RESUMEN

BACKGROUND: Exercise interventions for mild cognitive impairment (MCI) have been extensively studied. However, there is no bibliometric study on exercise interventions for MCI. This study aimed to identify the collaborative networks, research hotspots, evolution trends, and future directions. METHODS: Relevant documents were retrieved from the Web of Science Core Collection database. VOSviewer was used to analyze the co-authorship of the author, countries and institutions, and the keywords co-occurrence. CiteSpace was used to detect burst keywords' research trends. RESULTS: A total of 569 articles were included and showed an overall increasing trend in annual publications. The most influential subject categories, authors, journals, country, and institutions were "geriatrics gerontology," "Doi, Takehiko and Shimada, Hiroyuki," "Journal of Alzheimer's Disease," USA, and "Veterans Health Administration," respectively. The research hotspots are "effectiveness," "neural mechanism" and "correlation" of exercise interventions, and the emerging trend is "intervention quality." CONCLUSION: This area is in a rapid development phase, whereby research hotpots are focused and the research trend is clear. The highly productive authors and institutions have made outstanding contributions and the subject categories present an interdisciplinary trend. However, there is weak cooperation between countries and institutions, and a substantial research gap exists between developed and developing countries. Future research may highlight the intervention quality, emphasizing the combination with virtual reality technology.

Asunto(s)

Bibliometría , Disfunción Cognitiva , Terapia por Ejercicio , Humanos , Disfunción Cognitiva/terapia , Terapia por Ejercicio/métodos , Salud Global , Ejercicio Físico

RESUMEN

Background: The pacing strategy embodies the tactical behavior of athletes in distributing their energy across different segments of a race; therefore, a quantitative analysis of pacing strategies in marathon races could deepen the understanding of both pacing behavior and physical capacity in marathon athletics. Objective: The objective of this systematic review was to synthesize and characterize pacing strategies in marathon road races by exploring the categories of pacing strategies and the factors that influence these strategies during marathon events. Methods: Preferred Reporting Items for Systematic Reviews guidelines were followed for systematic searches, appraisals, and syntheses of literature on this topic. Electronic databases such as Science Direct, SPORTDiscuss, PubMed, and Web of Science were searched up to July 2024. Records were eligible if they included pace performance measurements during competition, without experimental intervention that may influence their pace, in healthy, adult athletes at any level. Results: A total of 39 studies were included in the review. Twenty-nine were observational studies, and 10 were experimental (randomized controlled trials). The assessment of article quality revealed an overall median NOS score of 8 (range 5-9). The included studies examined the pacing profiles of master athletes and finishers in half-marathon (n = 7, plus numbers compared to full marathon), full-marathon (n = 21), and ultramarathon (n = 11) road races. Considering that some studies refer to multiple pacing strategies, in general, 5 studies (∼13 %) reported even pacing, 3 (∼8 %) reported parabolic pacing, 7 (∼18 %) reported negative pacing, and 30 (∼77 %) reported positive pacing during marathon competitions. Gender, age, performance, pack, and physiological and psychological factors influence pacing strategies. Conclusion: This study synthesized pacing performance in marathons and highlighted the significance of examining pacing strategies in these events, offering valuable insights for coaches and athletes. Several key findings were highlighted: (1) pacing profiles and pacing ranges were identified as the primary indicators of pacing strategies; (2) the pacing strategy was found to be dynamic, with the most substantial effects attributed to gender and distance; and (3) three distinct types of pacing strategies for marathons were classified: positive, negative, and even pacing. These findings advance the understanding of marathon pacing strategies by shedding light on the factors that influence athletes' pacing decisions and behaviors. Additionally, these findings offer practical benefits, aiding athletes in making well-informed tactical choices and developing effective pace plans to enhance marathon performance. However, due to the complex nature of marathon racing, further research is required to explore additional factors that might impact pacing strategies. A better grasp of optimal pacing strategies will foster progress in this area and serve as a basis for future research and advancements.

RESUMEN

BACKGROUND: Depression and anxiety are common mental disorders in later life. Digital intelligence interventions overcome the limitations of conventional psychotherapy and offer new treatments for depression and anxiety. However, the effectiveness among older adults remains unclear. METHODS: Databases including Pubmed, Web of Science, the Cochrane Library, Medline, CINAHL, PsycINFO, and Embase were searched for Randomized Controlled Trials (RCTs) from inception to November 22, 2023. Statistical analyses were conducted using Stata 18.0 and Review Manager 5.4. RESULTS: The initial search found 9369 papers, with 21 meeting the inclusion criteria (e.g., RCTs involving older adults aged 50 and older that assessed digital intelligence interventions on depression and anxiety symptoms). Meta-analyses revealed that, compared to control groups, digital intelligence interventions significantly reduced depression symptoms (SMD: -0.58; 95 % CI: -0.80, -0.35) and anxiety symptoms (SMD: -0.39; 95 % CI: -0.58, -0.19). Subgroup analysis revealed that internet-based Cognitive Behavioral Therapy (iCBT), interventions lasting 7 to 10 weeks, and the use of the Patient Health Questionnaire (PHQ) and Generalized Anxiety Disorder-7 (GAD-7) scales, especially in other regions, had the most pronounced effects. CONCLUSIONS: Digital intelligence interventions reduce depressive and anxious symptoms in older adults, supporting the development of evidence-based treatment guidelines in the digital era.

RESUMEN

Bovine viral diarrhea-mucosal disease (BVD-MD) is a contagious disease in cattle, caused by the bovine viral diarrhea virus (BVDV). This virus continues to spread globally, exerting pressure on both public health and the economy. Despite its impact, there are currently no effective drugs for treating BVDV. This study utilized Madin-Darby bovine kidney (MDBK) cells as a model to investigate the antiviral effects of melatonin against Bovine Viral Diarrhea Virus (BVDV) and its connection with endoplasmic reticulum (ER) stress. Our results show that melatonin can suppress BVDV proliferation in MDBK cells by modulating the endoplasmic reticulum (ER) stress-mediated NF-κB pathway and autophagy. Specifically, melatonin alleviated ER stress, inhibited the activation of IκBα and p65, regulated autophagy, and reduced the expression levels of pro-inflammatory cytokines. Further, when we treated BVDV-infected cells with the ER stress inducer thapsigargin, it led to significant activation of the NF-κB pathway and autophagy. Conversely, treating the cells with the ER stress inhibitor 4-phenylbutyric acid reversed these effects. These findings suggest that melatonin exerts its antiviral effects primarily through the PERK-eIF2α-ATF4 of ER stress-mediated NF-κB pathway and autophagy. Overall, our study underscores the potential of melatonin as an effective protective and therapeutic option against BVDV, offering insights into its anti-infective mechanisms.

Asunto(s)

Antivirales , Autofagia , Virus de la Diarrea Viral Bovina , Estrés del Retículo Endoplásmico , Melatonina , FN-kappa B , Transducción de Señal , Replicación Viral , Melatonina/farmacología , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Autofagia/efectos de los fármacos , Bovinos , FN-kappa B/metabolismo , Replicación Viral/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Virus de la Diarrea Viral Bovina/efectos de los fármacos , Virus de la Diarrea Viral Bovina/fisiología , Línea Celular , Antivirales/farmacología , Diarrea Mucosa Bovina Viral/tratamiento farmacológico , Diarrea Mucosa Bovina Viral/virología

RESUMEN

OBJECTIVES: Emerging research has investigated the potential impact of several modifiable risk factors on the risks of rheumatoid arthritis (RA), but the findings did not yield consistent results. This study aimed to comprehensively explore the genetic causality between modifiable risk factors and the susceptibility of RA risk using the Mendelian randomization (MR) approach. METHODS: Genetic instruments for modifiable risk factors were selected from several genome-wide association studies at the genome-wide significance level (p < 5 × 10-8), respectively. Summary-level data for RA were sourced from a comprehensive meta-analysis. The causal estimates linking modifiable risk factors to RA risk were assessed using MR analysis with inverse variance weighting (IVW), MR-Egger, weighted, and weighted median methods. RESULTS: After Bonferroni correction for multiple tests, we found the presence of causality between educational attainment and RA, where there were protective effects of educational attainment (college completion) (odds ratio [OR] = 0.50, 95% CI = 0.36, 0.69, p = 2.87E-05) and educational attainment (years of education) (OR = 0.93, 95% CI = 0.90, 0.96, p = 4.18E-06) on the lower RA risks. Nevertheless, smoking initiation was observed to be associated with increased RA risks (OR = 1.27, 95% CI = 1.09, 1.47, p = .002). Moreover, there was no indication of horizontal pleiotropy of genetic variants during causal inference between modifiable risk factors and RA. CONCLUSIONS: Our study reveals the genetic causal impacts of educational attainment and smoking on RA risks, suggesting that the early monitoring and recognition of modifiable risk factors would be beneficial for the preventive counseling/treatment strategies for RA.

Asunto(s)

Artritis Reumatoide , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Artritis Reumatoide/genética , Artritis Reumatoide/epidemiología , Artritis Reumatoide/diagnóstico , Humanos , Factores de Riesgo , Medición de Riesgo , Escolaridad , Fumar/efectos adversos , Fumar/epidemiología , Fenotipo , Polimorfismo de Nucleótido Simple , Factores Protectores

RESUMEN

Introduction: Air pollution is speculated to increase the risk of Coronavirus disease-2019 (COVID-19). Nevertheless, the results remain inconsistent and inconclusive. This study aimed to explore the association between ambient air pollution (AAP) and COVID-19 risks using a meta-analysis with meta-regression modelling. Methods: The inclusion criteria were: original studies quantifying the association using effect sizes and 95 % confidence intervals (CIs); time-series, cohort, ecological or case-crossover peer-reviewed studies in English. Exclusion criteria encompassed non-original studies, animal studies, and data with common errors. PubMed, Web of Science, Embase and Google Scholar electronic databases were systemically searched for eligible literature, up to 31, March 2023. The risk of bias (ROB) was assessed following the Agency for Healthcare Research and Quality parameters. A random-effects model was used to calculate pooled risk ratios (RRs) and their 95 % CIs. Results: A total of 58 studies, between 2020 and 2023, met the inclusion criteria. The global representation was skewed, with major contributions from the USA (24.1 %) and China (22.4 %). The distribution included studies on short-term (43.1 %) and long-term (56.9 %) air pollution exposure. Ecological studies constituted 51.7 %, time-series-27.6 %, cohorts-17.2 %, and case crossover-3.4 %. ROB assessment showed low (86.2 %) and moderate (13.8 %) risk. The COVID-19 incidences increased with a 10 µg/m3 increase in PM2.5 [RR = 4.9045; 95 % CI (4.1548-5.7895)], PM10 [RR = 2.9427: (2.2290-3.8850)], NO2 [RR = 3.2750: (3.1420-3.4136)], SO2 [RR = 3.3400: (2.7931-3.9940)], CO [RR = 2.6244: (2.5208-2.7322)] and O3 [RR = 2.4008: (2.1859-2.6368)] concentrations. A 10 µg/m3 increase in concentrations of PM2.5 [RR = 3.0418: (2.7344-3.3838)], PM10 [RR = 2.6202: (2.1602-3.1781)], NO2 [RR = 3.2226: (2.1411-4.8504)], CO [RR = 1.8021 (0.8045-4.0370)] and O3 [RR = 2.3270 (1.5906-3.4045)] was significantly associated with COVID-19 mortality. Stratified analysis showed that study design, exposure period, and country influenced exposure-response associations. Meta-regression model indicated significant predictors for air pollution-COVID-19 incidence associations. Conclusion: The study, while robust, lacks causality demonstration and focuses only on the USA and China, limiting its generalizability. Regardless, the study provides a strong evidence base for air pollution-COVID-19-risks associations, offering valuable insights for intervention measures for COVID-19.

RESUMEN

AIM: To analyze the changes in scientific output relating to Leber congenital amaurosis (LCA) and forecast the study trends in this field. METHODS: All of the publications in the field of LCA from 2002 to 2022 were collected from Web of Science (WOS) database. We analyzed the quantity (number of publications), quality (citation and H-index) and development trends (relative research interest, RRI) of published LCA research over the last two decades. Moreover, VOSviewer software was applied to define the co-occurrence network of keywords in this field. RESULTS: A total of 2158 publications were ultimately examined. We found that the focus on LCA kept rising and peaked in 2015 and 2018, which is consistent with the development trend of gene therapy. The USA has contributed most to this field with 1162 publications, 56 674 citations and the highest H-index value (116). The keywords analysis was divided into five clusters to show the hotspots in the field of LCA, namely mechanism-related, genotype-related, local phenotype-related, system phenotype-related, and therapy-related. We also identified gene therapy and anti-retinal degeneration therapy as a major focus in recent years. CONCLUSION: Our study illustrates historical research process and future development trends in LCA field. This may help to guide the orientation for further clinical diagnosis, treatment and scientific research.

RESUMEN

PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) is regarded as an accelerated aging disease. Aging-related genes in COPD are still poorly understood. METHOD: Data set GSE76925 was obtained from the Gene Expression Omnibus (GEO) database. The "limma" package identified the differentially expressed genes. The weighted gene co-expression network analysis (WGCNA) constructes co-expression modules and detect COPD-related modules. The least absolute shrinkage and selection operator (LASSO) and the support vector machine recursive feature elimination (SVM-RFE) algorithms were chosen to identify the hub genes and the diagnostic ability. Three external datasets were used to identify differences in the expression of hub genes. Real-time reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the expression of hub genes. RESULT: We identified 15 differentially expressed genes associated with aging (ARDEGs). The SVM-RFE and LASSO algorithms pinpointed four potential diagnostic biomarkers. Analysis of external datasets confirmed significant differences in PIK3R1 expression. RT-qPCR results indicated decreased expression of hub genes. The ROC curve demonstrated that PIK3R1 exhibited strong diagnostic capability for COPD. CONCLUSION: We identified 15 differentially expressed genes associated with aging. Among them, PIK3R1 showed differences in external data sets and RT-qPCR results. Therefore, PIK3R1 may play an essential role in regulating aging involved in COPD.

Asunto(s)

Envejecimiento , Enfermedad Pulmonar Obstructiva Crónica , Máquina de Vectores de Soporte , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Envejecimiento/genética , Perfilación de la Expresión Génica , Fosfatidilinositol 3-Quinasa Clase Ia/genética , Algoritmos , Bases de Datos Genéticas , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Biomarcadores/metabolismo , Redes Reguladoras de Genes

RESUMEN

In practical applications, polyurethane (PU) foam must be rigid to meet the demands of various industries and provide comfort and protection in everyday life. PU foam components are extensively used in structural foam, thermal insulation, decorative panels, packaging, imitation wood, and floral foam, as well as in models and prototypes. Conventional technology for producing PU foam parts often leads to defects such as deformation, short shots, entrapped air, warpage, flash, micro-bubbles, weld lines, and voids. Therefore, the development of rigid PU foam parts has become a crucial research focus in the industry. This study proposes an innovative manufacturing process for producing rigid PU foam parts using silicone rubber molds (SRMs). The deformation of the silicone rubber mold can be predicted based on its wall thickness, following a trend equation with a correlation coefficient of 0.9951. The volume of the PU foam part can also be predicted by the weight of the PU foaming agent, as indicated by a trend equation with a correlation coefficient of 0.9824. The optimal weight ratio of the foaming agent to water, yielding the highest surface hardness, was found to be 5:1. The surface hardness of the PU foam part can also be predicted based on the weight of the water used, according to a proposed prediction equation with a correlation coefficient of 0.7517. The average surface hardness of the fabricated PU foam part has a Shore O hardness value of approximately 75. Foam parts made with 1.5 g of water added to 15 g of a foaming agent have the fewest internal pores, resulting in the densest interior. PU foam parts exhibit excellent mechanical properties when 3 g of water is added to the PU foaming agent, as evidenced by their surface hardness and compressive strength. Using rigid PU foam parts as a backing material in the proposed method can reduce rapid tool production costs by about 62%. Finally, an innovative manufacturing process for creating large SRMs using rigid PU foam parts as backing material is demonstrated.

RESUMEN

The severity of periodontitis can be analyzed by calculating the loss of alveolar crest (ALC) level and the level of bone loss between the tooth's bone and the cemento-enamel junction (CEJ). However, dentists need to manually mark symptoms on periapical radiographs (PAs) to assess bone loss, a process that is both time-consuming and prone to errors. This study proposes the following new method that contributes to the evaluation of disease and reduces errors. Firstly, innovative periodontitis image enhancement methods are employed to improve PA image quality. Subsequently, single teeth can be accurately extracted from PA images by object detection with a maximum accuracy of 97.01%. An instance segmentation developed in this study accurately extracts regions of interest, enabling the generation of masks for tooth bone and tooth crown with accuracies of 93.48% and 96.95%. Finally, a novel detection algorithm is proposed to automatically mark the CEJ and ALC of symptomatic teeth, facilitating faster accurate assessment of bone loss severity by dentists. The PA image database used in this study, with the IRB number 02002030B0 provided by Chang Gung Medical Center, Taiwan, significantly reduces the time required for dental diagnosis and enhances healthcare quality through the techniques developed in this research.

RESUMEN

BACKGROUND: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. METHODS: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. FINDINGS: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. INTERPRETATION: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. FUNDING: Singapore NMRC, USFDA, MRC.

Asunto(s)

Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Adulto , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Inmunogenicidad Vacunal , Inmunidad Humoral , Vacunación/métodos , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven , Infección Irruptiva

RESUMEN

The study aimed to investigate the pattern and trend of Musculoskeletal (MSK) disorders in people aged 5-19 years from 1990 to 2021. The data was sourced from the Global Burden of Disease study 2021. The Age-standardized DALYs rates (ASDR), age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and age-standardized incidence rate (ASIR) and their corresponding average annual percent change (AAPC) for MSK disorders were evaluated by sex, region, and sociodemographic index (SDI) quintiles. Globally, the ASPR of MSK disorders among children and adolescents increased per 100,000 population from 3048.66 (95% confidence interval [CI]: 2336.68-3887.02) in 1990 to 3105.46 (95% CI: 2421.09-3904.95) in 2021 (AAPC 0.06 [95% CI: 0.05-0.07]). In 2021, individuals aged 15-19 experienced the highest burden compared to those aged 5-9 and 10-14. In 2021, high SDI countries had the highest ASIR, ASPR, ASDR of MSK disorders. The AAPC of ASPR in high SDI countries showed a stark contrast to that in low SDI countries for the same period (AAPC 0.48 vs. AAPC -0.03). From 1990 to 2021, in low SDI and low-middle SDI countries, the increase in DALYs was primarily due to population growth. However, in middle SDI, high-middle, and high SDI countries, the increases were mainly due to epidemiological changes. Globally, patients aged 10-14 experienced better care compared to those in the 5-9 and 15-19 age groups. Specific preventive health measures are needed for females and adolescents aged 15-19 in high SDI countries.

Asunto(s)

Carga Global de Enfermedades , Enfermedades Musculoesqueléticas , Humanos , Adolescente , Niño , Enfermedades Musculoesqueléticas/epidemiología , Masculino , Femenino , Carga Global de Enfermedades/tendencias , Preescolar , Adulto Joven , Prevalencia , Incidencia , Salud Global , Distribución por Edad

RESUMEN

In competitive sports, momentum encompasses positive or negative changes in cognition, physiology, emotions, and behavior caused by sudden or a series of continuous events. Momentum occurring during basketball games leads to significant performance variation regarding positive net points differences for a specific team within a certain period. This study designed a quantitative framework based on two performative dimensions (time constraints and point differentials) to accurately identify momentum in basketball games, and explored the role of momentum in games. We identified 2,083 momentum occurrences in 372 professional elite basketball games. The number of momentum occurrences for winning teams is significantly higher than for losing teams (1.78 ± 0.47 Difference Value, p < 0.001); the correlation between momentum and game outcomes decreased as each quarter progressed. To distinguish the influence of contextual variables on momentum, we divided games into five types based on the team quality differences between the team and the opponent team. The decision tree model shows that first-quarter momentum is critical in games where weaker teams defeat stronger teams. This study provides insights for basketball coaches to formulate game strategies. More importantly, the momentum conceptual framework can help researchers identify and capture momentum, offering inspiration and reference for subsequent research.

RESUMEN

Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled proliferation of plasma cells in the bone marrow. MM patients with aggressive progression have poor survival, emphasizing the urgent need for identifying new therapeutic targets. Here, we show that the leukocyte immunoglobulin-like receptor B1 (LILRB1), a transmembrane receptor conducting negative immune response, is a top-ranked gene associated with poor prognosis in MM patients. LILRB1 deficiency inhibits MM progression in vivo by enhancing the ferroptosis of MM cells. Mechanistic studies reveal that LILRB1 forms a complex with the low-density lipoprotein receptor (LDLR) and LDLR adapter protein 1 (LDLRAP1) to facilitate LDL/cholesterol uptake. Loss of LILRB1 impairs cholesterol uptake but activates the de novo cholesterol synthesis pathway to maintain cellular cholesterol homeostasis, leading to the decrease of anti-ferroptotic metabolite squalene. Our study uncovers the function of LILRB1 in regulating cholesterol metabolism and protecting MM cells from ferroptosis, implicating LILRB1 as a promising therapeutic target for MM patients.

Asunto(s)

Colesterol , Ferroptosis , Homeostasis , Receptor Leucocitario Tipo Inmunoglobulina B1 , Mieloma Múltiple , Receptores de LDL , Humanos , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Mieloma Múltiple/genética , Receptor Leucocitario Tipo Inmunoglobulina B1/metabolismo , Ferroptosis/genética , Colesterol/metabolismo , Receptores de LDL/metabolismo , Receptores de LDL/genética , Animales , Línea Celular Tumoral , Ratones , Antígenos CD

RESUMEN

Hypertension has become a major contributor to the morbidity and mortality of cardiovascular diseases worldwide. Despite the evidence of the anti-hypertensive effect of gastrodia-uncaria granules (GUG) in hypertensive patients, little is known about its potential therapeutic targets as well as the underlying mechanism. GUG components were sourced from TCMSP and HERB, with bioactive ingredients screened. Hypertension-related targets were gathered from DisGeNET, OMIM, GeneCards, CTD, and GEO. The STRING database constructed a protein-protein interaction network, visualized by Cytoscape 3.7.1. Core targets were analyzed via GO and KEGG using R package ClusterProfiler. Molecular docking with AutodockVina 1.2.2 revealed favorable binding affinities. In vivo studies on hypertensive mice and rats validated network pharmacology findings. GUG yielded 228 active ingredients and 1190 targets, intersecting with 373 hypertension-related genes. PPI network analysis identified five core genes: AKT1, TNF-α, GAPDH, IL-6, and ALB. Top enriched GO terms and KEGG pathways associated with the anti-hypertensive properties of GUG were documented. Molecular docking indicated stable binding of core components to targets. In vivo study showed that GUG could improve vascular relaxation, alleviate vascular remodeling, and lower blood pressure in hypertensive animal models possibly through inhibiting inflammatory factors such as AKT1, mTOR, and CCND1. Integrated network pharmacology and in vivo experiment showed that GUG may exert anti-hypertensive effects by inhibiting inflammation response, which provides some clues for understanding the effect and mechanisms of GUG in the treatment of hypertension.

RESUMEN

BACKGROUND: Stroke often results in significant respiratory dysfunction in patients. Respiratory muscle training (RMT) has been proposed as a rehabilitative intervention to address these challenges, but its effectiveness compared to routine training remains debated. This systematic review and meta-analysis aim to evaluate the effects of RMT on exercise tolerance, muscle strength, and pulmonary function in post-stroke patients. AIM: To systematically assess the efficacy of RMT in improving exercise tolerance, respiratory muscle strength, and pulmonary function in patients recovering from a stroke, and to evaluate whether RMT offers a significant advantage over routine training modalities in enhancing these critical health outcomes in the post-stroke population. METHODS: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, a comprehensive search across PubMed, Embase, Web of Science, and the Cochrane Library was conducted on October 19, 2023, without temporal restrictions. Studies were selected based on the predefined inclusion and exclusion criteria focusing on various forms of RMT, control groups, and outcome measures [including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), maximal voluntary ventilation (MVV), peak expiratory flow (PEF), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and 6-min walking test (6MWT)]. Only randomized controlled trials (RCTs) were included. Data extraction and quality assessment were conducted independently by two reviewers using the Cochrane Collaboration's risk of bias tool. Statistical analyses, including those using the fixed-effect and random-effects models, sensitivity analysis, and publication bias assessment, were performed using Review Manager software. RESULTS: A total of 15 RCTs were included. Results indicated significant improvements in MIP (12.51 cmH2O increase), MEP (6.24 cmH2O increase), and various pulmonary function parameters (including FEV1, FVC, MVV, and PEF). A substantial increase in 6MWT distance (22.26 meters) was also noted. However, the heterogeneity among studies was variable, and no significant publication bias was detected. CONCLUSION: RMT significantly enhances walking ability, respiratory muscle strength (MIP and MEP), and key pulmonary function parameters (FEV1, FVC, MVV, and PEF) in post-stroke patients. These findings support the incorporation of RMT into post-stroke rehabilitative protocols.

RESUMEN

Background: In non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) is the most common subtype. RNA modification has become the frontier and hotspot of current tumor research. Results: In this study, 109 genes that regulate RNA modifications were identified according to The Cancer Genome Atlas (TCGA). A differential gene expression analysis identified 46 differentially expressed RNA modification regulatory genes (DERRGs). LUAD samples were stratified into two distinct clusters based on the expression of these DERRGs. A significant correlation was observed between these clusters and patient survival rates, as well as clinical features. Furthermore, a four-DERRG signature (EIF3B, HNRNPC, IGF2BP1, and METTL3) developed using LASSO regression. According to the calculated risk scores from this signature, LUAD patients were categorized into high-risk and low-risk groups. Patients in the low-risk group exhibited a more favorable prognosis. A prognostic nomogram was crafted, integrating the four-DERRGs signature with clinical parameters. The nomogram was revealed that OS, age, clinical stage, immune cell infiltration, and immune checkpoint molecule expression were significantly linked to the OS of LUAD. GSEA analysis found that the DERRGs were primarily regulated immune pathways. Conclusions: This study developed four DERRGs signatures and formulated a nomogram model for precise prognosis estimation in LUAD patients. The study's insights are instrumental for advancing diagnosis, prognosis, and therapeutic strategies for LUAD.

RESUMEN

BACKGROUND: Anti leucine-rich, glioma inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) is the second most common AE, where the trafficking and recycling of the pathogenic immunoglobulin (IgG) can be controlled by the neonatal crystallizable fragment receptor (FcRn), making the latter as a candidate therapeutic target. Efgartigimod is an antagonist of FcRn, its ability to increase the degradation of IgGs and improve the health and quality of life of patients. ADAPT trail indicated its rapid efficacy and safety on myasthenia gravis. However, there is currently no case reported using efgartigimod for the treatment of anti-LGI1-associated AE. CASE DESCRIPTION: The patient presented with five episodes of generalized tonic-clonic seizures in the past 2 weeks. The patient had no abnormal signs on magnetic resonance imaging. Electroencephalogram examinations showed an increase in bilateral symmetric or asymmetric slow activity, without any clear epileptic waves. The cerebrospinal fluid (CSF) examination results indicated a slight increase in protein (47 mg/dL). The anti-LGI1 antibody titer in serum was 1:100 and that in CSF was 1:3.2. The treatment with intravenous methylprednisolone 1000 mg once a day combined with levetiracetam tablets failed to completely control the patient's seizures. Thus, 10 mg/kg efgartigimod was administered intravenously once a week for 2 weeks. After 2 weeks of treatment, serum levels of anti-LGI1 antibody and IgG decreased and the patient's epilepsy did not recur in the next 3 months. CONCLUSIONS: This is the first case report of using efgartigimod to treat anti-LGI1-associated AE. The combination of efgartigimod and methylprednisolone resulted in favorable outcomes, indicating that this is an optional treatment plan.

Asunto(s)

Autoanticuerpos , Encefalitis , Humanos , Encefalitis/tratamiento farmacológico , Encefalitis/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Enfermedad de Hashimoto/tratamiento farmacológico , Femenino , Masculino , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/inmunología

RESUMEN

Biodegradation stands as an eco-friendly and effective approach for organic contaminant remediation. However, research on microorganisms degrading sodium benzoate contaminants in extreme environments remains limited. In this study, we report to display the isolation of a novel hot spring enriched cultures with sodium benzoate (400 mg/L) as the sole carbon source. The results revealed that the phylum Pseudomonadota was the potential sodium benzoate degrader and a novel genus within the family Geminicoccaceae of this phylum. The isolated strain was named Benzoatithermus flavus SYSU G07066T and was isolated from HNT-2 hot spring samples. Genomic analysis revealed that SYSU G07066T carried benABC genes and physiological experiments indicated the ability to utilize sodium benzoate as a sole carbon source for growth, which was further confirmed by transcriptomic data with expression of benABC. Phylogenetic analysis suggested that Horizontal Gene Transfer (HGT) plays a significant role in acquiring sodium benzoate degradation capability among prokaryotes, and SYSU G07066T might have acquired benABC genes through HGT from the family Acetobacteraceae. The discovery of the first microorganism with sodium benzoate degradation function from a hot spring enhances our understanding of the diverse functions within the family Geminicoccaceae. This study unearths the first novel genus capable of efficiently degrading sodium benzoate and its evolution history at high temperatures, holding promising industrial applications, and provides a new perspective for further exploring the application potential of hot spring "microbial dark matter".

Asunto(s)

Biodegradación Ambiental , Manantiales de Aguas Termales , Filogenia , Benzoato de Sodio , Benzoato de Sodio/metabolismo , Manantiales de Aguas Termales/microbiología , Contaminantes Químicos del Agua/metabolismo , Multiómica