Impact of Folic Acid on the Resistance of Non-small Cell Lung Cancer Cells to Osimertinib by Regulating Methylation of DUSP1 / 中国肺癌杂志

BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.

Dilemma and promotion strategy of “dual channel”management policy for China’s medical insurance negotiated drugs / 中国药房

OBJECTIVE To provide reference for the smooth implementation of the “dual channel” management policy for China’s medical insurance negotiated drugs. METHODS Based on Smith policy implementation process model， the dilemmas for the implementation of “dual channel” policy for medical insurance negotiated drugs were analyzed from four aspects： implementation details and regulatory system， drug selection， drug provision and quality control， the situation of medical insurance funds and information technology capabilities. The corresponding promotion strategies were put forward. RESULTS & CONCLUSIONS The “dual channel” policy for medical insurance negotiated drugs in China might face implementation difficulties such as a lack of clear implementation rules and a full process supervision system， the suitability and operability of some medical insurance negotiated drugs need to be considered in the “dual channel” management， difficulties in drug allocation and quality control， differences in the management and operation of medical insurance funds in different regions， and insufficient informatization capability. In this regard， this study suggests that measures， such as improving the implementation rules of the “dual channel” policy， enhancing the rationality of the “dual channel” drug catalog， establishing a dynamic exit mechanism for “dual channel” pharmacies， promoting professional delivery services， and improving the electronic prescription circulation platform， which can be taken to enhance the implementation effect of the “dual channel” policy.

Effect of multi-target transcranial direct current stimulation on performance of working memory-postural control dual-task in healthy adults / 中国康复理论与实践

ObjectiveTo investigate the effect of multi-target transcranial direct current stimulation (tDCS) and single-target tDCS on the performance of working memory-postural control dual-task in healthy adults, and to compare the regulatory effect of the two stimulation protocols. MethodsFrom November, 2020 to February, 2021, 19 healthy adults in Shanghai University of Sport were recruited and randomly accepted multi-target tDCS, single-target tDCS and sham stimulation with at least one week interval between any two stimulation protocols. The target areas of multi-target tDCS included left dorsal lateral prefrontal cortex (L-DLPFC) and bilateral primary motor cortex (M1), and single-tDCS only applied to L-DLPFC. Before and after stimulation, participants completed walking and standing balance tests under single task and dual-task conditions with the second task being a N-back task. The dual-task postural control performance, dual-task cost (DTC) and working memory performance were observed before and after stimulation. ResultsSignificant differences were observed among three stimulation protocols in the changes of stride variability (F = 3.792, P = 0.029), DTC of stride variability (F = 3.412, P = 0.040) and velocity of center of pressure (Vcop) (F = 3.815, P = 0.029). The stride variability (P = 0.047) and Vcop (P = 0.015) were significantly lower and the decrease in DTC of stride variability tended to be significant (P = 0.073) following multi-target tDCS, as compared to sham stimulation. Single-target tDCS significantly decreased the changes of stride variability (P = 0.011), DTC of stride variability (P = 0.014) and Vcop (P = 0.025), as compared to sham stimulation. Compared with single target tDCS, multi-target tDCS reduced the changes of the dual-task cost of the area of center of pressure (P = 0.035). Moreover, no significant difference was observed among the three stimulation protocols in the changes of each measure in the working memory test (P > 0.05). ConclusionBoth multi-target tDCS and single-target tDCS can improve the performance of working memory-postural control dual-task in healthy adults, and compared with single-target tDCS, multi-target tDCS has some advantages in regulating postural control.

Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Subtipos de Dislexia do Desenvolvimento Descritos no Português Brasileiro: Uma Revisão Integrativa / Developmental Dyslexia Subtypes Described in Brazilian Portuguese: An Integrative Review / Subtipos de Dislexia del Desarrollo Descritos en Portugués Brasileño: Una Revisión Integradora

A heterogeneidade na dislexia do desenvolvimento pode ser compreendida por meio dos subtipos de dislexia do desenvolvimento (SDD), porém não foram encontrados estudos que avaliassem a literatura brasileira sobre SDD. A presente revisão buscou responder quais SDD foram identificados no português brasileiro. Foram incluídos estudos empíricos, em inglês ou português, que descrevessem ao menos um SDD, bem como critérios diagnósticos, com participantes brasileiros. As buscas foram realizadas nas bases Scielo, Pubmed e Google Scholar. Como resultado, foram encontrados 11 estudos referentes a seis SDD, sendo as dislexias fonológicas e de superfície as mais presentes, e foram descritas as definições, critérios de identificação e instrumentos de avaliação utilizados em cada estudo. Foi discutida a heterogeneidade de definições, critérios de identificação e instrumentos de avaliação encontrados. Destacam-se o pequeno número de relatos em comparação com a literatura internacional e a necessidade de tarefas padronizadas, validadas e sensíveis aos SDD no português brasileiro.(AU)

The present review aimed to explore the subtypes of developmental dyslexia (SDD), identified in the Brazilian literature, considering the heterogeneity in developmental dyslexia. This review included empirical studies in English or Portuguese, involving Brazilian students, and describing at least one SDD, along with diagnostic criteria. Searches were conducted in the Scielo, Pubmed and Google Scholar databases. The review identified 11 studies, which covered six different SDD. Phonological and surface dyslexia were the most commonly reported subtypes. The review discussed the variations in definitions, identification criteria, and evaluation instruments used in these studies. It also highlighted the limited number of reports in the Brazilian literature compared to international sources and emphasized the need for standardized, validated tasks in Brazilian Portuguese that are SDD-sensitive.(AU)

La heterogeneidad en la dislexia del desarrollo puede comprenderse a través de los subtipos de dislexia del desarrollo (SDD), pero no se encontraron estudios que evalúen la literatura brasileña sobre SDD. Esta revisión buscó responder cuáles los SDD se han identificado en el portugués brasileño. Se incluyeron estudios empíricos con participantes brasileños en inglés o portugués que describieran al menos un SDD y sus criterios de diagnósticos. Las búsquedas se realizaron en las bases de datos Scielo, Pubmed y Google Scholar. Como resultado, se encontraron 11 estudios relacionados con seis SDD, siendo las dislexias fonológicas y de superficie las más comunes, y se describieron las definiciones, criterios de identificación e instrumentos de evaluación utilizados en cada estudio. Se discutió la heterogeneidad de definiciones, criterios de identificación y herramientas de evaluación encontradas. Se destaca el escaso número de informes en comparación con la literatura internacional y la necesidad de tareas estandarizadas, validadas y sensibles a SDD en el portugués brasileño.(AU)

Biterapia con atazanavir/ritonavir más raltegravir versus terapia triple en segunda línea: Ensayo ARTE / ATV/r+RAL (DT) after failure with NNRTI

Antecedentes: La terapia dual ha surgido como un nuevo concepto para el tratamiento del VIH. Este estudio tenía como objetivo comparar un régimen dual basado en ATV/r + RAL (TD) frente a estándar de tres drogas con ATV/r + TDF/FTC (TT) luego del fracaso de un primer esquema ba-sado en INNTR.ClinicalTrials.gov, Número: NCT01829802.Método: Estudio piloto abierto, multicéntrico y aleatoriza-do. Resultado primario: proporción de sujetos con ARN del VIH-1 menor a 50 copias/mL en semana 48 (S48). Resulta-dos secundarios: discontinuaciones asociadas a eventos adversos (EA), tiempo transcurrido hasta la supresión viral, desarrollo de mutaciones de resistencia a la integrasa y proteasa, cambio en recuento de CD4. Resultados: De los 57 participantes seleccionados, 34 fue-ron asignados aleatoriamente para recibir: TD (n: 18) o TT (n: 16). En semana 48, 67% (n: 12/18) en TD tuvo respues-ta virológica y 88% (n: 14/16) en rama según el análisis FDA, intención de tratamiento/expuestos (p = NS) y 73% (TD) y 93% (TT) según análisis por protocolo (p = NS). El cambio de CD4 entre basal - S48: +119 y +52 células/µL en DT y TT, respectivamente. Cuatro participantes en TD y uno en TT presentaron fracaso virológico en la semana 48. Un participante desarrolló una mutación de resistencia a integrasa (155H).Conclusión: ATV/r+RAL como terapia dual de segunda línea mostró una tendencia al fracaso virológico más frecuente, en comparación con TT, aunque el estudio piloto no tenía potencia para demostrar esta diferencia. Este estudio está registrado en ClinicalTrials.gov, Número: NCT01829802

Background: Dual therapy has emerged as a novel concept for HIV treatment. This study was aimed at comparing a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among individuals failing first NNRTI-containing treatment.Methods: Randomized multicenter open-label pilot study. Primary outcome: proportion of subjects with plasma HIV-1 RNA below the limit of detection (<50 copies/mL) at 48 weeks (W48). Secondary outcomes: proportion of discontinuation due to adverse events (AEs), time until viral suppression, time until loss of virological response, development of integrase resistance mutations, and absolute change in CD4 counts. The primary outcome was analyzed using the FDA snapshot analysis.Results: Out of 57 participants screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At W48, virological response was achieved in 67% (n: 12/18) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and 73% and 93% by per-protocol analysis (p = NS). CD4 cell count median change from baseline to W48 was +119 and + 52 cell/µL in DT and TT, respectively. Four participants receiving DT and one TT presented virological failure at W48, with low pVL. One participant developed an integrase resistance mutation (155H) and suppressed later on TT.Conclusion: ATV/r+RAL as second-line therapy showed a trend to more frequent virological failure, compared to TT, although the study was unpowered to prove this difference. No major differences were seen in tolerance or toxicity.This study is registered with ClinicalTrials.gov, Number: NCT01829802

EVALUATION OF FUNCTIONAL OUTCOME OF DUAL MOBILITY CUPS IN TOTAL HIP ARTHROPLASTY IN ARTHRITIS HIP AND FEMORAL NECK FRACTURES

Background- Osteoarthritis hip and femoral neck fractures in old age can be treated by total hip arthroplasty using dual mobility cup designs. The posterior approach (Kocher-Langenbeck) was used earlier however, lateral (Harding) and anterior approach (Smith-Petersen) are more often used. Evaluation of functional outcomes of total h Aim- ip arthroplasty using dual mobility cups in patients with osteoarthritis hip and femur neck fractures in terms of time of surgery, re-operation rate and mortality in 1 year, length of hospital stay and post-operative complications, using Harris Hip Score (HHS). Study Design- Hospital based prospective cohort study. Material and Methods- 40 cases were include in the study of which, 20 cases are of osteoarthritis hip and 20 cases are of femur neck fracture managed by dual mobility total hip arthroplasty. Clinical and functional outcome was graded using HHS. Anatomical reduction was assessed at 8 weeks, 3months, 6 months and 9 months. The mean HHS at 8 weeks, 3months, 6 months and 9 mont Result- hs in osteoarthritis hip was 56.40, 69.80, 80.90 and 91.50 and in femur neck fractures was 51.10, 63.50, 74.60 and 84.50, achieved. Better result was found in osteoarthritis hip. Conclusion- We concluded that using dual mobility total hip arthroplasty in osteoarthritis hip is far better than femur neck fractures due to better clinical and functional outcome, better anatomical reduction.

Changes in food habits and food-related satisfaction before and during the COVID-19 pandemic in dual-earner families with adolescents

Introduction: Food habits have been associated with positive outcomes during the COVID-19 pandemic. Family members may share protective factors, but each member may also respond differently to the pandemic. Aim: To examine food habits in different-sex dual-earner parents with adolescents, comparing reports from late 2019 before the pandemic (T1) and mid- 2020 during the pandemic (T2) in Temuco, Chile. Method: A sample of 193 families composed of mother, father, and one adolescent aged 10 to 15 responded to a questionnaire at T1 and T2. Non-parametric tests were used to compare family food-related habits and the satisfaction with food-related life of each family member at T1 and T2. An Actor-Partner Interdependence Model was conducted to explore relations between T1 and T2 variables and between family members. Results: Frequency of family meals increased during the pandemic, and mothers increased their cooking hours. All family members improved their diet quality during the pandemic. Perceived family meal atmosphere and satisfaction with food-related life did not change. T1 food habits were not associated with T2 satisfaction with food-related life. Conclusion: These families changed their food-related habits during the pandemic, but their food-related life assessment was similar before and during the pandemic.

Introducción: Las prácticas alimentarias se han asociado con mayor bienestar durante la pandemia por COVID-19. Aunque en una familia se comparten condiciones de vida, cada miembro puede responder de modo diferente a la pandemia. Objetivo: Examinar las prácticas alimentarias en parejas con doble ingreso e hijos adolescentes, comparando reportes antes de la pandemia (finales de 2019, T1) y durante la pandemia (mediados de 2020, T2) en Temuco, Chile. Método: 193 familias compuestas por madre, padre y un hijo adolescente de 10 a 15 años respondieron un cuestionario en T1 y T2. Se utilizaron pruebas no-paramétricas para comparar hábitos alimentarios y satisfacción con la alimentación para cada miembro de la familia en T1 y T2. Se exploraron las relaciones entre variables en T1 y T2, y entre miembros de la familia usando el modelo de interdependencia de actor-compañero. Resultados: La frecuencia de las comidas familiares y las horas que la madre dedicó diariamente a cocinar aumentaron durante la pandemia. Los tres miembros de la familia mejoraron la calidad de su dieta durante la pandemia. La atmósfera percibida de comidas familiares y la satisfacción con la alimentación no cambiaron. Los hábitos alimentarios del T1 no incidieron en la satisfacción con la alimentación en T2. Conclusión: Los hábitos alimenticios de estas familias cambiaron durante la pandemia, pero la evaluación de su vida alimentaria fue similar antes y durante la pandemia.

Estudantes-atletas: reflexões acerca de seu desenvolvimento / Student-athletes: reflections about their development / Estudiantes-deportistas: reflexiones sobre su desarrollo

O presente ensaio tem como objetivo refletir sobre o desenvolvimento do estudante-atleta, tendo como base o documento intitulado Modelo de Desenvolvimento Esportivo, proposto pelo Comitê Olímpico do Brasil. Ao longo do texto, são discutidos os desafios do estudante-atleta ao seguir a carreira-dupla, bem como sobre a dupla-carreira no Brasil e no mundo. Por fim, sugere-se a criação de uma legislação nacional e de políticas institucionais que promovam o acesso, a permanência e a finalização da formação destes estudantes-atletas. (AU).

The present study aimed to reflect on the development of student-athletes based on the document named Sports Development Model proposed by the Brazilian Olympic Committee. Throughout the ext, the student-athlete and their challenges when following a dual ca-reer are discussed, as well as the dual career in Brazil and in the world. Finally, it is suggested the development of national legislation and insti-tutional policies that promote access, permanence and finalization of the graduation for these student-athletes (AU).

Este ensayo tuvo como objetivo reflexionar sobre el desar-rollo de los estudiantes-atletas a partir del documento titulado Modelo de Desarrollo Deportivo, propuesto por el Comité Olímpico de Brasil. A lo largo del texto, se discute el estudiante-atleta y sus desafíos al se-guir una carrera dual, así como la carrera dual en Brasil y en el mundo. Finalmente, se sugiere la creación de legislación nacional y políticas ins-titucionales que promuevan el acceso, permanencia y culminación de la formación de estos estudiantes deportistas (AU).

The Relationship between Bone Mineral Densitometry and Visceral Adiposity Index in Postmenopausal Women / A relação entre a densitometria mineral óssea e o índice de adiposidade visceral em mulheres na pós-menopausa

Abstract Objective It was aimed to compare visceral adiposity index (VAI) levels in patients with normal bone mineral density (BMD), osteopenia, and osteoporosis. Methods One hundred twenty postmenopausal women (40 with normal BMD, 40 with osteopenia, and 40 with osteoporosis) between the ages of 50 to 70 years were included in the study. For females, the VAI was calculated using the formula (waist circumference [WC]/[36.58 + (1.89 x body mass index (BMI))]) x (1.52/High-density lipoprotein [HDL]-cholesterol [mmol/L]) x (triglyceride [TG]/0.81 [mmol/L]). Results The time of menopause from the beginning was similar in all groups. Waist circumference was found to be higher in those with normal BMD than in the osteopenic and osteoporotic groups (p = 0.018 and p < 0.001, respectively), and it was also higher in the osteopenic group than in the osteoporotic group (p = 0.003). Height and body weight, BMI, blood pressure, insulin, glucose, HDL-cholesterol, and homeostasis model assessment-insulin resistance (HOMA-IR) levels were similar in all groups. Triglyceride levels were found to be higher in the normal BMD group, compared with the osteoporotic group (p = 0.005). The level of VAI was detected as higher in those with normal BMD, compared with the women with osteoporosis (p = 0.002). Additionally, the correlation analysis showed a positive correlation between dual-energy X-ray absorptiometry (DXA) spine T-scores, WC, VAI, and a negative correlation between DXA spine T-scores and age. Conclusion In our study, we found higher VAI levels in those with normal BMD, compared with women with osteoporosis. We consider that further studies with a larger sample size will be beneficial in elucidating the entity.

Resumo Objetivo O objetivo foi comparar os níveis de índice de adiposidade visceral (IVA) em pacientes com densidade mineral óssea (DMO) normal osteopenia e osteoporose. Métodos Cento e vinte mulheres na pós-menopausa (40 com DMO normal 40 com osteopenia e 40 com osteoporose) com idades entre 50 e 70 anos foram incluídas no estudo. Para o sexo feminino o VAI foi calculado pela fórmula (circunferência da cintura [CC]/[36 58 + (1 89 x índice de massa corporal (IMC))]) x (1 52/lipoproteína de alta densidade [HDL]-colesterol [mmol/L]) x (triglicerídeo [TG]/0 81 [mmol/L]). Resultados O tempo de menopausa desde o início foi semelhante em todos os grupos. A circunferência da cintura foi maior naqueles com DMO normal do que nos grupos osteopênicos e osteoporóticos (p = 0 018 e p < 0 001 respectivamente) e também foi maior no grupo osteopênico do que no grupo osteoporótico (p = 0 003) . Altura e peso corporal IMC pressão arterial insulina glicose HDL-colesterol e os níveis de avaliação do modelo de homeostase-resistência à insulina (HOMA-IR) foram semelhantes em todos os grupos. Os níveis de triglicerídeos foram maiores no grupo DMO normal em comparação com o grupo osteoporótico (p = 0 005). O nível de VAI foi detectado como maior naquelas com DMO normal em comparação com as mulheres com osteoporose (p = 0 002). Além disso a análise de correlação mostrou uma correlação positiva entre a absorciometria de raios-X de dupla energia (DXA) nas pontuações T da coluna CC VAI e uma correlação negativa entre as pontuações T da coluna DXA e a idade. Conclusão Em nosso estudo encontramos níveis mais elevados de VAI naquelas com DMO normal em comparação com mulheres com osteoporose. Consideramos que novos estudos com maior tamanho amostral serão benéficos na elucidação da entidade.

Anticancer potential of Solanum lycopersicum L. extract in human lung epithelial cancer cells A549

The study aimed to reveal the phytochemical profile, free radical scavenging potential, and anticancer activity of Solanum lycopersicum L. leaf extract (SLLE). According to the study, SLLE contains plant secondary metabolites that are beneficial for health, like phenolics, flavonoids, ascorbic acid, alkaloids, and terpenoids. The SLLE has shown potential free radical scavenging potential in DPPH and ABTS free radical scavenging analysis and its EC50 values (concentration required to inhibit 50% of free radicals) were determined as 481.29 ± 33.82 and 527.56 ± 20.34 µg/mL, respectively. The SLLE has the ability to scavenge free radicals and could be used to treat illnesses brought on by oxidative stress. The anticancer activity of SLLE was assessed by MTT, LDH, micro-morphological, live/dead dual staining, and caspase-3 analysis. In the MTT assay, the IC50 value (concentration required to inhibit 50% of cell viability) of SLLE was determined as 190.41 ± 4.77 µg/mL. Furthermore, SLLE has shown potential anticancer activity by adversely affecting the plasma membrane integrity and escalating the caspase-3 levels. In the biomedical field, SLLE could be highly useful to treat cancer.

Characteristics of cortical activation in older adults under cognition-balance dual tasks / 中国康复理论与实践

ObjectiveTo explore the characteristics of balance and cortical activation in older adults when performing cognition-balance dual tasks. MethodsFrom January to April, 2023, 20 healthy older adults were non-targeted recruited. They completed six tasks of close eyes & fixed platform (CF), close eyes & fixed platform & cognitive task (CFc), open eyes & sway-referenced platform (OS), open eyes & sway-referenced platform & cognitive task (OSc), close eyes & sway-referenced platform (CS), and close eyes & sway-referenced platform & cognitive task (CSc) on the Balance SD, wearing functional near-infrared spectroscopy caps. The overal stability index (OSI) was measured with Balance SD. The premotor cortex (PMC), sensorimotor cortex (SMC) and prefrontal cortex (PFC) were as regions of interest (ROIs), and the β values were calculated. ResultsThe OSI was more as CFc than as CF (Z = -2.014, P < 0.05), and was less as CSc than as CS (Z = -2.063, P < 0.05). The β values of bilateral ROIs were all more as CFc than as CF (|Z| > 2.464, |t| > 3.733, P < 0.05), and as OSc than as OS (|t| > 2.308, P < 0.05); the β value of the right SMC was more as CSc than as CS (t = -2.912, P < 0.05). The number of correct counts was less as CSc than as CFc and OSc (|Z| > 3.643, P < 0.001). ConclusionBalance has been impaired under dual tasks for older adults, while activation of cerebral cortex increases. However, for more difficult balance task, older adults would preferentially maintain postural balance under dual tasks, while cognitive performance decreases, which may be the results from no more activation of cerebral cortex under dual tasks.

Design, synthesis and biological evaluation of PARP-1/PI3K dual-target inhibitors / 中国药科大学学报

@#Phosphatidylinositol-3-kinase (PI3K) inhibitors can increase the sensitivity of tumor cells to Poly ADP-ribose polymerase-1 (PARP-1) inhibitors. Therefore, the simultaneous inhibition of the PARP-1 and PI3K activities are expected to overcome the drug resistance of PARP-1 inhibitors.In our previous work, two compounds XW-1 and WZ-1 with excellent activities against PARP-1 and PI3K were obtained with the limitation to further study due to their poor water solubility.Therefore, XW-1 and WZ-1 were chosen as lead compounds to optimize their solubility by introducing a salt-forming site via a urea group, and 11 novel compounds were designed and synthesized. The structure of all target compounds was confirmed by 1H NMR, 13C NMR, and HRMS.The enzyme activities of the compounds against PARP-1 and PI3K were measured, and the results showed that most of the compounds demonstrated good inhibitory activities against PARP-1 and PI3K.Based on the above result, the inhibitory activities of compounds 8b, 8e, and 8f against MDA-MB-231, MDA-MB-468, HCC1937, HCT116, and olaparib-resistant HCT116R were determined by MTT, respectively.Additionally, the structure-activity relationship was discussed. The results showed that these compounds displayed excellent antiproliferation activity.Among them, compound 8f demonstrated antiproliferation remarkably against all five tumor cells, which was more potent than that of olaparib, and was comparable to that of BKM120.Furthermore, the solubility of hydrochloride salts of compound 8b and 8f was significantly improved compared to the lead compounds.The results of this study will provide a theoretical basis for the further development of PARP-1 and PI3K dual-target inhibitors with good pharmaceutical properties and strong inhibitory activities.

Development and optimization of a cell screening system for farnesoid X receptor agonist / 生物工程学报

This study aims to develop an improved cell screening system for farnesoid X receptor (FXR) agonists based on a dual luciferase reporter gene system. FXR response element (FXRE) fragments from FXR target genes were cloned and inserted into upstream of firefly luciferase (Luc) gene in the plasmid pGL4-luc2P-Hygro. In combination with the internal reference plasmid containing renilla luciferase, a dual luciferase reporter gene system was developed and used for high throughput screening of FXR agonists. After studying the effects of over-expression of RXR, mouse or human FXR, various FXRE fragments, and different ratio of FXR plasmid amount to reporter gene plasmid, induction efficiency of the screening system was optimized by the known FXR agonist GW4064, and Z factor for the system reached 0.83 under optimized conditions. In summary, an improved cell screening system based on double luciferase reporter gene detection system was developed to facilitate the discovery of FXR agonists, where a new enhanced FXRE element was formed by a superposition of multiple FXRE fragments from FXR target genes, instead of a superposition of traditional IR-1 (inverted repeats-1) fragments.

Dupla carreira no Brasil de 2018 a 2023: um panorama dos estudos recentes / Dual career in Brazil from 2018 to 2023: an overview of recent studies / Carrera dual en Brasil de 2018 a 2023: un panorama de los estudios recientes

RESUMO Este artigo analisou como as publicações sobre dupla carreira (DC) no Brasil abordaram esse tema conceitualmente e metodologicamente. Realizamos uma revisão narrativa dos estudos publicados entre 2018 e 2023, e os analisamos a partir dos tipos de abordagens metodológicas, os conceitos e o direcionamento dessas pesquisas brasileiras. Notamos que a DC é vista como objeto de conciliação de rotinas a partir das idiossincrasias de cada grupo de investigação, carecendo de aprofundamento sobre possíveis causas para má gestão das agendas do estudante-atleta. Sugerimos uma maior interação entre os grupos de pesquisa, buscando mínimos consensos entre os investigadores sobre a noção de DC tal como a adoção de métodos holísticos que auxiliem a captar a complexidade desse fenômeno social.

ABSTRACT We analyse the conceptual and methodological approaches taken by Brazilian research on the Dual Career (DC). We conducted a narrative review of published studies between 2018 and 2023; we analysed them based on the methodological approach, the concept used, and their basic premises that support research. We observe that DC is viewed as the form of combining routines by Brazilian researchers, conducting debate from their theoretical perspectives. Still, we note little engagement among these researchers to provide a combination approach to deep knowledge about DC and their issues with managing student-athletes schedules. So, we suggest more interaction among Brazilian research groups, seeking consensus to adopt holistic research methods that aid in understanding the DC complexity.

RESUMEN Ese artículo analizó cómo las recientes publicaciones se acercaron conceptual y metodológicamente a la Carrera Dual (CD) en Brasil. Revisamos los artículos desde 2018 a 2023, y los analizamos a través de sus metodologías, conceptos y premisas teóricas que los basaron los investigadores. Observamos que la CD fue acercada como la manera de compaginar rutinas y los investigadores conducían al debate desde sus perspectivas teóricas. También notamos poco involucro entre los investigadores, lo que puede limitar la interpretación a cerca de la CD y la manera de compaginar a las agendas de los estudiantes-deportistas. Por lo tanto, sugerimos una interacción entre los investigadores brasileños, buscando acuerdos para adoptar metodologías holísticas para comprender el fenómeno de la CD.

Dual career in European-funded projects: a critical analysis and review / Dupla carreira em projetos europeus com financiamento atribuido: uma revisão e análise crítica / Carrera dual en proyectos financiados europeos: un análisis y revisión crítica

ABSTRACT This study aimed to review the projects financed between 2014 and 2022 under the ERASMUS+ programme of the European Commission to examine the past and present implementation of the dual career (DC) of elite sportspersons and to highlight potential gaps to guide future project proposals. Findings showed a relevant focus of the financed projects on the micro and multi-dimensional aspects of DC of athletes as the main target group, implementing training courses/programmes in different settings, and partnerships mostly composed by educational institutions and NGOs. In the future, sports bodies should engage more in partnerships, whereas DC of employee-sportspersons as athletes and sports staff should be implemented, with a strong focus on the project's long-term impact and sustainability.

RESUMO Este estudo teve como objetivo rever os projetos financiados entre 2014 e 2022 no âmbito do programa ERASMUS+ da Comissão Europeia de forma a melhor perceber a implementação dos mesmos no âmbito da dupla carreira (DC) de atletas de elite e destacar eventuais lacunas para orientar futuras propostas de projetos. Os resultados encontrados apontam para uma maior predominância dos aspectos micro e multidimensionais da DC, sendo os atletas o principal grupo-alvo, propondo-se a implementação de cursos/programas de formação em diferentes contextos, assim como parcerias maioritariamente compostas por instituições de ensino e ONG's. Surge ainda recorrentemente a nota de, no futuro, os organismos desportivos se envolverem mais em parcerias, e a extensão da DC a outros agentes como os treinadores e árbitros, assim como o alargamento ao enquadramento dado pelo mocal de trabalho (mercado de trabalho), sempre com a tónica colocada no impacto e na sustentabilidade do projeto a longo prazo.

RESUMEN Este estudio tuvo como objetivo revisar los proyectos financiados entre los años 2014 y 2022 dentro el programa ERASMUS+ de la Comisión Europea, para analizar el presente y el pasado de la implementación de la carrera dual (DC) de deportistas de élite, resaltando posibles errores que permitan guiar futuras propuestas de proyectos. Los resultados mostraron un importante foco de los proyectos en aspectos micro y multidimensionales de la CD de los atletas como principal punto a destacar, implementando cursos/programas de entrenamiento en diferentes entornos y colaboraciones compuestas principalmente por instituciones educativas y ONGs. En el futuro, los organismos deportivos deberían participar más con asociaciones, así como que se debería implementar la DC de los empleados-deportistas como atletas y como personal deportivo, con un fuerte enfoque en el impacto y la sostenibilidad del proyecto a largo plazo.

A exigência do esporte de alta-competição e o desenvolvimento pleno dos atletas: a necessidade de uma relação simbiótica / The demands of high-competition sport and the full development of athletes: the need for a symbiotic relationship / Las exigencias del deporte de alta competición y el desarrollo pleno de los deportistas: la necesidad de una relación simbiótica

RESUMO O presente ensaio discute a Dupla Carreira (DC) em contexto europeu e a natureza simbiótica das habilidades adquiridas ao longo da vida, contribuindo para uma transição saudável ao mercado de trabalho no final da carreira esportiva. Nessa esteira evolutiva do suporte à DC fica evidente a produção conjunta do conhecimento em nível regional, nacional e internacional entre os Estados-Membros da União Europeia, assim como a proposição de políticas de amparo tanto aos atletas estudantes quanto aos atores que participam do processo de DC. A apresentação das Diretrizes para a DC em conjunto com os programas More Than Gold e EMPATIA ressaltam a importância do suprimento a nível micro, meso e macroestrutural, fornecendo experiências que induzem à ampliação do conceito de atleta estudante para sportsperson.

ABSTRACT This essay discusses the dual career (DC) in a European context and its symbiotic nature present in the skills acquired throughout life that contribute to a healthy transition to the job market at the end of the sports career. In this evolutionary path of DC support, the joint production of knowledge at a regional, national and international level, between the member states of the European Union, is evident, as well as the proposal of policies to support student athletes, and actors who participate in the DC process. The presentation of the Guidelines for DC and the More Than Gold and EMPATIA programs highlight the importance of supply at the micro, meso and macro structural level, experiences that induce the expansion of the concept of student athlete to sportsperson.

RESUMEN Este ensayo analiza la carrera dual (DC) en un contexto europeo y su naturaleza simbiótica presente en las habilidades adquiridas a lo largo de la vida que contribuyen a una transición saludable al mercado laboral al final de la carrera deportiva. Por lo tanto, el apoyo al DC destaca la producción conjunta de conocimiento a nivel regional, nacional e internacional, entre los estados miembros de la Unión Europea, así como la propuesta de políticas para apoyar a los estudiantes deportistas y actores que participan en el proceso de DC. La presentación de los Lineamientos para DC y los programas Más Than Gold y EMPATHY resaltan la importancia de ofrecer a nivel micro, meso y macro estructural, experiencias que induzcan a ampliar el concepto de estudiante deportista a sportsperson.

Facilitadores e barreiras para a dupla carreira do estudante-atleta de elite: uma revisão integrativa / Facilitators and barriers to elite student-athlete dual careers: an integrative review / Facilitadores y barreras para la doble carrera del estudiante atleta de élite: una revisión integradora

RESUMO O objetivo deste artigo é sistematizar informações de pesquisas realizadas com estudantes-atletas de elite de diversos países, bem como fornecer uma síntese sobre os facilitadores e as barreiras para dupla carreira. A pesquisa foi realizada no Portal de Periódicos da Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes), em um total de 24 artigos, entre os quais 19 foram publicados a partir de 2018, ao passo que 18 abordaram exclusivamente participantes europeus. Identificou-se facilitadores e barreiras à dupla carreira atuando nos níveis individual, social e de setores fora do ambiente esportivo, em que esforços para o apoio ao estudante-atleta se concentraram nos âmbitos político e institucional. Avanços na dimensão científica e em propostas práticas pautadas em evidências se apresentam como desafios para a área.

ABSTRACT The purpose of this article is to systematize information from research conducted with elite student-athletes from different countries and provide a synthesis of facilitators and barriers to dual careers through a search of the CAPES Journals Portal. Twenty-four articles were included. Of these, 19 were published in 2018, 18 of which dealt exclusively with European participants. Facilitators and barriers to dual careers were identified at the individual, societal and non-sporting levels, and efforts to support student-athletes should focus on the political and institutional levels. Advances in the scientific dimension and practical, evidence-based proposals are presented as challenges for the field.

RESUMEN El objetivo de este artículo es sistematizar la información procedente de investigaciones realizadas con estudiantes-deportistas de élite de diferentes países y ofrecer una síntesis sobre los facilitadores y las barreras a la doble carrera, a través de una búsqueda realizada en el Portal de Revistas CAPES. Se incluyeron 24 artículos. De ellos, 19 se publicaron en 2018; 18 abordaban exclusivamente participantes europeos. Se identificaron facilitadores y barreras para las carreras duales a nivel individual, social y del sector no deportivo, y que los esfuerzos para apoyar a los estudiantes-deportistas deberían centrarse en las esferas política e institucional. Los avances en la dimensión científica y en las propuestas prácticas basadas en pruebas se presentan como retos.

Efectos de la proteína whey, leucina y entrenamiento de fuerza en la composición corporal / Effects of whey protein, leucine and resistance training on body composition

INTRODUCCIÓN: Los deportistas y las personas activas que entrenan la fuerza para lograr un aumento de su masa muscular tienen requerimientos calóricos y proteicos aumentados, por esta razón emplean diversas estrategias como la suplementación con proteína whey aislada y aminoácidos aislados como la leucina después del entrenamiento sustentados en la premisa de que promueven el incremento en la síntesis de proteínas musculares, y por ende un aumento de la masa magra. OBJETIVO: Comparar cambios de la composición corporal aplicando el método de Absorciometría Dual de Rayos X (DEXA) en personas físicamente activas expuestas a un programa de entrenamiento de la fuerza con la suplementación de proteína whey aislada y/o leucina durante 12 semanas. METODOLOGÍA: estudio aleatorizado prospectivo longitudinal en un grupo de 10 varones físicamente activos, los cuales fueron asignados al azar en 3 grupos de suplementación con proteína whey aislada, leucina o la mezcla de ambas bajo el mismo protocolo de entrenamiento de la fuerza. Se evaluó la composición corporal en 3 momentos: semana 0, semana 6 y semana 12 de la intervención. RESULTADOS: En las condiciones evaluadas no se observaron cambios estadísticamente significativos de las variables de composición corporal y fuerza en los diferentes protocolos de suplementación: leucina, proteína whey aislada con leucina y proteína whey aislada. CONCLUSIONES: Se observaron resultados superiores de la masa magra y la fuerza en el grupo de la suplementación de proteína whey aislada con leucina con respecto a los demás grupos, cabe aclarar que por el tamaño de muestra no alcanzó a ser estadísticamente significativo.

INTRODUCTION: Athletes and active people who work hard to increase their muscle mass have increased caloric and protein requirements. For this reason, they use different strategies such as whey protein isolate supplementation and/or branched-chain amino acids after sustained training on the premise that they promote an increase in muscle protein synthesis, and therefore an increase in lean mass. OBJECTIVE: To compare body composition changes in physically active people exposed to a strength training program withwhey protein isolate and/or leucine supplementation for 12 weeks. METHODS: Longitudinal prospective randomized study in a group of 10 physically active males, which were randomly assigned to 3 supplementation groups with whey protein isolate, leucine, or a mixture of both, under the same strength training protocol. Body composition was evaluated in 3 moments: week 0, week 6 and week 12 of the intervention. RESULTS: In the evaluated conditions, no statistically significant changes were observed in the variables of body composition and strength based on the different supplementation protocols: Leucine, protein with leucine and protein. CONCLUSIONS: Compared with the other groups, higher results were observed in lean mass and strength in group using the whey protein isolate supplementation with leucine. It should be noted that due to the size of the sample, the difference was not statistically significant.