Glycyrrhiza Glabra Extract Modulates Type 1 T Helper (TH1) and Regulatory T Cell-Related Immune Responses in an Animal Model of Breast Cancer.

Background: It is well-known that TH1 and Treg cells exert anti- and pro-tumorigenic activity, respectively. Thus, TH1 cell suppression together with Treg cell hyperactivation contribute to tumor development. Glycyrrhiza glabra (G. glabra) has various immunomodulatory and anti-tumorigenic properties. Objective: To explore the impacts of G. glabra extract on different parameters related to TH1 and Treg cells using a breast cancer (BC) model. Methods: Four groups of Balb/C mice bearing 4T1 cell-induced BC were treated intraperitoneally with either saline or G. glabra extract at dosages of 50, 100 and 150 mg/kg (G. glabra-50, G. glabra-100, and G. glabra-150, respectively). After sacrificing animals on day 26, the frequency of splenic TH1 and Treg cells, the levels of serum IFN-γ, TGF-ß, and IL-12, and intra-tumoral expressions of granzyme-B, T-bet, and FOXP3 were assessed. Results: Compared to untreated tumor control (UTC) group, treatment with G. glabra-50, G. glabra-100, or G. glabra-150 increased the survival rate, percentage of TH1 cells, and T-bet expression. Conversely, they reduced the percentage of Treg cells, and serum TGF-ß levels. In comparison to the UTC group, treatment with G. glabra-50 and G. glabra-150 increased the serum IL-12 levels. Treatment with G. glabra-100 and G. glabra-150 boosted granzyme-B expression. Treatment with G. glabra-150 elevated IFN-γ levels, while treatment with G. glabra-50 decreased the FOXP3 expression. IL-12 levels were higher in mice treated with G. glabra-150 compared to those treated with G. glabra-100. Conclusion: Treatment of mice with BC using G. glabra extract improved survival rate, reduced tumor growth, and modulated T cell-mediated immune responses.

Leptin/lipopolysaccharide-treated dendritic cell vaccine improved cellular immune responses in an animal model of breast cancer.

PURPOSE: In dendritic cells (DCs), leptin as an immune-regulating hormone, increases the IL-12 generation whereas it reduces the IL-10 production, thus contributing to TH1 cell differentiation. Using a murine model of breast cancer (BC), we evaluated the impacts of the Leptin and/or lipopolysaccharide (LPS)-treated DC vaccine on various T-cell-related immunological markers. MATERIALS AND METHODS: Tumors were established in mice by subcutaneously injecting 7 × 105 4T1 cells into the right flank. Mice received the DC vaccines pretreated with Leptin, LPS, and both Leptin/LPS, on days 12 and 19 following tumor induction. The animals were sacrificed on day 26 and after that the frequency of the splenic cytotoxic T lymphocytes (CTLs) and TH1 cells; interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor growth factor beta (TGF-ß) generation by tumor lysate-stimulated spleen cells, and the mRNA expression of T-bet, FOXP3 and Granzyme B in the tumors were measured with flow cytometry, ELISA and real-time PCR methods, respectively. RESULTS: Leptin/LPS-treated mDC group was more efficient in blunting tumor growth (p = .0002), increasing survival rate (p = .001), and preventing metastasis in comparison with the untreated tumor-bearing mice (UT-control). In comparison to the UT-control group, treatment with Leptin/LPS-treated mDC also significantly increased the splenic frequencies of CTLs (p < .001) and TH1 cells (p < .01); promoted the production of IFN-γ (p < .0001) and IL-12 (p < .001) by splenocytes; enhanced the T-bet (p < .05) and Granzyme B (p < .001) expression, whereas decreased the TGF-ß and FOXP3 expression (p < .05). CONCLUSION: Compared to the Leptin-treated mDC and LPS-treated mDC vaccines, the Leptin/LPS-treated mDC vaccine was more effective in inhibiting BC development and boosting immune responses against tumor.

Vaccination with celecoxib-treated dendritic cells improved cellular immune responses in an animal breast cancer model.

PURPOSE: Prostaglandin E2 (PGE2), a product of cyclooxygenase (COX) pathway of arachidonic acid, exerts inhibitory impacts on dendritic cell (DC) activity to repress anti-tumor immune responses. Therefore, targeting COX during DC vaccine generation may enhance DC-mediated antitumor responses. We aimed to investigate the impacts of DC vaccine treated with celecoxib (CXB), a selective COX2 inhibitor, on some T cell-related parameters. MATERIALS AND METHODS: Breast cancer (BC) was induced in BALB/c mice, and then they received DC vaccine treated with lipopolysaccharide (LPS-mDCs), LPS with a 5 â€‹µM dose of CXB (LPS/CXB5-mDCs) and LPS with a 10 â€‹µM dose of CXB (LPS/CXB10-mDCs). The frequency of splenic Th1 and Treg cells and amounts of IFN-γ, IL-12 and TGF-ß production by splenocytes, as well as, the expression of Granzyme-B, T-bet and FOXP3 in tumors were determined using flow cytometry, ELISA, and real-time PCR, respectively. RESULTS: Compared with untreated tumor group (T-control), treatment with LPS/CXB5-mDCs and LPS/CXB10-mDCs decreased tumor growth (P â€‹= â€‹0.009 and P â€‹< â€‹0.0001), escalated survival rate (P â€‹= â€‹0.002), increased the frequency of splenic Th1 cells (P â€‹= â€‹0.0872, and P â€‹= â€‹0.0155), increased the IFN-γ (P â€‹= â€‹0.0003 and P â€‹= â€‹0.0061) and IL-12 (P â€‹= â€‹0.001 and P â€‹= â€‹0.0009) production by splenocytes, upregulated T-bet (P â€‹= â€‹0.062 and P â€‹< â€‹0.0001) and Granzyme-B (P â€‹= â€‹0.0448 and P â€‹= â€‹0.4485), whereas decreased the number of Treg cells (P â€‹= â€‹0.0014, and P â€‹= â€‹0.0219), reduced the amounts of TGF-ß production by splenocytes (P â€‹= â€‹0.0535 and P â€‹= â€‹0.0169), and reduced the expression of FOXP3 (P â€‹= â€‹0.0006 and P â€‹= â€‹0.0057) in comparison with T-control group. CONCLUSIONS: Our findings show that LPS/CXB-treated DC vaccine potently modulated antitumor immune responses in a mouse BC model.

The assessment of affected factors on cytomegalovirus and rubella virus prevalence in females in Hamadan, Iran.

Cytomegalovirus (CMV) and rubella are considered as dangerous viral infections to the fetus. The findings of this research can clear the possible progress made thus far toward prevention in this part of the country. The data of all referees to genetic center of Shahid Beheshti Hospital in Hamadan, including the rubella and CMV tests were recorded in questionnaires and analyzed by logistic regression models. Univariate and multivariate logistic regression were utilized to assess the affected factors on CMV and Rubella separately. STATA and SPSS16 statistical software were used with setting P-value as 0.05. Logistic regression analysis indicates a statistically significant relationship between CMV IgM and on occupation (P=0.045), pregnancy (P=0.03) and years of referring the patients (P<0.001). The results of multivariate logistic regression analysis showed that job was significantly affected on the CMV infection [OR (95% C.I) = 1.71(1.1-2.83)]. Univariate logistic regression showed that age (P=0.001), the residential area (P=0.03), pregnancy (P=0.03), the marital status (P=0.022) and years of referring the patients (P<0.0001) has a significant effect on rubella IgG. However, multivariate logistic regression analysis also showed that residential status (OR=1.77) and age (OR=0.63) were significantly affected on the Rubella infection. The high level of IgG positivity against rubella in females may highlight the considerable impact of increasing public vaccination in this part of Iran. Also, the current data demonstrating frequency of primary infections with CMV in females which support the conclusion that regular prenatal screening tests is justified.

The Study of Genetic Relationship Among Third Generation Cephalosporin-resistant Salmonella enterica Strains by ERIC-PCR.

BACKGROUND AND OBJECTIVES: Salmonella is an important food-borne pathogen responsible for disease in humans and animals. The aim of this study was to investigate the genetic relationship among third generation cephalosporin-resistant Salmonella enterica strains by Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR. METHODS: The study included all Salmonella isolates obtained from clinical cases in a pediatric hospital in Tehran, Iran during 2006 to 2009. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute. The genetic relationship between third generation cephalosporins-resistant Salmonella enterica strains was determined using ERIC-PCR. RESULTS: Of 136 Salmonella enterica isolates recovered from pediatric patients, six isolates including four Salmonella enterica serotype Infantis and two Salmonella enterica serotype Enteritidis showed an extended-spectrum cephalosporins resistant phenotype. ERIC-PCR differentiated Salmonella enterica serotypes Infantis and Enteritidis into 2 distinct clusters arbitrarily named as E1 and E2. Profile E1 was found in two Salmonella enterica serotype Enteritidis isolates, and profile E2 was found in four Salmonella enterica serotype Infantis isolates. CONCLUSION: Extended-spectrum cephalosporins resistant Salmonella could be attributed to a few predominant serotypes including Enteritidis and Infantis in this study. Genetic analysis using ERIC-PCR showed that closely related clones are responsible for the occurrence of extended-spectrum cephalosporins resistant Salmonella infection in Tehran.