inflammatory skin diseases. However, whether IL-17 plays a similar role and how does it work in the pathogenesis of orf is unclear. In this study, we found that during orf development, numerous inflammatory cells, especially neutrophils, infiltrated in the damaged lip tissue. Meanwhile, the production of IL-17 was increased in the lesion site. Further evidence showed that IL-17 potently stimulated the production of several chemokines that are crucial for neutrophil migration. In addition, IL-17 was mostly produced by CD4+ T cells and gamma delta T (γδ T) cells of the skin. In conclusion, the present study highlighted a critical role of IL-17-driven inflammation in the pathogenesis of orf and suggested that this cytokine may be a potential therapeutic target of this disease in goats.

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Objective: This study aims to analyze the prevalence of dyslipidemia and identify the cardiovascular disease (CVD) risk stratification among older adults living in Quanzhou, China's southeast coastal region, where the ancient Maritime Silk Road starts. Methods: A population-based cross-sectional survey of 2,018 adults was conducted in 60-98-year-old residents in Quanzhou from September 2016 to March 2018 using multistage stratified cluster random sampling. The 10-year CVD risk was also estimated by applying the Chinese model recommended by the Chinese Guidelines for Prevention of Cardiovascular Diseases. Results: The overall prevalence of dyslipidemia among older adults was 56.8%. The prevalence of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C) and high triglyceride (TG) were 8.4%, 13.9%, 23.1% and 11.4%, respectively. The mean levels of TC, LDL-C, HDL-C and TG were 5.12±1.18, 3.37±0.81, 1.03±0.27 and 1.65±0.76 mmol/L, respectively. Older adults had low risk, moderate risk and high risk for CVD, which were 49.7%, 36.8% and 13.5%, respectively. Age, body mass index and abdominal obesity were significantly associated with the risk of increasing LDL-C levels and were positively correlated to CVD risk. Conclusion: The prevalence of high TC, high LDL-C, low HDL-C and high TG was relatively low among older adults in Quanzhou, but their lipid levels were high. Approximately half of the elderly adults had moderate or high CVD risk. The personalized primary prevention and control of CVD are recommended for elderly people to identify high-risk individuals.

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The aim of the present study was to prove that a mouse model closely simulates human oral cancer progression by comparing the expression levels of transforming growth factor (TGF)-ß1, E-cadherin, N-cadherin, tumor protein (TP)53, RB1 inducible coiled-coil (RB1CC)1 and hypoxia inducible factor (HIF)-1α at different stages of oral squamous cell carcinoma (OSCC) in humans and mice. The expression levels of TGF-ß1, E-cadherin, N-cadherin, TP53, RB1CC1, and HIF-1α were detected by immunohistochemical staining in normal oral mucosa, oral mucosa dysplasia, OSCC primary tumor and carcinoma tissues from lymph node metastases. Tissue samples were obtained from human specimens and the Balb/c mouse model of lymphatic metastases oral carcinoma, induced by 4-nitroquinoline-1-oxide in drinking water. The results indicated no significant differences in the expression levels of TGF-ß1, E-cadherin, N-cadherin, TP53, RB1CC1 and HIF-1α between humans and mice, at any stage of OSCC examined (P>0.05). The expression of TGF-ß1, N-cadherin, TP53 and RB1CC1 increased in different stages of OSCC in both humans and mice. The expression of E-cadherin decreased from normal oral mucosa to OSCC, and increased in lymph node metastases in both human and mouse samples. The expression of HIF-1α increased from normal oral mucosa to OSCC, and decreased in lymph node metastases in both human and mouse samples. Additionally, the expression of p53 was positively correlated with that of RB1CC1 in human and mouse samples (r=0.971, P=0.029; r=0.97, P=0.03). Overall, the similar expression of multiple molecules in both human and mouse carcinoma prove that the mouse model of lymphatic metastases from oral carcinoma established in the present study may closely mimic human oral cancer.

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OBJECTIVES: Heterogeneous cells appear in multiple organs during the same time period as the primary lesion of some tumors is clinically detected. These heterogeneous cells are also known as disseminated tumor cells (DTCs). However, the characteristics of DTCs that disseminate during oral carcinogenesis remain unclear. MATERIALS AND METHODS: A mouse 4NQO model of lymph node metastasis in oral squamous cell carcinoma was established. Tissue samples of the tongue, bone marrow and submandibular lymph node were collected. Five stages (stage 0~stage IV) of carcinogenesis in each experimental animal were classified by two pathologists. After immunohistochemical staining of cytokeratin, the DTCs were isolated from bone marrow samples (stage II) by the laser capture microdissection (LCM) technique during oral carcinogenesis. Genomic amplification of bone marrow DTCs was performed, and homozygous deletion of the RB1CC1 gene was analyzed. After confirming the presence of disseminated tumor cells in stage II bone marrow samples, a comprehensive study among various stages of lymph node tissue was conducted using the same method. RESULTS: DTCs that spread from the primary tumor were discovered in stage II bone marrow samples and in stage I, stage II and stage III submandibular lymph node samples through immunohistochemical staining. These spreading cells had different levels of homozygous exon deletion in the RB1CC1 and TP53 genes. CONCLUSION: Early spreading of epithelial cells may occur during the carcinogenesis of oral cancer. DTCs of oral carcinoma may show different chromosome aberrations from matched primary tumor cells.