The role of Aedes aegypti in inducing/aggravating IgE-mediated allergic airway disease: extensive computational studies for identification of allergenic proteins.

Respiratory allergies have become a major public health concern and affect one-third of the world's population. Several factors like environmental changes, industrialization, and immunologic interactions are reported to contribute to allergic respiratory diseases. Immunological reactions because of mosquito bite (allergic proteins) have been reported to have a high contribution to IgE-mediated allergic airway disease but they are largely ignored. In this study, we aim to predict the potential allergens (proteins) from Aedes aegypti that might play a role in the reactions of IgE-mediated allergic airway diseases. The allergens are identified from an extensive literature search and the 3D structures were prepared using the SwissDock server. Computational studies were performed to identify the potential allergens that might be responsible for IgE-mediated allergies. Our docking and molecular dynamics (MD) simulation results suggest that ADE-3, an allergen from Aedes aegypti, has the highest docking score and is predicted to be responsible for IgE-mediated allergic reaction(s). Overall, this study highlights the importance of immunoinformatics, and the obtained information can be used for designing prophylactic peptide vaccine candidates and inhibitors for controlling IgE-mediated inflammations.Communicated by Ramaswamy H. Sarma.

Antioxidant and Anti-Inflammatory Effects of Zingiber officinale roscoe and Allium subhirsutum: In Silico, Biochemical and Histological Study.

In this study, the antioxidant and anti-inflammatory effects of Zingiber officinale roscoe and Allium subhirsutum aqueous extracts were examined in a carrageenan-induced acute inflammation model. Some markers of inflammation such as hematological parameters, fibrinogen and C-reactive protein were measured. Variables reflecting oxidative stress included thiobarbituric acid reactive substances (TBARS), advanced oxidation of protein products (AOPP), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione were determined in both inflamed foci and erythrocytes. The in silico molecular docking simulation showed that the main components of Zingiber officinale roscoe and Allium subhirsutum bound to toll-like receptor 6 (TLR6) with high affinities. Moreover, histological examinations of paw edema were carried out. Both Zingiber officinale roscoe and Allium subhirsutum ameliorated the induced inflammation and oxidative stress status as outlined by anti-edematous, antioxidant and anti-inflammatory activities. Our investigation lends pharmacological support to the medical uses of these spices in the management of inflammatory disorders and oxidative damage. The results of the in silico assay satisfactory explain the in vivo effects as compared with indomethacin.

Carvacrol Induced Program Cell Death and Cell Cycle Arrest in Androgen-Independent Human Prostate Cancer Cells via Inhibition of Notch Signaling.

BACKGROUND: Several studies have revealed that abnormal activation of Notch signaling is closely related with the development and progression of prostate cancer. Although there are numerous therapeutic strategies, a more effective modality with least side effects is urgently required for the treatment of prostate cancer. Carvacrol is a monoterpenoid phenol and majorly present in the essential oils of Lamiaceae family plants. Many previous reports have shown various biological activities of carvacrol like antioxidant, antiinflammatory and anticancer properties. Recently, we have shown potent anticancer property of carvacrol against prostate cancer cell line DU145. In the current study, we report the chemopreventive and therapeutic potential of carvacrol against another prostate cancer cell line PC-3 with its detailed mechanism of action. METHODS: To determine the effect of the carvacrol on prostate cancer cells, the cell viability was estimated by MTT assay and cell death was estimated by LDH release assay. The apoptotic assay was performed by DAPI staining and FITC-Annexin V assay. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Cell cycle analysis was performed by flow cytometry. Gene expression analysis was performed by quantitative real time PCR. RESULTS: Our results suggested that the carvacrol treatment significantly reduced the cell viability of PC-3 cells in a dose- and time-dependent manner. The antiproliferative action of carvacrol was correlated with apoptosis which was confirmed by nuclear condensation, FITC-Annexin V assay, modulation in expression of Bax, Bcl-2 and caspase activation. The mechanistic insight into carvacrol-induced apoptosis leads to finding of elevated level of Reactive Oxygen Species (ROS) and mitochondrial membrane potential disruption. Cell cycle analysis revealed that carvacrol prevented cell cycle in G0/G1 that was associated with decline in expression of cyclin D1 and Cyclin-Dependent Kinase 4 (CDK4) and augmented expression of CDK inhibitor p21. Having been said the role of hyperactivation of Notch signaling in prostate cancer, we also deciphered that carvacrol could inhibit Notch signaling in PC-3 cells via downregulation of Notch-1, and Jagged-1. CONCLUSION: Thus, our previous and current findings have established the strong potential of carvacrol as a chemopreventive agent against androgen-independent human prostate cancer cells.

Physico-chemical and clinico-immunologic studies on the allergenic significance of Aspergillus tamarii, a common airborne fungus.

Aspergillus-derived inhalant allergens play an important role in the etiology of allergic respiratory diseases. In the present study, we investigated the allergenic potential of Aspergillus tamarii, quantified its airborne content, identified its major/minor allergens, evaluated heterogeneity of patients' IgE response to its allergens and cross-reactivity of its allergens with other Aspergillus allergens. Skin prick tests with A tamarii extract were performed on 300 patients of bronchial asthma/allergic rhinitis and 20 healthy volunteers. Sixty-six patients (22%) elicited positive cutaneous reactions to A tamarii extract. Only one of the 20 non-allergic healthy volunteer showed a mild positive cutaneous reaction. Allergen-specific IgE levels increased with increase in patients' cutaneous response (0% in negative to 100% in 3+/4+). The skin positivity and allergen-specific IgE levels were significantly higher in patients compared to healthy volunteers (P>0.05). However, no differences were found for these two parameters among patients of bronchial asthma, allergic rhinitis and bronchial asthma with allergic rhinitis. The airborne A tamarii allergen content was highest in February and October. A tamarii extract revealed at least 22 proteins (13.3-120 kDa). Seventeen of these proteins bound patients' IgE with six being major allergens (13.3, 23, 25, 34, 39.5, 43 kDa). Three major allergens (13.3, 34, 43 kDa) were found to cross-react with A flavus and one (34 kDa) with A niger. Our results revealed that A tamarii allergen(s) are present in the air, which might serve as important inhalant allergens in IgE-mediated allergic respiratory diseases.

Quantification of airborne Aspergillus allergens: redefining the approach.

BACKGROUND: Airborne Aspergillus species are significant environmental components involved in the pathogenesis and persistence of allergic respiratory diseases. The detection and quantification of airborne allergens is important to elucidate the clinical implications of environmental exposure of patients suffering with allergic asthma and/or allergic rhinitis. OBJECTIVE: The authors report a simple volumetric approach to measure atmospheric concentration of four common airborne species of Aspergillus-A. flavus, A. fumigatus, A. niger, and A. tamarii. METHODS: As particulate aeroallergens may also exist in amorphous form in addition to morphologically identifiable fungal spores/hyphae, a volumetric technique using membrane filters was developed for simultaneous quantification of (a) viable Aspergillus counts, i.e., colony-forming units (cfu)/m(3), and (b) actual Aspergillus allergen content (ng/m(3)) in the air. Further, immunochemically quantified airborne Aspergillus allergens were compared with their corresponding colony counts. RESULTS: The average monthly aerial counts of the four Aspergillus species recorded during the sampling year were A. flavus: 0.25-15.2 cfu/m(3); A. fumigatus: 1.25-15.6 cfu/m(3); A. niger: 0.75-16.0 cfu/m(3); and A. tamarii: 0.5-11.8 cfu/m(3) of air. Aerial Aspergillus allergen(s) concentration varied from species to species: A. flavus: 26.8-680.8 ng; A. fumigatus: 18.0-380.4 ng; A. niger: 28.2-1879.0 ng; and A. tamarii: 9.2-238.3 ng/m(3) of air. Seasonal distribution of airborne colony counts of the four species didn't correlate with their respective allergen content. CONCLUSION: Aspergillus allergens were present in the air of Delhi area throughout the year with seasonal variations. The authors feel that by using the immunochemical technique it will be possible to measure actual exposure of patients to various airborne Aspergillus allergens.