Combined vaccines against angiotensin II receptor type 1 and alpha 1D-adrenergic receptor for hypertension.

PURPOSE: Compared with monotherapy, combination therapy with multiple antihypertensive drugs has demonstrated superior efficacy in the management of hypertension. The aim of this study was to explore the efficacy of multitarget combined vaccines in achieving simultaneous antihypertensive and target organ protection effects. METHODS: Our team has developed ATRQß-001 and ADRQß-004 vaccines targeting Ang II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR), respectively. In NG-nitroarginine methyl ester ( l -NAME) + abilities spontaneously hypertensive rats (SHRs) model, SHRs were simultaneously inoculated with ATRQß-001 and ADRQß-004 vaccines. Histological and biochemical analyses were performed to evaluate the antihypertensive effects and target organ protection of the ATRQß-001 and ADRQß-004 combined vaccines in comparison with those of the single vaccine. RESULTS: Both ATRQß-001 and ADRQß-004 vaccines induced robust antibody production, resulting in persistent high antibody titers in rats. Notably, the combined administration of both vaccines significantly decreased SBP in SHRs compared with treatment with a single vaccine, both before and after l -NAME administration. Furthermore, the combined vaccine regimen demonstrated superior efficacy in protecting against vascular remodeling, myocardial hypertrophy and fibrosis, and kidney injury in SHRs. Mechanistically, the combined vaccines exhibited significantly downregulated the expression of angiotensin II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR). Importantly, no apparent immune-related adverse effects were observed in animals immunized with the combined vaccines. CONCLUSION: Preliminary findings from this investigation suggest that co-administration of the novel ATRQß-001 and ADRQß-004 vaccines holds potential as a groundbreaking therapeutic strategy for managing hypertension.

IL-1 signaling pathway, an important target for inflammation surrounding in myocardial infarction.

Acute myocardial infarction is an important cardiovascular disease worldwide. Although the mortality rate of myocardial infarction (MI) has improved dramatically in recent years due to timely treatment, adverse remodeling of the left ventricle continues to affect cardiac function. Various immune cells are involved in this process to induce inflammation and amplification. The infiltration of inflammatory cells in the infarcted myocardium is induced by various cytokines and chemokines, and the recruitment of leukocytes further amplifies the inflammatory response. As an increasing number of clinical anti-inflammatory therapies have achieved significant success in recent years, treating myocardial infarction by targeting inflammation may become a novel therapeutic option. In particular, successful clinical trials of canakinumab have demonstrated the important role of the inflammatory factor interleukin-1 (IL-1) in atherosclerosis. Targeted IL-1 therapy may decrease inflammation levels and improve cardiac function in patients after myocardial infarction. This article reviews the complex series of responses after myocardial infarction, including the involvement of inflammatory cells and the role of cytokines and chemokines, focusing on the progression of the IL-1 family in myocardial infarction as well as the performance of current targeted therapy drugs in experiments.

The novel vaccines targeting interleukin-1 receptor type I.

OBJECTIVE: There is mounting evidence indicating that atherosclerosis represents a persistent inflammatory process, characterized by the presence of inflammation at various stages of the disease. Interleukin-1 (IL-1) precisely triggers inflammatory signaling pathways by binding to interleukin-1 receptor type I (IL-1R1). Inhibition of this signaling pathway contributes to the prevention of atherosclerosis and myocardial infarction. The objective of this research is to develop therapeutic vaccines targeting IL-1R1 as a preventive measure against atherosclerosis and myocardial infarction. METHODS: ILRQß-007 and ILRQß-008 vaccines were screened, prepared and then used to immunize high-fat-diet fed ApoE-/- mice and C57BL/6J mice following myocardial infarction. Progression of atherosclerosis in ApoE-/- mice was assessed primarily by oil-red staining of the entire aorta and aortic root, as well as by detecting the extent of macrophage infiltration. The post-infarction cardiac function in C57BL/6J mice were evaluated using cardiac ultrasound and histological staining. RESULTS: ILRQß-007 and ILRQß-008 vaccines stimulated animals to produce high titers of antibodies that effectively inhibited the binding of interleukin-1ß and interleukin-1α to IL-1R1. Both vaccines effectively reduced atherosclerotic plaque area, promoted plaque stabilization, decreased macrophage infiltration in plaques and influenced macrophage polarization, as well as decreasing levels of inflammatory factors in the aorta, serum, and ependymal fat in ApoE-/- mice. Furthermore, these vaccines dramatically improved cardiac function and macrophage infiltration in C57BL/6J mice following myocardial infarction. Notably, no significant immune-mediated damage was observed in immunized animals. CONCLUSION: The vaccines targeting the IL-1R1 would be a novel and promising treatment for the atherosclerosis and myocardial infarction.

Effects of running on recovery of function in athletes with knee osteoarthritis / Efeitos da corrida na recuperação de função em atletas com osteoartrite de joelho / Efectos de la corrida en la recuperación de función en deportistas con osteoartritis de rodilla

ABSTRACT Introduction Running can promote health prevent obesity, cardiovascular, and cerebrovascular diseases, among other chronic diseases. Much research reports the benefits of this aerobic resistance exercise, but little is known about the impacts of running on knee osteoarthritis. Objective To observe and study the clinical effect of running on pain and function improvement in patients with knee osteoarthritis. Methods Seventy cases that met the inclusion criteria were selected and randomly divided into control and observation groups. Patients in the observation group received eight weeks of neuromuscular exercise (NEMEX) and eight weeks of quadriceps muscle strength training while the control group was subjected to a running protocol. Patients were assessed using the Western Ontario and McMaster Universities Pain Scale and Osteoarthritis Index (WOMAC) after 1, 2, 4 and 8 weeks of treatment. Results After 1, 2, 4, and 8 weeks of treatment, the WOMAC function scores of the two groups significantly improved compared to that found before treatment (P < 0.05); There was no difference between the two groups before treatment and after 1, 2 weeks of treatment. After 4 and 8 weeks of treatment, the function of the observation group was better than that of the control group; the difference was statistically significant (t= -4.287, -6.355, P<0.05). Conclusions NEMEX training methods and quadriceps muscle strength training can effectively improve patients' functional level, but NEMEX improves more significantly than quadriceps muscle strength training. Evidence level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução A corrida pode promover a saúde, prevenir a obesidade, doenças cardiovasculares e cerebrovasculares entre outras doenças crônicas. Muitas pesquisas relatam os benefícios desse exercício de resistência aeróbica, mas pouco conhecimento há sobre os impactos da corrida na osteoartrite do joelho. Objetivo Observar e estudar o efeito clínico da corrida na melhora da dor e da função em pacientes com osteoartrite de joelho. Métodos Setenta casos que preencheram os critérios de inclusão foram selecionados e divididos aleatoriamente em grupos controle e observação. Os pacientes do grupo de observação receberam 8 semanas de exercício neuromuscular (NEMEX) e 8 semanas de treinamento de força muscular do quadríceps enquanto o grupo controle foi sujeitado a um protocolo de corrida. Os pacientes foram avaliados usando a Escala de Dor e o Índice de Osteoartrite das Universidades Western Ontario and McMaster (WOMAC) após 1, 2, 4 e 8 semanas de tratamento. Resultados Após 1, 2, 4 e 8 semanas de tratamento, os escores de função WOMAC dos dois grupos melhoraram significativamente comparados ao encontrado antes do tratamento (P <0,05). Não houve diferença entre os dois grupos antes do tratamento e após 1, 2 semanas de tratamento. Após 4 e 8 semanas de tratamento, a função do grupo de observação foi melhor que a do grupo controle, a diferença foi estatisticamente significativa (t= -4,287, -6,355, P<0,05). Conclusões Ambos os métodos de treinamento NEMEX e o treinamento de força muscular do quadríceps podem efetivamente melhorar o nível funcional dos pacientes, e o NEMEX melhora mais significativamente do que o treinamento de força muscular do quadríceps. Nível de evidência II; Estudos terapêuticos - Investigação de resultados.

RESUMEN Introducción La corrida puede promover la salud, prevenir la obesidad, enfermedades cardiovasculares y cerebrovasculares, entre otras enfermedades crónicas. Muchas investigaciones informan los beneficios de este ejercicio de resistencia aeróbica, pero se sabe poco sobre los impactos de correr en la osteoartritis de rodilla. Objetivo Observar y estudiar el efecto clínico de la corrida sobre el dolor y la mejora funcional en pacientes con artrosis de rodilla. Métodos Setenta casos que cumplieron con los criterios de inclusión fueron seleccionados y divididos aleatoriamente en grupos de control y observación. Los pacientes del grupo de observación recibieron 8 semanas de ejercicio neuromuscular (NEMEX) y 8 semanas de entrenamiento de fuerza de los cuádriceps, mientras que el grupo de control se sometió a un protocolo de corrida. Los pacientes fueron evaluados utilizando la escala de dolor y el índice de osteoartritis de las universidades de Western Ontario y McMaster (WOMAC) después de 1, 2, 4 y 8 semanas de tratamiento. Resultados Después de 1, 2, 4 y 8 semanas de tratamiento, las puntuaciones de función WOMAC de los dos grupos mejoraron significativamente en comparación con las encontradas antes del tratamiento (P < 0,05). No hubo diferencia entre los dos grupos antes del tratamiento y después de 1, 2 semanas de tratamiento. Después de 4 y 8 semanas de tratamiento, la función del grupo de observación fue mejor que la del grupo control, la diferencia fue estadísticamente significativa (t= -4.287, -6.355, P<0.05). Conclusiones Tanto los métodos de entrenamiento NEMEX como el entrenamiento de la fuerza muscular del cuádriceps pueden mejorar eficazmente el nivel funcional de los pacientes, y NEMEX mejora de forma más significativa que el entrenamiento de la fuerza muscular del cuádriceps. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.