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An oval to rod-shaped, Gram-stain-positive, strictly anaerobic bacterium, designated LFL-14T, was isolated from the faeces of a healthy Chinese woman. Cells of the strain were non-spore-forming, grew optimally at 37â°C (growth range 30-45â°C) and pH 7.0 (growth range 6.0-9.0) under anaerobic conditions in the liquid modified Gifu anaerobic medium (mGAM). The result of 16S rRNA gene-based analysis indicated that LFL-14T shared an identity of 94.7â0% with Eubacterium ventriosum ATCC 27560T, indicating LFL-14T represented a novel taxon. The results of genome-based analysis revealed that the average nucleotide identity (ANI), the digital DNA-DNA hybridisation (dDDH) and average amino acid identity (AAI) between LFL-14T and its phylogenetically closest neighbour, Eubacterium ventriosum ATCC 27560T, were 77.0â%, 24.6 and 70.9â%, respectively, indicating that LFL-14T represents a novel species of the genus Eubacterium. The genome size of LFL-14T was 2.92 Mbp and the DNA G+C content was 33.14 mol%. We analysed the distribution of the genome of LFL-14T in cohorts of healthy individuals, type 2 diabetes patients (T2D) and patients with non-alcoholic fatty liver disease (NAFLD). We found that its abundance was higher in the T2D cohort, but it had a low average abundance of less than 0.2â% in all three cohorts. The percentages of frequency of occurrence in the T2D, healthy and NAFLD cohorts were 48.87â%, 16.72â% and 13.10â% respectively. The major cellular fatty acids of LFL-14T were C16â:â0 (34.4â%), C17â:â0 2-OH (21.4â%) and C14â:â0 (11.7â%). Additionally, the strain contained diphosphatidylglycerol (DPG) and phosphatidylethanolamine (PE), as well as unidentified phospholipids and unidentified glycolipids. The glucose fermentation products of LFL-14T were acetate and butyrate. In summary, On the basis of its chemotaxonomic, phenotypic, phylogenetic and phylogenomic properties, strain LFL-14T (= CGMCC 1.18005T = KCTC 25580T) is identified as representing a novel species of the genus Eubacterium, for which the name Eubacterium album sp. nov. is proposed.
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Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Eubacterium , Ácidos Graxos , Fezes , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Humanos , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Feminino , Eubacterium/genética , Eubacterium/isolamento & purificação , Eubacterium/classificação , Fezes/microbiologia , Butiratos/metabolismo , Genoma Bacteriano , China , AdultoRESUMO
OBJECTIVE: To identify suitable reference genes for gene expression studies in rat dorsal root ganglia (DRG) neurons. METHODS: The raw cycle threshold (Ct) values of 12 selected reference genes were obtained via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in neurons at different developmental stages or under different treatments. Two strategies were employed to screen the most stable reference genes: the genes were ranked according to the coefficient of biological variation and further validated using geNorm and NormFinder programs. The stable and unstable reference genes were subsequently used as internal controls to assess their effects on target gene expression. RESULTS: All reference genes showed varying degrees of fluctuation in Ct values during the growth process of neurons or after different treatments. 18S ribosomal RNA (Rn18s) and ß-actin (Actb) exhibited the most significant changes, while ubiquitin C (Ubc), hypoxanthine phosphoribosyl transferase (Hprt), and mitochondrial ribosomal protein L10 (Mrpl10) showed relatively minor changes. The most stable and unstable genes obtained by different evaluation methods varied slightly. Overall, Actb was found to be the most unstable reference gene, while Hprt was the relatively most stable reference gene. The use of unstable reference genes Actb and ankyrin repeat domain 27 (Ankrd27) as internal controls led to high variability within the control group, ultimately affecting the determination of target gene expression. In contrast, the stable reference gene Hprt had small inter-assay variation and high stability. CONCLUSIONS: Our observations indicate that Hprt is a proper endogenous reference gene for qRT-PCR analysis in rat DRG neurons and thus provides a critical molecular basis for the genetic characterization in neurological disorders.
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Gânglios Espinais , Transcrição Reversa , Animais , Ratos , Neurônios , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Telehealth and online health information provide patients with increased access to healthcare services and health information in chronic disease management of older patients with chronic diseases, addressing the challenge of inadequate health resources and promoting active and informed participation of older patients in chronic disease management. There are few qualitative studies on the application of telehealth and online health information to chronic disease management in older patients. Chronic obstructive pulmonary disease is one of the most common chronic diseases in older adults. Telehealth is widely used in the management of chronic obstructive pulmonary disease. The purpose of this study was to explore the perceptions and experiences of older patients and healthcare providers in the application of telehealth and online health information to chronic disease management of chronic obstructive pulmonary disease. METHODS: A qualitative descriptive study with data generated from 52 individual semi-structured interviews with 29 patients [Law of the People's Republic of China on the protection of the rights and interests of older people (2018 Revised Version) = >60 years old] with chronic obstructive pulmonary disease and 23 healthcare providers. The inductive thematic analysis method was used for data analysis. RESULTS: Four themes and 16 sub-themes were identified in this study. Four themes included: faced with a vast amount of online health information, essential competencies and personality traits ensuring older patients' participation and sustained use, user experience with the use of technology, being in a complex social context. CONCLUSION: The ability of patients to understand health information should be fully considered while facilitating access to online health information for older patients. The role of health responsibility and user experience in older patients' participation and sustained use of telehealth and online health information needs to be emphasised. In addition, the complex social context is a determining factor to be considered, particularly the complex impact of a reliance on offspring and social prejudice on the behaviour of older adults using telehealth and online health information.
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Doença Pulmonar Obstrutiva Crônica , Telemedicina , Idoso , Gerenciamento Clínico , Pessoal de Saúde , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Pesquisa QualitativaRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major public health challenge globally. The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived T-cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19. METHODS: In this study, several SARS-CoV-2-derived human leukocyte antigen (HLA)-I binding peptides were predicted by NetMHCpan-4.1 and selected by Popcover to achieve pancoverage of the Chinese population. The top 5 ranked peptides derived from each protein of SARS-CoV-2 were then evaluated using peripheral blood mononuclear cells from unexposed individuals (negative for SARS-CoV-2 immunoglobulin G). RESULTS: Seven epitopes derived from 4 SARS-CoV-2 proteins were identified. It is interesting to note that most (5 of 7) of the SARS-CoV-2-derived peptides with predicted affinities for HLA-I molecules were identified as HLA-II-restricted epitopes and induced CD4+ T cell-dependent responses. These results complete missing pieces of pre-existing SARS-CoV-2-specific T cells and suggest that pre-existing T cells targeting all SARS-CoV-2-encoded proteins can be discovered in unexposed populations. CONCLUSIONS: In summary, in the current study, we present an alternative and effective strategy for the identification of T-cell epitopes of SARS-CoV-2 in healthy subjects, which may indicate an important role in the development of peptide vaccines for COVID-19.
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Vacinas contra COVID-19/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Epitopos de Linfócito T/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Humanos , Leucócitos Mononucleares/imunologia , SARS-CoV-2RESUMO
BACKGROUND: Comprehensive geriatric assessment (CGA) interventions can improve functional ability and reduce mortality in older adults, but the effectiveness of CGA intervention on the quality of life, caregiver burden, and length of hospital stay remains unclear. The study aimed to determine the effectiveness of CGA intervention on the quality of life, length of hospital stay, and caregiver burden in older adults by conducting meta-analyses of randomised controlled trials (RCTs). METHODS: A literature search in PubMed, Embase, and Cochrane Library was conducted for papers published before February 29, 2020, based on inclusion criteria. Standardised mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CIs) was calculated using the random-effects model. Subgroup analyses, sensitivity analyses, and publication bias analyses were also conducted. RESULTS: A total of 28 RCTs were included. Overall, the intervention components common in different CGA intervention models were interdisciplinary assessments and team meetings. Meta-analyses showed that CGA interventions improved the quality of life of older people (SMD = 0.12; 95% CI = 0.03 to 0.21; P = 0.009) compared to usual care, and subgroup analyses showed that CGA interventions improved the quality of life only in participants' age > 80 years and at follow-up ≤3 months. The change value of quality of life in the CGA intervention group was better than that in the usual care group on six dimensions of the 36-Item Short-Form Health Survey questionnaire (SF-36). Also, compared to usual care, the CGA intervention reduced the caregiver burden (SMD = - 0.56; 95% CI = - 0.97 to - 0.15, P = 0.007), but had no significant effect on the length of hospital stay. CONCLUSIONS: CGA intervention was effective in improving the quality of life and reducing caregiver burden, but did not affect the length of hospital stay. It is recommended that future studies apply the SF-36 to evaluate the impact of CGA interventions on the quality of life and provide supportive strategies for caregivers as an essential part of the CGA intervention, to find additional benefits of CGA interventions.
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Avaliação Geriátrica , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Sobrecarga do Cuidador , Cuidadores , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To understand the perceptions and experiences of older patients with chronic obstructive pulmonary disease (COPD) and healthcare professionals (HCPs) regarding shared decision-making in pulmonary rehabilitation (PR). DESIGN: A qualitative study using single, semi-structured interviews, and thematic analysis. SETTING: Face-to-face interviews were conducted in the Jiangnan University, in hospital and in patients' homes. PARTICIPANTS: Twenty-two older patients with COPD and 29 HCPs. METHODS: An initial codebook and semi-structured interview guide were developed based on the shared decision-making 3-circle conceptual model. Thematic analysis was used to analyze data. RESULTS: The study identified 10 themes that describe the perceptions and experiences of patients and HCPs involved in PR decision-making: (1) patients' confidence, (2) patients' perceptions of the cost-benefit of decisions, (3) patients' perceived stress about the consequences of decision-making, (4) HCPs' perceived stress on shared decision-making, (5) cognitive biases of patients toward illness and rehabilitation, (6) shared decision-making as a knowledge gap, (7) the knowledge gap between patients and HCPs, (8) authority effect, (9) family support, (10) human resources. These themes were then divided into three groups according to their characteristics: (1) the feelings of the participants, (2) knowledge barriers, and (3) support from the social system. CONCLUSION: Patients and HCPs described their negative perceptions and experiences of participating in decision-making in PR. The implementation of shared decision-making in PR is currently limited; therefore, health education for patients and families should be strengthened and a training system for HCPs in shared decision-making should be established.
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Pessoal de Saúde , Doença Pulmonar Obstrutiva Crônica , Atenção à Saúde , Humanos , Percepção , Pesquisa QualitativaRESUMO
BACKGROUND: The application of telemedicine in home pulmonary rehabilitation interventions for the management of patients with chronic obstructive pulmonary disease (COPD) has achieved promising results. OBJECTIVE: This study aimed to develop a WeChat official account (Pulmonary Internet Explorer Rehabilitation [PeR]) based on social media. It further evaluated the effect of PeR on the quality of life, symptoms, and exercise self-efficacy of patients with COPD. METHODS: The functional modules of PeR were developed by a multidisciplinary team according to the electronic health-enhanced chronic care model (eCCM) components. A total of 106 patients were randomly selected (53 in the PeR group and 53 in the outpatient face-to-face group [FtF]). Pulmonary rehabilitation intervention was conducted for 3 months, and the outcome was observed for 3 months. The primary outcome was patient quality of life measured with the COPD assessment test (CAT). The secondary outcomes were evaluated using the modified Medical Research Council scale (mMRC), exercise self-regulatory efficacy scale (Ex-SRES), and St George's Respiratory Questionnaire (SGRQ). RESULTS: The intention-to-treat analysis was used in the study. A total of 94 participants completed the 6-month pulmonary rehabilitation program. No statistically significant differences were observed in CAT (F1,3=7.78, P=.001), Ex-SRES (F1,3=21.91, P<.001), and mMRC scores (F1,3=29.64, P<.001) between the two groups with the variation in time tendency. The Ex-SRES score had a significant effect on the CAT score (P=.03). The partial regression coefficient of Ex-SRES to CAT was 0.81, and Exp (B) was 2.24. CONCLUSIONS: The telemedicine technology was effective using the eCCM combined with a behavioral intervention strategy centering on self-efficacy. Pulmonary rehabilitation at home through PeR and FtF could improve the sense of self-efficacy and quality of life and alleviate symptoms in patients with COPD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022770; https://tinyurl.com/tmmvpq3.
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Doença Pulmonar Obstrutiva Crônica/reabilitação , Qualidade de Vida/psicologia , Telemedicina/métodos , Idoso , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Background: Telemedicine market in China has been rapidly developing. However, no systematic review has been published in China. Details of the implementation of telemedicine interventions in the chronic obstructive pulmonary disease (COPD) in China have not been described, and the effectiveness of telemedicine interventions is still unclear. Therefore, in this review, we describe the implementation details of telemedicine intervention in China and access the efficacy of telemedicine. Materials and Methods: A literature search was conducted in Embase, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), Wan Fang Data, and China Science and Technology Journal Database by July 9, 2018. Results: A total number of 24 studies were meta-analyzed. There are many differences during the implementation of telemedicine in China. Quality of life in the group of the telemedicine intervention was better than that in the control group (mean difference = -4.93 [95% confidence interval; CI -6.86 to -3.01], p < 0.00001), but the heterogeneity is high (I2 = 86%, p = 0.0001). The rates of hospitalization were lower than those in the control group (odds ratio = 0.24 [95% CI 0.20-0.29], p < 0.00001), and the heterogeneity was low (I2 = 25%, p = 0.14). Conclusion: The implementation of telemedicine in China has not yet been standardized. Nonetheless, results of our review indicated that telemedicine in China can improve the quality of life and reduce the rates of hospitalization in COPD patients.
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Doença Pulmonar Obstrutiva Crônica , Telemedicina , China , Hospitalização , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de VidaRESUMO
OBJECTIVE: This study aimed to develop and validate an eMCI-CHD tool based on clinical data to predict mild cognitive impairment (MCI) risk in patients with coronary heart disease (CHD). METHODS: This cross-sectional study prospectively collected data from 400 patients with coronary heart disease (aged 55-90 years, 62% men) from July 2022 to September 2023 and randomized (7:3 ratio) them into training and validation sets. After determining the modeling variables through least absolute shrinkage and selection operator regression analysis, four ML classifiers were developed: logistic regression, extreme gradient boosting (XGBoost), support vector machine, and random forest. The performance of the models was evaluated using area under the ROC curve, accuracy, sensitivity, specificity, and F1 score. Decision curve analysis was used to assess the clinical performance of the established models. The SHapley Additive exPlanations (SHAP) method was applied to determine the significance of the features, the predictive model was visualized with a nomogram, and an online web-based calculator for predicting CHD-MCI risk scores was developed. RESULTS: Of 400 CHD patients (average age 70.86 ± 8.74 years), 220 (55%) had MCI. The XGBoost model demonstrated superior performance (AUC: 0.86, accuracy: 78.57%, sensitivity: 0.74, specificity: 0.84, F1: 0.79) and underwent validation. An online tool (https://mr.cscps.com.cn/mci/index.html) with seven predictive variables (APOE gene typing, age, education, TyG index, NT-proBNP, C-reactive protein, and occupation) assessed MCI risk in CHD patients. CONCLUSION: This study highlights the potential for predicting MCI risk among CHD patients using an ML model-driven nomogram and risk scoring tool based on clinical data.
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Introduction: Peripheral nerve injuries, especially those involving long-distance deficits, pose significant challenges in clinical repair. This study explores the potential of continuous microcurrent electrical nerve stimulation (cMENS) as an adjunctive strategy to promote regeneration and repair in such cases. Methods: The study initially optimized cMENS parameters and assessed its impact on Schwann cell activity, neurotrophic factor secretion, and the nerve regeneration microenvironment. Subsequently, a rat sciatic nerve defect-bridge repair model was employed to evaluate the reparative effects of cMENS as an adjuvant treatment. Functional recovery was assessed through gait analysis, motor function tests, and nerve conduction assessments. Additionally, nerve regeneration and denervated muscle atrophy were observed through histological examination. Results: The study identified a 10-day regimen of 100uA microcurrent stimulation as optimal. Evaluation focused on Schwann cell activity and the microenvironment, revealing the positive impact of cMENS on maintaining denervated Schwann cell proliferation and enhancing neurotrophic factor secretion. In the rat model of sciatic nerve defect-bridge repair, cMENS demonstrated superior effects compared to control groups, promoting motor function recovery, nerve conduction, and sensory and motor neuron regeneration. Histological examinations revealed enhanced maturation of regenerated nerve fibers and reduced denervated muscle atrophy. Discussion: While cMENS shows promise as an adjuvant treatment for long-distance nerve defects, future research should explore extended stimulation durations and potential synergies with tissue engineering grafts to improve outcomes. This study contributes comprehensive evidence supporting the efficacy of cMENS in enhancing peripheral nerve regeneration.
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The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.
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Fezes , Microbioma Gastrointestinal , Humanos , Fezes/microbiologia , Clostridiales/genética , Clostridiales/metabolismo , Clostridiales/isolamento & purificação , Clostridiales/classificação , Probióticos/metabolismo , Metabolômica , Genômica , Masculino , Filogenia , Feminino , Genoma BacterianoRESUMO
Background: Growing observational studies have shown that abnormal systemic iron status is associated with Coronary heart disease (CHD). However, these results from observational studies was not entirely consistent.It remains unclear whether this relationship represents causality.It is necessary to explore the causal relationship between iron status and CHD and related cardiovascular diseases (CVD). Objective: We aimed to investigate the potential casual relationship between serum iron status and CHD and related CVD using a two-sample Mendelian randomization (MR) approach. Methods: Genetic statistics for single nucleotide polymorphisms (SNPs) between four iron status parameters were identified in a large-scale genome-wide association study (GWAS) conducted by the Iron Status Genetics organization. Three independent single nucleotide polymorphisms (SNPs) (rs1800562, rs1799945, and rs855791) aligned with four iron status biomarkers were used as instrumental variables. CHD and related CVD genetic statistics We used publicly available summary-level GWAS data. Five different MR methods random effects inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and Wald ratio were used to explore the causal relationship between serum iron status and CHD and related CVD. Results: In the MR analysis, we found that the causal effect of serum iron (OR = 0.995, 95% CI = 0.992-0.998, p = 0.002) was negatively associated with the odds of coronary atherosclerosis (AS). Transferrin saturation (TS) (OR = 0.885, 95% CI = 0.797-0.982, p = 0.02) was negatively associated with the odds of Myocardial infarction (MI). Conclusion: This MR analysis provides evidence for a causal relationship between whole-body iron status and CHD development. Our study suggests that a high iron status may be associated with a reduced risk of developing CHD.
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Background: Growing evidence suggests that Coronary artery disease (CAD) is associated with cognitive impairment. However, these results from observational studies was not entirely consistent, with some detecting no such association. And it is necessary to explore the causal relationship between CAD and cognitive impairment. Objective: We aimed to explore the potential causal relationship between CAD and cognitive impairment by using bidirectional two-sample mendelian randomization (MR) analyses. Methods: Instrument variants were extracted according to strict selection criteria. And we used publicly available summary-level GWAS data. Five different methods of MR [random-effect inverse-variance weighted (IVW), MR Egger, weighted median, weighted mode and Wald ratio] were used to explore the causal relationship between CAD and cognitive impairment. Results: There was little evidence to support a causal effect of CAD on cognitive impairment in the forward MR analysis. In the reverse MR analyses, We detect causal effects of fluid intelligence score (IVW: ß = -0.12, 95% CI of -0.18 to -0.06, P = 6.8 × 10-5), cognitive performance (IVW: ß = -0.18, 95% CI of -0.28 to -0.08, P = 5.8 × 10-4) and dementia with lewy bodies (IVW: OR = 1.07, 95% CI of 1.04-1.10, P = 1.1 × 10-5) on CAD. Conclusion: This MR analysis provides evidence of a causal association between cognitive impairment and CAD. Our findings highlight the importance of screening for coronary heart disease in patients of cognitive impairment, which might provide new insight into the prevention of CAD. Moreover, our study provides clues for risk factor identification and early prediction of CAD.
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New York-esophageal cancer 1 (NY-ESO-1) belongs to the cancer testis antigen (CTA) family, and has been identified as one of the most immunogenic tumor-associated antigens (TAAs) among the family members. Given its ability to trigger spontaneous humoral and cellular immune response and restricted expression, NY-ESO-1 has emerged as one of the most promising targets for cancer immunotherapy. Cancer vaccines, an important element of cancer immunotherapy, function by presenting an exogenous source of TAA proteins, peptides, and antigenic epitopes to CD4+ T cells via major histocompatibility complex class II (MHC-II) and to CD8+ T cells via major histocompatibility complex class I (MHC-I). These mechanisms further enhance the immune response against TAAs mediated by cytotoxic T lymphocytes (CTLs) and helper T cells. NY-ESO-1-based cancer vaccines have a history of nearly two decades, starting from the first clinical trial conducted in 2003. The current cancer vaccines targeting NY-ESO-1 have various types, including Dendritic cells (DC)-based vaccines, peptide vaccines, protein vaccines, viral vaccines, bacterial vaccines, therapeutic whole-tumor cell vaccines, DNA vaccines and mRNA vaccines, which exhibit their respective benefits and obstacles in the development and application. Here, we summarized the current advances in cancer vaccines targeting NY-ESO-1 for solid cancer treatment, aiming to provide perspectives for future research.
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Vacinas Anticâncer , Neoplasias , Masculino , Humanos , Linfócitos T CD8-Positivos , Anticorpos , Imunoterapia , Vacinas Bacterianas , Neoplasias/terapiaRESUMO
OBJECTIVE: Observational studies had demonstrated a link between sleep disturbances and cognitive decline. Here, we aimed to investigate the causal association between genetically predicted sleep traits and cognitive impairment using Mendelian randomization (MR). METHODS: Using strict criteria, we selected genetic variants from European ancestry Genome-wide association studies (GWAS) from the Sleep Disorders Knowledge Portal and UK Biobank as instrumental variables for several sleep traits, including insomnia, sleep duration, daytime sleepiness, daytime napping, and chronotype. Summary statistics related to cognitive impairment were derived from five different GWAS, including the Social Science Genetic Association Consortium. The role of self-reported sleep trait phenotypes in the etiology of cognitive impairment was explored using inverse-variance weighted (IVW) tests, MR-Egger tests, and weighted medians, and sensitivity analyses were conducted to ensure robustness. RESULTS: In the main IVW analysis, sleep duration (reaction time: ß = -0.05, 95% CI -0.07 to -0.04, p = 1.93×10-12 ), daytime sleepiness (average cortical thickness: ß = -0.12, 95% CI -0.22 to -0.02, p = 0.023), and daytime napping (fluid intelligence: ß = -0.47, 95% CI -0.87 to -0.07, p = 0.021; hippocampal volume in Alzheimer's disease: ß = -0.99, 95% CI -1.64 to -0.35, p = 0.002) were significantly negatively correlated with cognitive performance. However, any effects of insomnia and chronotype on cognitive impairment were not determined. CONCLUSIONS: Our findings highlighted that focusing on sleep behaviors or distinct sleep patterns-particularly sleep duration, daytime sleepiness, and daytime napping, was a promising approach for preventing cognitive impairment. This study also shed light on risk factors for and potential early markers of cognitive impairment risk factors.
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Disfunção Cognitiva , Distúrbios do Sono por Sonolência Excessiva , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Sono/genética , Disfunção Cognitiva/genética , FenótipoRESUMO
Background: The coexistence of coronary artery disease (CAD) and cognitive impairment has become a common clinical phenomenon. However, there is currently limited research on the etiology of this disease cluster, discovery of biomarkers, and identification of precise intervention targets. Methods: We explored the causal connections between gut microbiota, blood metabolites, and the disease cluster of CAD combined with cognitive impairment through two-sample Mendelian randomization (TSMR). Additionally, we determine the gut microbiota and blood metabolites with the strongest causal associations using Bayesian model averaging multivariate Mendelian randomization (MR-BMA) analysis. Furthermore, we will investigate the mediating role of blood metabolites through a two-step Mendelian randomization design. Results: We identified gut microbiota that had significant causal associations with cognitive impairment. Additionally, we also discovered blood metabolites that exhibited significant causal associations with both CAD and cognitive impairment. According to the MR-BMA results, the free cholesterol to total lipids ratio in large very low density lipoprotein (VLDL) was identified as the key blood metabolite significantly associated with CAD. Similarly, the cholesteryl esters to total lipids ratio in small VLDL emerged as the primary blood metabolite with a significant causal association with dementia with lewy bodies (DLB). For the two-step Mendelian randomization analysis, we identified blood metabolites that could potentially mediate the association between genus Butyricicoccus and CAD in the potential causal links. Conclusion: Our study utilized Mendelian randomization (MR) to identify the gut microbiota features and blood metabolites characteristics associated with the disease cluster of CAD combined with cognitive impairment. These findings will provide a meaningful reference for the identification of biomarkers for the disease cluster of CAD combined with cognitive impairment as well as the discovery of targets for intervention to address the problems in the clinic.
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Disfunção Cognitiva , Doença da Artéria Coronariana , Microbioma Gastrointestinal , Humanos , Hotspot de Doença , Doença da Artéria Coronariana/genética , Teorema de Bayes , Análise da Randomização Mendeliana , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/genética , Biomarcadores , LipídeosRESUMO
Ruminococcus gnavus is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being. We postulate the ambiguities of its function in different cases may be attributed to strain-level variability of genomic features of R. gnavus. We performed comparative genomic and pathogenicity prediction analysis on 152 filtered high-quality genomes, including 4 genomes of strains isolated from healthy adults in this study. The mean G+C content of genomes of R. gnavus was 42.73±0.33 mol%, and the mean genome size was 3.46±0.34 Mbp. Genome-wide evolutionary analysis revealed R. gnavus genomes were divided into three major phylogenetic clusters. Pan-core genome analysis revealed that there was a total of 28 072 predicted genes, and the core genes, soft-core genes, shell genes and cloud genes accounted for 3.74â% (1051/28â¯072), 1.75â% (491/28â¯072), 9.88â% (2774/28â¯072) and 84.63â% (23â¯756/28â¯072) of the total genes, respectively. The small proportion of core genes reflected the wide divergence among R. gnavus strains. We found certain coding sequences with determined health benefits (such as vitamin production and arsenic detoxification), whilst some had an implication of health adversity (such as sulfide dehydrogenase subunits). The functions of the majority of core genes were unknown. The most widespread genes functioning in antibiotic resistance and virulence are tetO (tetracycline-resistance gene, present in 75 strains) and cps4J (capsular polysaccharide biosynthesis protein Cps4J encoding gene, detected in 3 genomes), respectively. Our results revealed genomic divergence and the existence of certain safety-relevant factors of R. gnavus. This study provides new insights for understanding the genomic features and health relevance of R. gnavus, and raises concerns regarding predicted prevalent pathogenicity and antibiotic resistance among most of the strains.
Assuntos
Clostridiales , Ruminococcus , Adulto , Animais , Humanos , Ruminococcus/genética , Filogenia , Clostridiales/genética , GenômicaRESUMO
Background: Ischemic heart disease and degenerative encephalopathy are two main sources of disease burden for the global elderly population. Coronary heart disease (CHD) and cognitive impairment, as representative diseases, are prevalent and serious illnesses in the elderly. According to recent research, patients with CHD are more likely to experience cognitive impairment and their cognitive ability declines more quickly. Vascular risk factors have been associated with differences in cognitive performance in epidemiological studies, but evidence in patients with CHD is more limited. Inextricably linked between the heart and the brain. Considering the unique characteristics of recurrent cognitive impairment in patients with CHD, we will further study the related risk factors. We tried to investigate the potential predictors of cognitive impairment in patients with CHD through a prospective, cross-sectional study. Methods: The cross-sectional study design will recruit 378 patients with CHD (≥65 years) from Xiyuan Hospital of China Academy of Chinese Medical Sciences. The subjects' cognitive function is evaluated with MoCA scale, and they are divided into cognitive impairment group and normal cognitive function group according to the score results. Demographic data, disease characteristics (results of coronary CT/ angiography, number of stents implanted, status of diseased vessels), laboratory tests (biochemistry, coagulation, serum iron levels, pulse wave velocity), metabolites (blood samples and intestinal metabolites), and lifestyle (smoking, alcohol consumption, sleep, physical activity) will be assessed as outcome indicators. Compare the two groups and the correlation analysis will be performed on the development of mild cognitive impairment. Mann-Whitney U or X2 test was selected to describe and evaluate the variation, and logistics regression analysis was employed to fit the prediction model. After that, do the calibration curve and decision curve to evaluate the model. The prediction model will be validated by a validation set. Discussion: To explore the risk factors related to mild cognitive impairment (MCI) in patients with CHD, a new predictive model is established, which can achieve advanced intervention in the occurrence of MCI after CHD. Owing to its cross-sectional study design, the study has some limitations, but it will be further studied by increasing the observation period, adding follow-up data collection or prospective cohort study. The study has been registered with the China Clinical Trials Registry (ChiCTR2200063255) to conduct clinical trials.
RESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major global public health challenge, with the emergence of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current vaccines or monoclonal antibodies may not well be protect against infection with new SARS-CoV-2 variants. Unlike antibody-based treatment, T cell-based therapies such as TCR-T cells can target epitopes that are highly conserved across different SARS-CoV-2 variants. Reportedly, T cell-based immunity alone can restrict SARS-CoV-2 replication. METHODS: In this study, we identified two TCRs targeting the RNA-dependent RNA polymerase (RdRp) protein in CD8 + T cells. Functional evaluation by transducing these TCRs into CD8 + or CD4 + T cells confirmed their specificity. RESULTS: Combinations of inflammatory and anti-inflammatory cytokines secreted by CD8 + and CD4 + T cells can help control COVID-19 in patients. Moreover, the targeted epitope is highly conserved in all emerged SARS-CoV-2 variants, including the Omicron. It is also conserved in the seven coronaviruses that infect humans and more broadly in the subfamily Coronavirinae. CONCLUSIONS: The pan-genera coverage of mutant epitopes from the Coronavirinae subfamily by the two TCRs highlights the unique strengths of TCR-T cell therapies in controlling the ongoing pandemic and in preparing for the next coronavirus outbreak.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/terapia , Epitopos , Receptores de Antígenos de Linfócitos T/genética , Anticorpos Monoclonais/uso terapêutico , RNA Polimerase Dependente de RNA , Citocinas , Epitopos de Linfócito T/genéticaRESUMO
T-cell receptor (TCR)-transduced T (TCR-T) cell therapy has shown promising efficacy in the clinical treatment of malignant cancers. However, the populations covered by reported TCRs are still limited. Tumor infiltrating lymphocytes (TILs) are natural reservoirs of tumor-reactive T cells and TCRs. Approaches are required for the fast and cost-effective identification of tumor-reactive TCRs from TILs. The widely employed TCR identification approaches by the clonal expansion of TILs involve a TCR singularization process for the direct pairing of TCR Vα and the Vß chain. However, the clonal expansion of T cells is well known to require extensive time and effort due to the involvement of T cell cultures. Several single-cell multiplexing PCR methods followed by Sanger sequencing have been developed, representing a cost-effective and fast approach for single-cell TCR identification. In this study, an RNA-based preamplification step was included in the single-cell TCR sequencing, which can reduce the multiplexing PCR amplification to one round. Moreover, the cDNA product of RNA preamplification is derived from the whole genome mRNA, instead of TCR mRNA only by multiplexing primers-based DNA preamplification, which is valuable for many other analyses (e.g., phenotypic analysis) of the tumor-reactive T cells that can be correlated with the identified TCRs. The feasibility for both single α chain and dual α chain TILs of this approach highlights its potential value as a rapid and cost-effective sequencing strategy for the development of TCR-T therapies for solid cancers.