Department Of Biochemistry And Microbial Sciences

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Author: search.filters.author.Jain, AklankHas files: Yes

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    Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium.
    (PLOS, 2018) Nadella, Vinod; Singh Sandhya; Jain, Aklank; Jain, Manju; Vasquez, Karen M.; Sharma, Ashok; Tanwar, Pranay; Rath, Goura Kishore; Prakash Hridayesh.
    Solid tumors are covered by stroma, which is hypoxic in nature and composed of various non‐malignant components such as endothelial cells, fibroblasts, and pericytes that support tumor growth. Tumor stroma represents a mechanical barrier for tumor infiltration of CD8+ effector T cells in particular. In this context, our previous studies have demonstrated the therapeutic impact of Low‐Dose Radiation (LDR)‐primed and M1‐retuned (iNOS+) peritumoral macrophages that produce inducible nitric oxide, have immunological roles on tumor infiltration of effector T cells, cancer‐related inflammation, and subsequent tumor immune rejection in a mouse model of pancreatic cancer. These findings suggested a possible modification of tumor endothelium by LDR‐primed macrophages. In line with these observations, here we demonstrate the influence of LDR in down‐modulating HIF‐1 in irradiated tumors in the course of polarization of irradiated tumor‐associated macrophages toward an M1 phenotype. Furthermore, we demonstrate that M1 macrophages which are primed by LDR can directly influence angiogenic responses in eNOS+ endothelial cells which produce nitric oxide having both vascular and physiological roles. Furthermore, we demonstrate that naïve macrophages, upon differentiating to an M1 phenotype either by Th1 stimuli or LDR, potentially modify sphingosine‐1‐phosphate/VEGF‐induced angiogenic signaling in tumor‐derived endothelial cells with tumorigenic potential, thus indicating the significance of iNOS+ macrophages in modulating signaling in eNOS+ tumor‐derived endothelium. Our study suggests that iNOS+ macrophages can activate tumor endothelium which may contribute to cancer‐directed immunotherapy in particular.
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    Atypical leishmaniasis: A global perspective with emphasis on the Indian subcontinent
    (Public Library of Science, 2018) Thakur L.; Singh K.K.; Shanker V.; Negi A.; Jain, Aklank; Matlashewski G.; Jain, Manju
    Background: Among the neglected tropical diseases, leishmaniasis continues to be prevalent in many tropical and subtropical countries despite international, national, and local efforts towards its control and elimination over the last decade. This warrants a critical evaluation of such factors as under-reporting, asymptomatic infections, post kala azar dermal leishmaniasis (PKDL) cases, and drug resistance. In this review, we highlight lesser-understood atypical presentations of the disease involving atypical parasite strains against a background of classical leishmaniasis with a focus on the Indian subcontinent. Methods and findings: A literature review based on endemic areas, the nature of disease manifestation, and underlying causative parasite was performed with data collected from WHO reports for each country. Searches on PubMed included the term 'leishmaniasis' and ' eishmaniasis epidemiology' alone and in combination with each of the endemic countries, Leishmania species, cutaneous, visceral, endemic, non-endemic, typical, classical, atypical, and unusual with no date limit and published in English up to September 2017. Our findings portray a scenario with a wider distribution of the disease in new endemic foci, with new discoveries of parasite-driven atypical disease manifestations in different regions of the world. Unlike the classical picture, some Leishmania species are associated with more than one disease presentation, e.g., the L. donovani complex, generally associated with the visceral form, is now also associated with a cutaneous disease presentation, while L. tropica species complex, known to cause cutaneous disease, can cause viscerotropic disease. This phenomenon points towards the discovery of novel parasite variants as etiologic agents of atypical disease manifestations and represents an excellent opportunity to identify and study genes that control disease virulence and tropism. Conclusions: The increased recognition of atypical leishmaniasis as an outcome of parasite variants has major implications for leishmaniasis control and elimination. Identifying molecular correlates of parasite isolates from distinct regions associated with different disease phenotypes is required to understand the current epidemiology of leishmaniasis in regions with atypical disease.-2018 Thakur et al. http://creativecommons.org/licenses/by/4.0/.