Gene UCHL1 expresses specifically in mouse uterine decidual cells in response to estrogen.

UCHL1 is expressed specifically in the brain and gonads of almost all studied model organisms including Drosophila, zebrafish, amphibians, and mammals, suggesting a high degree of evolutionary conservation in its structure and function. Although UCHL1 has been involved in spermatogenesis in mice, its specific expression in mammal placenta remains elusive. Our previous work has revealed that UCHL1 is highly expressed in oocytes, and has been involved in mouse ovarian follicular development. Here, we further examined UCHL1 expression change in endometria during early natural pregnancy, with different stages of the estrous cycle and pseudopregnancy as control. The UCHL1 gene deletion model showed that UCHL1 protein is associated with endometrial development, and its deletion leads to infertility. Notably, we demonstrate evidence showing the distinct expression pattern of UCHL1: weak expression over the uterine endometria, strong expression in decidualized stromal cells at the implantation site with a peak at pregnancy D6, and a shift with primary decidualization to secondary decidualized zones. Using the delayed implantation, the delayed implantation activation, and the artificial decidualization models, we have demonstrated that strong expression of UCHL1 occurred in response to decidualization and estrogen stimulation. These observations suggest that during the early proliferation and differentiation of mouse uterine decidua, UCHL1 expression is up-regulated, and formed an unique intracellular distribution mode. Therefore, we proposed that UCHL1 is involved in decidualization, and possibly in response to estrogen regulation.

Meta-analysis of acupuncture combined with paroxetine in the treatment of depression.

OBJECTIVE: To systematically evaluate the clinical efficacy of acupuncture combined with paroxetine in the treatment of depression. METHODS: The research literature on the treatment of depression with acupuncture and moxibustion combined with paroxetine was collected using keywords in PubMed, Embase, Web of Science, Cochrane Library, CNKI, World Wide Web, Chinese Biomedical Literature and other public publication databases. Collaborative screening of literature was performed according to pre-established inclusion and exclusion criteria. The data in the literature were extracted, the quality of the literature was evaluated, and the RevMan software was used for statistical analysis. RESULTS: This study finally included 21 research papers involving 1733 clinical patients. The main evaluation indicators for clinical patients were Hamilton Depression Rating Scale (HAMD), total clinical response rate, Rating Scale for Side Effects (SERS) and Treatment Emergent Symptom Scale (TESS). SERS was developed by Asberg. The Chinese version was revised by Zhang Mingyuan (Chairman of the Chinese Medical Association Mental Health Society) et al. The SERS is divided into 14 items, all of which use a 4-point scoring method (none, mild, moderate and severe, respectively). This scale is mainly used to assess the side effects of antidepressants. TESS was compiled by the NIMH of the United States in 1973. It has the most comprehensive items and the widest coverage among the scales of its kind, including not only common adverse symptoms and signs, but also several laboratory test results. Meta-analysis of the above results showed that compared with the control group, the acupuncture combined with paroxetine treatment group showed lower HAMD score (WMD=-4.18 [-5.04, -3.31], P<0.001), higher total response rate (OR=4.01 [3.01, 5.33], P<0.001), lower SERS score (WMD=-2.54 [-4.58, -0.51], P<0.001) and lower TESS score (WMD=-4.39 [-5.15, -3.62], P<0.001), and the differences were statistically significant. CONCLUSION: The therapeutic effect of acupuncture combined with paroxetine on depression is better than that of conventional drug treatment, and its safety is comparable to that of conventional treatment.

Zhi Zhen Fang formula reverses Hedgehog pathway mediated multidrug resistance in colorectal cancer.

Zhi-Zhen-Fang (ZZR), a Traditional Chinese Medicine (TCM) formula, has been clinically used in China to treat drug-resistant colorectal cancer (CRC) patients as an adjuvant. In this study, the efficacy of ZZR in suppressing multidrug resistance (MDR) on CRC was evaluated in vitro and in vivo. We observed that ZZR enhanced the sensitivity of chemotherapeutic drugs and induced apoptosis in a dose- and time-dependent mannner in CRC MDR cells. Interestingly, signaling of Hedgehog pathway, particularly Gli1, was also inhibited by ZZR. This effect of ZZR in reversing drug resistance and suppressing Gli1 was attenuated by a Hedgehog activator (SAG). Furthermore, ZZR inhibited MDR CRC tumor growth in a xenograft mouse model as well as downregulated Gli1 levels. This study provided the first direct evidence demonstrating ZZR can attenuate MDR by repressing Hedgehog signaling in human CRC.