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INTRODUCTION: Chikungunya fever is a disease caused by infection with the Chikungunya virus, transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Despite its self-limited character, more than 60% of patients have chronic recurrent arthralgia with debilitating pain that lasts for years. AIM: The objective of this review was to gather and analyze evidence from the literature on potential therapeutic strategies with molecules from natural products for the treatment of Chikungunya fever. METHODS: A search was performed for clinical trials, observational studies, in vitro or in vivo, without restriction of the year of publication or language in electronic databases (Medline/PubMed, EMBASE, Google Scholar, The Cochrane Library, LILACS (BVS), clinical trial registries (Clinical Trials.gov), digital libraries from CAPES theses and dissertations (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) and conference abstracts. A quality assessment of the selected studies was performed using the SYRCLE, RoB2 and SciRAP tools. RESULTS: 42 studies were included, which showed molecules with potential antiviral pharmacological activity or with activity in reducing the joint complications caused by CHIKV infection. CONCLUSIONS: Among the molecules found in the survey of references, regarding the class of secondary metabolites, flavonoids stood out and for this reason, the molecules may be promising candidates for future clinical trials. Overall, evidence from in vitro studies was of acceptable quality; in vivo and intervention studies showed a high risk of bias, which is a limitation of these studies.
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About 80â¯% of brain disorders have a genetic basis. The pathogenesis of most neurodegenerative diseases is associated with a myriad of genetic defects, epigenetic alterations (DNA methylation, histone/chromatin remodeling, miRNA dysregulation), and environmental factors. The emergence of new sequencing technologies and tools to study the epigenome has led to identifying predictive biomarkers for earlier diagnosis, opening up the possibility of prophylactical interventions. As a result, advances in pharmacogenetics and pharmacoepigenomics now allow for personalized treatments based on the profile of each patient and the specific genetic and epigenetic mechanisms involved. This Review highlights the complexity of neurodegenerative diseases and the variability in patient responses to pharmacotherapy, emphasizing the influence of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of drugs used to treat those conditions. We specifically discuss the potential modulatory effect of several genetic polymorphisms associated with an increased risk of developing different neurodegenerative diseases. We explore genetic and genomic technologies and the potential of analyzing individual-specific drug metabolism to predict and influence drug response and associated clinical outcomes. We also provide insights into the mechanism of action of the drugs under investigation and their potential impact on disease-modifying pathways. Finally, the Review underscores the great potential of this field to enhance the effectiveness and safety of drug treatments through personalized medicine.
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Epigénesis Genética , Enfermedades Neurodegenerativas , Farmacogenética , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/genética , Farmacogenética/métodos , Epigénesis Genética/efectos de los fármacos , Animales , Epigenómica/métodosRESUMEN
Objetivo: Evaluar cualitativamente la experiencia de pacientescon esclerosis múltiple (PEM) y cuidadores familiares (CFPEM)vinculados al programa de esclerosis múltiple del HospitalUniversitario Nacional de Colombia (PrEM-HUNC), durantela formación y consolidación de una comunidad compasiva(CC), para la inclusión social y promoción de calidad de vida.Materiales y Método: estudio cualitativo interpretativo, conentrevistas a profundidad a nueve colaboradores. Con elmétodo de análisis de espiral de Creswell y Poth, emergieroncuatro categorías y un tema.Resultados: el tema Un nido comunitario de crecimientoytransformación señala el proceso de conformación de la CCcomo una experiencia que posibilitó cambios de significadosen torno a la enfermedad, la situación personal y familiar;revela un proceso de descubrimiento y aprendizaje deconformación de diferentes relaciones y roles.Conclusiones: La CC es una opción para construcción deredes de apoyo, fortalecimiento de las capacidades personalesy familiares, una forma para hacer frente a los diferentesimpactos y retos que implica vivir con esclerosis múltiple,se constituye en una alternativa para la promoción de lacalidad de vida y la inclusión social.(AU)
Objective: to qualitatively evaluate the experienceof patients with multiple sclerosis (PEM) and familycaregivers (CFPEM) linked to the multiple sclerosisprogram of the National University Hospital ofColombia (PrEM-HUNC), during the formation andconsolidation of a compassionate community (CC),for social inclusion and promotion of quality of life.Materials and Method: qualitative interpretativestudy, with in-depth interviews to nine collaborators.With Creswell and Poth's spiral analysis method,four categories and one topic emerged. Results: the theme "A Community Nest of Growth andTransformation" points out the process of shaping theCC as an experience that made possible changes in themeanings surrounding the disease and the personaland family situation; reveals a process of discovery andlearning of shaping different relationships and roles.Conclusions: The CC is an option for building supportnetworks, strengthening personal and family capacities,a way to address the different impacts and challengesof living with multiple sclerosis; it is an alternative tothe promotion of quality of life and social inclusion.(AU)
Objetivo: avaliar qualitativamente a experiência depacientes com esclerose múltipla (PEM) e cuidadoresfamiliares (CFPEM) vinculados ao programa de esclerosemúltipla do Hospital Universitário Nacional de Colombia(PrEM-HUNC), durante a formação e consolidação deuma comunidade compassiva (CC), para a inclusãosocial e promoção da qualidade de vida.Materiais e Método: estudo qualitativo interpretativo,com entrevistas em profundidade com nove colaboradores.Com o método em espiral de Creswell e Poth, quatrocategorias e um tema emergiram.Resultados: o tema Um ninho comunitário de crescimentoe transformação revela o processo de conformação daCC como uma experiência que possibilitou mudanças designificados em torno da doença, da situação pessoal efamiliar; revela um processo de descoberta e aprendizagemde obter diferentes relacionamentos e papéis.Conclusões: a CC é uma opção para a construção deredes de apoio, fortalecendo as capacidades pessoais efamiliares, uma forma de enfrentar os diversos impactose desafios que o viver com esclerose múltipla implica,sendo uma opção para a promoção da qualidade devida e inclusão social.(AU)
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Humanos , Masculino , Femenino , Calidad de Vida , Esclerosis Múltiple/enfermería , Cuidadores , Apoyo Social , Colombia , Investigación CualitativaRESUMEN
JOURNAL/nrgr/04.03/01300535-202419110-00033/figure1/v/2024-03-08T184507Z/r/image-tiff Dysregulation of G9a, a histone-lysine N-methyltransferase, has been observed in Alzheimer's disease and has been correlated with increased levels of chronic inflammation and oxidative stress. Likewise, microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis, especially in multifactorial diseases such as Alzheimer's disease. Therefore, our aim has been to provide partial insights into the interconnection between G9a, microRNAs, oxidative stress, and neuroinflammation. To better understand the biology of G9a, we compared the global microRNA expression between senescence-accelerated mouse-prone 8 (SAMP8) control mice and SAMP8 treated with G9a inhibitor UNC0642. We found a downregulation of miR-128 after a G9a inhibition treatment, which interestingly binds to the 3' untranslated region (3'-UTR) of peroxisome-proliferator activator receptor γ (PPARG) mRNA. Accordingly, Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group. We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor. To confirm these antioxidant effects, we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult. In this setting, treatment with G9a inhibitor increases both cell survival and antioxidant enzymes. Moreover, up-regulation of PPARγ by G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis. In addition, we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression. Finally, PPARγ/GADD45α potentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition. Altogether, we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due, at least in part, by the modulation of PPARγ-dependent pathways by miR-128.
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Objective: This paper explores sociodemographic determinants and geographic disparities in COVID-19 booster uptake among fully vaccinated adults in Nueces County, Texas, USA with a population of over 353,000. Methods: A logistic generalized additive model was applied to analyze 184,252 official vaccination records of fully vaccinated adults over the period between December 2020 and August 2022. An individual's odds in receiving a booster shot were estimated with a host of sociodemographic characteristics as predictors. Results: Model estimation results reveal that male (odds ratio 0.836, 95% confidence interval 0.835-0.836, p < 0.001) and Hispanic residents (odds ratio 0.944, 95% confidence interval 0.943-0.945, p < 0.001) in the county were less likely to take a booster shot. Between the ages of 25 and 75, booster uptake increased with age (age 75 vs. 45 odd ratio 3.058, 95% confidence interval 3.052-3.063, p < 0.001). Booster uptake was lower in rural areas (odds ratio 0.804, 95% confidence interval 0.795-0.814, p < 0.001) and communities with high social vulnerability (highest vs. moderate vulnerability odd ratio 0.800, 95% confidence interval 0.767-0.836, p < 0.001). Conclusion: Empirical results confirm that booster uptake varied across individuals and communities of different socioeconomic and demographic characteristics. To advance health equity, a more inclusive vaccine campaign should pay particular attention to those underserved populations.
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Humanos , Masculino , Anciano , Herida Quirúrgica/microbiología , Revascularización Miocárdica , Cirugía Torácica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Microbiología , Técnicas Microbiológicas , Pacientes Internos , Evaluación de Síntomas , Examen FísicoRESUMEN
INTRODUCTION: Multiple sclerosis (MS) is a leading cause of disability among young adults, but standard clinical scales may not accurately detect subtle changes in disability occurring between visits. This study aims to explore whether wearable device data provides more granular and objective measures of disability progression in MS. METHODS: Remote Assessment of Disease and Relapse in Central Nervous System Disorders (RADAR-CNS) is a longitudinal multicenter observational study in which 400 MS patients have been recruited since June 2018 and prospectively followed up for 24 months. Monitoring of patients included standard clinical visits with assessment of disability through use of the Expanded Disability Status Scale (EDSS), 6-minute walking test (6MWT) and timed 25-foot walk (T25FW), as well as remote monitoring through the use of a Fitbit. RESULTS: Among the 306 patients who completed the study (mean age, 45.6 years; females 67%), confirmed disability progression defined by the EDSS was observed in 74 patients, who had approximately 1392 fewer daily steps than patients without disability progression. However, the decrease in the number of steps experienced over time by patients with EDSS progression and stable patients was not significantly different. Similar results were obtained with disability progression defined by the 6MWT and the T25FW. CONCLUSION: The use of continuous activity monitoring holds great promise as a sensitive and ecologically valid measure of disability progression in MS.
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Personas con Discapacidad , Esclerosis Múltiple , Dispositivos Electrónicos Vestibles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de la Discapacidad , Esclerosis Múltiple/diagnóstico , Prueba de Paso , Caminata/fisiología , AdultoRESUMEN
OBJECTIVES: To examine the associations of cardiorespiratory fitness (VO2 max) and muscular strength with indicators related to the risk scale, such as perceived competence, sensation seeking, competitiveness, risk taking and risk perception in sports. DESIGN: Cross-sectional study. SETTING: High schools from the Region of Murcia (Spain). PARTICIPANTS: Three-hundred-and-seventeen adolescents participated (mean age: 13.69±1.2 years old). PRIMARY AND SECONDARY OUTCOME MEASURES: Body mass, body height, Course-Navette test, upper limb strength and psychoeducational factors that determine the propensity towards sports accidents in school children, the Sports Accident Propensity Scale were evaluated. It was performance t-test for independent samples, stepwise multiple linear regression models and a multiple mediation analysis. RESULTS: The analysis showed significant differences with respect to sex in height, VO2 max, handgrip strength and in all factors of the questionnaire (p=0.02-<0.01). Adolescents who presented greater VO2 max, strength in the handgrip test and age showed a higher score in factors 1 and 3. Higher scores in factor 2 were associated with better VO2 max and strength in handgrip test. Youngers and better values of strength in the handgrip showed higher score in factors 4 and 5. The mediation analysis with two mediating variables (handgrip strength and VO2 max) showed a significant indirect effect. When handgrip strength and VO2 max were included in the equations, the association between sex and each factor ceased to be significant. CONCLUSION: This study highlights the potential benefits of muscular strength (handgrip) and VO2 max in the perceived risk scale, and the variable of age on this. TRIAL REGISTRATION NUMBER: Clinical trial: NCT05544370 (pre-results).
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Fuerza de la Mano , Aptitud Física , Niño , Humanos , Adolescente , Estudios Transversales , Personalidad , PercepciónRESUMEN
Introduction: Esports have experienced tremendous growth in recent years. In the scientific field, previous research has shown the determining role of psychology in competitive performance, but little is known about the factors that may be more determinant. In addition, in the amateur field, where fun and enjoyment are the most important factors, it has been observed that players can see their psychological state altered due to different factors, but it is not known if the outcome of the game (win or lose) can be influential. For this reason, the aim of the present investigation was to analyze changes in players' mood between three consecutive games as a function of the outcome of each game. Methods: A total of 14 amateur players participated in the research, all of them with previous experience and being regular League of Legends players. The participants completed the POMS questionnaire before the start of each game and the outcome of each game was recorded at the end. Results: The results showed that no significant pre-game differences were found in any of the games, regardless of winning or losing. Significant differences were found in the pre-game mood between the first and second game, according to the outcome of the first game, and between the second and third game, according to the outcome of the second game. Between the first and second games, there was a significant increase in depression (p = 0.038) and anger (p = 0.003) when the first game was lost; and between the second and third games, there was a decrease in tension (p = 0.003) and anger (p = 0.022) when the second game was won. In addition, it should be noted that fatigue increased significantly after each game, regardless of the outcome, and with respect to the change in mood, this was more noticeable when the first game was lost and the second was won, as significant changes were observed in tension (p = 0.028), depression (p = 0.030) and anger (p = 0.006). Conclusion: Pre-match mood does not influence post-match performance, but mood changes do occur between successive matches depending on the outcome of the match.
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INTRODUCTION: Waning immunity after vaccination justifies the need for additional effective COVID-19 treatments. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate mucosal immunity, which can prevent SARS-CoV-2 main immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections using an enteral route, which point to potential effects on time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID-19. SUMMARY: This pilot clinical trial investigated the effect of buccopharyngeal administered high polyphenolic olive oil on COVID-19 incidence, duration, and severity. IMPORTANCE: Waning immunity after vaccination justifies the need of further research for additional effective treatments for COVID-19. OBJECTIVE: Immunomodulation of local immune response at the buccopharyngeal mucosa could hypothetically activate mucosal immunity, which would in turn difficult SARS-CoV-2 immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections, using an enteral route, which suggest potential shortening of time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Double blind, randomized pilot clinical trial conducted at a single site, Talavera de la Reina, Spain. Potential study participants were identified by simple random sampling from the epidemiological database of contact patients recently diagnosed of COVID-19 during the study period. A total of 88 adult participants were enrolled and 84 completed the 3-month study, conducted between July 1, 2021 and August 31, 2022. INTERVENTION: Participants were randomized to receive oromucosal administered high polyphenolic olive oil, 2 mL twice a day for 3 months or no treatment. MAIN OUTCOME AND MEASURES: Primary outcomes were incidence, duration, and severity of COVID-19 after intervention. RESULTS: There were no differences in incidence between both groups but there were significant differences in duration, the median time to resolution of symptoms was 3 days in the high polyphenolic olive oil group compared with 7 days in the no-treatment group. Although time to resolution is directly related to severity, this study did not find any differences in severity. CONCLUSION AND RELEVANCE: Among full-vaccinated adults recent infected with COVID-19, a daily intake of tiny quantities of oromucosal administered high polyphenolic olive oil before infection significantly improved the time to symptom resolution. This finding strongly support the appropriateness of further deep research on the use of oromucosal administered high polyphenolic olive oil as an effective immune strategy against COVID-19.
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COVID-19 , Adulto , Humanos , SARS-CoV-2 , Aceite de Oliva , Resultado del Tratamiento , Factores de TiempoAsunto(s)
Humanos , Masculino , Femenino , Anciano , Medio Rural , Osteoporosis/diagnóstico , Atención Primaria de Salud , Fracturas Óseas , DensitometríaRESUMEN
The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes.
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Esclerosis Múltiple , Humanos , Caminata , Prueba de Paso , FatigaRESUMEN
Objective: A prospective cross-sectional investigation of 170 thyroid nodules (TN) between January 2020 and December 2021 at Alpha Imagen was conducted to determine cut-off points (C/O) for elastography measurements and their diagnostic accuracy. Methods: Nodules were categorized by ACR TI-RADS, Alpha Score (AS), and Bethesda; all were evaluated using 2D Shear Wave Real Time Elastography (RT-SWE), point Shear Wave (pSWE), and Strain Elastography (SE). Data was assessed with ROC curves, the Shapiro-Wilk test, T test, Chi-square test, and ANOVA. Results: C/O were as follows: RTSWE Emax of 115kPa and 6.5 m/s, Emean of 47.5 kPa and 4.1 m/s, pSWE (average) of 52.4 kpa and 4.15 m/s; sensitivity of 81.2% and specificity of 57.6%, with a PPV of 72.4% and NPV of 70.0%. SE Value A had a C/O of 0.20%, with a sensitivity of 84%, specificity of 57%, PPV of 72.4% and NPP of 73.6%. The Strain Ratio nodule/tissue C/O was calculated as 2.69, with a sensitivity of 84%, specificity of 57%, PPV of 72.3%, and NPV of 73.5%. The RLBIndex quality control must be at least 92%; for pSWE, we suggest a mean interquartile ratio of ≤15.7% for kPa and 8.1% for m/s. The recommended depth is between 1.2 and 1.5 cm, and commonly used ROI boxes were 3x3 and 5x5mm. Conclusion: 2D-SWE and pSWE with Emax and Emean demonstrated C/O with excellent diagnostic accuracy. To maximize the correct classification of TN, we suggest combining ACR TI-RADS and AS with any of the elastography measurements assessed here.
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Diagnóstico por Imagen de Elasticidad , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Estudios Prospectivos , Estudios Transversales , Curva ROCRESUMEN
Objective: The aim of this study was to evaluate the association between changes in the autonomic control of cardiorespiratory system induced by walk tests and outcome measures in people with Multiple Sclerosis (pwMS). Methods: Electrocardiogram (ECG) recordings of 148 people with Relapsing-Remitting MS (RRMS) and 58 with Secondary Progressive MS (SPMS) were acquired using a wearable device before, during, and after walk test performance from a total of 386 periodical clinical visits. A subset of 90 participants repeated a walk test at home. Various MS-related symptoms, including fatigue, disability, and walking capacity were evaluated at each clinical visit, while heart rate variability (HRV) and ECG-derived respiration (EDR) were analyzed to assess autonomic nervous system (ANS) function. Statistical tests were conducted to assess differences in ANS control between pwMS grouped based on the phenotype or the severity of MS-related symptoms. Furthermore, correlation coefficients (r) were calculated to assess the association between the most significant ANS parameters and MS-outcome measures. Results: People with SPMS, compared to RRMS, reached higher mean heart rate (HRM) values during walk test, and larger sympathovagal balance after test performance. Furthermore, pwMS who were able to adjust their HRM and ventilatory values, such as respiratory rate and standard deviation of the ECG-derived respiration, were associated with better clinical outcomes. Correlation analyses showed weak associations between ANS parameters and clinical outcomes when the Multiple Sclerosis phenotype is not taken into account. Blunted autonomic response, in particular HRM reactivity, was related with worse walking capacity, yielding r = 0.36 r = 0.29 (RRMS) and r > 0.5 (SPMS). A positive strong correlation r > 0.7 r > 0.65 between cardiorespiratory parameters derived at hospital and at home was also found. Conclusion: Autonomic function, as measured by HRV, differs according to MS phenotype. Autonomic response to walk tests may be useful for assessing clinical outcomes, mainly in the progressive stage of MS. Participants with larger changes in HRM are able to walk longer distance, while reduced ventilatory function during and after walk test performance is associated with higher fatigue and disability severity scores. Monitoring of disorder severity could also be feasible using ECG-derived cardiac and respiratory parameters recorded with a wearable device at home.
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This study investigates the possibility of using municipal solid waste incineration fly ash as a supplementary cementitious material to replace part of the clinker in cement. Life cycle assessment has shown that the partial replacement of clinker with blast furnace slag (CEM III) reduces cement's global warming potential by ~30%, while replacing clinker with fly ash reduces it by up to 55%. When using CEM III as the control binder in cement in which 55 wt% of the clinker was replaced with hydrothermally treated fly ash, the flexural strength decreased by ~60% and the compressive strength by ~65%. When the fly ash was mixed with calcined and vitrified demolition materials, flexural strength decreased by ~30% and compressive strength by ~50%. The hardening of the hydraulic binders fixed the heavy metals in the municipal solid waste incineration fly ash.
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5-Bromodeoxyuridine (BrdU) exposure leads to senescence, but the mechanistic details remain elusive. In this issue, En A et al. unveil a role of the HBR domain in histone H2B as a potential mediator of the effects of BrdU both in yeast and in human cells. Comment on: https://doi.org/10.1111/febs.16584.
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Nucleosomas , Proteínas de Saccharomyces cerevisiae , Humanos , Nucleosomas/genética , Bromodesoxiuridina , Histonas/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
BACKGROUND: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDDs) and Multiple Sclerosis (MS). METHODS: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse-Central Nervous System) program. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. RESULTS: Participants with MDDs (N = 255) and MS (N = 214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. A lower mean HR and HR variation were observed between pre and during lockdown during the day for MDDs and during the night for MS. HR variation during rest periods also decreased between pre- and post-lockdown in both clinical conditions. We observed a reduction in physical activity for MDDs and MS upon the introduction of lockdowns. The group with MDDs exhibited a net increase in social interaction via social network apps over the three periods. CONCLUSIONS: Behavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.
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Cellular senescence is a stable type of cell cycle arrest triggered by different stresses. As such, senescence drives age-related diseases and curbs cellular replicative potential. Here, we show that 3-deazaadenosine (3DA), an S-adenosyl homocysteinase (AHCY) inhibitor, alleviates replicative and oncogene-induced senescence. 3DA-treated senescent cells showed reduced global Histone H3 Lysine 36 trimethylation (H3K36me3), an epigenetic modification that marks the bodies of actively transcribed genes. By integrating transcriptome and epigenome data, we demonstrate that 3DA treatment affects key factors of the senescence transcriptional program. Remarkably, 3DA treatment alleviated senescence and increased the proliferative and regenerative potential of muscle stem cells from very old mice in vitro and in vivo. Moreover, ex vivo 3DA treatment was sufficient to enhance the engraftment of human umbilical cord blood (UCB) cells in immunocompromised mice. Together, our results identify 3DA as a promising drug enhancing the efficiency of cellular therapies by restraining senescence.