Browsing by Author "Mukesh Samant"

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Induction of Th1-type cellular responses in cured/exposed Leishmania-infected patients and hamsters against polyproteins of soluble Leishmania donovani promastigotes ranging from 89.9 to 97.1 kDa
(2008) Shraddha Kumari; Mukesh Samant; Prashant Khare; Shyam Sundar; Sudhir Sinha; Anuradha Dube
Earlier, we have identified soluble antigenic fraction ranging from 68 to 97.4 kDa (F2-fraction) of Leishmania donovani promastigote, which induced Th1-immunostimulatory cellular responses in both cured Leishmania patients/hamsters and exhibited significant prophylactic potential against experimental visceral leishmaniasis (VL). In the present study, we have further fractionated F2-fraction by continuous elution SDS-PAGE and subjected them to re-evaluation for their ability to induce cellular responses. Out of seven sub-fractions: F2.1-F2.7, only four F2.4-F2.7 (89.9-97.1 kDa), individually or in pooled sub-fractions (P4-7), stimulated Th1-type remarkable lymphoproliferative, NO, IFN-γ and IL-12 responses in Leishmania-infected cured/exposed patients and hamsters. Interestingly, optimum Th1-responses were obtained with P4-7 suggesting the presence of immunostimulatory molecules in it and may be exploited for developing a successful subunit vaccine against VL. © 2008 Elsevier Ltd. All rights reserved.
Leishmania donovani: Immunostimulatory cellular responses of membrane and soluble protein fractions of splenic amastigotes in cured patient and hamsters
(2012) Shraddha Kumari; Pragya Misra; Rati Tandon; Mukesh Samant; Shyam Sundar; Anuradha Dube
Visceral leishmaniasis (VL), caused by the intracellular parasite Leishmania donovani, L. chagasi and L. infantum is characterized by defective cell-mediated immunity (CMI) and is usually fatal if not treated properly. An estimated 350 million people worldwide are at risk of acquiring infection with Leishmania parasites with approximately 500,000 cases of VL being reported each year. In the absence of an efficient and cost-effective antileishmanial drug, development of an appropriate long-lasting vaccine against VL is the need of the day. In VL, the development of a CMI, capable of mounting Th1-type of immune responses, play an important role as it correlate with recovery from and resistance to disease. Resolution of infection results in lifelong immunity against the disease which indicates towards the feasibility of a vaccine against the disease. Most of the vaccination studies in Leishmaniasis have been focused on promastigote- an infective stage of parasite with less exploration of pathogenic amastigote form, due to the cumbersome process of its purified isolation. In the present study, we have isolated and purified splenic amastigotes of L. donovani, following the traditional protocol with slight modification. These were fractionated into five membranous and soluble subfractions each i.e MAF1-5 and SAF1-5 and were subjected for evaluation of their ability to induce cellular responses. Out of five sub-fractions from each of membrane and soluble, only four viz. MAF2, MAF3, SAF2 and SAF3 were observed to stimulate remarkable lymphoproliferative, IFN-γ, IL-12 responses and Nitric Oxide production, in Leishmania-infected cured/exposed patients and hamsters. Results suggest the presence of Th-1 type immunostimulatory molecules in these sub-fractions which may further be exploited for developing a successful subunit vaccine from the less explored pathogenic stage against VL. © 2012 Kumari et al.
Proteomic approaches for discovery of new targets for vaccine and therapeutics against visceral leishmaniasis
(2008) Shraddha Kumari; Awanish Kumar; Mukesh Samant; Shyam Sundar; Neeloo Singh; Anuradha Dube
Visceral leishmaniasis (VL) is the most devastating type caused by Leishmania donovani, Leishmania infantum, and Leishmania chagasi. The therapeutic mainstay is still based on the antiquated pentavalent antimonial against which resistance is now increasing. Unfortunately, due to the digenetic life cycle of parasite, there is significant antigenic diversity. There is an urgent need to develop novel drug/ vaccine targets against VL for which the primary goal should be to identify and characterize the structural and functional proteins. Proteomics, being widely employed in the study of Leishmania seems to be a suitable strategy as the availability of annotated sequenced genome of Leishmania major has opened the door for dissection of both protein expression/regulation and function. Advances in clinical proteomic technologies have enable to enhance our mechanistic understanding of virulence/pathogenicity/host-pathogen interactions, drug resistance thereby defining novel therapeutic/vaccine targets. Expression proteomics exploits the differential expression of leishmanial proteins as biomarkers for application towards early diagnosis. Further using immunoproteomics efforts were also focused on evaluating responses to define parasite T-cell epitopes as vaccine/diagnostic targets. This review has highlighted some of the relevant developments in the rapidly emerging field of leishmanial proteomics and focus on its future applications in drug and vaccine discovery against VL. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Synergistic combination of doxorubicin with fisetin for the treatment of lymphoma
(Elsevier B.V., 2025) Sumeet Singh; Virendra Pratap Singh; Ranjeet Kumar Singh; Vinita Gouri; Biplob Koch; Mukesh Samant
Lymphoma is a common cancer of the lymphatic system, and its treatment presents considerable clinical difficulties due to the constraints of existing medicines. Anticancer drug such as Doxorubicin (DOX) is an effective chemotherapeutic drug that is frequently used to treat lymphoma and other cancers; however, it is linked with considerable toxicities. Fisetin, a naturally occurring flavonoid, exhibits anticancer properties and has the potential to augment the therapeutic effects of DOX. This study explores the synergistic effects of combining DOX with fisetin in the treatment of lymphoma. The combination of DOX and fisetin significantly inhibits cell viability, induced membrane blabbing, chromatin condensation, and promoted apoptosis compared to monotherapies. The study also showed that the synergistic effect of fisetin along with DOX significantly promotes apoptosis in DL cells through intracellular ROS generation, mitochondrial aggregation at the periphery of the nucleus and, increased p53, Bax, cytochrome c, caspase 3, caspase 9, and cleaved caspase 9 expression. Additionally, combination therapy not only increased the mean survival of the treated group animals but also reduced the tumor burden. While histopathological parameters have shown overall improvement in combination therapy. This study proposes a novel combinational therapy for the treatment of lymphoma and requires further clinical investigation. © 2025