Induced Susceptibility of Host Is Associated with an Impaired Antioxidant System Following Infection with Cryptosporidium parvum in Se-Deficient Mice

BACKGROUND: Susceptibility or resistance to infection with Cryptosporidium parvum (C.parvum) correlates with Selenium (Se) deficiency in response to infection. Both adult Se-adequate and Se-deficient mouse models of cryptosporidiosis were used to study the cell-mediated immune response during the course of C. parvum infection. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples from mouse models were used for Se status. The concentration of MDA, SOD, GPx and CAT in blood has revealed that lower Se level exist in Se-deficient mice. Mesenteric lymph node (MLN) lymphocytes from both mouse models were proliferated after ex vivo re-stimulation with C. parvum sporozoite antigen. The study of the cytokine profiles from the supernatant of proliferated MLN cells revealed that Se-adequate mice produced higher levels of Th1 (IFN-gamma and IL-2) and moderate amounts of Th2 (IL-4) cytokines throughout the course of infection. Whereas, MLN cells from Se-deficient mice produced lower levels of IFN-gamma, IL-2 and IL-4 cytokines. The counts of total white cell and CD3, CD4, CD8 cell in Se-adequate were higher than that in Se-deficient mice. SIGNIFICANCE: These results suggest that Cell immunity is affected by Se status after infection with C. parvum from kinetic changes of different white cells and cytokine. In conclusion, induced susceptibility of host is associated with an impaired antioxidant system following infection with C. parvum in C57BL/6 Selenium deficient mice

CCL3 and CCL20-recruited dendritic cells modified by melanoma antigen gene-1 induce anti-tumor immunity against gastric cancer ex vivo and in vivo

<p>Abstract</p> <p>Background</p> <p>To investigate whether dendritic cell (DC) precursors, recruited by injection of <b>chemokine ligand 3 (CCL3) and CCL20</b>, induce anti-tumor immunity against gastric cancer induced by a DC vaccine expressing melanoma antigen gene-1 (MAGE-1) ex vivo and in vivo.</p> <p>Methods</p> <p>B6 mice were injected with CCL3 and CCL20 via the tail vein. Freshly isolated F4/80^-B220^-CD11c⁺cells cultured with cytokines were analyzed by phenotype analysis and mixed lymphocyte reaction (MLR). For adenoviral (Ad)-mediated gene transduction, cultured F4/80^-B220^-CD11c⁺cells were incubated with Ad-MAGE-1. Vaccination of stimulated DC induced T lymphocytes. The killing effect of these T cells against gastric carcinoma cells was assayed by MTT. INF-γ production was determined with an INF-γ ELISA kit. In the solid tumor and metastases model, DC-based vaccines were used for immunization after challenge with MFC cells. <b>Tumor size, survival of mice, and number of pulmonary metastatic foci were used to assess the therapeutic effect of DC vaccines</b>.</p> <p>Results</p> <p>F4/80^-B220^-CD11c⁺cell numbers increased after <b>CCL3 and CCL20 </b>injection. Freshly isolated F4/80^-B220^-CD11c⁺cells cultured with cytokines were phenotyically identical to typical DC and gained the capacity to stimulate allogeneic T cells. These DCs were transduced with Ad-MAGE-1, which were prepared for DC vaccines expressing tumor antigen. T lymphocytes stimulated by DCs transduced with Ad-MAGE-1 exhibited specific killing effects on gastric carcinoma cells and produced high levels of INF-γ ex vivo. In vivo, tumor sizes of the experimental group were much smaller than both the positive control group and the negative control groups (<it>P </it>< 0.05). Kaplan-Meier survival curves showed that survival of the experimental group mice was significantly longer than the control groups (<it>P </it>< 0.05). In addition, MAGE-1-transduced DCs were also a therapeutic benefit on an established metastatic tumor, resulting in a tremendous decrease in the number of pulmonary metastatic foci.</p> <p>Conclusions</p> <p><b>CCL3 and CCL20</b>-recruited DCs modified by adenovirus-trasnsduced, tumor-associated antigen, MAGE-1, can stimulate anti-tumor immunity specific to gastric cancer ex vivo and in vivo. This system may prove to be an efficient strategy for anti-tumor immunotherapy.</p

Clinicopathologic Significance of HIF-1α, CXCR4, and VEGF Expression in Colon Cancer

We investigated the clinicopathologic significance of HIF-1, CXCR4, and VEGF expression using immumohistochemistry in human colon cancer. HIF-1, CXCR4, and VEGF high expression levels were correlated positively with TNM stage, lymph node involvement, and distant metastasis Furthermore, we found that combined high expression of any two of the three molecules (P = .028 for HIF-1/CXCR4, P = .007 for HIF-1/VEGF, and P = .004 for CXCR4/VEGF) had stronger correlation with lymph node metastasis than did each alone. However, a relationship with distant metastasis is seen only with the combinations CXCR4/VEGF (P = .069 for HIF-1/CXCR4, P = .062 for HIF-1/VEGF, and P = .035 for CXCR4/VEGF) as compared with those of single molecule high expression alone. Combined expression of all three molecules strongly correlates with lymph node metastasis and distant metastasis. The mRNA expression of HIF-1, CXCR4, and VEGF were quantified by real-time PCR in different colon cancer tissue samples, the experiment results shown that fresh colon tissue samples significantly overexpressed CXCR4 and VEGF mRNA compared with negative control. Therefore, the disease-free survival of all patients after curative resection can be considered in association with all three markers expression

Parasite Species Associated With Wild Plateau Pika (Ochotona Curzoniae) In Southeastern Qinghai Province, China

A survey was conducted to determine the prevalence and seasonal abundance of egg, larval, and adult stages of helminths; oocyts of protozoans; and ectoparasites of plateau pikas (Ochotona curzoniae) in seven areas of southeastern Qinghai Province, China, during August 2006 and May 2007. Fecal samples collected from 430 plateau pikas were examined by the modified McMaster technique, which revealed that 83% of the samples contained eggs from two or more helminth species. Mean fecal egg counts were generally moderate and showed the same trend irrespective of the age or sex of the pikas. The prevalence and counts of cestode eggs showed strong seasonal relationships that corresponded with the rainfall pattern in the study area during the study period. Of the 430 plateau pika examined at necropsy, 89% contained adult nematode or cestode species, but none of these contained adult trematode species or protozoans. Overall, six genera of adult nematodes including Oesophagostomum sp., Cephaluris coloradensis, Eugenuris schumakowiescsi, Haemonchus sp., Trichuris sp., and Chbertiinae sp.; three genera of adult cestodes including Schizorchis sp., Ochotonae sp., and Hymenolepis nana; three ectoparasite species including Hypoderma curzonial, Pulex sp., and Ixodes ovatus; and one proscolex stage of a cestode, Echinococcus multilocularis or Echinococcus shiquicus, were encountered during the study. Other genera examined occurred in low numbers, which did not allow any meaningful comparisons. Overall, results suggest that four parasite species, Hypoderma curzonial, Pulex sp., Ixodes ovatus Neumann, and Cephaluris coloradensis, may be regulating factors in controlling future numbers of plateau pika in this study area. These data provide evidence of a natural biologic control mechanism of plateau pika on grassland habitats, and may be of use for identifying the mechanism of transmission of parasites between plateau pika, livestock, and humans

Inhibition of ERK activation enhances the repair of double-stranded breaks via non-homologous end joining by increasing DNA-PKcs activation

AbstractNon-homologous end joining (NHEJ) is one of the major pathways that repairs double-stranded DNA breaks (DSBs). Activation of DNA-PK is required for NHEJ. However, the mechanism leading to DNA-PKcs activation remains incompletely understood. We provide evidence here that the MEK–ERK pathway plays a role in DNA-PKcs-mediated NHEJ. In comparison to the vehicle control (DMSO), etoposide (ETOP)-induced DSBs in MCF7 cells were more rapidly repaired in the presence of U0126, a specific MEK inhibitor, based on the reduction of γH2AX and tail moments. Additionally, U0126 increased reactivation of luciferase activity, which resulted from the repair of restriction enzyme-cleaved DSBs. Furthermore, while inhibition of ERK activation using the dominant-negative MEK1K97M accelerated the repair of DSBs, enforcing ERK activation with the constitutively active MEK1Q56P reduced DSB repair. In line with MEK activating ERK1 and ERK2 kinases, knockdown of either ERK1 or ERK2 increased DSB repair. Consistent with the activation of DNA-PKcs being required for NHEJ, we demonstrated that inhibition of ERK activation using U0126, MEK1K97M, and knockdown of ERK1 or ERK2 enhanced ETOP-induced activation of DNA-PKcs. Conversely, enforcing ERK activation by MEK1Q56P reduced ETOP-initiated DNA-PKcs activation. Taken together, we demonstrate that ERK reduces NHEJ-mediated repair of DSBs via attenuation of DNA-PKcs activation

IQGAP2, A candidate tumour suppressor of prostate tumorigenesis

AbstractLoss of IQGAP2 contributes to the tumorigenesis of hepatocellular carcinoma and gastric cancer. However, whether IQGAP2 also suppresses prostate tumorigenesis remains unclear. We report here that IQGAP2 is a candidate tumour suppressor of prostate cancer (PC). Elevated IQGAP2 was detected in prostatic intraepithelial neoplasia (PIN), early stages of PCs (Gleason score ≤3), and androgen-dependent LNCaP PC cells. However, IQGAP2 was expressed at substantially reduced levels not only in prostate glands and non-tumorigenic BPH-1 prostate epithelial cells but also in advanced (Gleason score 4 or 5) and androgen-independent PCs. Furthermore, xenograft tumours that were derived from stem-like DU145 cells displayed advanced features and lower levels of IQGAP2 in comparison to xenograft tumours that were produced from non stem-like DU145 cells. Collectively, these results suggest that IQGAP2 functions in the surveillance of prostate tumorigenesis. Consistent with this concept, ectopic IQGAP2 reduced the proliferation of DU145, PC3, and 293T cells as well as the invasion ability of DU145 cells. While ectopic IQGAP2 up-regulated E-cadherin in DU145 and PC3 cells, knockdown of IQGAP2 reduced E-cadherin expression. In primary PC and DU145 cells-derived xenograft tumours, the majority of tumours with high levels of IQGAP2 were strongly-positive for E-cadherin. Therefore, IQGAP2 may suppress PC tumorigenesis, at least in part, by up-regulation of E-cadherin. Mechanistically, overexpression of IQGAP2 significantly reduced AKT activation in DU145 cells and inhibition of AKT activation upregulated E-cadherin, suggesting that IQGAP2 increases E-cadherin expression by inhibiting AKT activation. Taken together, we demonstrate here that IQGAP2 is a candidate tumour suppressor of PC

Neutrophil-to-lymphocyte ratio and incident end-stage renal disease in Chinese patients with chronic kidney disease: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE)

Abstract Background Chronic kidney disease (CKD) leads to end-stage renal failure and cardiovascular events. An attribute to these progressions is abnormalities in inflammation, which can be evaluated using the neutrophil-to-lymphocyte ratio (NLR). We aimed to investigate the association of NLR with the progression of end stage of renal disease (ESRD), cardiovascular disease (CVD) and all-cause mortality in Chinese patients with stages 1–4 CKD. Methods Patients with stages 1–4 CKD (18–74 years of age) were recruited at 39 centers in 28 cities across 22 provinces in China since 2011. A total of 938 patients with complete NLR and other relevant clinical variables were included in the current analysis. Cox regression analysis was used to estimate the association between NLR and the outcomes including ESRD, CVD events or all-cause mortality. Results Baseline NLR was related to age, hypertension, serum triglycerides, total serum cholesterol, CVD history, urine albumin to creatinine ratio (ACR), chronic kidney disease-mineral and bone disorder (CKD-MBD), hyperlipidemia rate, diabetes, and estimated glomerular filtration rate (eGFR). The study duration was 4.55 years (IQR 3.52–5.28). Cox regression analysis revealed an association of NLR and the risk of ESRD only in patients with stage 4 CKD. We did not observe any significant associations between abnormal NLR and the risk of either CVD or all-cause mortality in CKD patients in general and CKD patients grouped according to the disease stages in particular. Conclusion Our results suggest that NLR is associated with the risk of ESRD in Chinese patients with stage 4 CKD. NLR can be used in risk assessment for ESRD among patients with advanced CKD; this application is appealing considering NLR being a routine test. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 )https://deepblue.lib.umich.edu/bitstream/2027.42/148285/1/12967_2019_Article_1808.pd

Aspect of Clusters Correlation at Light Nuclei Excited State

The correlation of $\alpha\alpha$ was probed via measuring the transverse momentum $p_{T}$ and width $\delta p_{T}$ of one $\alpha$, for the first time, which represents the spatial and dynamical essentialities of the initial coupling state in $^{8}$Be nucleus. The weighted interaction vertex of 3$\alpha$ reflected by the magnitudes of their relative momentums and relative emission angles proves the isosceles triangle configuration for 3$\alpha$ at the high excited energy analogous Hoyle states.Comment: 8 pages, 9 figure

Variation of Tensor Force due to Nuclear Medium Effect

The enhancement of $J^{\pi}(T)$=3$^{+}$(0) state with isospin $T=0$ excited by the tensor force in the free $^{6}$Li nucleus has been observed, for the first time, relative to a shrinkable excitation in the $^{6}$Li cluster component inside its host nucleus. Comparatively, the excitation of $J^{\pi}(T)$=0$^{+}$(1) state with isospin $T=1$ for these two $^{6}$Li formations take on an approximately equal excitation strength. The mechanism of such tensor force effect was proposed due to the intensive nuclear medium role on isospin $T$=0 state.Comment: 6 pages, 4 figure

Multi-alpha Boson Gas state in Fusion Evaporation Reaction and Three-body Force

The experimental evidence for the $\alpha$ Boson gas state in the $^{11}$C+$^{12}$C$\rightarrow$$^{23}$Mg$^{\ast}$ fusion evaporation reaction is presented. By measuring the $\alpha$ emission spectrum with multiplicity 2 and 3, we provide insight into the existence of a three-body force among $\alpha$ particles. The observed spectrum exhibited distinct tails corresponding to $\alpha$ particles emitted in pairs and triplets consistent well with the model-calculations of AV18-UX and chiral effective field theory of NV2-3-la*, indicating the formation of $\alpha$ clusters with three-body force in the Boson gas state.Comment: 7 pages, 6 figure