Different inflammatory mechanisms in lungs of severe and mild asthma: crosstalk of NF-kappa-B, TGFâ1, Bax, Bcl-2, IL-4 and IgE

Objective: To examine differences in the apoptotic, inflammatory, allergic and immunological features in the lungs of adults with asthma. Material and methods: Thirty‐six patients with mild asthma (MA), 16 with severe asthma (SA) and 20 healthy volunteers (HVs) were enrolled. Bronchoalveolar lavage fluid (BALF) was processed into cell‐free fluid for enzyme‐linked immunosorbent assay detecting soluble TGFβ1, IL‐4 and IgE and BALF lymphocytes for immunocytochemical staining of cellular Bax, Bcl‐2 and nuclear factor‐Kappa‐B (NFκB). Results: Cellular NFκB expression was higher in SA than in MA and HVs, while extracellular TGFβ1 was high in both the SA and MA groups but low in the HVs. Bcl‐2/Bax ratio was higher in SA than in MA and in MA than in HV groups and correlated significantly with NFκB level. Interestingly, the levels of IgE and, to a lesser extent, IL‐4 were higher in MA than in SA and both were much higher than in HVs, and were inversely correlated with NFκB level in the SA group and with TGFβ1 level in the MA group. Conclusions: NFκB has a central role in the perpetuation of persistent inflammation in SA and might induce apoptosis via Bcl‐2. The SA group appears not associated much with allergen‐based IgE and IL‐4 reactions as efficiently as in MA. This was supported by the lower levels of IgE and IL‐4 in SA compared to MA. TGFβ1 appears to be associated with asthma pathogenesis, especially allergen‐based MA

Tumor markers of bladder cancer : the schistosomal bladder tumors versus non-schistosomal bladder tumors.

Background: The aim of this study is to comparatively elucidate the underlying molecular pathways and clinicopathological criteria in schistosomal bladder tumor (SBT) versus non-schistosomal bladder tumor (NSBT). Methods: This study explored the role of p53, p16, bcl-2, ki-67, c-myc, Rb and EGFR, by using Immunohistochemistry assay, in 45 SBT and 39 NSBT patients in comparison with 16 schistosomal chronic cystitis (SC), 28 non-schistosomal chronic cystitis (NSC), and 20 normal control (CTL) subjects. The studied markers in SBT and NSBT were correlated with different clinicopathological criteria namely, tumor histopathology, grading, invasiveness, stage, and presentation of the disease. Results: SBT was associated with high grade invasive squamous cell carcinoma (SCC) while NSBT was associated with lower grade less invasive transitional cell carcinoma (TCC). The expression of p53, bcl-2, c-myc, and EGFR was higher in SBT than in NSBT while Rb was higher in NSBT than in SBT. However, p16 and ki-67 were not different between SBT and NSBT. The profile of molecular markers in SC was similar to NSC except for EGFR which was higher in SC than in NSC. Both SC and NSC showed higher level of p53, bcl-2, ki-67, and EGFR than in CTL group while p16, Rb, and c-myc were not different. p53 was associated with high grade SCC in both SBT and NSBT. Bcl-2 was associated with high grade invasive tumors in SBT and NSBT. P16 was associated with low grade, late stage, and recurrent SBT and high grade, invasive, late stage, and recurrent NSBT. Rb was associated with SCC in SBT, invasive tumors in NSBT, and late stage and recurrent presentation in both SBT and NSBT. C-myc was associated with high grade, invasive, and late stage SBT and SCC, high grade, invasive, and late stage NSBT. EGFR was associated with invasive SCC in SBT and invasive, high grade, and late stage TCC in NSBT. ki-67 was associated with invasive SBT and high grade late stage NSBT. Conclusion: SBT and NSBT showed distinct molecular profile of tumor development and progression which can be taken into consideration in fine adjusting the anti-cancer therapy for SBT and NSBT

Novel Epstein-Barr virus immunoglobulin G–based approach for the specific detection of nasopharyngeal carcinoma.

Purpose This study was designed to find a reliable Epstein-Barr virus (EBV) immunoglobulin (Ig) G–based diagnostic/screening test for nasopharyngeal carcinoma (NPC) able to demarcate between the NPC-related seropositivity of EBV IgG antibodies and that of other head and neck cancer (HNCA) and control groups. The NPC-associated immunosuppression affects EBV IgA much more than IgG, leading to inconsistent detection of NPC using EBV IgA antibodies. Materials and methods One hundred twenty-two HNCA patients, 42 NPC, 66 laryngeal carcinoma, and 14 hypopharyngeal carcinoma and 3 groups of 100 control subjects were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was used to find a specific cutoff value for the NPC-related seropositivity of EBV IgG antibodies. Results NPC group showed higher serum level of EBV IgG antibodies than control and other HNCA groups (P .05). The new cutoff value, mean + 2 SDs of the seropositives group of control subjects who had already been grouped by the traditional cutoff value, proved successful. It succeeded to demarcate between the NPC-related EBV IgG seropositivity and that issued from the persistent, latent, or reactivated EBV infection in the population (P < .05). The sensitivity/specificity of NPC detection by the new cutoff-based ELISA kit, 76.19% and 86%, was close or higher than that of EBV IgA antibodies. Conclusion EBV IgG-based ELISA could be used for the diagnosis of NPC using a new cutoff threshold that excludes the population baseline of EBV IgG seropositivity

Novel in-vitro antimicrobial activity of Vigna radiata (L.)R. Wilczek against highly resistant bacterial and fungal pthogens.

The ever rising resistant bacteria and fungi resulted in finding novel antimicrobial sources and agents. Studies confirmed that mung beans have increased phenolic compounds and enhanced defenses during germination. We hypothesized that antimicrobial activities might be found in sprouts of mung beans (MBS), or Vigna radiata (L.) R. Wilczek. The screening method was conducted using disc diffusion assay against 12 gram negative and positive bacteria, including multiple drug resistant (MDR) bacteria and 12 fungi. It was followed by the evaluation of the minimum inhibitory concentration and the minimum bactericidal concentration or the minimum fungicidal concentration. The screening results revealed potential antibacterial and antifungal activities by MBS extract against 11 out of 12 bacteria and 2 out of 10 fungi including remarkable antimicrobial activity against highly infectious MDR bugs such as Methicilline-resistant Staphylococcus aureus, MDR Escherichia coli O157:H7, MDR Pseudomonas aeruginosa, Klebsiella pneumoniae, S. aureus, and Salmonella Typhimurium as well as against human fungal pathogens, Trichophyton rubrum and Trichoderma harzianum. The potential antimicrobial activity of MBS reflects effective quality and quantity of polyphenolic compounds present after bean germination. This unprecedented study showed that MBS extract is a potential source for novel antimicrobials that are inexpensive and readily available at a large scale for pharmaceutical companies

A review : cancer research of natural products in Asia.

With the increasing level of the carcinogenic and mutagenic substances in the environment, the research to explore new anticancer compounds has become crucial day after day. Although, many chemical anticancer agents are available, the wide spectrum side effects and emergence of chemotherapy resistant cancer cells among patients have made cancer research and discovery of new anticancer agents from natural products particularly medicinal plants pivotal. This review highlights the cancer research led to new natural anticancer agents discovered by Asian scientists in the period from 2000 to 2008. This review focuses also on the evidence based scientific research that proved the importance of dietary habits particularly the vegetarian diet as a potent factor in reducing the risk of carcinogenesis. Many components isolated from plants have been approved to be potent anticancer agents. The plant-derived polyphenolic compounds are promising nutraceuticals for control of various disorders and cancer. These compounds may be the future developing anticancer drugs with no side effect and low cost for people all around the world. The much lower risk of colon, prostate and breast cancers in Asians, who consume more vegetables, fruits and tea than populations in the western hemisphere, raises the role of flavonoid components as protective factors against carcinogenesis

Severity of asthma: the role of CD25+,CD30+, NF-κB, and apoptotic markers

Objectives: We studied the role of the regulatory T cells CD4+CD25+ (Treg) and activated CD4+CD30+ cells in the pathogenesis of asthma and their association with apoptosis and NF-κB in patients with mild intermittent asthma (MA), severe persistent asthma (SA), and healthy volunteers (HV). Methods: Peripheral blood lymphocytes (PBL) were extracted from asthmatic patients during exacerbations, and CD4+ cells were separated using Dynal beads. Immunostaining of whole PBL for NF-κB, Bax, and Bcl-2, and immunostaining of CD4+ cells for CD25+ and CD30+ cells were performed using immunocytochemistry. Results: Treg cells were expressed at higher levels in MA than in HV and SA (P.05). Levels of NF-κB, Bcl-2, and Bcl-2/Bax increased, whereas those of Bax decreased, progressively, from MA to SA (P<.05). NF-κB levels correlated directly with the Bcl-2/Bax ratio and with CD4+CD30+ cells in SA and MA, whereas CD4+CD30+ cells correlated inversely with the Bcl-2/Bax ratio. Conclusions: Unregulated Treg cells probably return inflammatory responses to normal values during exacerbations in MA; however, expression of Treg cells was extensively diminished in SA, leading to probable loss of suppressive control over underlying immune reactions. CD4+CD30+ cells were associated with the pathogenesis of asthma but not with severity. NF-κB seems to be the central inflammatory factor in SA, with a remarkable loss of PBL apoptosis, diminished Treg levels, and high CD30+ cell levels that probably induce NF-κB, which in turn blocks the proapoptotic potential of CD30 induction itself

In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.

Background: It was hypothesized that the observed slight immunostimulatory effect of the 23-valent pneumococcal polysaccharide (pneumo-23) vaccine might be due to the presence of low levels of zwitterionic motifs. Therefore, it was hypothesized further that introducing zwitterionic motifs experimentally into polysaccharides of pneumo-23 vaccine might render it an effective immunostimulatory agent. Objective: This study was conducted to assess the in vitro immunostimulatory effect of zwitterionized pneumo-23 (Z-P23) vaccine compared with the nonzwitterionized commercial pneumo-23 (C-P23) vaccine. Methods: In vitro proliferation, ELISA-based in vitro cytokine synthesis (interleukin [IL]-2, interferon [IFN]-γ, and IL-10), and immunofluorescence microscopy-based immune cell profiling (CD4+, CD8+, and CD21+ cells) assays were used to evaluate the immunostimulatory effect of Z-P23 on peripheral blood mononuclear cells (PBMC) of immunosuppressed cancer (IC) patients and healthy control subjects in comparison with PBMC exposed to C-P23, concanavalin A (positive control), and phosphate-buffered saline (PBS) (negative control). Results: Z-P23 induced proliferation of PBMC in the IC (81.1%) and control (75.1%) groups significantly higher than that achieved with concanavalin A in the IC group (51.0%; P = 0.01) but not in the control group (89.2%; P = NS). This was also significantly higher than that achieved with C-P23 in the IC (4.8%; P < 0.001) and control (6.2%; P < 0.001) groups. Z-P23 induced IL-2 and IFN-γ synthesis in the IC group (0.61 and 0.45 ng/mL, respectively) significantly more than that with C-P23 (0.4 and 0.45 ng/mL; P = 0.002 and P <0.001), concanavalin A (0.45 and 0.31 ng/mL; P = 0.021 and P = 0.03), and PBS (0.41 and 0.29 ng/mL; P = 0.005 and P = 0.04) but not the control group. Z-P23 induced expansion of CD4+, CD8+, and CD21+ lymphocytes (39.3%, 42.7%, and 8.1%, respectively) in the IC group higher than that with C-P23 (28.3%, 30.1%, and 5.5%; P = 0.01, P = 0.003, and P = NS), concanavalin A (27.2%, 35.8%, and 4.1%; P = 0.02, P = 0.048, and P = 0.035), and PBS (25.6%, 31.9%, and 4.2%; P = 0.018, P = 0.02, and P = 0.045). Conclusion: The in vitro immunostimulatory potential of Z-P23 was clearly observed on PBMC of IC patients as well as, to a lesser extent, healthy control subjects, stimulating the synthesis of core cytokines of T-helper 1, and primarily inducing CD4+ and CD8+T cells

Streptococcus bovis/gallolyticus induce the development of colorectal cancer.

The role, of microbial agents and the infection of the intestinal mucosa in the carcinogenesis, or the development of colorectal cancer (CRC) is one of the hot topics in the field of CRC where much research has been done. However, this topic has long been underestimated by most of the related books. This chapter is intended to cover the relationship of CRC development with bacteria implicated in the development of CRC such as S. bovis, S. gallolyticus, S. equines, S. infantarius, E .coli, C. difficile…etc. However, S. gallolyticus and S. bovis will be discussed thoroughly in this chapter as they are considered the prototype for intestinal microorganisms related to CRC and colorectal premalignant lesions

An anticancer composition.

The present invention relates to an anticancer composition for treating cancer. The anticancer composition comprises of an active ingredient having an effective amount of Vigna radiata L. extract. The Vigna radiata L. extract having anticancer activity against cervical cancer cell and hepatocarcinoma cell. The Vigna radiata sprout

An antimicrobial composition.

The present invention relates to an antimicrobial composition for use as antiviral, antibacterial and antifungal agent from natural product. The composition comprises an active ingredient with an effective amount of Vigna radiate L. extract