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OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.
Subject(s)
Male , Animals , Mice , Colitis, Ulcerative/pathology , Immunity, Innate , Butyric Acid/therapeutic use , Sophora , Gastrointestinal Microbiome , Lymphocytes , Colon , Colitis/pathology , Disease Models, Animal , Mice, Inbred C57BLABSTRACT
Diosgenin is widely distributed in many plants, such as Polygonatum sibiricum, Paris polyphylla, Dioscorea oppositifolia, Trigonella foenum-graecum, Costus speciosus, Tacca chantrieri, which has good anti-tumor activity and preferable effects on preventing atherosclerosis, protecting the heart, treating diabetes, etc. This review combed through the anti-tumor mechanisms of diosgenin encompassing lung, breast, gallbladder, liver, oral cavity, stomach, bladder, bone marrow, etc. Besides, it was discovered that diosgenin mainly exerts its effect by inhibiting tumor cell migration, suppressing tumor cell proliferation and growth, and inducing cell apoptosis. However, problems like low yield and bioavailability frequently exist in natural diosgenin. This review introduced methods such as structural modification, dosage form optimization and combination medication to improve the yield and anti-tumor activity of diosgenin. Via the summary of this paper, it is expected to provide theoretical basis for the rational exploitation and utilization of diosgenin.
Subject(s)
Apoptosis , Biological Products , Cell Proliferation , Diosgenin/pharmacology , TrigonellaABSTRACT
Objective The purpose of this study was to investigate the mechanism of Bmi-1 regulating the sensitivity of non-small cell lung cancer (NSCLC) to chemotherapy by observing its effects on multidrug-resistance protein 1 (MDR1) and apoptosis-related proteins. Methods Small interfering RNAs (siRNA) targeting Bmi-1 were transfected into A549 and A549/DDP cells of NSCLC and the logarithmic-phase cells were randomly divided into a siRNA-Bmi-1, a siRNA-negative control and a blank control group. The A549 cells were treated with siRNA-Bmi-1, DDP or Bmi-1+DDP, or left untreated (the control). CCK8 assay was employed to measure the 50% inhibitory concentration (IC50) of cisplatin in the A549 and A549/DDP cells before and after treatment. The apoptosis of the cells was detected by flow cytometry, the mRNA expression of Bmi-1 determined by RT-PCR, and the relationship of Bmi-1 with MDR1 and cleaved caspase-3 proteins analyzed by Western blot. Results After transfection, the relative mRNA and protein expressions of Bmi-1 in the A549 and A549/DDP cells were significantly lower in the siRNA-Bmi-1 than in the blank control group (P < 0.05), but higher in the A549/DDP than in the A549 cells. The survival rates of the A549 and A549/DDP cells were decreased with the increased concentration of cisplatin (P < 0.05), even lower in the Bmi-1+DDP than in the DDP subgroup (P < 0.05). The apoptosis rate of the A549 cells was markedly higher in the Bmi-1+DDP than in the DDP, Bmi-1 and control groups ([39.65±3.41]% vs [23.11±1. 62] %, [2.05±1.56]% and [1.98±1.05]%, P < 0.05). After 24 hours of treatment with DDP, both the expressions of Bmi-1 and MDR1 were remarkably elevated, while the down-regulation of Bmi-1 significantly decreased the expression of MDR1 and increased that of cleaved caspase-3. Conclusion The expression of siRNA-Bmi-1 makes non-small lung cancer cells more sensitive to cisplatin, which might be associated with its inhibition of MDR1 expression and activation of apoptosis-related proteins.
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Objective In order to further optimize the cultivation program of clinical medicine undergraduates and promote the cultivation of medical students to adapt to the newest development. To understand and evaluate the post competency of clinical medical undergraduates and then establish a scientific and reasonable evaluation index system to further improve the quality of medical undergraduate talent training.Methods Combing with the Methods of literature research, Delphi method and hierarchical analysis, an evaluation index system of post competency of clinical undergraduate graduates based on the standard of clinical medicine professional certification is constructed .Results The evaluation index system of post competency of clinical graduates includes 4 first level indicators, 11 second level indicators and 63 third level indicators. The 4 first level can be divided into clinical ability, professional quality, science and scholarship., health and society by weight.Conclusion It is an effective way to cultivate medical talents to construct the evaluation index system of post competency of clinical undergraduates, which will contribute to the construction of "Healthy China".