Native bees are important pollinators of cultivated and wild plants. Although much importance has been accorded them in many countries of the world, India has largely ignored the role of these important ecosystem service providers for too long. The consequence is public apathy toward these beneficial insects. This study has attempted to find out the general ''bee awareness'' of people living in agrarian societies in a socioeconomically underdeveloped Indian district through picture-based questionnaire surveys and has also attempted to determine the effectiveness of information divulgation in changing people's perception toward native bees. Opinion of the people on honeybee health in this district has also been explored. It has been found that traditional knowledge of bees is largely restricted to the honey-producing species of the genus Apis, and even though other native species are frequently encountered by the people, there is a substantial lack of awareness about their true nature and importance. However, the study suggests that through right training, this situation may favorably be altered. Multiple regression analysis of socioeconomic factors determining bee knowledge of respondents revealed that women were > 4 times better at identifying native bees than men, both with or without given information, and the higher the level of education the better people were at identifying native bees. People considered pesticides and their irregular application to be the major killers of honeybees. This study generates hope for involvement of local people in native as well as honeybee conservation and management through proper awareness campaigns and right education.
The specific apoptotic role of T11TS has been well established in glioma animal models. T11TS specifically induces the glioma cells to die an apoptotic death via immune cross-talk with the two intracranial immune competent cells-microglia and the brain-infiltrating lymphocytes. To unearth the molecular cascades operative within the glioma cells and to some extent in the two interacting immunocytes, we had initiated studies where preliminary findings not only had indicated the involvement of death receptors but had also hinted to the involvement of other apoptotic regulators. Hence, to identify the molecular pathway of apoptosis involving other apoptotic regulators in the three cell types, the cells were studied for the intrinsic apoptotic death regulators that were engaged to maintain the mitochondrial membrane integrity. The proteins that were selected could be divided into three broad classes-the Bcl-2 family of proteins-Bid, Bax and Bcl-2; the guardian of the genome p53 and the proteins downstream of mitochondria-Apaf-1, cytochrome c, caspase-9 and caspase-3. Activated Bid as well as maximal p53 expression was observed in the first dose of T11TS thus dually activating the pro-apoptotic Bax in the first and second dose in the glioma cells. Concurrently, the pro-survival protein Bcl-2's expression level was very much down-regulated in the same two doses favoring the internal microenvironment to proceed for apoptosis. High expression of cytochrome c and Apaf-1 and the presence of active caspase-9 and active caspase-3 in all the T11TS-treated tumor-bearing groups further adjudicated apoptosis of the glioma cells with clear involvement of mitochondrial death pathway in the T11TS-treated animals. Even though expression of the apoptotic regulators remained more or less the same indicating the involvement of mitochondria in the two interacting immunocytes, the intensity of expression of these proteins was much lower than the tumor cells. The present work focuses on the mechanistic approach of how T11TS mediates apoptosis and hence is the first approach of its kind in the field of immunology where the immunotherapeutic molecule's mode of action has been worked out.
The crucial role of angiogenesis in malignant glioma progression makes it a potential target of therapeutic intervention in glioma. Previous studies from our lab showed that sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) has potent anti-neoplastic and immune stimulatory effects in rodent glioma model. In the present study we investigated the anti-angiogenic potential of T11TS and deciphered the underlying molecular mechanism of its anti-angiogenic action in malignant glioma. Vascular endothelial growth factor (VEGF) signaling is crucial for initiating tumor angiogenic responses. The present preclinical study was designed to evaluate the effect of T11TS therapy on VEGF and VEGFR-2 expression in glioma associated brain endothelial cells and to determine the effects of in vivo T11TS administration on expression of PTEN and downstream pro-survival PI3K/Akt/eNOS pathway proteins in glioma associated brain endothelial cells. T11TS therapy in rodent glioma model significantly downregulated expression of VEGF along with its receptor VEGFR-2 and inhibited the expression of pro-survival PI3K/Akt/eNOS proteins in glioma associated brain endothelial cells. Furthermore, T11TS therapy in glioma induced rats significantly upregulated brain endothelial cell PTEN expression, inhibited eNOS phosphorylation and production of nitric oxide in glioma associated brain endothelial cells. Taken together our findings suggest that T11TS can be introduced as an effective angiogenesis inhibitor in human glioma as T11TS targets multiple levels of angiogenic signaling cascade impeding glioma neovascularisation.
T-cell-mediated immune responses are typically low in conditions of malignant glioma which has been known to cause marked immunesuppression and dysregulate major T-cell signaling molecules. Thus, T-cell-based immunotherapies are currently in vogue in the treatment of malignant glioma. The novel glycopeptide, T11TS/S-LFA-3/S-CD58 has previously been shown by our group to be highly efficacious in glioma abrogation in in vivo and in vitro conditions. This glycopeptide ligands to the costimulatory CD2 molecule on T-cells, causing profound immune stimulation leading to glioma abrogation, suggesting probable involvement of T11TS in modulation of the T-cell signaling pathway. The present study offers a multi-targeted approach towards repair of some of the key components of the immunological synapse at the T-cell-APC interface and is therefore the first of its kind to offer a holistic model of restoration of immunological synapse components so as to trigger T-cells towards activation against glioma. The study thus indicates that the totally dysregulated molecular events at the immunological synapse in glioma are restored back to normal levels with the administration of T11TS, which finally culminates in glioma abrogation. The present study thus delineates an important T-cell signaling approach whereby T11TS acts as an anti-neoplastic agent, thus helping to chart out newer avenues in the fight against gliomas.
During glioma development, angiogenesis plays a crucial role in growth and vascularization of primary brain tumors. T11 target structure (T11TS), a bioactive molecule, has been documented as an anti-neoplastic agent in glioma-induced rats and also in human glioma in vitro. This novel molecule induces apoptosis of tumor cells by way of immune potentiation and impairs the glioma cell cycle, but its role in glioma angiogenesis has not been worked out in detail. Matrix metalloproteinases (MMPs) are enzymes promoting tumor angiogenesis by enzymatically remodeling the extracellular matrix and altering surface protein expression such as integrin αv and the matrix-bound proteins like TGF-β1. The present study was formulated to assess the efficacy of T11TS in the modulations of MMP-2 and -9 and their endogenous inhibitors (TIMP-1 and TIMP-2) as well as modulations of integrin αv and TGF-β1 in glioma-induced rats and also on the phenotypic markers of endothelial cells (CD31 and CD34). The parameters used were zymography, western blot, and flow cytometric analyses. It was observed that T11TS administration significantly downregulates the expression of matrix metalloproteinase-2 and -9 along with its ligand integrin αv and upregulates TIMP-1 and TIMP-2. In situ immunofluorescence and FACS results revealed that T11TS administration decreased the expression of the phenotypic markers (CD31/PECAM1, CD34), inhibiting the cell grip and also downregulating TGF-β1 expression (ELISA) from microglia cells in the glioma microenvironment. These results suggest that T11TS suppresses the expression of positive angiogenic growth factors and potentiates the expression of negative regulators in glioma-associated endothelial cells (ECs), resulting in an anti-angiogenic effect on glioma-induced angiogenesis.
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