This study aimed to examine the effects of the glycosaminoglycan (GAG) chain in urinary trypsin inhibitor (UTI) on uterine cervical fibroblasts (UCFs) and to apply the findings to the development of more effective therapeutic drugs for the management of preterm birth. Methods: We prepared GAG chain-remodeled UTIs by hydrolysis and /or transglycosylation by testicular hyaluronidase. These UTIs were added to UCFs obtained from gynecology operations, and the effects of UTIs on the release of IL-8, IL-6, MMP-8, and MMP-9 were examined. Results: UTIs that were not hydrolyzed tended to reduce IL-8 release more strongly than GAG chain-hydrolyzed UTIs. IL-6 was not affected by GAG chain hydrolysis of UTIs. GAG chain-hydrolyzed UTIs tended to reduce MMP-8 and MMP-9 release more strongly than non-hydrolyzed UTIs. Conclusions: Our findings suggest that the GAG chain of UTI might reduce hyaluronan during cervical ripening by reducing IL-8 release and has opposite effects on reducing MMP-8 and MMP-9 release related to collagen degradation. This insight may be helpful in the development of more effective therapeutic drugs for the management of preterm birth.
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequently observed treatment-related adverse effect, particularly associated with taxane-based chemotherapy, which affects the quality of life of the patients. To date, CIPN has been subjectively evaluated by patients or physicians. Intraepidermal electrical stimulation (IES) may be applied to evaluate the function of small fibers by measuring pain threshold, and assess the degree of diabetic peripheral neuropathy. The aim of the present study was to evaluate CIPN objectively by using IES. The pain threshold measured by IES in patients with gynecological cancer who underwent taxane-based chemotherapy was compared with the clinical grading scale of peripheral neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). A total of 57 patients were evaluated (151 measurements). The median age of the patients was 63 years. The number of measurements with clinical grades of 0, 1 and ≥2 was 49, 57 and 45, respectively. The mean pain threshold was 0.1, 0.14 and 0.18 mA for grades 0, 1 and ≥2, respectively. Therefore, the mean pain threshold significantly increased with the progression of the clinical grade. The measurement of pain threshold by using IES may be a reliable indicator for quantitative evaluation of CIPN.
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