ABSTRACT
Fibrosing interstitial lung diseases (ILDs) are characterized by the gradual and irreversible accumulation of scar tissue in the lung parenchyma. The role of the immune response in the pathogenesis of pulmonary fibrosis remains unclear. In recent years, substantial advancements have been made in our comprehension of the pathobiology driving fibrosing ILDs, particularly concerning various age-related cellular disturbances and immune mechanisms believed to contribute to an inadequate response to stress and increased susceptibility to lung fibrosis. Emerging studies emphasize cellular senescence as a key mechanism implicated in the pathobiology of age-related diseases, including pulmonary fibrosis. Cellular senescence, marked by antagonistic pleiotropy, and the complex interplay with immunity, are pivotal in comprehending many aspects of lung fibrosis. Here, we review progress in novel concepts in cellular senescence, its association with the dysregulation of the immune response, and the evidence underlining its detrimental role in fibrosing ILDs.
Subject(s)
Cellular Senescence , Lung Diseases, Interstitial , Pulmonary Fibrosis , Humans , Cellular Senescence/immunology , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/pathology , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/pathology , Animals , Lung/immunology , Lung/pathology , ImmunityABSTRACT
Designing and developing inhibitors against the epigenetic target DNA methyltransferase (DNMT) is an attractive strategy in epigenetic drug discovery. DNMT1 is one of the epigenetic enzymes with significant clinical relevance. Structure-based de novo design is a drug discovery strategy that was used in combination with similarity searching to identify a novel DNMT inhibitor with a novel chemical scaffold and warrants further exploration. This study aimed to continue exploring the potential of de novo design to build epigenetic-focused libraries targeted toward DNMT1. Herein, we report the results of an in-depth and critical comparison of ligand- and structure-based de novo design of screening libraries focused on DNMT1. The newly designed chemical libraries focused on DNMT1 are freely available on GitHub.
Subject(s)
DNA (Cytosine-5-)-Methyltransferase 1 , Drug Design , Enzyme Inhibitors , Ligands , DNA (Cytosine-5-)-Methyltransferase 1/antagonists & inhibitors , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Humans , Small Molecule Libraries/pharmacology , Small Molecule Libraries/chemistry , Structure-Activity RelationshipABSTRACT
Food insecurity has been associated with negative short, medium, and long-term health consequences, which are more detrimental for children and adolescents. These effects may depend on the coping strategies developed to deal with food shortages. The present research aimed at exploring coping strategies in food insecure households with children and adolescents in Uruguay, incorporating sociological theoretical insights from Bourdieu. A qualitative approach based on individual semi-structured interviews was used. A total of 40 interviews were conducted with adults who had parental responsibilities of children and adolescents and who received different types of food assistance, between July and December 2022, in four cities. Results showed that adults tend to develop a wide range of coping strategies aimed at: reducing food expenditure, increasing the availability of money for purchasing food, increasing food availability and/or rationing the food available in the household. Some of the strategies were implemented regardless of the severity of food insecurity, whereas others were characteristic of the moderate and severe levels of the construct. Evidence to support the mediation effect of coping strategies on health outcomes was found. Discourses suggested that lower accumulation of economic and cultural capital may be aligned with the adoption of less socially accepted mechanisms to access to food. Expressions of a specific habitus aimed at securing food were identified among participants with more deprivations. Taken together, the findings suggest that coping strategies may not be a universal or invariant sequence according to the severity of food insecurity and stress the importance of considering households' resources and local context for the development of strategies to improve access to food.
Subject(s)
Coping Skills , Family Characteristics , Food Insecurity , Qualitative Research , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Food Assistance , Income , Socioeconomic Factors , UruguayABSTRACT
The bacterial flagellum is a complex structure formed by more than 25 different proteins, this appendage comprises three conserved structures: the basal body, the hook and filament. The basal body, embedded in the cell envelope, is the most complex structure and houses the export apparatus and the motor. In situ images of the flagellar motor in different species have revealed a huge diversity of structures that surround the well-conserved periplasmic components of the basal body. The identity of the proteins that form these novel structures in many cases has been elucidated genetically and biochemically, but in others they remain to be identified or characterized. In this work, we report that in the alpha proteobacteria Cereibacter sphaeroides the novel protein MotK along with MotE are essential for flagellar rotation. We show evidence that these periplasmic proteins interact with each other and with MotB2. Moreover, these proteins localize to the flagellated pole and MotK localization is dependent on MotB2 and MotA2. These results together suggest that the role of MotK and MotE is to activate or recruit the flagellar stators to the flagellar structure.
Subject(s)
Bacterial Proteins , Periplasmic Proteins , Bacterial Proteins/metabolism , Periplasmic Proteins/metabolism , Rotation , Flagella/metabolism , Periplasm/metabolismABSTRACT
BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Granulomatosis with Polyangiitis , Microscopic Polyangiitis , Humans , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/drug therapy , Microscopic Polyangiitis/diagnosis , Microscopic Polyangiitis/complications , Antibodies, Antineutrophil Cytoplasmic/therapeutic use , Retrospective Studies , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Myeloblastin , RecurrenceABSTRACT
We report the complete genome sequence of deformed wing virus and black queen cell virus isolated from Argentinean's honeybees. These sequence data will be valuable for future research on the viral variants present in the country and the development of strategies to control the spread of these viruses in apiaries.
ABSTRACT
Exposing pigs to heat stress (HS) seems to modify the intestinal microbiota which may compromise the integrity of the small intestine epithelia. Probiotics, live microorganisms, can help pigs to maintain a healthy intestinal environment. Eighty pigs (21.6â ±â 3.4 kg body weight) exposed to HS or thermal neutral (TN) conditions were used to evaluate the effect of a Bacillus subtilis-based probiotic on performance, body temperature, and intestinal integrity. Treatments were: TN pigs fed a control diet without (TN-C) or with 1â ×â 106 CFU probiotic/g of feed (TN-P), and HS pigs fed a control without (HS-C) or with probiotic (HS-P). The control diet was formulated with wheat, soybean meal, and free amino acids (AA). Feed and water were freely available during the 21-d study. At completion, samples from duodenum, jejunum, and ileum were collected to analyze epithelial histology and tight junction protein expression; antioxidant activity, and free AA and metabolites in serum. Relative abundance of Lactobacillus, Bifidobacterium, Escherichia coli, and Bacillus in ileal content was analyzed. Ambient temperature in the TN room ranged from 19 to 25 °C, and in HS room from 30 to 38.5 °C. Intestinal temperature in HS-P pigs was lower than in HS-C pigs. Weight gain and feed intake reduced, but feed:gain and respiration rate increased in HS compared to TN pigs, regardless of diet (Pâ <â 0.01). Probiotic increased weight gain and improved feed:gain (Pâ <â 0.05) in both TN and HS pigs, but feed intake did not differ. Heat stress decreased villi height in jejunum and villi height:crypt depth in duodenum and jejunum (Pâ <â 0.05). Probiotic increased villi height in duodenum and ileum, and villi height:crypt depth in all small intestine segments (Pâ <â 0.05). Relative abundance of Lactobacillus and Bifidobacterium tended to reduce, and E. coli tended to increase (Pâ <â 0.10) in ileal content of HS-C pigs. Ileal relative abundance of Bacillus was higher (Pâ <â 0.01) in HS-P pigs than in HS-C and TN-C pigs. Cystathionine, homocysteine, hydroxylysine, α-amino-adipic acid, citrulline, α-amino-n-butyric acid, P-Ser, and taurine were higher in HS than in TN pigs (Pâ <â 0.05). These data confirm the negative effect of HS on performance, body temperature, and intestinal integrity of pigs. These data suggest that supplementing 1â ×â 106 CFU probiotic/g of feed based on Bacillus subtilis DSM 32540 may help to counteract the negative effects of HS on the performance and intestinal integrity of pigs.
High ambient temperature provokes heat stress in animals, and pigs are highly affected showing low performance, and intestinal integrity and microbiota compromised. Probiotics could help pigs to maintain a healthy intestinal environment. We analyzed the effect of a probiotic based on Bacillus subtilis on growth performance, intestinal integrity of small intestine, intestinal microbiota, antioxidant activity, and serum concentration of amino acids in pigs under heat stress (HS) and thermal neutral (TN) conditions. Ambient temperature under TN and HS conditions was 1925 and 3038.5 °C, respectively. Weight gain and feed intake reduced in HS pigs compared to TN pigs, but probiotic increased weight gain in both TN and HS pigs. Heat stress decreased villi size in duodenum and jejunum, and probiotic restored them. Relative abundance of Lactobacillus and Bifidobacterium reduced and Escherichia coli increased in the small intestine content of HS pigs; probiotic increased the abundance of Bacillus. The activity of antioxidant enzymes increased in HS pigs fed the probiotic diet. Serum concentration of amino acid metabolites was affected by HS. These data suggest that supplementing a Bacillus subtilis-based probiotic may help to counteract the negative effects of HS on the performance and intestinal integrity of pigs.
Subject(s)
Antioxidants , Probiotics , Swine , Animals , Bacillus subtilis , Escherichia coli , Diet/veterinary , Probiotics/pharmacology , Heat-Shock Response , Citrulline , Weight Gain , Animal Feed/analysis , Hot TemperatureABSTRACT
The study of rainfall thresholds is vital in understanding the factors that trigger landslides, being one of the criteria applied to landslide early warning systems that aim to mitigate their consequences. These thresholds enable the prediction of landslide occurrences as a function of rainfall measurements. This work presents an overview of the parameters involved in defining rainfall thresholds based on scientific articles published between 2008 and 2021 that discuss the subject through statistical or physical methods. These articles provided data such as publication information, threshold types, details on the data used in the works, methodology, and application of the threshold in early warning systems. There was a significant increase in research papers on this theme during this period, possibly due to the strategies advocated by the Sendai Framework. However, some regions of the world severely affected by landslides are barely mentioned in these studies. The results indicate specific trends, such as those found in the methods used to define rainfall thresholds and the parameters relating to the database when a statistical approach was used. Certain deficiencies were found, such as those concerning geological-geotechnical conditions for categorizing thresholds, the time scales of rainfall data, rain gauge density, and the criteria to define the accumulated rainfall period to be considered.
ABSTRACT
Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases.
Subject(s)
Cellular Senescence , Senescence-Associated Secretory Phenotype , Humans , Iron , Kidney , FibrosisABSTRACT
Tener peso alto es una característica que ha sido devaluada y denigrada socialmente, convirtiendo a las personas de cuerpos grandes en víctimas de estereotipos, prejuicios y discriminación, lo que se ha denominado estigmatización por el peso, fenómeno que ocurre especialmente en mujeres. El objetivo de este estudio fue describir las experiencias de estigma de peso de mujeres con obesidad que viven en el sur de Chile. Participaron seis mujeres entre 20 y 57 años a través de entrevistas semi-estructuradas realizadas de manera remota. Mediante Análisis Fenomenológico Interpretativo se identificaron cuatro supratemas y diversos subtemas, los supratemas son: 1. La obesidad como parte de la persona. 2. Las experiencias de sentirse discriminada. 3. Todo gira en función del peso. 4. Lo que la sociedad piensa de la obesidad, los que en su conjunto permiten caracterizar la experiencia de vivir con obesidad y sufrir el estigma asociado al peso en distintos ámbitos de sus vidas, incluso en contextos sanitarios. Las consecuencias de esta experiencia son diversas y negativas, destacando el impacto que tiene en su autoestima y las constantes emociones negativas que derivan de las situaciones de discriminación. Estos resultados ponen de manifiesto la importancia de avanzar hacia la diversidad y aceptación corporal, lo que supone un desafío a la sociedad en general y en particular a los proveedores de salud, ya que se requiere de intervenciones libres de prejuicios y orientadas a la salud y el bienestar de las personas.
Carrying a high weight is a characteristic that has been devalued and socially denigrated, turning people with large bodies into victims of stereotypes, prejudice, or discrimination, which has been called weight stigmatisation, a phenomenon that occurs especially in women. The aim of this study was to describe the weight stigma experiences of women with obesity who live in southern Chile. Six women between 20 and 57 years of age participated in semi-structured interviews conducted remotely. Through Interpretative Phenomenological Analysis four supra-themes and several sub-themes were identified, the supra-themes are: 1. Obesity as part of the person. 2. Experiences of feeling discriminated. 3. Everything is about weight. 4. what society thinks of obesity, which together allow characterising the experience of living with obesity and suffering the weight stigma in different areas of their lives, including in health contexts. The consequences of this experience are diverse and negative, highlighting the impact it has on their self-esteem and the constant negative emotions that derive from discrimination situations. These results highlight the importance of moving toward body diversity and acceptance, which is a challenge for society in general and health care providers in particular, as it requires interventions free from prejudice and orientated to the health and well-being of individuals.
ABSTRACT
Introducción: En la adolescencia son frecuentes los comportamientos sexuales de riesgo asociados a desinformación y falta de asesoramiento de la familia y de los profesionales de enfermería, lo que constituye un problema de salud pública. Objetivo: Analizar las evidencias científicas que existen sobre intervenciones de enfermería exitosas en el marco de la educación sexual orientada a la población escolar adolescente. Método: Revisión bibliográfica en las bases de datos Dialnet, LILACS y Pubmed. Los criterios de inclusión consideraron documentos que contenían intervenciones de enfermería escolar en educación sexual en población adolescente. Respecto a la selección por calidad metodológica de los artículos, se recurrió a lectura crítica, mediante la aplicación de la lista de comprobación CASPe. Luego se emplearon técnicas de análisis de contenido y se presentaron los resultados en tablas. Resultados: Las intervenciones de enfermería en educación demostraron efectos positivos sobre la salud sexual de los adolescentes, al mejorar sus conocimientos en prevención de embarazo e infecciones de transmisión sexual y disminuir significativamente la probabilidad de cometer conductas de riesgo. Conclusión: Según la bibliografía seleccionada se concluye que la enfermera escolar es un recurso indispensable para padres y educadores, al implementar programas educativos que promueven un desarrollo sexual saludable en los adolescentes.
Introdução: Na adolescência, são frequentes os comportamentos sexuais de risco associados à desinformação e à falta de orientação da família e dos profissionais de enfermagem, o que constitui um problema de saúde pública. Objetivo: Analisar as evidências científicas sobre intervenções de enfermagem bem-sucedidas no âmbito da educação sexual voltada para a população escolar adolescente. Método: Revisão bibliográfica nas bases de dados Dialnet, LILACS e Pubmed. Os critérios de inclusão consideraram documentos que continham intervenções de enfermagem escolar em educação sexual na população adolescente. Para a seleção dos artigos quanto à qualidade metodológica, foi utilizada a leitura crítica, aplicando a lista de verificação CASPe. Foram empregadas técnicas de análise de conteúdo e os resultados foram apresentados em tabelas. Resultados: As intervenções de enfermagem na educação demonstraram efeitos positivos na saúde sexual dos adolescentes, melhorando seu conhecimento sobre gravidez e prevenção de infecções sexualmente transmissíveis e reduzindo significativamente a probabilidade de cometer comportamentos de risco. Conclusão: De acordo com a bibliografia selecionada, conclui-se que o enfermeiro escolar é um recurso indispensável para pais e educadores na implementação de programas educacionais que promovam o desenvolvimento sexual saudável em adolescentes.
Introduction: In adolescence, risky sexual behaviors associated with misinformation and lack of advice from the family and nursing professionals are frequent, which constitutes a public health problem. Objective: To analyze the scientific evidence on successful nursing interventions within the framework of sexual education oriented to the adolescent school population. Method: Bibliographic review in the Dialnet, LILACS and Pubmed databases. Inclusion criteria considered documents containing school nursing interventions in sex education in the adolescent population. Regarding the selection of articles for methodological quality, critical reading was used, by applying the CASP checklist. Content analysis techniques were then used and the results were presented in tables. Results: Nursing interventions in education showed positive effects on the sexual health of adolescents, improving their knowledge of pregnancy and sexually transmitted infection prevention and significantly reducing the probability of committing risky behaviors. Conclusion: According to the selected bibliography, it is concluded that the school nurse is an indispensable resource for parents and educators, implementing educational programs that promote healthy sexual development in adolescents.
ABSTRACT
(analítico) Desde una mirada intercultural, se exploraron los significados de infancia en la agricultura familiar campesina, así como sus implicaciones en términos de trabajo y provisión de cuidados a niños y niñas. A partir de la tensión entre los significados universales de infancia basados en un enfoque de derechos y el trabajo en el campo del cual participan las personas desde temprana edad, se realizó un estudio cualitativo con diseño de teoría fundamentada y aplicación de entrevistas a mujeres cuidadoras y profesionales de programas de desarrollo rural en Chile. Se evidenció que a medida que la infancia aumenta en actoría social, disminuyen las prácticas de trabajo y se profundizan las de cuidado. Los resultados alientan a pensar en la proyección de una ontología de la niñez rural.
(analytical) Using an intercultural perspective, this study explores the meanings of childhood in the rural peasant population, as well as the implications of these meanings on the allocation of tasks and providing care to boys and girls. Taking into account the tension between universal meanings of childhood that draw on rights-based perspectives and the traditional practice of children working in agriculture, we conducted a qualitative study using a grounded theory methodology. Interviews were conducted with women caregivers and staff who work in rural development programs in Chile. The study's results show that as childhood has had an increasing value with children becoming more and more recognized as social actors, traditional child work practices in agriculture have decreased and care practices have been strengthened. The author concludes that the results of the research have consequences when thinking about an ontology for rural children.
(analítico) A partir de uma perspectiva intercultural, exploramos os significados da infância entre famílias voltadas para agricultura familiar camponesa, bem como suas implicações em termos de trabalho e prestação de cuidados às meninos e meninas. Considerando a tensão existente entre os significados universais da infância a partir de uma abordagem de direitos e o trabalho no campo, no qual as pessoas se engajam desde muito cedo, realizamos um estudo qualitativo, com base na teoria fundamentada, onde realizamos entrevistas com mulheres cuidadoras e profissionais dos programas de desenvolvimento rural no Chile. Evidenciamos que à medida que a infância adquiriu um valor ao nível da atuação social, as práticas de trabalho diminuíram e as práticas de cuidado se aprofundaram. Conclui-se sobre as consequências dos resultados para pensar uma ontologia da infância rural.
Subject(s)
Child Labor , ChildABSTRACT
Exposing pigs to heat stress (HS) provokes higher death of intestinal cells, resulting in elevated endogenous intestinal losses (EIL) of amino acids (AA) and damage to intestinal epithelia. Arginine (Arg) is precursor for the synthesis of polyamines, which are involved in proliferation of intestinal cells and restoration of the intestinal epithelia. Thus the effect of adding L-Arg to diets for HS pigs on the EIL of AA was analyzed. Twelve pigs (23.1 ± 1.1 kg body weight) implanted with T-type cannulas at the end of ileum were individually housed and allowed 15-days for surgery recovery under thermoneutral (TN) conditions (22 ± 2 °C). Following, the pigs were randomly assigned to one of three treatments: TN pigs fed a semi-purified, corn starch-3% casein basal diet (TN-B); HS pigs with the basal diet (HS-B); HS pigs consuming the basal diet supplemented with 0.20% L-Arg (HS-Arg). The experiment consisted of two 9-day periods; each period included 7-days of adaptation to their respective diet, followed by a 2-day ileal digesta collection period. Digesta was collected during 12 consecutive hours each day. The pigs were fed twice a-day. Ambient temperature (AT) inside the TN and HS rooms ranged from 18.6 to 27.6 °C and from 29.5 to 40.7 °C, respectively. Body temperature followed a pattern similar to that of AT. The daily EIL of indispensable AA increased (P < 0.01) in the HS-B pigs compared to both the TN-B and the HS-Arg pigs, however, there was no EIL difference between the TN-B and the HS-Arg pigs (P > 0.05). Likewise, with the exception of serine, daily losses of endogenous dispensable AA in the HS-B pigs were higher (P < 0.01) in comparison with those of TN-B and HS-Arg pigs. In summary, HS exposure compared to TN conditions increases the loss of endogenous AA, but dietary supplementation with L-Arg helped to counteract the negative HS effect.
Subject(s)
Amino Acids , Heat Stress Disorders , Animals , Amino Acids/metabolism , Animal Feed/analysis , Arginine/pharmacology , Dietary Supplements , Heat Stress Disorders/prevention & control , Heat Stress Disorders/veterinary , Heat Stress Disorders/metabolism , Heat-Shock Response , SwineABSTRACT
Drugs that selectively kill senescent cells (senolytics) improve the outcomes of cancer, fibrosis and age-related diseases. Despite their potential, our knowledge of the molecular pathways that affect the survival of senescent cells is limited. To discover senolytic targets, we performed RNAi screens and identified coatomer complex I (COPI) vesicle formation as a liability of senescent cells. Genetic or pharmacological inhibition of COPI results in Golgi dispersal, dysfunctional autophagy, and unfolded protein response-dependent apoptosis of senescent cells, and knockdown of COPI subunits improves the outcomes of cancer and fibrosis in mouse models. Drugs targeting COPI have poor pharmacological properties, but we find that N-myristoyltransferase inhibitors (NMTi) phenocopy COPI inhibition and are potent senolytics. NMTi selectively eliminated senescent cells and improved outcomes in models of cancer and non-alcoholic steatohepatitis. Our results suggest that senescent cells rely on a hyperactive secretory apparatus and that inhibiting trafficking kills senescent cells with the potential to treat various senescence-associated diseases.
Subject(s)
Neoplasms , Senotherapeutics , Mice , Animals , Golgi Apparatus/metabolism , Cellular Senescence , Neoplasms/metabolism , FibrosisABSTRACT
Virtual small molecule libraries are valuable resources for identifying bioactive compounds in virtual screening campaigns and improving the quality of libraries in terms of physicochemical properties, complexity, and structural diversity. In this context, the computational-aided design of libraries focused against antidiabetic targets can provide novel alternatives for treating type II diabetes mellitus (T2DM). In this work, we integrated the information generated to date on compounds with antidiabetic activity, advances in computational methods, and knowledge of chemical transformations available in the literature to design multi-target compound libraries focused on T2DM. We evaluated the novelty and diversity of the newly generated library by comparing it with antidiabetic compounds approved for clinical use, natural products, and multi-target compounds tested in vivo in experimental antidiabetic models. The designed libraries are freely available and are a valuable starting point for drug design, chemical synthesis, and biological evaluation or further computational filtering. Also, the compendium of 280 transformation rules identified in a medicinal chemistry context is made available in the linear notation SMIRKS for use in other chemical library enumeration or hit optimization approaches.
ABSTRACT
Las enfermedades cardiovasculares están determinadas por ciertos factores de riesgos, la prevalencia y sinergia de éstos genera un de-terminado riesgo cardiovascular que deteriora la calidad de vida de quienes lo padecen. La realización de actividad física es considerada como una herramienta útil para disminuir uno de los factores de riesgo más importantes, la obesidad, medida mediante el índice de masa corporal. Sin embargo, no todos los seres humanos poseen las mismas características y capacidades físicas, por ende, la realización de ejercicio está restringida a éstas. Es en este sentido que se desarrolla el siguiente informe, el cual contempla una revisión sistemática que enfrenta a dos terapias complementarias: Yoga v/s Tai Chi, buscando la evidencia que permita la recomendación de una de ellas para la disminución de IMC en personas mayores con DM2. Los artículos fueron extraídos desde la plataforma académica PubMed, sometidos a 3 cribados de búsqueda, y criterios de inclusión y exclusión, resultando en la obtención de 4 artículos para el análisis, a partir de esta observación se obtiene que la realización de yoga es beneficiosa para la disminución de el IMC al caso índice. Por ende, se recomienda el uso de la terapia complementaria yoga, puesto que esta favorece la reducción del IMC en pacientes con enfermedades crónicas no transmisibles en comparación a la terapia complementaria Tai Chi[AU]
Cardiovascular diseases are determined by certain risk factors, the prevalence and synergy of which generates a certain cardiovascular risk that deteriorates the quality of life of those who suffer from it. Physical activity is considered a useful tool for reducing one of the most important risk factors, obesity, measured by the body mass index. However, not all human beings have the same physical capacities, therefore, exercise is restricted to them. It is in this sense that the following report is developed, which contemplates a systematic review that confronts two complementary therapies: yoga v/s Tai Chi, looking for the evidence that allows the recommendation of one of them for the decrease of BMI in elderly people with DM2.The articles were extracted from the academic platform PubMed, subjected to 3 search screens, and inclusion and exclusion criteria, resulting in obtaining 4 articles for analysis, from this observation it is obtained that the performance of yoga is beneficial for the decrease of the BMI to the index case. Therefore, the use of yoga complementary therapy is recommended, since it favors the reduction of BMI in patients with chronic noncommunicable diseases compared to Cardiovascular diseases are determined by certain risk factors, the prevalence and synergy of which generates a certain cardiovascular risk that deteriorates the quality of life of those who suffer from it. Physical activity is considered a useful tool for reducing one of the most important risk factors, obesity, measured by the body mass index. However, not all human beings have the same physical capacities, therefore, exercise is restricted to them. It is in this sense that the following report is developed, which contemplates a systematic review that confronts two complementary therapies: yoga v/s Tai Chi, looking for the evidence that allows the recommendation of one of them for the decrease of BMI in elderly people with DM2.The articles were extracted from the academic platform PubMed, subjected to 3 search screens, and inclusion and exclusion criteria, resulting in obtaining 4 articles for analysis, from this observation it is obtained that the performance of yoga is beneficial for the decrease of the BMI to the index case. Therefore, the use of yoga complementary therapy is recommended, since it favors the reduction of BMI in patients with chronic noncommunicable diseases compared to Tai Chi complementary[AU]
As doenças cardiovasculares são determinadas por certos factores de risco, cuja prevalência e sinergia geram um certo risco cardio-vascular que deteriora a qualidade de vida das pessoas que delas sofrem. A atividade física é considerada uma ferramenta útil para reduzir um dos factores de risco mais importantes, a obesidade, medida pelo índice de massa corporal. No entanto, nem todos os seres humanos têm as mesmas características físicas e, por isso, o exercício é restrito a eles. É nesse sentido que se desenvolve o pre-sente relatório, que contempla uma revisão sistemática que con-fronta duas terapias complementares: yoga v/s Tai Chi, buscando as evidências que permitam a recomendação de uma delas para a diminuição do IMC em idosos com DM2. Os artigos foram ex-traídos da plataforma acadêmica Pubmed, submetidos a 3 telas de busca, e critérios de inclusão e exclusão, resultando na obtenção de 4 artigos para análise, a partir desta observação obtém-se que a realização do yoga é benéfica para a redução do IMC para o caso índice. Portanto, recomenda-se a utilização da terapia complemen-tar yoga, uma vez que favorece a redução do IMC em pacientes com doenças crónicas não transmissíveis em comparação com a terapia complementar Tai Chi[AU]
Subject(s)
Humans , Male , Female , AgedABSTRACT
Work-family interface (WFI) theory has identified many stressors that influence work-family dynamics from the standpoint of employees. However, work-family facilitators, as well as the effects of gender differences and the impact of sociocultural environments that differ from a formal employment situation, have received much less attention. Our research aimed to fill these theoretical gaps by analyzing the facilitators and stressors involved in work-family dynamics and determining their consequences for farm women's physical, psychological, and social health. We used a qualitative method with a grounded theory design to collect data via semi-structured interviews with 46 farm women from the region of Araucanía in Chile. Our results explain how facilitators, stressors, and outcomes take place in a process of work-family balance that, paradoxically, implies exhausting journeys, a gender-based overload, a risk of diffuse body pain and distress, and a lack of time for personal healthcare and productive autonomy. Addressing these issues requires a comprehensive approach involving improved healthcare infrastructure and services focused on changing the pressures that the farming WFI exerts on rural women.
ABSTRACT
BACKGROUND: Exercise intolerance, muscle weakness, dyspnoea, and fatigue are frequent complications in symptomatic sarcoidosis patients. Pulmonary rehabilitation improves exercise capacity, symptoms, and quality of life in patients with chronic respiratory diseases. Our objective was to systematically determine the effects of pulmonary rehabilitation in patients with sarcoidosis. METHODS: A systematic review was conducted in seven databases. Studies that applied pulmonary rehabilitation in patients with sarcoidosis were reviewed. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. RESULTS: Of the 406 reports returned by the initial search, five articles reporting on 184 patients were included in the data synthesis. Two studies included multi-component exercise, one inspiratory muscle training, one a physical activity incentivisation programme, and one a telerehabilitation program. In the intervention group (IG), we found significant improvement in exercise capacity (SMD 1.65, 95%CI 0.45, 2.86 points, p = 0.006). If we only analyse the studies that performed the 6-min walking test, the IG walked 40.3 (CI95% 20.3, 60.2) m higher than the control group (CG) (p < 0.001). Additionally, dyspnoea score was reduced (MD -0.42 95%CI -0.75, -0.10, p = 0.002). However, fatigue, quality of life and pulmonary function did not show any change. CONCLUSION: Pulmonary rehabilitation could improve exercise capacity and dyspnoea perception in patients with sarcoidosis.