ABSTRACT
Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.
ABSTRACT
ß,ß-Dimethylacrylshikonin (DA) is a major component of Radix Lithospermum erythrorhizon and has various biological activities. We have investigated the inhibitory effect of DA on the growth of hepatocellular carcinoma in vitro and in vivo. Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis. Hence, perturbed Notch signaling may contribute to tumorigenesis. In the present study, we evaluated whether DA could be an effective inhibitor on cell growth in human gastric cancer cell line, and also the molecular mechanisms. Using multiple cellular and molecular approaches such as MTT assay, colony formation assay, DAPI staining, flow cytometry, real-time PCR and Western blot analysis, we found that DA inhibited cell growth in a dose- and time-dependent manner. Biochemical analysis revealed the involvement of cell cycle regulated proteins in DA-mediated of G0-G1 arrest of SGC-7901 cells. Furthermore, DA treatment led to reduced Notch-1 activation, expression of Jagged-1 and its downstream target Hes-1 in vitro and in vivo. Our data demonstrated that DA is a potent inhibitor of progression of gastric cancer cells, which could be due to attenuation of Notch-1. We also suggest that DA could be further developed as a potential therapeutic agent for the treatment of gastric cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Naphthoquinones/pharmacology , Receptor, Notch1/physiology , Stomach Neoplasms/drug therapy , Animals , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Down-Regulation , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Female , G1 Phase/drug effects , Humans , Mice , Mice, Inbred BALB C , Naphthoquinones/therapeutic use , Receptor, Notch1/antagonists & inhibitors , Resting Phase, Cell Cycle/drug effects , Signal Transduction , Transplantation, HeterologousABSTRACT
<p><b>OBJECTIVE</b>To study the analgesic effects and sites of oxymatrine-carbenoxolone sodium complex (OCSC).</p><p><b>METHOD</b>Adopting formalin test, warm water tail-flick test and intracerebroventricularly (icv) injection to observe the analgesic effects of OCSC in mice.</p><p><b>RESULT</b>Intraperitoneally injecting (ip) OCSC (75, 150 mg x kg(-1)) remarkedly inhibited the pain of mice in the formalin test and prolonged latent phases of tail-shrinking of mice, icy OCSC (1.875, 3.75, 7.5 mg x kg(-1)) significantly prolonged latent phases of tail-shrinking of mice, it had dose-dependent effect with concentration.</p><p><b>CONCLUSION</b>The result indicated that OCSC has obvious analgesic effects and its mechanism may be involved in central nervous system (CNS).</p>
Subject(s)
Animals , Female , Male , Mice , Alkaloids , Chemistry , Analgesics , Chemistry , Pharmacology , Therapeutic Uses , Carbenoxolone , Chemistry , Pharmacology , Therapeutic Uses , Dose-Response Relationship, Drug , Mice, Inbred ICR , Pain , Drug Therapy , Quinolizines , ChemistryABSTRACT
Objective To investigate the analgesic effect of oxysophoridine(OSR)and the influence of verapamil(Ver)on the antinociception of OSR when two drugs were co-administrated in mice.Methods The number of writhing within 15 min after ip different doses of OSR was observed in painful mouse mo- dels caused by acetic acid.The hot plate method was used to assess nociceptive sensitivity of CaCl_2 and Ver before ip OSR.Nitric oxide(NO)in serum was measured by spectrophotometry.Results The number of writhing was decreased and the latency of licking the hind paws was prolonged in a dose-dependent manner after ip OSR.The antinociception of OSR could be antagonized by CaCl_2 and enhanced by Ver.No inter- ference was detected in serum volume of NO.Conclusion These results suggest that OSR can antagonize the acute pain caused by acetic acid and hot plate in a dose-dependent manner in mice.Calcium channel blocker could enhance the effect of OSR.
