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BACKGROUND@#All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. @*METHODS@#ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. @*RESULTS@#We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. @*CONCLUSIONS@#Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.
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The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.
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Camundongos , Animais , Depressão/etiologia , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo , SerotoninaRESUMO
Objective To assess the effectiveness of puncturing Sifeng points (EX-UE10) and pricking Back-Shu points in treating dyspepsia due to chemotherapy for triple-negative breast cancer (TNBC). Method Sixty patients were randomized into an observation group (30 cases) and a control group (30 cases). The observation group was intervened by puncturing Sifeng points and pricking Back-Shu points, once a week. The selected Back-Shu points included bilateral Pishu (BL20), Weishu (BL21) and Geshu (BL17). The control group was treated by promoting gastrointestinal motility (itopride hydrochloride 50 mg) and supplementing digestive enzymes (compound azintamide tablets). The two groups were observed before and after treatment in terms of traditional Chinese medicine (TCM) symptom score, nutritional status score and Karnofsky Performance Score (KPS). The therapeutic efficacies were also assessed. Result The total effective rate was 93.3％ (28/30) in the observation group versus 70.0％ (21/30) in the control group, and the between-group difference was statistically significant (P<0.05). The TCM symptom score showed significant improvement in both groups after treatment (P<0.01), and the improvement in the observation group was more significant than that in the control group (P<0.01). After treatment, the score of Patient Generated-Subjective Global Assessment (PG-SGA) decreased significantly in both groups (P<0.01), while there was no significant difference in the score between the two groups (P>0.05). The KPS score increased significantly in both groups after treatment (P<0.01), and there was a significant difference between the two groups (P<0.05), indicating a more significant improvement of KPS score in the observation group. Conclusion Puncturing Sifeng plus pricking Back-Shu points is effective in treating dyspepsia due to chemotherapy for TNBC. It can improve patient's appetite and quality of life.
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<p><b>OBJECTIVE</b>To summarize the recent findings of dysregulation of signaling pathways and miRNAs in chronic lymphocytic leukemia (CLL).</p><p><b>DATA SOURCES</b>We searched PubMed database with the keywords "chronic lymphocytic leukemia", "signal pathway", or "miRNA" for relevant articles in recent years.</p><p><b>STUDY SELECTION</b>Research articles and reviews about signaling pathways and miRNAs in CLL were chosen for review.</p><p><b>RESULTS</b>Dysregulation of signaling pathways, such as B cell receptor , toll-like receptor, PI3K, nuclear factor κB, notch signaling pathway, Wnt/Fzd signaling pathway, and Hedgehog and Janus kinases/signal transducers and activators of transcription signaling pathway, as the terminal events of the aberrant gene expression and the pro-survival effects of microenvironment, plays a crucial role in the process of CLL. miRNAs, a novel found noncoding RNA, which regulate gene expression at transcription or post-transcription level and correlate with pathogenesis of CLL provide us new avenues to better evaluating prognosis and therapy of it.</p><p><b>CONCLUSION</b>Further investigation of the dysregulation of signaling pathways and miRNAs and their relationship may provide us a new prospective to understand the pathogenesis of CLL and may provide us new strategies to resolve the clinical nodi in treatment of CLL.</p>