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Our group previously showed that 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) is a potent neuroprotective agent in the treatment of ischemic stroke in rats. As its mode of action was not well defined, we determined if its therapeutic effect includes altering an immune response to experimental ischemic stroke in rats. In the current study, 2-BFI significantly reduced stroke-induced brain infarct volume and it also decreased neurological deficits. Its anti-immune effects were determined based on flow cytometry measurements of both the 2-BFI-induced changes in the Th17/ Treg cell balance ratio and ELISA measurements of proinflammatory IL-17A and anti-inflammatory IL-10 cytokine expression levels in the brain and peripheral blood following ischemic strokes. 2-BFI blunted the stroke-induced increases in this ratio, which resulted from suppression of the rises in the Th17 cell number whereas the proportion of Treg cells increased. Stroke also induced increases in IL-17A expression levels whereas the IL-10 expression levels declined. 2-BFI treatment inhibited the rises in IL-17A expression levels whereas the corresponding declines in IL-10 were suppressed by this agent. Sunitinib supplier Therefore, one of the neuroprotective effects of 2-BFI in the treatment of cerebral strokes stems from its suppression of rises in the Th17/Treg balance along with corresponding changes in related cytokines modulating development of this condition.Background Aloperine can exert antitumor effects in colorectal cancer; however, it remains obscure whether aloperine can reverse the cisplatin resistance in colorectal cancer (CRC). Objective To explore the roles of aloperine in the chemosensitivity of the DDP-resistant colorectal cancer cell line HT-29 (HT-29/DDP) and the related mechanism. Results Aloperine can inhibit the proliferation of both HT-29 and HT-29/DDP cells in a dose-dependent manner; moreover, aloperine can significantly increase the sensitivity of HT-29/DDP cells to DDP; finally, HIF-1α and p-ERK was upregulated in HT-29/DDP cells and transient over-expression of HIF-1α has blocked aloperine+DDP induced anti-proliferative and pro-apoptotic effects on HT-29/DDP cells. Conclusion We are reporting for the first time that aloperine can increase the sensitivity of HT-29/DDP cells to DDP and reverse cisplatin resistance via downregulating the HIF-1α /ERK signaling pathway.Gingival mesenchymal stem cells (GMSCs) have great potential in bone tissue regeneration. However, it is not well known how on exosomes derived from GMSCs affect the functions of bone-related cells. In this study, we explored the impact of GMSCs-derived exosomes (GMSCs-Exos) on pre-osteoblast MC3T3-E1 proliferation, migration and osteogenic differentiation. Results of CCK-8 assay showed that GMSCs-Exos had no effect on proliferation of pre-osteoblasts. Further, we found that GMSCs-Exos promoted the migration of pre-osteoblasts and osteogenic differentiation of MC3T3-E1 as revealed by enhanced Alizarin red staining, elevated alkaline phosphatase (ALP) activity and upregulated expression of osteogenic genes. This study provides new insights into the potential exosome-mediated paracrine mechanism of GMSCs in bone regeneration.This study was performed to examine the effect of Interleukin-10 (IL-10) modified bone marrow mesenchymal stem cells (BMSCs) on hypertrophic scar formation on the rabbit ear hypertrophic scar model. Rabbit BMSCs were obtained by whole bone marrow adherence method and IL-10-modified BMSCs (IL-10BMSCs) were established by transfecting BMSCs with an adenovirus. We treated the rabbit ear hypertrophic scar with BMSCs and IL-10-BMSCs, then evaluated the area and measured the height of the hypertrophic scar, and detected expression using real-time PCR and western blot. Compared with wild type BMSCs, the proliferative capability of IL-10 modified BMSCs was significantly reduced, but the expression of IL-10 in IL-10-BMSCs was significantly increased. After treating with a local injection of BMSCs or IL-10-BMSCs in the rabbit ear hypertrophic scar, we found that the time of wound healing, the area and height of scar were all significantly reduced in the IL-10-BMSCs group when compared to those in the BMSCs group. Moreover, the expression of Collagen-I, α-SMA, TNF-α, IL-6 and IL-1β mRNA, the number of CD45-positive cells, CD3-positive cells and ED-1-positive cells, and the expression of p-IKBα / IKBα, p-p65 / p65, p-JNK / JNK and p-c-JUN / c-JUN in the scar of the IL-10-BMSCs group were significantly lower than those in BMSCs group. IL-10 modified BMSCs prevented hypertrophic scar formation in the rabbit ear hypertrophic scar model, and the results suggest this could be due to the inhibition of inflammation by IL-10 modified BMSCs through the JNK / NF-κB pathway.Torreya nucifera is an evergreen tree in the family Taxaceae, the seeds, leaves, and stems of which have long been used as edible products and herbal medicines in Korea. Previous studies of biological activity have shown that T. nucifera has antioxidant and anti-inflammatory effects. However, the effect of T. nucifera leaves on melanogenesis are yet to be studied. In this investigation, we used B16F10 melanoma cells to test the efficacy of T. nucifera leaf hot water extract (TLWE). α-melanocyte stimulating hormone (α-MSH) stimulated B16F10 melanoma cells were treated with various concentrations of TLWE (50, 100, and 200 μg/mL). The results showed that TLWE reduced the melanin content and cellular tyrosinase activity in a concentration-dependent manner. It also inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase (MAPK) signaling pathway. The compounds catechin and ρ-coumaric acid, which are known to have a whitening effect on skin, were detected by HPLC analysis. These results suggest that TLWE has an anti-melanogenic effect. In addition, the safety of TLWE was tested. The results of the skin irritation test showed that TLWE is harmless to the human skin, even at higher concentrations than those used in the experiment. Therefore, we suggest that the water extract of T. nucifera leaves has potential for use as a skin-whitening agent.

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