RESUMEN
Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe joint damage and disability. However, the specific mechanism of RA has not been thoroughly clarified over the past decade. Nitric oxide (NO), a kind of gas messenger molecule with many molecular targets, is demonstrated to have significant roles in histopathology and homeostasis. Three nitric oxide synthases (NOS) are related to producing NO and regulating the generation of NO. Based on the latest studies, NOS/NO signaling pathways play a key role in the pathogenesis of RA. Overproduction of NO can induce the generation and release of inflammatory cytokines and act as free radical gas to accumulate and trigger oxidative stress, which can involve in the pathogenesis of RA. Therefore, targeting NOS and its upstream and downstream signaling pathways may be an effective approach to managing RA. This review clearly summarizes the NOS/NO signaling pathway, the pathological changes of RA, the involvement of NOS/NO in RA pathogenesis and the conventional and novel drugs based on NOS/NO signaling pathways that are still in clinical trials and have good therapeutic potential in recent years, with an aim to provide a theoretical basis for further exploration of the role of NOS/NO in the pathogenesis, prevention and treatment of RA.
Asunto(s)
Artritis Reumatoide , Óxido Nítrico , Humanos , Óxido Nítrico/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Óxido Nítrico Sintasa/metabolismo , Radicales Libres , Estrés OxidativoRESUMEN
Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer's disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.
Asunto(s)
Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Acetilcolina/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Colinérgicos/uso terapéutico , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Transducción de SeñalRESUMEN
A new series of derivatives characterized by the presence of the 3,4,5-trimethoxylbenzamide substituted benzofurans were synthesized and evaluated for antiproliferative activity against four cancer cell lines and one normal human cell line. Among them, derivative 6g with greatest cytotoxicity significantly inhibited the growth of MDA-MB-231, HCT-116, HT-29 and HeLa cell lines with IC50 values of 3.01, 5.20, 9.13, and 11.09 µM, respectively. Importantly, 6g possessed excellent selectivity over non-tumoral cell lines HEK-293 (IC50 > 30 µM). Moreover, mechanistic studies revealed that 6g induced HeLa cells arrested in G2/M phase in a concentration-dependent manner, and inhibited polymerization of tubulin via a consistent way with CA-4. In general, these observations suggest that 6g is a promising anti-cancer lead and is worth further investigation to generate potential antitumor agents.
Asunto(s)
Benzamidas/síntesis química , Benzamidas/uso terapéutico , Polimerizacion/efectos de los fármacos , Moduladores de Tubulina/uso terapéutico , Tubulina (Proteína)/química , Benzamidas/farmacología , Diseño de Fármacos , Células HeLa , Humanos , Estructura Molecular , Relación Estructura-Actividad , Moduladores de Tubulina/farmacologíaRESUMEN
OBJECTIVE: To apply needle-knife to treat lumber disc herniation (LDH) and surface electromyography were used to analyze biomechanical characteristic of patient's lumber muscle to make a comprehensive evaluation on its efficacy. METHODS: Thirty patients who met the inclusive criteria were selected and treated with needle-knife, once a week for 2 weeks. Visual analogue scale (VAS), ASLR and JOA score before and after treatment were observed. Surface electromyography was applied to test the surface electromyography signals. AEMG, MFs and MPF were calculated before and after the treatment. RESULTS: After treatment, VAS was significantly reduced, ASLR, JOA, AEMG and MPF were obviously increased, and the absolute value of MFs was lowed (all P < 0.01). CONCLUSION: The needle-knife could significantly relieve lumbar muscle strength, muscle tone and muscle fatigue, improve in the imbalance of lumbar extensor muscle group, leading to the recovery of biomechanical characteristic, and the clinical efficacy is superior.