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6. HUVECs with KNDC1 knockout mediated by CRISPR/Cas9 have anti-aging ability

Author

SUN Jing-yu, YAO He, HU Gang, WEI Jie, GUO Jun, ZHANG Xin, LIN Ya-jun

Subjects
kndc1, crispr/cas9 system, gene editing, human umbilical vein endothelial cell, Medicine
Abstract

Objective To knock out the KNDC1 of human umbilical vein endothelial cells (HUVECs) by CRISPR/Cas9 gene editing technology and observe its anti-aging ability. Methods Five sgRNAs targeting KNDC1 Exon1, Exon2 and Exon3 were designed by online software and were constructed into CRISPR/Cas9 vector. After sequence confirmation, the recombinant plasmids were transfected into HeLa cells and HUVECs. After 48 h, KNDC1 mRNA levels and protein expression levels were detected by real-time PCR and Western blot; cell senescence was measured by SA-β-gal staining; intracellular reactive oxygen species were detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. Results The sequencing results showed that all the 5 sgRNAs were inserted into the CRISPR/Cas9 vector, the sequence was correct and these vectors were successfully constructed. After transfecting 5 recombinant vectors into HeLa cells, it was found that the knockout efficiency of vectors No. 4 and No. 5 was higher, and then the recombinant vectors of No. 4 and 5 were transfected into HUVECs. Compared with the control plasmid, the KNDC1 mRNA level and protein expression level in HUVECs transfected with recombinant plasmids 4 and 5 were significantly decreased (P＜0.05). The number of senescent HUVECs and the level of intracellular reactive oxygen species were significantly reduced. Conclusions The KNDC1 of HUVECs can be effectively knocked out by CRISPR/Cas9 technology, and HUVECs with KNDC1 knockout have anti-aging ability.

Published
2020

33. Additional file 2: of Percutaneous closure versus medical therapy for stroke with patent foramen Ovale: a systematic review and meta-analysis

Author

Zhang, Xin-Lin, Kang, Li-Na, Wang, Lian, and Xu, Biao

Subjects
cardiovascular diseases
Abstract

Figure S1. Flow diagram of study selection. Table S1. Main inclusion and exclusion criteria of included randomized trials. Table S2. Definitions of degree of shunting and atrial septal aneurysm in randomized trials. Table S3. Primary and secondary endpoints of included randomized trials. Table S4. Definitions of composite outcome, major bleeding, recurrent stroke and TIA in randomized trials. Table S5. Risk of bias of included randomized trials. Table S6. Study quality of included comparative observational studies using the Newcastle-Ottawa scale. Figure S2. The composite outcome of recurrent stroke, TIA and all-cause death with device closure versus medical therapy from randomized controlled trials and adjusted observational studies. Table S7. Subgroup analysis of the major outcomes based on study designs, number of patients and duration of follow-up. Table S8. Subgroup analysis of the composite outcome in randomized trials. Table S9. Subgroup analysis of recurrent ischemic stroke in randomized trials. Table S10. Meta-regression analysis in randomized trials exploring the potential for effect modification by multiple variables, including Moderate to severe PFO, atrial septal aneurysm, index event of stroke, and anticoagulation in medical treatment. (DOCX 594Â kb)

Published
2018
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35. Long-term and Temporal Outcomes of Transcatheter Versus Surgical Aortic-valve Replacement in Severe Aortic Stenosis: A Meta-analysis.

Author

Zhang, Xin-Lin, Zhang, Xiao-Wen, Lan, Rong-Fang, Chen, Zheng, Wang, Lian, Xu, Wei, and Xu, Biao

Abstract

Supplemental Digital Content is available in the text Objective: To determine the 5-year and temporal performance of TAVR versus SAVR. Background: TAVR has become a valuable treatment for severe aortic stenosis but the long-term safety and efficacy remain unclear. Methods: Databases were searched until October 6, 2019 for randomized trials with ≥5 years' follow-up. Primary outcome was all-cause mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled with random-effects models. Results: We included 4 trials with 3,758 patients. TAVR was associated with a significantly higher 5-year all-cause mortality than SAVR (OR, 1.19; 95% CI, 1.03–1.37; P = 0.02). Landmark analysis showed no significant difference within 2 years (OR, 0.92; 95% CI, 0.79–1.08; P = 0.33) but a statistically higher mortality in TAVR between 2 and 5 years (OR, 1.32; 95% CI, 1.14–1.52; P = 0.0002), with significant difference between these 2 temporal phases (P for interaction = 0.001). Similar interaction was found for cardiovascular mortality and several other outcomes. Rates of all-cause mortality or disabling stroke, permanent pacemaker implantation, aortic-valve rehospitalization, and reintervention were higher, but rates of major bleeding and new-onset fibrillation were lower in TAVR at 5 years. The incidences of myocardial infarction, stroke, and transient ischemic attack were not statistically different between TAVR and SAVR. Conclusions: TAVR was associated with a significantly higher all-cause mortality at 5 years compared with SAVR. Of note, all-cause mortality presented a characteristic temporal pattern showing increased risk between 2 and 5 years but not within 2 years. Longer-term follow-up data are warranted. [ABSTRACT FROM AUTHOR]

Published
2021
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41. Association Between the MUC5B Promoter Polymorphism rs35705950 and Idiopathic Pulmonary Fibrosis

Author

Zhu, Qing-Qing, Zhang, Xin-Lin, Zhang, Si-Min, Tang, Shao-Wen, Min, Hai-Yan, Yi, Long, Xu, Biao, and Song, Yong

Subjects
Polymorphism, Genetic, Asian People, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Meta-Analysis of Observ Studies in Epidemiology, Humans, Genetic Predisposition to Disease, Promoter Regions, Genetic, Mucin-5B, Idiopathic Pulmonary Fibrosis, White People, Research Article
Abstract

Supplemental Digital Content is available in the text, Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. A number of studies reported the association between MUC5B promoter polymorphism rs35705950 and IPF, but substantial inconsistent findings were observed and the strength of association remains unclear. The aim of the study was to investigate the association between rs35705950 and IPF in different ethnic populations. PubMed, EMBASE, Web of Science, and CENTRAL were searched from their inception to April 15, 2015. Allelic and phenotypic comparisons were conducted separately, as were comparisons in Caucasian and Asian populations. A meta-analysis with trial sequential analysis was conducted. Nine studies presented in 7 full-text articles were included, encompassing 2733 IPF patients and 5044 controls. Six studies were carried out in the Caucasian population, and 3 in the Asian population. Minor T allele was associated with an increased risk of IPF compared with G allele (odds ratio [OR] 4.85, 95% confidence interval [CI] 3.79–6.21, P = 5.88 × 10−36), as were TG and TT genotypes compared with GG genotype (TG vs GG: OR 6.20, 95% CI 5.14–7.48, P = 1.70 × 10−81; TT vs GG: OR 11.29, 95% CI 5.69–22.40, P = 4.22 × 10−12), in an allele dose-dependent manner. These observations were confirmed in trial sequential analysis in both populations. The strength of association was more remarkable in the Caucasian population than in the Asian population, and no homozygous TT genotype was detected in the Asian population in our study. Our study revealed strong association between the MUC5B promoter rs35705950 polymorphism and the risk of IPF. The strength of association between rs35705950 minor T allele and IPF susceptibility was particularly evident in the Caucasian population, and milder but still significant in the Asian population.

Published
2015

44. Possible involvement of TGF-β/periostin in fibrosis of right atrial appendages in patients with atrial fibrillation

Author

Wu, Han, Xie, Jun, Li, Guan-Nan, Chen, Qin-Hua, Li, Ran, Zhang, Xin-Lin, Kang, Li-Na, and Xu, Biao

Subjects
Adult, Male, Time Factors, Biopsy, Blotting, Western, Middle Aged, Fibrosis, Immunohistochemistry, Up-Regulation, Treatment Outcome, Recurrence, Transforming Growth Factor beta, Atrial Fibrillation, cardiovascular system, Catheter Ablation, Humans, Original Article, Atrial Appendage, Female, cardiovascular diseases, Collagen, Cell Adhesion Molecules
Abstract

Atrial fibrosis contributes to development and recurrence of atrial fibrillation (AF). TGF-β and periostin have been reported to be involved in fibrogenesis. Here we investigated the role of TGF-β and periostin in atrial fibrosis of AF and in the recurrence of AF after surgery ablation. Western blot, Masson staining, immunohistochemistry and colorimetry were performed to detect the degree of atrial fibrosis and the expression of TGF-β, periostin and collagens in 70 biopsies of right atrial appendage (RAA) obtained in this study. Then the patients who received surgical ablation were followed up for about one year. The results showed an increasing gradient of atrial expression of TGF-β, periostin and collagens paralleled by a higher level of atrial fibrosis in control, SR and AF groups. The expression of TGF-β and periostin was significantly correlated with fibrotic markers. In addition, LAD and the expression of TGF-β were larger or higher in recurrence group than that in nonrecurrence group after surgery ablation. The results suggest that upregulated expression of TGF-β and periostin in RAAs is correlated with the degree of atrial fibrosis in patients with AF.

Published
2015

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