ABSTRACT
Ginsenoside Rh2 has been shown to have an anti-tumor effect on a wide range of cancers. A previous study has shown that ginsenoside Rh2 can inhibit the proliferation of the human lung adenocarcinoma A549 cell line in a dose-dependent manner by activating caspase-8/3 activity to promote apoptosis. However, the association of the JNK signaling pathways and transcription factors with ginsenoside Rh2 in the suppression of non-small cell lung cancer has not yet been reported. In this study, we found that ginsenoside Rh2 can activate the JNK/MAPKs signaling pathway and increase the phosphorylation and transcriptional activity of the transcription factors AP-1 and ATF2. Ginsenoside Rh2 also reduced the expression of transcription factors E2F1 and c-Myc. Furthermore, ginsenoside Rh2 affected the expression levels of cyclin D1 and the CDK4 protein, which are key regulatory factors of the G1/S cyclin-dependent kinase. The anti-proliferative and induced apoptotic effects of ginsenoside Rh2 on A549 cell provide evidence to support the application of traditional Chinese medicine to lung cancer treatment.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Ginsenosides/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , MAP Kinase Signaling System/drug effects , A549 Cells , Activating Transcription Factor 2/metabolism , Adenocarcinoma/enzymology , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Apoptosis/drug effects , Caspase 8/metabolism , Cell Growth Processes/drug effects , Cell Proliferation/drug effects , G1 Phase Cell Cycle Checkpoints/drug effects , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Transcription Factor AP-1/metabolismABSTRACT
Nontuberculous mycobacteria are ubiquitous in outside environment and animals. As for nontuberculous mycobacteria infection, there is only limited information in humans regarding infection and the subsequent immune response, especially for Mycobacterium neoaurum. Here, haematoxylin-eosin and Ziehl-Neelsen staining were used to observe pathological changes and detect acid-fast bacilli in organ samples in mouse model. Flow cytometry and quantitative real-time polymerase chain reaction were performed to analyze the contribution of Th1, Th17 and Tregs to the host immune response. M. neoaurum caused chronic infection in mice, resulting in infiltrates with large aggregates of inflammatory cells, especially macrophages, in lung tissues. Our results indicated that 72% of CD4+ T cells appeared in the early days of infection, which was followed by a decrease to 47% by day 32, and then a rise to 76% by day 56. Moreover, we found higher frequency of IFN-g-producing CD4+ T cells and elevated mRNA expression of the transcription factor T-bet in the lungs; however, we observed lower mRNA expression of the transcription factor RORgt and lower frequency of IL-17-producing CD4+ T cells. A transient relative decrease in the number of Treg cells was observed in the lungs; however, the number of Tregs did not change significantly between the first and last day following infection. Thus, M. neoaurum causes chronic infection in C57BL/6 mice, with Th1, Th17, and Tregs playing a prominent role in the host response. The present study may lay the basis for further studies on the mechanisms underlying infection with nontuberculous mycobacteria.
Subject(s)
Host-Pathogen Interactions/immunology , Mycobacterium Infections/immunology , Mycobacterium Infections/microbiology , Mycobacterium/immunology , T-Lymphocytes, Regulatory/immunology , Th1 Cells/immunology , Th17 Cells/immunology , Adaptive Immunity , Animals , Bacterial Load/immunology , Colony Count, Microbial , Female , Forkhead Transcription Factors/metabolism , Gene Expression Regulation , Lung/metabolism , Lung/microbiology , Lung/pathology , Lymphocyte Subsets/immunology , Mice, Inbred C57BL , Mycobacterium/growth & development , Mycobacterium Infections/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
We examined the influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. Sixty rats with spinal cord injury were divided into an experimental group and a control group and given neural stem cells or an equivalent amount of phosphate-buffered saline by intravenous transplantation, respectively. Basso, Beattie, and Bresnahan (BBB) motor function assessment was performed in rats at different times after transplantation, and von Willebrand factor (vWF) immunofluorescence and Western blot analysis of vascular endothelial growth factor (VEGF) protein were also performed. The BBB scores of rats in the 2 groups were both zero before transplantation. The BBB score gradually increased over time. The BBB score of the experimental group showed no significant difference compared with that of the control group (P > 0.05) 7 days after transplantation. The BBB score of the experimental group was significantly improved compared with that of the control group 14 days after transplantation (P < 0.05). vWF-positive cells and VEGF protein expression in the experimental group were significantly increased compared with those in the control group 7 and 14 days after transplantation, respectively (P < 0.05). Neural stem cell transplantation may promote angiogenesis by inducing VEGF expression as well as improve functional recovery of limb movements.
Subject(s)
Neovascularization, Physiologic , Neural Stem Cells/cytology , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/therapy , Stem Cell Transplantation , Animals , Cell Culture Techniques , Disease Models, Animal , Immunohistochemistry , Male , Neovascularization, Physiologic/genetics , Rats , Recovery of Function , Spinal Cord Injuries/genetics , Time Factors , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , von Willebrand Factor/genetics , von Willebrand Factor/metabolismABSTRACT
The Japanese eel population has dramatically declined since the 1970s. In order to conserve this species, the background genetic structure affecting these populations should be well documented. Previous genetic studies of this species have produced seemingly conflicting results, ranging from no detectable heterogeneity to small, but statistically significant variance. This study investigates the population structure of Japanese glass eels collected from 10 localities in China in 2009 using a mitochondrial DNA (mtDNA) control region and 19 polymorphic microsatellite loci. Results revealed evidence of low genetic differentiation using both mtDNA (FST = 0.001, P = 0.291) and microsatellite data (FST = 0.003, P = 0.008). Pairwise F-statistic values generated from mtDNA and microsatellite DNA were similar, showing little evidence of significant genetic differentiation. The minimum spanning haplotype network constructed using mtDNA control regions produced no clear phylogeographic structure. The Mantel test revealed no significant correlation with distances for both mtDNA and microsatellite DNA. Therefore, our results suggest a panmictic population of Japanese eels in China, which should be conserved as a single management unit.
Subject(s)
Eels/genetics , Endangered Species , Microsatellite Repeats/genetics , Population/genetics , Animals , China , DNA, Mitochondrial/genetics , Eels/growth & development , Genetics, Population , PhylogenyABSTRACT
As part of the WHO Network for HIV Isolation and Characterization, we PCR amplified, cloned, and sequenced gp120 and gp160 genes from 12 HIV-1 isolates collected in four WHO-sponsored vaccine evaluation sites (Brazil, Rwanda, Thailand, Uganda). Envelope clones were derived from PBMC-grown isolates obtained from asymptomatic individuals within 2 years of seroconversion. Analysis of their deduced amino acid sequences identified all but one to contain an uninterrupted open reading frame. Transient expression and biological characterization of selected gp160 constructs identified six clones to encode full length and functional envelope glycoproteins. Phylogenetic analysis of their nucleotide sequences revealed that they represent HIV-1 subtypes A, B, C, and E. Since current knowledge of HIV-1 envelope immunobiology is almost exclusively derived from subtype B viruses, these reagents should facilitate future envelope structure, function and antigenicity studies on a broader spectrum of viruses. This should assist in the design and evaluation of effective vaccines against HIV-1.