Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or “sendotypes”), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan

Association of age-related hearing loss with cognitive impairment and dementia: an umbrella review

BackgroundHearing loss, cognitive impairment and dementia have become common problems for older adults. Currently, systematic reviews and meta-analyses of the association between age-related hearing loss (ARHL) with cognitive impairment and dementia may have inconsistent results. To explore and validate the association between ARHL with cognitive impairment and dementia through summarizing and evaluating existing evidence.MethodsFrom inception to February 01, 2023, PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched. AMSTAR 2 was used to evaluate methodological quality and GRADE system was used to evaluate evidence quality. We summarized the basic characteristics of the included studies and extracted effect data for ARHL with cognitive impairment and dementia. Forest plots were used to describe the relative risk associated with ARHL and cognitive impairment, and the relative risk associated with ARHL and dementia, respectively.ResultsA total of 11 systematic reviews and meta-analyses met the inclusion criteria. Overall, the methodological quality of the included SRs/MAs was moderate and the quality of the evidence was low. The combined results found that the pooled risk ratio of ARHL and cognitive impairment was 1.30 (random-effects; 95% CI 1.16 to 1.45), and the pooled risk ratio of ARHL and dementia was 1.59 (random-effects; 95% CI 1.34 to 1.90).ConclusionBased on the evidence reported in this umbrella review, age-related hearing loss is significantly associated with cognitive impairment and dementia. Hearing loss may be a high risk factor for cognitive impairment and dementia in older adults

Bibliometric analysis of worldwide research trends on breast cancer about inflammation

BackgroundThe most prevalent cancer and the second-leading cause of cancer-related mortality in women is breast cancer. Growing interest has been shown in recent years in learning more about the processes behind the development of breast cancer. It has been shown that persistent inflammation may play a significant role in the advancement of breast cancer. However, a comprehensive and objective analysis on the state of inflammation in breast cancer research is still lacking. This study was aim to undertake a bibliometric analysis of breast cancer research associated with inflammation between 2013 and 2022 in order to identify the trends, dynamics, and scientific outputs in the field.MethodsFrom 2013 to 2022, original and review publications on breast cancer and inflammation-associated research were retrieved from the Web of Science Core Collection (WOSCC) database. To examine the position of yearly publications, journals, nations, institutions, and authors, we employed two bibliometric tools (CiteSpace and VOSviewer). After that, by examining keyword visualization and keyword bursts, we determined the hot research fields related to inflammation in breast cancer.Resultswe discovered 6902 publications regarding inflammation in breast cancer by using our retrieval approach. In terms of the number of publications, The United States ranked first in the global study, followed by China and Italy. In terms of institutions, the University of Texas System, UT MD Anderson Cancer Center, and University of California System are in the top 3 for the quantity of publications published. The most popular journal for this field research is “CANCERS.” Ueno NT, Woodward WA, Cristofanilli M, and others have made significant contributions to the understanding of inflammation in breast cancer. In the end, we conducted a biclustering analysis on keywords and discovered three clusters that represent research hotspots.ConclusionAccording to the global trend, the research output of inflammation in breast cancer is increasing. The information provided in this article, including the cooperation network information of authors, nations, journals, and institutions, may help researchers to better understand hotspots and developing patterns in this discipline. At present, the focus of study gradually shifts from “phenotype study” to “therapeutic research”. It is recommended to pay attention to the latest hot spots, such as targeted therapy, antimicrobial activity and nanoparticle

Recessive variants in plakophilin-2 contributes to early-onset arrhythmogenic cardiomyopathy with severe heart failure

AIMS Plakophilin-2 (PKP2) is the most prevalent mutant gene causing arrhythmogenic cardiomyopathy (ACM) and PKP2 carriers are prone to develop ventricular arrhythmic events. The objective of this study is to use integrated analysis of whole genome sequencing (WGS) and transcriptome sequencing (RNAseq) to identify deep intronic and/or coding variants that cause aberrant splicing events in ACM patients, and hence, to test the hypothesis that recessive variants in PKP2 may lead to early-onset ACM with severe heart failure. METHODS AND RESULTS We performed WGS and RNAseq in 27 heart transplanted ACM patients. By integrated analysis of WGS/RNAseq, we discovered that two patients with PKP2 variants were affected in recessive pattern. One patient had aberrant splicing arising from two intronic variants that led to exon skipping and exon retention. We screened three additional recessive PKP2 variants in 47 non-heart transplanted ACM patients. We compared the clinical characteristics of recessive PKP2 (n = 5) and heterozygous PKP2 carriers (n = 18), and found that recessive PKP2 variant carriers all had early-onset ACM with left ventricular dysfunction. We examined truncating PKP2 variants in explanted hearts and confirmed that truncated PKP2 was not translated. Moreover, the morphology of intercalated disc in recessive PKP2 variants carriers was similar to normal heart suggesting little intercalated disc remodelling. CONCLUSION By using combined implementation of WGS RNAseq, we were able to demonstrate that recessive variants in PKP2 may contribute to early-onset ACM with severe heart failure. These findings may play a role in risk stratification of ACM based on genetic testing in clinical practice

Intrinsic Immunogenic Tumor Cell Death Subtypes Delineate Prognosis and Responsiveness to Immunotherapy in Lung Adenocarcinoma

Recent studies have highlighted the combination of activation of host immunogenic cell death (ICD) and tumor-directed cytotoxic strategies. However, overall multiomic analysis of the intrinsic ICD property in lung adenocarcinoma (LUAD) has not been performed. Therefore, the aim of this study was to develop an ICD-based risk scoring system to predict overall survival (OS) and immunotherapeutic efficacy in patients. In our study, both weighted gene co-expression network analysis (WGCNA) and LASSO-Cox analysis were utilized to identify ICDrisk subtypes (ICDrisk). Moreover, we identify genomic alterations and differences in biological processes, analyze the immune microenvironment, and predict the response to immunotherapy in patients with pan-cancer. Importantly, immunogenicity subgroup typing was performed based on the immune score (IS) and microenvironmental tumor neoantigens (meTNAs). Our results demonstrate that ICDrisk subtypes were identified based on 16 genes. Furthermore, high ICDrisk was proved to be a poor prognostic factor in LUAD patients and indicated poor efficacy of immune checkpoint inhibitor (ICI) treatment in patients with pan-cancer. The two ICDrisk subtypes displayed distinct clinicopathologic features, tumor-infiltrating immune cell patterns, and biological processes. The ISlowmeTNAhigh subtype showed low intratumoral heterogeneity (ITH) and immune-activated phenotypes and correlated with better survival than the other subtypes within the high ICDrisk group. This study suggests effective biomarkers for the prediction of OS in LUAD patients and immunotherapeutic response across Pan-cancer and contributes to enhancing our understanding of intrinsic immunogenic tumor cell death

Table_1_Ten-year trends of the clinicopathological characteristics, surgical treatments and survival outcomes of operable lung cancer patients in monocenter: a retrospective cohort study.DOCX

BackgroundLung cancer is one of the cancers with the highest morbidity and mortality. During the last decade, the trends of clinical characteristics, surgical treatments and survival of lung cancer patients in China have remained unclear.MethodsAll lung cancer patients operated on from 2011 to 2020 were identified in a prospectively maintained database of Sun Yat-sen University Cancer Center.ResultsA total of 7,800 lung cancer patients were included in this study. Within the past 10 years, the average age at diagnosis of the patients remained stable, the proportion of asymptomatic, female and nonsmoking patients increased, and the average tumor size decreased from 3.766 to 2.300 cm. In addition, the proportion of early stage and adenocarcinoma increased, while that of squamous cell carcinoma decreased. Among the patients, the proportion of patients having video-assisted thoracic surgery increased. More than 80% of the patients underwent lobectomy and systematic nodal dissection over the 10 years. Additionally, both the average postoperative length of stay and 1-, 3-, and 6-month postoperative mortality decreased. Moreover, the 1-, 3-, and 5-year overall survival (OS) rates of all the operable patients increased from 89.8, 73.9, and 63.8% to 99.6, 90.7, and 80.8%, respectively. The 5-year OS rates of the patients with stage I, II, and III lung cancer were 87.6, 79.9, and 59.9%, respectively, which were higher than those in other published data.ConclusionThere were significant changes in the clinicopathological characteristics, surgical treatments and survival outcomes of the patients with operable lung cancer from 2011 to 2020.</p

Image_1_Ten-year trends of the clinicopathological characteristics, surgical treatments and survival outcomes of operable lung cancer patients in monocenter: a retrospective cohort study.tif

BackgroundLung cancer is one of the cancers with the highest morbidity and mortality. During the last decade, the trends of clinical characteristics, surgical treatments and survival of lung cancer patients in China have remained unclear.MethodsAll lung cancer patients operated on from 2011 to 2020 were identified in a prospectively maintained database of Sun Yat-sen University Cancer Center.ResultsA total of 7,800 lung cancer patients were included in this study. Within the past 10 years, the average age at diagnosis of the patients remained stable, the proportion of asymptomatic, female and nonsmoking patients increased, and the average tumor size decreased from 3.766 to 2.300 cm. In addition, the proportion of early stage and adenocarcinoma increased, while that of squamous cell carcinoma decreased. Among the patients, the proportion of patients having video-assisted thoracic surgery increased. More than 80% of the patients underwent lobectomy and systematic nodal dissection over the 10 years. Additionally, both the average postoperative length of stay and 1-, 3-, and 6-month postoperative mortality decreased. Moreover, the 1-, 3-, and 5-year overall survival (OS) rates of all the operable patients increased from 89.8, 73.9, and 63.8% to 99.6, 90.7, and 80.8%, respectively. The 5-year OS rates of the patients with stage I, II, and III lung cancer were 87.6, 79.9, and 59.9%, respectively, which were higher than those in other published data.ConclusionThere were significant changes in the clinicopathological characteristics, surgical treatments and survival outcomes of the patients with operable lung cancer from 2011 to 2020.</p

Novel Risk Prediction Model to Determine Adverse Heart Failure Outcomes in Arrhythmogenic Right Ventricular Cardiomyopathy

Background Patients with arrhythmogenic right ventricular cardiomyopathy are at risk for life-threatening ventricular tachyarrhythmias, but progressive heart failure (HF) may occur in later stages of disease. This study aimed to characterize potential risk predictors and develop a model for individualized assessment of adverse HF outcomes in arrhythmogenic right ventricular cardiomyopathy. Methods and Results Longitudinal and observational cohorts with 290 patients with arrhythmogenic right ventricular cardiomyopathy from the Fuwai Hospital in Beijing, China, and 99 patients from the University Heart Center in Zurich, Switzerland, with follow-up data were studied. The primary end point of the study was heart transplantation or death attributable to HF. The model was developed by Cox regression analysis for predicting risk and was internally validated. During 4.92±3.03 years of follow-up, 48 patients reached the primary end point. The determinants of the risk prediction model were left ventricular ejection fraction, serum creatinine levels, moderate-to-severe tricuspid regurgitation, and atrial fibrillation. Implantable cardioverter-defibrillators did not reduce the occurrence of adverse HF outcomes. Conclusions A novel risk prediction model for arrhythmogenic right ventricular cardiomyopathy has been developed using 2 large and well-established cohorts, incorporating common clinical parameters such as left ventricular ejection fraction, serum creatinine levels, tricuspid regurgitation, and atrial fibrillation, which can identify patients who are at risk for terminal HF events, and may guide physicians to assess individualized HF risk and to optimize management strategies

Table_2_Ten-year trends of the clinicopathological characteristics, surgical treatments and survival outcomes of operable lung cancer patients in monocenter: a retrospective cohort study.DOCX

BackgroundLung cancer is one of the cancers with the highest morbidity and mortality. During the last decade, the trends of clinical characteristics, surgical treatments and survival of lung cancer patients in China have remained unclear.MethodsAll lung cancer patients operated on from 2011 to 2020 were identified in a prospectively maintained database of Sun Yat-sen University Cancer Center.ResultsA total of 7,800 lung cancer patients were included in this study. Within the past 10 years, the average age at diagnosis of the patients remained stable, the proportion of asymptomatic, female and nonsmoking patients increased, and the average tumor size decreased from 3.766 to 2.300 cm. In addition, the proportion of early stage and adenocarcinoma increased, while that of squamous cell carcinoma decreased. Among the patients, the proportion of patients having video-assisted thoracic surgery increased. More than 80% of the patients underwent lobectomy and systematic nodal dissection over the 10 years. Additionally, both the average postoperative length of stay and 1-, 3-, and 6-month postoperative mortality decreased. Moreover, the 1-, 3-, and 5-year overall survival (OS) rates of all the operable patients increased from 89.8, 73.9, and 63.8% to 99.6, 90.7, and 80.8%, respectively. The 5-year OS rates of the patients with stage I, II, and III lung cancer were 87.6, 79.9, and 59.9%, respectively, which were higher than those in other published data.ConclusionThere were significant changes in the clinicopathological characteristics, surgical treatments and survival outcomes of the patients with operable lung cancer from 2011 to 2020.</p