Hinrichsenwilliamson4286

The current study revealed the relationship between the receptor affinity of antipsychotic drugs and the time-to-onset of dysphagia, which should aid in the selection of antipsychotic drugs, while preventing dysphagia.Objective Several studies have suggested an involvement of the immune system in the occurrence and development of chronic obstructive pulmonary disease (COPD), but the mechanism is still unclear. The aim of this study was to explore the mechanism of ginsenoside in inhibiting inflammation by regulating FOXP3 in COPD. Methods Eighty COPD patients were selected and 35 healthy people were enrolled in the study to determine clinical efficacy, observation index, and SGRQ scores. Percentage of Treg and Th17 cells were detected by flow cytometry; HE staining was used to detect the effect of ginsenoside therapy on pathological changes of COPD in mice. Additionally, we transfected FOXP3 inhibitor; RT-PCR and western blot were used to detect the inflammation related genes and proteins. Results The basic information of the patients were comparable. The clinical outcome in the treatment group was better than that in the control group, which indicated that ginsenoside has a certain therapeutic effect on COPD patients. The lung function and 6MWT distance results indicated that ginsenoside could stabilize the clinical symptoms of COPD patients and improve their quality of life. Flow cytometry results showed that ginsenoside can increase Treg expression while reducing Th17 cell expression. RT-PCR and western blot results showed that the expression of TNF-α and IL-17 in the model group was significantly increased after treatment, obviously caused by an increased expression of FOXP3. Conclusion Ginsenoside can inhibit inflammation in COPD by up-regulating FOXP3.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. 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). selleckchem 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.The co-administration of voriconazole (VCZ) and Wuzhi tablet (WZ) is frequently prescribed for solid organ transplantation patients in China. However, the pharmacokinetic interactions between VCZ and WZ as well as its bioactive constituents, such as schisandrin A and schisandrol B, remain unknown. Therefore, the effects of WZ and the two lignans on the metabolism of VCZ and the potential role of cytochromeP450 (CYP450), especially cytochrome P450 2C19 (CYP2C19), were investigated. The results showed that WZ extensively inhibited the activities of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Noteworthy, 2.5 mg/mL WZ almost completely inhibited the activity of 2C19, and the inhibition ratio reached 78.6±3% and 63.5±4.6% for schisandrin A and schisandrol B at concentrations 100 μM, respectively. In addition, rats were treated with a single or consecutive 14 day oral dose of WZ (250 mg/kg), schisandrol B (10 mg/kg) and schisandrin A (10 mg/ kg). In rats treated with WZ, the AUC0-∞ value for intravenous VCZ dosing was increased by 80.2% (single dose, p less then 0.05) and 66.4% (dosage for 14 day, p less then 0.05) and the Cmax was increased by 10.5% (p less then 0.05) and (20.6%, p less then 0.05), respectively, much greater than that when VCZ (28 mg/kg) was given alone. Unexpectedly, the AUC and Cmax values after schisandrol B and schisandrin A treatment were significantly increased. However, the mRNA expression of liver CYP2C19 and the protein expression of liver CYP2C19 were surprisingly increased after treatment with WZ, schisandrol B and schisandrin A in rats. Therefore, attention should be paid to when WZ and VCZ are administered concomitantly, as dosage adjustment might become necessary. Further clinical study is warranted to validate the interaction between WZ and VCZ.A prodrug of levofloxacin (LVFX), cilexetil ester of LVFX (LVFX-CLX), was synthesized to examine whether the prodrug can avoid chelate formation with metal cations in the gastrointestinal tract. LVFX-CLX exhibited a 10-times higher partition coefficient than LVFX. In vitro, LVFX was precipitated by 76.1% in the presence of a 10-times higher concentration of aluminium chloride (Al3+), but LVFX-CLX was not. LVFX-CLX was rapidly hydrolyzed enzymatically by rat plasma, intestinal mucosal and liver homogenates at 37 °C, but not by pancreatic enzymes and luminal fluid. The minimum inhibitory concentration values of LVFX-CLX against S. aureus, E. coli and P. aeruginosa were far higher than that of LVFX. In rats, area under the plasma concentration-time curve from zero to 4 h (AUC0-4h) of LVFX after oral administration of LVFX-CLX was 1.34-fold higher than that after LVFX, though it did not reach significance level. Co-administration of Al3+ with LVFX and LVFX-CLX in rats decreased AUC0-4h of plasma LVFX by 75% and 60%, respectively, however, the AUC0-4h of plasma LVFX after co-administration of LVFX-CLX and Al3+ was 2.2-times higher than that after co-administration of LVFX and Al3+. These results suggested that the use of LVFX-CLX may reduce the modulation of intestinal microflora caused by LVFX and the suppressive effect of Al3+ on intestinal absorption of LVFX.Objective To review clinical studies on the nocebo effect. PubMed was searched for relevant clinical studies as well as studies on the relationship between the nocebo effect and genes. Data sources A total of 35 clinical studies on the nocebo effect and one study on its relationship with genes were selected for review. All were conducted outside Japan. Results and conclusion An increasing number of clinical studies on the nocebo effect are being published. The 36 studies selected for review were grouped into the following five categories (1) studies of how differences in participant characteristics such as personality affect susceptibility to the nocebo effect, (2) studies of how differences in provision of information about side effects affect susceptibility to the nocebo effect, (3) studies of how nocebo conditioning affects susceptibility to the nocebo effect, (4) studies of nocebo response mechanisms, and (5) studies of the nocebo effect and genetic polymorphisms. The first four categories comprised 5, 19, 8, and 3 studies, respectively, and the fifth comprised 1 study.