Increasing evidence suggests that white matter disorders based on myelin sheath impairment may underlie the neuropathological changes in schizophrenia. But it is unknown whether enhancing remyelination is a beneficial approach to schizophrenia. To investigate this hypothesis, we used clemastine, an FDA-approved drug with high potency in promoting oligodendroglial differentiation and myelination, on a cuprizone-induced mouse model of demyelination. The mice exposed to cuprizone (0.2% in chow) for 6 weeks displayed schizophrenia-like behavioral changes, including decreased exploration of the center in the open fi eld test and increased entries into the arms of the Y-maze, as well as evident demyelination in the cortex and corpus callosum. Clemastine treatment was initiated upon cuprizone withdrawal at 10 mg/kg per day for 3 weeks. As expected, myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes (APC-positive) and myelin basic protein. More importantly, the clemastine treatment rescued the schizophrenia-like behavioral changes in the open field test and the Y-maze compared to vehicle, suggesting a beneficial effect via promoting myelin repair. Our fi ndings indicate that enhancing remyelination may be a potential therapy for schizophrenia.
Previously, a number of microRNAs (miRNAs) have been reported to be dysregulated in cervical cancer, and dysregulated miRNAs may play crucial roles in the development and progression of cervical cancer. Hence, investigating the detailed roles of miRNAs that are aberrantly expressed in cervical cancer and the underlying molecular mechanisms is essential for early diagnosis and effective therapeutic approaches. miRNA-877 (miR-877) was found to be downregulated in hepatocellular carcinoma and renal cell carcinoma, and function as a tumor-suppressive miRNA. However, how miR-877 exerts an effect in cervical cancer progression and its underlying molecular mechanisms remains to be elucidated. In the current study, reverse transcription-quantitative PCR was performed to determine miR-877 expression in cervical cancer tissues and cell lines. The effects of miR-877 overexpression on cervical cancer cell proliferation and invasion were evaluated using MTT and Transwell cell invasion assays. In the present study, miR-877 was significantly downregulated in cervical cancer tissues and cell lines, and the decreased expression levels of miR-877 were significantly associated with increased International Federation of Gynecology and Obstetric stage as well as increased lymph node metastasis in patients with cervical cancer. Upregulation of miR-877 using miR-877 mimics resulted in the decreased proliferation and invasion of cervical cancer cells. Metastasis-associated in colon cancer-1 (MACC1) was assessed using bioinformatics analyses to determine whether it could be a potential target gene of miR-877, and the results were confirmed using a luciferase reporter assay. Furthermore, MACC1 was markedly upregulated in cervical cancer tissues, and its level was negatively correlated with the miR-877 level. Overexpression of miR-877 resulted in decreased expression levels of MACC1 in cervical cancer cells at both the mRNA and protein levels. In addition, the functional effects of MACC1 knockdown were similar to those induced by upregulated miR-877 in cervical cancer cells. MACC1 restored miR-877 overexpression-mediated suppression of cervical cancer cell proliferation and invasion. In conclusion, miR-877 may play an antitumor role in cervical cancer by directly targeting MACC1, which suggests that this miRNA may be a promising therapeutic target for the treatment of patients with such an aggressive gynecological cancer.
Flash glucose monitoring (FGM) was introduced in China in 2016, and it might improve HbA1c measurements and reduce glycaemic variability during T1DM therapy. A total of 146 patients were recruited from October 2018 to September 2019 in Liaocheng. The patients were randomly divided into the FGM group or self-monitoring blood glucose (SMBG) group. Both groups wore the FGM device for multiple 2-week periods, beginning with the 1st, 24th, and 48th weeks for gathering data, while blood samples were also collected for HbA1c measurement. Dietary guidance and insulin dose adjustments were provided to the FGM group patients according to their Ambulatory Glucose Profile (AGP) and to the SMBG group patients according to their SMBG measurements taken 3–4 times daily. All of the participants underwent SMBG measurements on the days when not wearing the FGM device. At the final visit, HbA1c, time in range (TIR), duration of hypoglycaemia and the number of diabetic ketoacidosis (DKA) events were taken as the main endpoints. There were no significant difference in the baseline characteristics of the two groups. At 24 weeks, the HbA1c level of the FGM group was 8.16 ± 1.03%, which was much lower than that of the SMBG group (8.68 ± 1.01%) (p = 0.003). The interquartile range (IQR), mean blood glucose (MBG), and the duration of hypoglycaemia in the FGM group also showed significant declines, compared with the SMBG group (p < 0.05), while the TIR increased in the FGM group [(49.39 ± 17.54)% vs (42.44 ± 15.49)%] (p = 0.012). At 48 weeks, the differences were more pronounced (p < 0.01). There were no observed changes in the number of episodes of DKA by the end of the study [(0.25 ± 0.50) vs (0.28 ± 0.51), p = 0.75]. Intermittent use of FGM by T1DM patients can improve their HbA1c and glycaemic control without increasing the hypoglycaemic exposure in insulin-treated individuals with type 1 diabetes in an developing country.
The study was designed to test whether circulating autoantibodies against associated antigens (TAAs) were altered in early cervical cancer and benign cervical tumors. A total of 111 cervical cancer patients, 137 cervical benign tumor patients, and 160 healthy volunteers matched in age were recruited in this study. The expression of autoantibodies was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs. One-way ANOVA test showed that there was no difference in the CD25 autoantibody expression among the cervical cancer group, benign tumor group, and healthy control group (P = 0.063; P = 0.191). The expression of autoantibodies against survivin and TP53 in the cervical cancer group was significantly higher than that in the benign tumor group (P < 0.001; P < 0.001). The levels of autoantibodies against cyclinB-1 and ANXA-1 were higher in the cervical cancer group than in the healthy control group (P = 0.010; P = 0.001), while autoantibodies in the cervical cancer group showed no difference in expression compared with that in the benign tumor group. The panel of five TAAs showed a sensitivity of 37.8 % and a specificity of 90 %, which was much higher than the sensitivity of the single-TAA testing group. The data from this study further support our previous hypothesis that the detection of autoantibodies for the diagnosis of a specific cancer type can be enhanced using a panel of several selected TAAs as target antigens.
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