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Objective To explore the effect of melatonin ( MLT) on the initiation of puberty in female mice and on the expression level of phosphatidylinositol-3-kinases ( PI3K)/protein kinase B ( Akt)/mammalian target of rapamycin (mTOR) signaling pathway in the frypothalamus. Methods Seventy-eight 20-day-old female KM mice were randomly divided into melatonin (MLT) group and normal saline (NS) group, with 39 mice in each group. Starting at 22 days of age, the MLT group was given a subcutaneous injection of 1 mg/kg melatonin and the NS group was given an equal volume of saline. Thirty-two days of age were selected as the sampling point before puberty initiation and 13 mice were executed in each of the two groups, while 37 and 42 days of age were selected as the sampling point after puberty initiation and 13 mice were executed in each of the two groups. Observation of vaginal opening time in mice, weighing of ovaries and uterus to calculate organ indices. HE staining to observe the number of ovarian corpora lutea. The levels of serum luteinizing hormone (LH)were determined by ELISA. The mRNA and protein expression levels of PI3K/Akt/mTOR pathway in frypothalamus were detected by Real-time PCR and Western blotting. Results Compared with the normal saline group, mice in the melatonin group had significantly delayed vaginal opening time ( P < 0. 05 ) , decreased significantly ovarian and uterine volume and index (P<0. 05) , decreased significantly serum LH levels (P<0. 05) , and decreased significantly mRNA and protein expression levels of the frypothalamic PI3K/Akt/mTOR pathway (P<0. 05). Conclusion Melatonin delays puberty initiation in mice by a mechanism that ma)' be related to inhibition of the hypothalamic PI3K/Akt/mTOR signalling pathway.
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Objective To explore the roles and effects of gonadotropin inhibitory hormone gonadotropin-inhibitory hormone (GnIH)/RF amide-related peptide-3 (RFRP-3) on the uterus through the hypothalamic-pituitary reproductive axis. Methods Ovariectomized estrogen primed (OEP) rats model was divided into GnlH injection group and normal saline injection group with 15 rats in each group, 2 g/L GnlH (16 μl/kg) and normal saline (16 (μl/kg) were injected into the lateral ventricle of rats in the 2 groups respectively. 6 hours after injection, the uterine fluid of rats was obtained. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to separate the differential proteins in uterine fluid and UniProt was used to identify. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the proteinprotein interaction (PPI) network of the differentially expressed proteins was constructed using Cytoscape 3.7. 1 software. Hub proteins were detected from PPI network. Results The result showed that the differentially expressed proteins separating by LC-MS/MS were 419 identified by UniProt. Among them, 279 were up-regulated and 138 were down-regulated. GO analysis showed that the differentially expressed proteins were mainly involved in response to organic substance, response to oxygen-containing compound, response to endogenous stimulus, response to stress. The top five enriched pathways obtained in the KEGG pathway analysis (P<0.05) were carbon metabolism, gap junction, long-term depression, regulation of actin cytoskeleton, biosynthesis of amino acids. Five hub proteins involved albumin (Alb), alpha-enolase 1 (Enol), peroxiredoxin-6 (Prdx6), tissue inhibitor of matrix metalloproteinases-1 (Timp 1), Ras-related C3 botulinum toxin substrate 1 (Racl) were obtained by analyzing PPI network. Conclusion The result of this study indicate that GnlH may regulate the secretion of uterine cavity fluid protein through hypothalamic-pituitary reproductive axis. And regulate the physiological and pathological process of uterus by up-regulating Alb, Enol, Prdx6 and down-regulating Timpl and Racl.
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Objective To evaluate the effect of docetaxel(DTX)combined with a heptapeptide(LPLTPLP, namely P7)on the human triple-negative breast cancer cell line MDA-MB-231 in vitro.Methods The cell viability was measured by SRB assay followed by evaluation of their combination effect using the isobologram.Flow cytometry was performed to quantify apoptotic cells following treatment of DTX,P7 and DTX combined with P7 and the ex-pressions of the apoptosis-related proteins were determined by Western blot analysis.Results P7 synergized with DTX in cell viability detection.The apoptotic rate was highly increased with increasing Bax /Bcl-2 ratio after MDA-MB-231 cells were exposed to DTX and P 7 combination.Conclusions Combination of P 7 and DTX has synergistic effects on MDA-MB-231 cells characterized by increasing apoptosis activation,in which the expression of pro-apop-totic protein Bax increased with a decline in apoptotic protein Bcl-2.
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<p><b>OBJECTIVE</b>To investigate the effects of dexmedetomidine on renal microcirculatory perfusion in rabbits with renal ischemia/reperfusion (I/R) injury rabbit by quantitative analysis of contrast-enhanced ultrasound (CEUS).</p><p><b>METHODS</b>Twenty- four New Zealand rabbits were randomly divided into 3 groups (8 in each), including a control group, renal I/R injury group and dexmedetomidine group. In the latter two groups, the right kidney of the rabbits was resected and I/R injury was induced in the left kidney. In dexmedetomidine group, the rabbits received an intraperitoneal dose of 10 µg/kg dexmedetomidine 30 min before renal ischemia, and 24 h after reperfusion, the renal size and renal artery resistance (RI) were measured, and renal cortex perfusion was observed by CEUS. The time-to-peak intensity (TTP), peak signal intensity (PSI), gradient between start frame to peak frame (Grad) and area under the curve (AUC) were quantitatively analyzed using the time-intensity curves. Pathological changes of the kidney were also observed.</p><p><b>RESULTS</b>Compared with the control group, the rabbits in I/R and dexmedetomidine groups showed distinct changes of the renal size with obvious renal pathologies. RI, PPT and AUC all increased, and PSI and Grad decreased significantly in I/R and dexmedetomidine groups (P<0.05). Compared with I/R group, obvious improvement of the renal size and renal pathologies were observed in dexmedetomidine group, which showed significantly decreased RI, PPT and AUC and increased PSI and Grad (P<0.05).</p><p><b>CONCLUSION</b>CEUS combined with the time-intensity curve parameters allows quantitative and dynamic analysis of the protective effects of dexmedetomidine on microcirculatory perfusion in rabbits with renal I/R injury.</p>
Assuntos
Animais , Coelhos , Dexmedetomidina , Farmacologia , Modelos Animais de Doenças , Rim , Nefropatias , Tratamento Farmacológico , Microcirculação , Artéria Renal , Traumatismo por Reperfusão , Tratamento FarmacológicoRESUMO
Objective To investigate the action mechanism of Qingjin Huatan Decoction on regulating COPD rats with mucus hypersecretion in airway. Methods Fifty 6-8 week old Wistar male rats were randomly divided into healthy group, model group, Qingjin Huatan Decoction group, clarithromycin group, 10 rats in each group. Except for healthy group, all the other groups were used the combination method of injecting LPS and smudging to establish COPD models. The last three groups were fed with normal saline, Qingjin Huatan Decoction, clarithromycin respectively for 30 days. On the 31st day of the experiment, the rats were put to death to take lung tissue. 6 rats from each group were chosen randomly, and the protein expressions of NE, EGFR and MUC5AC mRNA in lung tissue were detected by real-time fluorescent quantitative PCR. Results The expressions of NE, MUC5AC mRNA in lung tissue of COPD rats were higher than the healthy group. Compared with model group, the expressions of NE mRNA and MUC5AC mRNA in Qingjin Huatan Decoction group and clarithromycin group were markedly lower, while the expressions of NE, MUC5AC mRNA in Qingjin Huatan Decoction group were significantly lower than those in clarithromycin group. The expression of EGFR mRNA in Qingjin Huatan Decoction group was lower than that in model group. Conclusion Qingjin Huatan Decoction can inhibit mucus hypersecretion in airway through NE/EGFR/MUC5AC signal transduction pathway.