ABSTRACT
Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.
ABSTRACT
Abstract The present study was aimed to investigate the clinical significance of methyl-CpG binding protein 2 (MECP2) in patients with postherpetic neuralgia (PHN). This prospective case control study enrolled 319 cases of PHN patients from April 2017~December 2019. The patients' sleep quality and quality of life were evaluated using the Pittsburgh sleep quality score and the SF- 36 scale, respectively. The serum levels of MECP2, CRP, IL -6 and TNF-α were tested using enzyme linked immunosorbent assay (ELISA). The pain condition of the patients was evaluated using the visual analogue scale (VAS). The levels of MECP2 were significantly increased in PHN patients compared with the patients without PHN. Serum MECP2 levels were the highest in patients with severe pain, and were the lowest in patients with mild pain. Similarly, the frequency of severe pain in patients with low expression of MECP2 was significantly lower than the patients with higher MECP2 expression. Besides, serum levels of inflammatory factors CRP, IL -6 and TNF-α were markedly increased in PHN patients, which were also increased with the increase of the severity of pain. CRP, IL -6 and TNF-α were positively correlated with serum levels of MECP2 in PHN patients. Before the study, patients with lower MECP2 levels showed a significantly higher SF-36 score and lower Pittsburgh and VAS scores than patients with higher levels of MECP2. However, after one month, no significant difference was found between the patients. ROC curve showed MECP2 had the potential as a diagnostic biomarker for PHN. In conclusion, higher serum MECP2 levels are associated with a more severe pain condition and increased release of inflammatory factors.
Resumen El objetivo de este estudio fue investigar la importancia clínica de la MECP2 en pacientes con neuralgia posherpética (NPH). Este estudio observacional prospectivo incluyó 319 pacientes con NPH entre abril de 2017 y diciembre de 2019. La calidad del sueño y la calidad de vida de los pacientes se evaluaron con la escala de calidad del sueño de Pittsburgh y la escala SF - 36, respectivamente. Los niveles séricos de MECP2, PCR, IL -6 y TNF-α fueron determinados por ELISA. Se utilizó la escala visual analógica (EVA) para evaluar la intensidad del dolor. Los niveles de MECP2 en pacientes con NPH aumentaron significativamente en comparación con los pacientes sin NPH. El nivel sérico de MECP2 fue más alto en pacientes con dolor grave y el más bajo en pacientes con dolor leve. Además, la incidencia de dolor grave en pacientes con baja expresión de MECP2 fue significativamente menor que en pacientes con alta expresión de MECP2. Además, los niveles séricos de PCR, IL -6 y TNF-α aumentaron significativamente en pacientes con NPH, y se incrementaron con el aumento del grado de dolor. Los niveles séricos de PCR, IL -6 y TNF-α en pacientes con NPH se correlacionaron positivamente con los niveles séricos de MECP2. Antes del estudio, los pacientes con niveles más bajos de MECP2 tenían puntuaciones significativamente más altas de SF - 36, y puntuaciones más bajas de Pittsburgh y EVA que los pacientes con niveles más altos de MECP2. Sin embargo, no se encontraron diferencias significativas entre los pacientes un mes después. Las curvas ROC mostraron que la MECP2 podría ser un biomarcador de diagnóstico para la NPH. En general, los niveles séricos más altos de la MECP2 se asociaron con condiciones de dolor más graves y un aumento de la liberación de factores inflamatorios.
ABSTRACT
Objective To investigate the effects of cinnamic acid to enhance the exercise endurance in mice .Methods Through the exhaustive swimming to establish mice exhaustive exercise model ,the mice were divided into control group ,exercise control group and exercise cinnamic group(n=10) ,the mice exhaustive swimming time were comparted ,blood lactic acid(LAC) lev‐els were used to explore the endurance of cinnamic acid in mice;the super oxide dismutase (SOD) ,malondialdehyde (MDA) and peroxidase (CAT) content in liver homogenates were used to detect mice endurance enhancement and antioxidant capacity of cin‐namic acid ,and expression of Na+ /K+‐ATP enzyme ,Ca2+ /Mg2+‐ATP enzyme on mice quadriceps by Western blot to further study its effect on improving exercise capacity in mice .Results Cinnamic acid significantly prolonged the swimming time of mice;Exercise cinnamic group compared with control group:although the LAC content in plasma elevated ,the difference was not statistically sig‐nificant(P>0 .05) ,SOD and CAT in liver homogenate was significantly decreased(P0 .05) ,the expression level of Na+ /K+‐ATP enzyme and Ca2+ /Mg2+‐ATP enzyme decreased significantly (P< 0 .01) .Exercise control group compared with control group:the LAC content in plasma increased significantly(P<0 .01) ,SOD and CAT in liver homogenate was significantly decreased(P<0 .01) ,MDA increased significantly(P< 0 .01) ,expression level of Na+ /K+‐ATP enzyme and Ca2+ /enzyme Mg2+‐ATP decreased significantly (P<0 .01);Exercise cinnamic group exercise control group:the LAC content in plasma was significantly reduced(P<0 .01) ,SOD and CAT in liver tissue significantly increased(P< 0 .01) ,MDA decreased significantly(P<0 .01) ,CAT decreased significantly(P<0 .01) ,the expression level of Na+ /K+‐ATP enzyme and Ca2+ /Mg2+‐ATP enzyme decreased significantly(P<0 .05) .Conclusion Cinnamic acid has good oxidation resistances and anti‐fatigue ability .