Monoclonal Antibody Targeting CGRP Relieves Cisplatin-Induced Neuropathic Pain by Attenuating Neuroinflammation.

Chemotherapy-induced neuropathic pain (CIPN) is a common side effect of antitumor chemotherapeutic agents. It describes a pathological state of pain related to the cumulative dosage of the drug, significantly limiting the efficacy of antitumor treatment. Sofas strategies alleviating CIPN still lack. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in many pathologic pains. In this study, we explored the effects of CGRP blocking on CIPN and potential mechanisms. Total dose of 20.7 mg/kg cisplatin was used to establish a CIPN mouse model. Mechanical and thermal hypersensitivity was measured using von Frey hairs and tail flick test. Western blot and immunofluorescence were utilized to evaluate the levels of CGRP and activated astrocytes in mouse spinal cord, respectively. In addition, real-time quantitative PCR (RT-qPCR) was used to detect the level of inflammatory cytokines such as IL-6, IL-1ß, and NLRP3 in vitro and in vivo. There are markedly increased CGRP expression and astrocyte activation in the spinal cord of mice following cisplatin treatment. Pretreatment with a monoclonal antibody targeting CGRP (ZR8 mAb) effectively reduced cisplatin-induced mechanical hypersensitivity and thermal nociceptive sensitization and attenuated neuroinflammation as marked by downregulated expression of IL-6, IL-1ß, and NLRP3 in the mice spinal cord and spleen. Lastly, ZR8 mAb does not interfere with the antitumor effects of cisplatin in tumor-bearing mice. Our findings indicate that neutralizing CGRP with monoclonal antibody could effectively alleviate CIPN by attenuating neuroinflammation. CGRP is a promising therapeutic target for CIPN.

Antagonistic potential against pathogenic microorganisms and hydrogen peroxide production of indigenous lactobacilli isolated from vagina of Chinese pregnant women.

OBJECTIVE: To investigate the indigenous lactobacilli from the vagina of pregnant women and to screen the isolates with antagonistic potential against pathogenic microorganisms. METHODS: The strains were isolated from pregnant women's vagina and identified using the API50CH system. The ability of the isolates to produce hydrogen peroxide was analyzed semi-quantitatively using the TMB-HRP-MRS agar. The antagonistic effects of the isolates on pathogenic microorganisms were determined with a double layer agar plate. RESULTS: One hundred and three lactobacilli strains were isolated from 60 samples of vaginal secretion from healthy pregnant women. Among them, 78 strains could produce hydrogen peroxide, in which 68%, 80%, 80%, and 88% had antagonistic effects against Candida albicans CMCC98001, Staphylococcus aureus CMCC26003, Escherichia coli CMCC44113, and Pseudomonas aeruginosa CMCC10110, respectively. CONCLUSION: The recovery of hydrogen peroxide-producing lactobacilli decreases with the increasing pregnant age and time. The most commonly isolated species from vagina of Chinese pregnant women are Lactobacillus acidophilus and Lactobacillus crispatus. Most of L. acidophilus and L. crispatus produce a high H2O2 level.