The Impact of SARS-CoV-2 Infection on Patients with Aortic Stenosis.

OBJECTIVE: To investigate the potential treatments for aortic stenosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using bioinformatics and systems biology. STUDY DESIGN: Observational study. Place and Duration of the Study: Jiading District Central Hospital affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China, from August to December 2022. METHODOLOGY: GSE147507 was chosen as the SARS-CoV-2 infection dataset from the Biotechnology Information (NCBI) GEO database, while GSE153555 was chosen as the dataset of patients with aortic stenosis (AS). This analysis predicted protein-drug interactions (PDIs) and found therapeutic compounds for AS and COVID-19. RESULTS: One hundred and four DEGs were shared between the two datasets. Researchers built a PPI network to identify 10 hub genes from the network. Researchers discovered that COVID-19 and AS shared certain pathogenic pathways and found a relationship between hub genes and transcription factors and miRNAs, as well as a connection between hub genes and proposed treatments. CONCLUSION: Hub genes were identified as potential pathogenic pathways in SARS-CoV-2 infection and AS. In addition, new prescription medication options for treating both illnesses were provided. KEY WORDS: SARS-CoV-2 infection, COVID-19, Aortic stenosis, Differentially expressed genes, Hub genes, Gene-disease, Drug molecule.

A Bioinformatic Approach Based on Systems Biology to Determine the Effects of SARS-CoV-2 Infection in Patients with Hypertrophic Cardiomyopathy.

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide. While COVID-19 generally affects the lungs, it also damages other organs, including those of the cardiovascular system. Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disorder. Studies have shown that HCM patients with COVID-19 have a higher mortality rate; however, the reason for this phenomenon is not yet elucidated. Herein, we conducted transcriptomic analyses to identify shared biomarkers between HCM and COVID-19 to bridge this knowledge gap. Differentially expressed genes (DEGs) were obtained using the Gene Expression Omnibus ribonucleic acid (RNA) sequencing datasets, GSE147507 and GSE89714, to identify shared pathways and potential drug candidates. We discovered 30 DEGs that were common between these two datasets. Using a combination of statistical and biological tools, protein-protein interactions were constructed in response to these findings to support hub genes and modules. We discovered that HCM is linked to COVID-19 progression based on a functional analysis under ontology terms. Based on the DEGs identified from the datasets, a coregulatory network of transcription factors, genes, proteins, and microRNAs was also discovered. Lastly, our research suggests that the potential drugs we identified might be helpful for COVID-19 therapy.

PD-L1 expression with respect to driver mutations in non-small cell lung cancer in an Asian population: a large study of 1370 cases in China.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression with respect to genetic alternations has not been well established in non-small cell lung cancer (NSCLC), especially in the Asian population. METHODS: We reviewed 1370 NSCLC patients from a prospectively maintained database. Immunohistochemistry was performed on tumor cells and tumor-infiltrating lymphocytes (TILs) using the VENTANA (SP142) anti-PD-L1 antibody. The tumor proportion score (TPS) cutoff values were set at ⩾1% and ⩾50%, and the immune proportion score (IPS) cutoff values were set at ⩾1% and ⩾10%. RESULTS: In tumor cells, PD-L1 positivity was observed in 405 (29.6%), 122 (8.9%), and 27 (2.0%) patients with TPS cutoff values at ⩾1% and ⩾50%. Contrastingly, TILs of 1154 (84.2%) and 346 (25.3%) patients stained positive at IPS cutoff values of ⩾1% and ⩾50%, respectively. PD-L1 expression was more common in patients who were mutation-negative irrespective of the TPS cutoff values and tumor size. PD-L1 expression in tumor cells was less frequent in patients harboring EGFR mutations (18.8% TPS ⩾ 1% and 4.6% TPS ⩾ 50%). Conversely, PD-L1 expression was high in the presence of KRAS mutations (47.3% TPS ⩾ 1% and 22.5% TPS ⩾ 50%). Overall, KRAS, BRAF, PICK3A, MET mutations and ROS1 and RET translocations were more frequent, while EGFR and HER2 mutations and ALK translocations were less frequent compared with the overall PD-L1 expression levels. Although the difference between TILs among the PD-L1-positive cases was comparatively small, PD-L1 positivity was less prevalent in EGFR-mutated tumors and more common in those with KRAS mutations, ROS1 translocations, BRAF mutations, or MET mutations. CONCLUSION: Our study showed the heterogeneity in PD-L1 expression with respect to nine major oncogenic drivers in China. Future studies are warranted to further clarify the association between PD-L1 expression and driver mutations in NSCLC.

WITHDRAWN: Toll-like receptor-4 Signaling Improved the Migration of Sca-1+stem/progenitor Cells.

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Experimental study of the anti-atherosclerotic effect of demethylzeylasteral.

This study aimed to confirm that atherosclerosis (AS) is a systemic immune-mediated chronic inflammatory disease and to investigate the anti-atherosclerotic effect of demethylzeylasteral by testing the immunocompetent cells and inflammatory mediators in the blood and atherosclerotic plaques of the rabbit model of AS. For this purpose, 60 male New Zealand white rabbits were given 150 g high-fat diet (1% cholesterol, 5% lard, and 15% egg yolk powder) daily for a total of 90 days. On day 61, the rabbits were randomly divided into the saline group (n=15), the rosuvastatin group (n=15), the low-dose demethylzeylasteral group (n=15), and the high-dose demethylzeylasteral group (n=15). The CD3+ T lymphocytes and the subsets CD4+, CD8+, and CD4+/CD8+, as well as the soluble interleukin-2 receptor (sIL-2R) were measured before and after the treatment. The contents of immunoglobulins IgG, IgA and IgM and the levels of complements C3 and C4 were also monitored. In addition, the level of anti-oxidized low-density lipoprotein (ox-LDL) antibody, the inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-6 and metalloproteinase-9 (MMP-9), the blood lipids triglyceride (TG), total cholesterol (TC), LDL cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and the severity of plaque lesions was also evaluated. Our results showed that the saline group, the rosuvastatin group and the low-dose demethylzeylasteral group had significantly lower activated T lymphocyte parameters CD3+, CD4+, CD8+ and CD4+/CD8+ (P<0.05), and significantly higher levels of sIL-2R, immunoglobulins IgG, IgA and IgM, complements C3 and C4, anti-ox-LDL antibody, TNF-α, IL-6 and MMP-9 (P<0.01) when compared with the high-dose demethylzeylasteral group. Moreover, TG, TC, LDL-C contents were found significantly lower and their HDL-C contents were significantly higher in high-dose demethylzeylasteral group (P<0.01) as compared to the other three groups. Furthermore, Sudan staining and haematoxylin and eosin staining of the thoracic aorta showed that, after 30-day treatment, the high-dose demethylzeylasteral group had the smoothest intima and the lightest plaque lesions among the four groups. Based on these results, we concluded that AS is a systemic immune-mediated chronic inflammatory disease and the relatively high dose of demethylzeylasteral used in the treatment of atherosclerotic rabbits could significantly alleviate AS. This implies that demethylzeylasteral may be considered as a suitable drug for anti-immunization therapy.

Clinical Study on efficacy of allopurinol in patients with acute coronary syndrome and its functional mechanism.

OBJECTIVE: To investigate the therapeutic effect of allopurinol treatment on acute coronary syndrome and to elucidate its possible mechanism. METHODS: Patients with acute coronary syndrome (n = 100) were recruited as research subjects in our hospital. The patients were randomly divided into two groups, an allopurinol group (n = 50) and a control group (n = 50). These two groups were treated with conventional antiplatelet, anticoagulation and anti-ischemic therapy; allopurinol therapy was added to the allopurinol group based on conventional treatment indications. Biochemical markers such as serum creatinine, uric acid, BNP, blood glucose and blood lipid were compared between the two groups. Indicators of oxidative stress and inflammatory response (MDA, OX-LDL, NO, hs-CRP and TNF-α), as well as cardiovascular events during 2-years follow-up, were recorded. RESULTS: On admission, there was no difference in serum creatinine, uric acid, BNP, blood glucose or lipid levels between the two groups (P > 0.05). However, after 1 month of treatment, these levels were improved in patients in the allopurinol group compared to the control group (P < 0.05). MDA, OX-LDL, hs-CRP and TNF-α decreased after treatment periods of 14 days and 1 month. They were also decreased at 3 month, 6 month, 1 year, and 2 year follow-up visits. However, data from the allopurinol group demonstrated significantly lower levels than in the control group (P < 0.05). Additionally, compared with the control group, allopurinol treatment significantly elevated the level of NO (P < 0.05). The total effective rates of the allopurinol group are much higher than in the control group for both angina pectoris (93.2% and 76%, respectively) and ECG (96% and 82%, respectively). Most patients in the allopurinol group (n = 40) and the control group (n = 41) received stent implantation with no significant difference shown between them. The incidence of cardiovascular events during 2 years of follow-up in the allopurinol group was 10%; it was 30% in the control group. CONCLUSION: Allopurinol has a remarkable effect in the treatment of ACS and can improve the oxidative stress and inflammatory reaction indicators of patients. The protective mechanism of allopurinol might be achieved by suppressing the secretion and release of inflammatory mediators such as TNF-α, hs-CRP, OX-LDL and MDA while increasing levels of NO.

[Detection of a new mutation (G1253T) of iduronate-2-sulfatase gene for the patient with mucopolysaccharidosis type II].

OBJECTIVE: To identify the mutations of iduronate-2-sulfatase (IDS) gene in mucopolysaccharidosis type II patients. METHODS: PCR-SSCP analysis was applied to detect the common mutations in the exons 2, 3, 5, 7, 8, 9 in IDS-gene of the patient. DNA sequencing and PCR-RFLP were applied to analyze the mutation detected by PCR-SSCP. RESULTS: A new mutation(1253G-->T) of exon 7 of the IDS gene was found by PCR-SSCP and DNA sequencing in the patient, The PCR-restriction enzyme digestion showed that enzyme digestion location appeared in the patient and his mother, which verified the results of sequencing analysis. CONCLUSION: The mutation of patient with MPSII could be detected effectively and quickly by the applications of PCR-SSCP, DNA sequencing and PCR-restriction enzyme digestion analysis, and the new mutation thus detected is necessary for the prenatal diagnosis of the pedigree.