Exploring Infantile Epileptic Spasm Syndrome: A Proteomic Analysis of Plasma Using the Data-Independent Acquisition Approach.

This study aimed to identify characteristic proteins in infantile epileptic spasm syndrome (IESS) patients' plasma, offering insights into potential early diagnostic biomarkers and its underlying causes. Plasma samples were gathered from 60 patients with IESS and 40 healthy controls. Data-independent acquisition proteomic analysis was utilized to identify differentially expressed proteins (DEPs). These DEPs underwent functional annotation through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Gene set enrichment analysis (GSEA) was employed for both GO (GSEA-GO) and KEGG (GSEA-KEGG) analyses to examine the gene expression profiles. Receiver operating characteristic (ROC) curves assessed biomarkers' discriminatory capacity. A total of 124 DEPs were identified in IESS patients' plasma, mainly linked to pathways, encompassing chemokines, cytokines, and oxidative detoxification. GSEA-GO and GSEA-KEGG analyses indicated significant enrichment of genes associated with cell migration, focal adhesion, and phagosome pathways. ROC curve analysis demonstrated that the combination of PRSS1 and ACTB, PRSS3, ACTB, and PRSS1 alone exhibited AUC values exceeding 0.7. This study elucidated the significant contribution of cytokines, chemokines, oxidative detoxification, and phagosomes to the IESS pathogenesis. The combination of PRSS1 and ACTB holds promise as biomarkers for the early diagnosis of IESS.

Tetrandrine alleviates pulmonary fibrosis by inhibiting alveolar epithelial cell senescence through PINK1/Parkin-mediated mitophagy.

Idiopathic pulmonary fibrosis (IPF) is a fatal and insidious interstitial lung disease. So far, there are no effective drugs for preventing the disease process. Cellular senescence plays a critical role in the development of IPF, with the senescence and insufficient mitophagy of alveolar epithelial cells being implicated in its pathogenesis. Tetrandrine is a natural alkaloid which is now produced synthetically. It was known that the tetrandrine has anti-fibrotic effects, but the efficacy and mechanisms are still not well evaluated. Here, we reveal the roles of tetrandrine on AECs senescence and the antifibrotic effects by using a bleomycin challenged mouse model of pulmonary fibrosis and a bleomycin-stimulated mouse alveolar epithelial cell line (MLE-12). We performed the ß-galactosidase staining, immunohistochemistry and fluorescence to assess senescence in MLE-12 cells. The mitophagy levels were detected by co-localization of LC3 and COVIX. Our findings indicate that tetrandrine suppressed bleomycin-induced fibroblast activation and ultimately blocked the increase of collagen deposition in mouse model lung tissue. It has significantly inhibited the bleomycin-induced senescence and senescence-associated secretory phenotype (SASP) in alveolar epithelial cells (AECs). Mechanistically, tetrandrine suppressed the decrease of mitochondrial autophagy-related protein expression to rescue the bleomycin-stimulated impaired mitophagy in MLE-12 cells. We revealed that knockdown the putative kinase 1 (PINK1) gene by a short interfering RNA (siRNA) could abolish the ability of tetrandrine and reverse the MLE-12 cells senescence, which indicated the mitophagy of MLE-12 cells is PINK1 dependent. Our data suggest the tetrandrine could be a novel and effective drug candidate for lung fibrosis and senescence-related fibrotic diseases.

Up-regulation of HSP90α in HDM-induced asthma causes pyroptosis of airway epithelial cells by activating the cGAS-STING-ER stress pathway.

Heat Shock protein 90 α (HSP90α), an main subtype of chaperone protein HSP90, involves important biological functions such as DNA damage repair, protein modification, innate immunity. However, the potential role of HSP90α in asthma occurrence and development is still unclear. This study aimed to elucidate the underlying mechanism of HSP90α in asthma by focusing on the cGAS-STING-Endoplasmic Reticulum stress pathway in inflammatory airway epithelial cell death (i.e., pyroptosis; inflammatory cell death). To accomplish that, we modeled allergen exposure in C57/6BL mice and bronchial epithelial cells with house dust mite. Protein technologies and immunofluorescence utilized to study the expression of HSP90α, activation of cGAS-STING pathway and pyroptosis. The effect of inhibitors on HDM-exposed mice detected by histological techniques and examination of bronchoalveolar lavage fluid. Results showed that HSP90α promotes asthma inflammation via pyroptosis and activation of the cGAS-STING-ER stress pathway. Treatment with the HSP90 inhibitor tanespimycin (17-AAG) significantly relieved airway inflammation and abrogated the effect of HSP90α on pyroptosis and cGAS-STING-ER stress in vitro and in vivo models of HDM. Further data indicated that up-regulation of HSP90α stabilized STING through interaction, which increased localization of STING on the ER. Activation of STING triggered ER stress and leaded to pyroptosis-related airway inflammation. The finding showed the potential role of pyroptosis caused by dysregulation of HSP90α on airway epithelial cells in allergic inflammation, suggested that targeting HSP90α in airway epithelial cells might prove to be a potential additional treatment strategy for asthma.

Effects of running on sports injuries during rehabilitation / Efeitos da corrida sobre as lesões esportivas durante a reabilitação / Efectos de la carrera en las lesiones deportivas durante la rehabilitación

ABSTRACT Introduction: Running is a simple, comfortable, low-cost aerobic exercise that promotes health and prevents obesity and heart and brain diseases. Its practice has grown considerably as therapy, and recent studies indicate that there may also be benefits during physical rehabilitation. Objective: Study the effects of running on sports injuries during rehabilitation. Methods: A search was made in the current medical literature to develop a therapeutic management plan. The experimental test method consisted of a study with 38 healthy runners. They were divided into healthy and injured groups according to their sports injuries. Within one year after the experiment, the physical function of the two groups of runners was evaluated again. The result was compared through mathematical statistics among other research methods. results: The total score of the injured group in the FMS test of screening general body movement function was ≤14 points; the comparison found that the athletes in the injured group generally showed weaker bilateral function than the healthy group. Conclusion: Running exercise is feasible in patients with sports injuries, medium intensity running can improve the speed of recovery in these patients. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A corrida é um exercício aeróbico simples, confortável e de baixo custo que pode promover a saúde e prevenir a obesidade, doenças cardíacas e cerebrais. Sua prática tem crescido bastante como uma terapia e estudos recentes indicam que possam haver benefícios também durante o processo de reabilitação física. Objetivo: Estudar os efeitos da corrida sobre lesões esportivas durante a reabilitação. Métodos: Efetuou-se uma pesquisa na literatura médica atual para elaborar um plano de conduta terapêutica. O método de teste experimental consistiu num estudo com 38 corredores saudáveis. Eles foram divididos em grupo saudável e grupo lesionado, de acordo com suas lesões esportivas. Dentro de um ano após o experimento, avaliou-se novamente a função física dos dois grupos de atletas. O resultado foi comparado através do método de estatística matemática entre outros métodos de pesquisa. Resultados: A pontuação total do grupo lesionado no teste FMS de triagem da função de movimento corporal geral foi de ≤14 pontos, a comparação constatou que os atletas do grupo lesionado geralmente mostraram uma função bilateral mais fraca do que o grupo saudável. Conclusão: O exercício de corrida mostrou-se viável em pacientes com lesões esportivas, uma corrida de média intensidade pode melhorar a velocidade de recuperação desses pacientes. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La carrera es un ejercicio aeróbico sencillo, cómodo y de bajo coste que puede promover la salud y prevenir la obesidad y las enfermedades cardíacas y cerebrales. Su práctica ha crecido mucho como terapia y estudios recientes indican que puede haber beneficios también durante el proceso de rehabilitación física. Objetivo: Estudiar los efectos de la carrera en las lesiones deportivas durante la rehabilitación. Métodos: Se realizó una búsqueda en la literatura médica actual para elaborar un plan de manejo terapéutico. El método de prueba experimental consistió en un estudio con 38 corredores sanos. Se dividieron en un grupo sano y otro lesionado según sus lesiones deportivas. Un año después del experimento, se volvió a evaluar la función física de los dos grupos de corredores. El resultado se comparó mediante el método de la estadística matemática, entre otros métodos de investigación. Resultados: La puntuación total del grupo lesionado en la prueba FMS de detección de la función de movimiento corporal general fue de ≤14 puntos, la comparación encontró que los atletas del grupo lesionado mostraron generalmente una función bilateral más débil que el grupo sano. Conclusión: Se demostró que el ejercicio de correr es factible en pacientes con lesiones deportivas, la carrera de intensidad media puede mejorar la velocidad de recuperación en estos pacientes. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.