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AnteayerPLOS ONE Medicine&Health

Downregulation of the CD151 protects the cardiac function by the crosstalk between the endothelial cells and cardiomyocytes via exosomes

by Luying Jiang, Jingbo Liu, Zhenjia Yang, Jianyu Wang, Wenkai Ke, Kaiyue Zhang, Chunran Zhang, Houjuan Zuo

Background

Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear.

Method and results

In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes.

Conclusion

Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis

by Hong Duo, Mengying Jin, Yanwei Yang, Rewaan Baheti, Yujia Feng, Zirui Fu, Yuyue Jiang, Lanzhuoying Zheng, Jing Wan, Huaqin Pan

Background

Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations.

Methods

Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI.

Results

Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83–1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09–3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83–1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments.

Conclusion

According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Influencing factors of falls among older adults in Chinese retirement institutions: A systematic review and meta-analysis

by Xiaoxing Huang, Yunlan Jiang, Yaxin Liu, Liyin Shen, Jing Pan, Yue Zhang

Background

The incidence of falling has always been high among the elderly, and it was easy to cause injuries to the elderly and seriously affect their quality of life. There were many studies have been conducted on risk factors affecting the fall of the elderly, but the results widely, retirement institutions as a gathering place for the elderly, there was currently no comprehensive analysis of the factors related to elderly falls in pension institutions. This study aimed to explore the influencing factors of falls among older adults in Chinese nursing homes.

Methods

Chinese and English databases were searched for literature published from database inception to 5 April 2023 on the influencing factors of falls among older adults in Chinese nursing homes. Two reviewers independently screened articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4 software.

Results

Eleven studies involving 3503 participants were included in the meta-analysis. The pooled estimate of falls among older adults in Chinese nursing homes was 32% [95% confidence interval (95%CI) (24.0%, 39.0%)]. The main influencing factors for falls among older adults in Chinese nursing homes were age (Odds Ratio (OR) = 1.53), gender (OR = 5.50), visual impairment (OR = 2.30), sedative-hypnotics (OR = 2.36), fear of falling (OR = 2.95), hypertension (OR = 3.72), static balance (OR = 2.02), three or more chronic diseases (OR = 5.63), cognitive status (OR = 2.64), walking aid use (OR = 1.98), fall-related chronic diseases (OR = 2.48), self-awareness of abilities (OR = 2.43), and frequent reminders for fall prevention (OR = 0.10).

Conclusion

Falls among older adults in Chinese nursing homes were common, and there were many influencing factors. Timely screening and intervention should be implemented to reduce the adverse consequences of falls on older adults.

Trial registration

Registration number: CRD42023421099.

Prime editing-mediated correction of the <i>CFTR</i> W1282X mutation in iPSCs and derived airway epithelial cells

by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao

A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.

Trends in cardiac rehabilitation rates among patients admitted for acute heart failure in Japan, 2009–2020

by Junghyun Kim, Jenny Jiang, Sophie Shen, Soko Setoguchi

Objectives

To describe inpatient and outpatient cardiac rehabilitation (CR) utilization patterns over time and by subgroups among patients admitted for acute heart failure (AHF) in Japan.

Background

Cardiac rehabilitation (CR) is a crucial secondary prevention strategy for patients with heart failure. While the number of older patients with AHF continues to rise, trends in inpatient and outpatient CR participation following AHF in Japan have not been described to date.

Methods

We conducted a retrospective cohort study of adult patients hospitalized for AHF in Japan between April 2008 and December 2020. Using data from the Medical Data Vision database, we measured trends in inpatient and outpatient CR participation following AHF. Descriptive analyses and summary statistics for AHF patients by CR participation status were reported.

Results

The analytic cohort included 88,052 patients. Among these patients, 37,810 (42.9%) participated in inpatient and/or outpatient CR. Of those, 36,431 (96.4%) participated in inpatient CR only and 1,277 (3.4%) participated in both inpatient and outpatient CR. Rates of inpatient CR rose more than 6-fold over the study period, from 9% in 2009 to 55% in 2020, whereas rates of outpatient CR were consistently low.

Conclusions

The rate of inpatient CR participation among AHF patients in Japan rose dramatically over a 12-year period, whereas outpatient CR following AHF was vastly underutilized. Further study is needed to assess the clinical effectiveness of inpatient CR and to create infrastructure and incentives to support and encourage outpatient CR.

Efficacy of mesenchymal stromal cells in the treatment of unexplained recurrent spontaneous abortion in mice: An analytical and systematic review of meta-analyses

by Xiaoxuan Zhao, Yijie Hu, Wenjun Xiao, Yiming Ma, Dan Shen, Yuepeng Jiang, Yi Shen, Suxia Wang, Jing Ma

Objectives

Unexplained recurrent spontaneous abortion (URSA) remains an intractable reproductive dilemma due to the lack of understanding of the pathogenesis. This study aimed to evaluate the preclinical evidence for the mesenchymal stromal cell (MSC) treatment for URSA.

Methods

A meticulous literature search was independently performed by two authors across the Cochrane Library, EMBASE, and PubMed databases from inception to April 9, 2023. Each study incorporated was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. The amalgamated standardized mean difference (SMD) accompanied by 95% confidence interval (CI) were deduced through a fixed-effects or random-effects model analysis.

Results

A total of ten studies incorporating 140 mice were subjected to data analysis. The MSC treatment yielded a significant reduction in the abortion rate within the URSA model (OR = 0.23, 95%CI [0.17, 0.3], PP = 0.01), IL10 (SMD 1.60, 95% CI [0.58, 2.61], P = 0.002), IFN-γ (SMD -1.66, 95%CI [-2.79, -0.52], P = 0.004), and TNF-α (SMD -1.98, 95% CI [-2.93, -1.04], PPP>0.05).

Conclusions

The findings underscore the considerable potential of MSCs in URSA therapy. Nonetheless, the demand for enhanced transparency in research design and direct comparisons between various MSC sources and administration routes in URSA is paramount to engendering robust evidence that could pave the way for successful clinical translation.

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