RESUMEN
Infections caused by drug-resistant pathogens are a worldwide challenge for public health. Antimicrobial peptides (AMPs) are regarded as promising antibiotic alternatives for the treatment of drug-resistant infections. In the present study, a series of small peptides were designed based on our previously reported sea snake AMP Hc-CATH. From them, the lead peptide HC1-D2, a truncated peptide entirely substituted by d-amino acids, was selected. HC1-D2 exhibited significantly improved stability and antibiofilm and anti-inflammatory activities. Meanwhile, HC1-D2 retained potent, broad-spectrum, and rapid antimicrobial properties against bacteria and fungi, especially drug-resistant bacteria. Moreover, HC1-D2 showed low propensity to induce bacterial resistance and low cytotoxicity and hemolytic activity. Notably, HC1-D2 showed potent in vivo anti-infective ability in mouse peritonitis models infected by both standard and drug-resistant bacteria. It significantly decreased the bacterial counts in the abdominal cavity and spleen of mice and apparently increased the survival rates of the mice. Acting through the MAPKs inflammatory pathway, HC1-D2 selectively induced the production of chemokine and the subsequent immune cell recruitment to the infection site, while inhibiting the production of pro-inflammatory cytokines with undesirable toxicities. These much improved properties make HC1-D2 a promising candidate for the development of novel peptide anti-infective agents against drug-resistant infections.
Asunto(s)
Antiinfecciosos , Infecciones Bacterianas , Hydrophiidae , Preparaciones Farmacéuticas , Animales , Antiinfecciosos/farmacología , Bacterias , Ratones , Pruebas de Sensibilidad Microbiana , Proteínas Citotóxicas Formadoras de PorosRESUMEN
To verify the therapeutic effects of the method of softening and lubricating the joints, and calming the endogenous wind in case of rheumatoid arthritis (RA) with the syndrome of channel blockage due to yin deficiency, 60 RA patients with the syndrome of channel blockage due to yin deficiency were randomly divided into a treatment group (40 cases) and a control group (20 cases) and treated respectively by the above method for the former and with Zheng Qing Feng Tong Ning Tablets ([symbol: see text]) for the latter. The result turned out to be that the effect in the treatment group was very satisfying. The treatment group obtained a better result in the accumulated points of syndrome and RA, morning rigidity of the joints, grip strength, 20m walking time and erythrocyte sedimentation rate (ESR) (P < 0.01 or P < 0.05). The above indicates that channel blockage due to yin deficiency is an important pathogenesis of RA, and calming the endogenous wind is a method of choice for treating RA.