Browsing by Author "Ranjeet Singh"

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Antiproliferative activity of Fe(ii), Co(ii), Ni(ii), Cu(ii), and Zn(ii) complexes of dithiocarbamate: synthesis, structural characterization, and thermal studies
(Royal Society of Chemistry, 2023) Anupam Singh; Kunal Shiv; Ranjeet Singh; M.K. Bharty; Partha Pratim Manna; Lal Bahadur Prasad
Five new metal complexes of Fe(ii) (1), Co(ii) (2), Ni(ii) (3), Cu(ii) (4), and Zn(ii) (5), derived from an N-cyclohexyl N-(3,4-dimethoxybenzyl) dithiocarbamate ligand, have been successfully synthesized and fully characterized by different analytical techniques i.e. elemental analyses, FT-IR, UV-Vis, 1H & 13C NMR, and HRMS. Furthermore, complexes 4 and 5 have been characterized by the SC-XRD technique. Complex 4 adopts a distorted square planar geometry around the Cu(ii) center while complex 5 adopts a distorted tetrahedral geometry around the Zn(ii) center. In addition, an eight-membered symmetric chair-like metallacycle ring containing two Zn(ii) centers has also been found in complex 5. XRD data also show that complexes 4 and 5 are stabilized by various weak intermolecular hydrogen bonding interactions. The course of the thermal degradation of metal complexes 1-5 has been examined by TG-DTA data which revealed that metal sulphide formed as the final residue. Complexes 1-5 demonstrated concentration-dependent cytotoxicity and growth inhibition of DL tumor cells. Among the compounds, complexes 1, 4, and 5 showed significant cytotoxicity and induced a loss in the viability of DL cells. Therapy with complexes 1, 4, and 5 protects DL tumor-bearing animals from exacerbation of the disease, increases lifespan, and significantly improves the histopathological parameters of the vascularized organ, including preventing metastasis. Overall cytotoxicity assay results indicate that all complexes have remarkable cytotoxic potential in comparison with the free ligand. © 2024 The Royal Society of Chemistry.
ATP-Decorated Mesoporous Silica for Biomineralization of Calcium Carbonate and P2 Purinergic Receptor-Mediated Antitumor Activity against Aggressive Lymphoma
(American Chemical Society, 2018) Prateek Srivastava; Sumit Kumar Hira; Divesh Narayan Srivastava; Vivek Kumar Singh; Uttam Gupta; Ranjeet Singh; Ram Adhar Singh; Partha Pratim Manna
Adenosine triphosphate (ATP) is an important transmitter that mediates various biological effects via purinergic receptors (P2 receptors) in cancer. We investigated the antitumor activity of ATP-decorated and doxorubicin (DOX)-loaded mesoporous silica with biomineralization of calcium carbonate against a highly aggressive and metastatic murine lymphoma called Dalton's lymphoma (DL). Our results suggest that this nanocomposite has unique effects with respect to the morphology and properties of calcium carbonate on the surface of the nanoparticle. DOX in the nanoparticles was prevented from quick release via the interactions of the phosphate group present on ATP and calcium carbonate. This construct is significantly tumoricidal against parental and DOX-resistant DL cells and is thus a promising candidate for applications in drug delivery. The composite nanomaterial has excellent biocompatibility with higher uptake and acts via the participation of the purinergic receptor P2X7. The nanocomposite induces significantly higher apoptosis in tumor cells compared with DOX alone. Treatment of DL-bearing mice with the construct significantly reduces tumor burden, in addition to augmenting the lifespan of tumor-bearing mice as demonstrated by a sustained healthy life of the animals and improved histopathological parameters. © 2018 American Chemical Society.
Biocompatible thermoresponsive N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide-based random copolymer: synthesis and studies of its composition dependent properties and anticancer drug delivery efficiency
(Royal Society of Chemistry, 2022) Sourov Mondal; Archana Kumari; Kheyanath Mitra; Abhineet Verma; Satyen Saha; Biswajit Maiti; Ranjeet Singh; Partha Pratim Manna; Pralay Maiti; Hironobu Watanabe; Masami Kamigaito; Biswajit Ray
A new acrylamide monomer, N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide (M3i), consisting of both isopropyl and isopropylamidopropyl moieties, has been synthesized from isopropylamine and N-isopropylacrylamide via an aza-Michael addition reaction followed by amidation with acryloyl chloride. The homopolymer of M3i (polyM3i) and a series of random copolymers of M3i and poly(ethylene glycol)methyl ether acrylate (PEGA: CH2 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 CHCO2(CH2CH2O)nMe, Mn = 480, n = 9 on average) with varying compositions have been synthesized via reversible addition-fragmentation chain transfer polymerization using 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) as well as 1-phenylethyl phenyl dithioacetate (PEPD) as a RAFT agent. These polymers have been characterized by 1H NMR, FTIR, GPC, UV-Vis, fluorescence, TGDTA, DSC, DLS, and TEM techniques. A lower critical solution temperature (LCST) and glass transition temperature (Tg) for polyM3i prepared using DDMAT were observed at 17 and 133 °C, respectively, while for a polymer formed using PEPD, no LCST was observed until 0 °C and its observed Tg was found at 127.3 °C. The polymers are thermally stable up to 300 °C. Upon an increase in the M3i content in the copolymers, LCST decreases, Tg increases, and the apparent hydrodynamic diameter decreases. Moreover, the effects of concentration and the addition of urea and sodium chloride on the LCST of the copolymer with an LCST close to body temperature were studied. Owing to the incorporation of PEGA, a higher critical micellar concentration and larger TEM particle size of this copolymer were observed with respect to those of polyM3i. The usefulness of the micelles of the copolymers as nano-carriers for the drug doxorubicin was explored. The in vitro tumoricidal activity of the micelles of the doxorubicin-loaded copolymers was also assessed against Dalton's lymphoma cells. © 2022 The Royal Society of Chemistry.
Chemokine-targeted nanoparticles: stimulation of the immune system in cancer immunotherapy
(Open Exploration Publishing Inc, 2023) Ranjeet Singh; Prateek Srivastava; Partha Pratim Manna
Surgery, chemotherapy, radiation therapy, and immunotherapy are potential therapeutic choices for many malignant and metastatic cancers. Despite adverse side effects and pain, surgery and chemotherapy continue to be the most common cancer treatments. However, patients treated with immunotherapy had better cancer control than those who got other treatments. There are two methods to activate immunological pathways: systemically and locally. To modify the tumor microenvironment (TME), the former uses systemic cytokine/chemokine (CK) delivery, whilst the latter uses immunological checkpoints or small molecule inhibitors. Organic and inorganic nanomaterials (NMs) enhanced the efficacy of cancer immunotherapy. NMs can transmit drugs, peptides, antigens, antibodies, whole cell membranes, etc. Surface-modified NMs precisely target and enter the tissues. The inner core of surface-modified NMs is composed of chemicals with limited bioavailability and biocompatibility, resulting in prolonged blood retention and decreased renal clearance. These platforms hinder or prevent many immune cell activities and modify the TME, enhancing the efficiency of cancer immunotherapy. By inhibiting CK/CK receptor signaling, cell migration and other immune responses could be controlled. Developing CK-targeted nanoparticles (NPs) that inhibit CK signaling or take advantage of the ligand-receptor connection is possible. Surface chemical modification of NMs with CKs or specific peptides has several medicinal applications, including tissue-specific drug delivery and limited cell migration in cancer-afflicted conditions. This review covers current developments in the role of different groups of CK-loaded NP in tumor therapy targeting immune cells and cancer. It also covers the role of NP targeting CK signaling which aids in immunogenic cell death (ICD) and induction of antitumor immunity. In addition, CK gene silencing and its capacity to prevent cancer metastasis as well as inhibition of immune cell migration to modulate the TME are discussed. © The Author(s) 2023.
Doxorubicin loaded pH responsive biodegradable ABA-type Amphiphilic PEG-b-aliphatic Polyketal-b-PEG block copolymer for therapy against aggressive murine lymphoma
(Elsevier Inc., 2020) Sumit Kumar Hira; Kheyanath Mitra; Prateek Srivastava; Shikha Singh; Sambhav Vishwakarma; Ranjeet Singh; Biswajit Ray; Partha Pratim Manna
A novel ABA-type polyethylene glycol (PEG)-b-polyketal (PK)-b-PEG block copolymer was synthesized via click reactions between the monoazido-monomethoxy-PEG and dialkyne terminated aliphatic polyketal with no carboxylic/amide linkages. Formation of the novel block copolymer was confirmed by 1H NMR, GPC, TGA, and DSC studies. The formed copolymer has shown faster degradation at acidic pH. Self-assembly of this block copolymer (average size 6.2 nm) was assessed by fluorescence study using pyrene as a probe. Doxorubicin loaded block copolymeric micelles (69.9 nm) have shown pH dependent elevated drug release at pH 6.4, indicating its potential as a pH responsive nano-carrier for anticancer therapy. The nano-sized copolymer demonstrated tumoricidal activities against the lymphoma of murine and human origin with significant levels of growth inhibition and apoptosis. Therapy with doxorubicin loaded copolymer reduced the tumor size and augmented the life span of the tumor bearing animals with improved histopathological parameters, compared with the untreated control. © 2019 Elsevier Inc.
Engineered Artesunate-Naphthalimide Hybrid Dual Drug for Synergistic Multimodal Therapy against Experimental Murine Lymphoma
(American Chemical Society, 2024) Debapriya RoyMahapatra; Ranjeet Singh; Ugir Hossain Sk; Partha Pratim Manna
Lymphoma can effectively be treated with a chemotherapy regimen that is associated with adverse side effects due to increasing drug resistance, so there is an emergent need for alternative small-molecule inhibitors to overcome the resistance that occurs in lymphoma management and overall increase the prognosis rate. A new series of substituted naphthalimide moieties conjugated via ester and amide linkages with artesunate were designed, synthesized, and characterized. In addition to the conjugates, to further achieve a theranostic molecule, FITC was incorporated via a multistep synthesis process. DNA binding studies of these selected derivatives by ultraviolet-visible (UV-vis), fluorescence spectroscopy, intercalating dye (EtBr, acridine orange)-DNA competitive assay, and minor groove binding dye Hoechst 33342-DNA competitive assay suggested that the synthesized novel molecules intercalated between the two strands of DNA due to its naphthalimide moiety and its counterpart artesunate binds with the minor groove of DNA. Napthalimide-artesunate conjugates inhibit the growth of lymphoma and induce apoptosis, including ready incorporation and reduction in cell viability. The remodeled drug has a significant tumoricidal effect against solid DL tumors developed in BALB/c mice in a dose-dependent manner. The novel drug appears to inhibit metastasis and increase the survival of the treated animals compared with untreated littermates. © 2024 American Chemical Society.
Erratum: Impact of climate change on Indian agriculture: A review (Climatic Change (2006) 78, (445-478) DOI: 10.1007/s10584-005-9042-x)
(2007) R.K. Mall; Ranjeet Singh; Akhilesh Gupta; G. Srinivasan; L.S. Rathore
[No abstract available]
Essential role of TNF-α in gamma c cytokine aided crosstalk between dendritic cells and natural killer cells in experimental murine lymphoma
(Elsevier B.V., 2020) Uttam Gupta; Sumit Kumar Hira; Ranjeet Singh; Ankush Paladhi; Prateek Srivastava; Partha Pratim Manna
Cooperative and cognitive interaction between the dendritic cells and natural killer cells was investigated for demonstrating the anti-tumor activity against an aggressive murine lymphoma, treated with doxorubicin. Crosstalk between the dendritic cells and the natural killer cells significantly reduced the proliferation of Dalton's lymphoma cells in a dose dependent manner. Treatment of Dalton's lymphoma cells with doxorubicin in vitro enhances the effects of crosstalk against the target cells. This crosstalk between the cells was regulated via stimulation with recombinant interleukin-15, and release of TNF-α which is critically important for the tumoricidal effects. Dendritic cells and the natural killer cells crosstalk activate both the cells and upregulate the expression of CD40, CD69 and CD86 on the dendritic cells. These findings provided new insight regarding these interactions and define a mechanism by which cellular immune response promotes tumoricidal activity against lymphoma in therapeutic setting. © 2019 Elsevier B.V.
Evaluation of regulatory T-cells in cancer immunotherapy: therapeutic relevance of immune checkpoint inhibition
(Springer, 2024) Ranjeet Singh; Prateek Srivastava; Partha Pratim Manna
The evolution of the complex immune system is equipped to defend against perilous intruders and concurrently negatively regulate the deleterious effect of immune-mediated inflammation caused by self and nonself antigens. Regulatory T-cells (Tregs) are specialized cells that minimize immune-mediated inflammation, but in malignancies, this feature has been exploited toward cancer progression by keeping the antitumor immune response in check. The modulation of Treg cell infiltration and their induction in the TME (tumor microenvironment) alongside associated inhibitory molecules, both soluble or membranes tethered in the TME, have proven clinically beneficial in boosting the tumoricidal activity of the immune system. Moreover, Treg-associated immune checkpoints pose a greater obstruction in cancer immunotherapy. Inhibiting or blocking active immune checkpoint signaling in combination with other therapies has proven clinically beneficial. This review summarizes the ontogeny of Treg cells and their migration, stability, and function in the TME. We also elucidate the Treg-associated checkpoint moieties that impede effective antitumor activity and harness these molecules for effective and targeted immunotherapy against cancer nuisance. © 2024, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Galunisertib Drives Treg Fragility and Promotes Dendritic Cell-Mediated Immunity against Experimental Lymphoma
(Elsevier Inc., 2020) Sumit Kumar Hira; Abhinandan Rej; Ankush Paladhi; Ranjeet Singh; Jayasree Saha; Indrani Mondal; Sankar Bhattacharyya; Partha Pratim Manna
Immunology; Immunity; Cancer © 2020 The Authors; Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-β receptor-I activation, currently under clinical trial in a variety of cancers. We have tested the combined effects of galunisertib- and interleukin-15-activated dendritic cells in an aggressive and highly metastatic murine lymphoma. Based on the tumor-draining lymph node architecture, and its histology, the combination therapy results in better prognosis, including disappearance of the disease-exacerbating regulatory T cells. Our data suggest that galunisertib significantly enhances the success of immunotherapy with IL-15-activated dendritic cells by limiting the regulatory T cells generation with consequent downregulation of regulatory T cells in the tumor-draining lymph nodes and vascularized organ like spleen. This is also associated with consistent loss p-SMAD2 and downregulation of Neuropilin-1, leading to better prognosis and positive outcome. These results connect the role of combined therapy with the consequent elimination of disease-exacerbating T regulatory cells in a metastatic murine lymphoma. © 2020 The Authors
Identification & characterization of leucine-rich repeat kinase 2 & parkin RBR E3 ubiquitin protein ligase variants in patients with Parkinson's disease
(Wolters Kluwer Medknow Publications, 2020) Tamali Halder; Shiv Verma; Janak Raj; Sharad Pandey; Ranjeet Singh; Vivek Sharma; Deepika Joshi; Parimal Das
Background & objectives: Parkinson's disease (PD) is a motor disorder that affects movement. More than 24 loci and 28 associated genes have been identified to be associated with this disease. The present study accounts for the contribution of two candidates, leucine-rich repeat kinase 2 ( LRRK2) and parkin RBR E3 ubiquitin protein ligase ( PRKN) in the PD patients, and their characterization in silico and in vitro. Methods: A total of 145 sporadic PD cases and 120 ethnically matched healthy controls were enrolled with their informed consent. Mutation screening was performed by direct DNA sequencing of the targeted exons of LRRK2 and all exons flanking introns of PRKN. The effect of the pathogenic PRKN variants on a drug (MG-132) induced loss of mitochondrial membrane potential (△ΨM) was measured by a fluorescent dye tetramethylrhodamine methyl ester (TMRM). Results: Twelve and 20 genetic variants were identified in LRRK2 and PRKN, respectively. Interestingly, five out of seven exonic LRRK2 variants were synonymous. Further assessment in controls confirmed the rarity of two such p.Y1527 and p.V1615. Among the pathogenic missense variations (as predicted in silico) in PRKN, two were selected (p.R42H and p.A82E) for their functional study in vitro, which revealed the reduced fluorescence intensity of TMRM as compared to wild type, in case of p.R42H but not the other. Interpretation & conclusions: About 6.2 per cent of the cases (9/145) in the studied patient cohort were found to carry pathogenic (as predicted in silico) missense variations in PRKN in heterozygous condition but not in case of LRRK2 which was rare. The presence of two rare synonymous variants of LRRK2 (p.Y1527 and p.V1615) may support the phenomenon of codon bias. Functional characterization of selected PRKN variations revealed p.R42H to cause disruption of mitochondrial membrane potential (△ΨM) rendering cells more susceptible to cellular stress. © 2020 Wolters Kluwer Medknow Publications. All rights reserved.
Impact of climate change on Indian agriculture: A review
(Springer Netherlands, 2006) R.K. Mall; Ranjeet Singh; Akhilesh Gupta; G. Srinivasan; L.S. Rathore
During the recent decade, with the growing recognition of the possibility of climate change and clear evidence of observed changes in climate during 20th century, an increasing emphasis on food security and its regional impacts has come to forefront of the scientific community. In recent times, the crop simulation models have been used extensively to study the impact of climate change on agricultural production and food security. The output provided by the simulation models can be used to make appropriate crop management decisions and to provide farmers and others with alternative options for their farming system. It is expected that in the coming decades with the increased use of computers, the use of simulation models by farmers and professionals as well as policy and decision makers will increase. In India, substantial work has been done in last decade aimed at understanding the nature and magnitude of change in yield of different crops due to projected climate change. This paper presents an overview of the state of the knowledge of possible effect of the climate variability and change on food grain production in India. © 2006 Springer Science+Business Media, Inc.
In silico studies and evaluation of antiparasitic role of a novel pyruvate phosphate dikinase inhibitor in Leishmania donovani infected macrophages
(Elsevier B.V., 2019) Mohammad Kashif; Sumit Kumar Hira; Anurag Upadhyaya; Uttam Gupta; Ranjeet Singh; Ankush Paladhi; Faez Iqbal Khan; Abdur Rub; Partha Pratim Manna
The present work deals with the identification and characterization of a novel inhibitor Z220582104, specific to pyruvate phosphate dikinase, for leishmanicidal activities against free promastigotes and intracellular amastigotes. We have used structure-based drug designing approaches and performed homology modelling, virtual screening and molecular dynamics studies. Primary mouse macrophages and macrophage cell line J774A1 were infected with promastigotes of Leishmania donovani. Both promastigotes and infected macrophages were subjected to treatment with the varying concentrations of Z220582104 or miltefosine for assessment of leishmanicidal activity. The novel inhibitor Z220582104 demonstrated growth inhibitory potential and reduced the viability of the free promastigotes in a concentration- and time-dependent manner. Z220582104 was also effective against the intracellular form of the parasites and reduced the number of amastigotes in macrophages and also lowered the parasite index, compared with the untreated infected macrophages. Although less effective compared with the miltefosine, Z220582104 is well tolerated by the dividing cells and normal human lymphocytes and monocytes with no adverse effects on the growth kinetics or viability. Our in silico and in vitro studies suggested that Leishmania donovani pyruvate phosphate dikinase could be a potential new drug target. © 2018 Elsevier B.V. and International Society of Chemotherapy
Leishmanicidal activity of an in Silico-screened novel inhibitor against ascorbate peroxidase of leishmania donovani
(American Society for Microbiology, 2020) Mohammad Kashif; Ankush Paladhi; Ranjeet Singh; Sankar Bhattacharyya; Sumit Kumar Hira; Partha Pratim Manna
Peroxidases are a heterogeneous family of enzymes that have diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defense system of Leishmania. In view of developing new and novel therapeutics, we performed in silico studies in order to search for a ligand library and identify new drug candidates and their physiological roles against promastigotes and intracellular amastigotes of Leishmania donovani. Our results demonstrated that the selected inhibitor ZINC96021026 has significant antileishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of valosin-containing protein (VCP), or p97, a member of the AAA-ATPase protein family which was derived from the scaffold of N2,N4-dibenzylquinazoline-2,4-diamine (DBeQ), targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus has a broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes, besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibit the parasite's ascorbate peroxidase, leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis. © 2020 American Society for Microbiology. All rights reserved.
Myths and superstition about epilepsy: A study from North India
(Wolters Kluwer Medknow Publications, 2018) Smriti Singh; Vijaya Nath Mishra; Alka Rai; Ranjeet Singh; Rameshwar Nath Chaurasia
Background: Epilepsy is a treatable chronic neurological disorder which is often linked to supernatural activities, due to lack of knowledge and awareness among the common people. The beliefs that outbreak of epilepsy as an unnatural or supernatural activities can be most frequently seen in rural population. One cannot say that the perception of urban populace is different from that of rural populace, but yes, they do differ at some extent. Objective: Knowledge, superstition, and myth toward epilepsy in North India. Methods: This is a questionnaire-based study (12 questions) conducted in neurology outpatient department of Banaras Hindu University, visited by more than hundreds of people from different province of northern India. This survey was also conducted in nearby areas of holy city Varanasi. People belonging to different socioeconomic background and educational level were surveyed to know their view regarding epilepsy. Results: In this survey conducted by our team, we came to the truth that urban population do consider epilepsy as an unnatural phenomenon and adopted different treatment tactics as given in this article. Conclusion: There is the urgent need of creating awareness among the common people through different means such as newspaper, television, organizing health camps, and training local health practitioners for epilepsy management. © 2018 Journal of Neurosciences in Rural Practice | Published by Wolters Kluwer-Medknow.
Nanoscale Diamond-Based Formulation as an Immunomodulator and Potential Therapeutic for Lymphoma
(Frontiers Media S.A., 2022) Ankush Paladhi; Abhinandan Rej; Debanjan Sarkar; Ranjeet Singh; Sankar Bhattacharyya; Prasanta Kumar Sarkar; Pulak Kanti Kar; Partha Pratim Manna; Sumit Kumar Hira
Integrative medicine practices, such as Ayurveda, are popular in India and many South Asian countries, yet basic research to investigate the concepts, procedures, and medical benefits of ayurvedic products has received little attention and is not fully understood. Here, we report a functional nanodiamond-based traditional Ayurvedic herbomineral formulation, Heerak Bhasma (Ayu_ND), for the treatment of solid tumors called Dalton’s lymphoma generated in CD1 mice. Ayu_ND-mediated immunostimulation significantly reduces tumor cell proliferation and induces apoptosis aided by the active participation of dendritic cells. Immunomodulatory Ayu_ND treatment is highly immunostimulatory and drives dendritic cells to produce TNF-α. Treatment with Ayu_ND significantly reduces the tumor volume, inhibits metastasis in distant vascularized organs, and increases the life span of tumor-bearing animals compared with untreated littermates. These events were associated with elevated serum levels of the protective cytokines IFN-γ and TNF-α and downregulated the disease, exacerbating TGF-β. Ayu_ND-mediated therapeutic success was also accompanied by the depletion of regulatory T cells and enhanced vaccine-induced T-cell immunity, guided by the restoration of the memory CD8+ T-cell pool and prevention of PD-1-mediated T cell exhaustion. The results provide a basis for further evaluation of ayurvedic formulations and drug efficacy in treating cancers. Copyright © 2022 Paladhi, Rej, Sarkar, Singh, Bhattacharyya, Sarkar, Kar, Manna and Hira.
Non-hierarchical Euclidean cluster analysis for grouping of diverse lentil (Lens Culinaris L. Medik.) genotypes
(DAV College, 2014) Prakash Singh; Ranjeet Singh
Two hundred forty five diverse genotypes of lentil (Lens culinaris Medik.) were evaluated in Augmented Block Design during Rabi season 2009-10 and 2010-11 for various quantitative traits, which indicated wide genetic variability for all the traits. Significant genotypic differences were observed for all the quantitative traits studied, indicating the considerable amount of variation among genotypes for each eleven characters. Heritability (broad sense) estimates were high (>88%) for all the quantitative traits except number of primary branches/plant. These 245 diverse genotypes were grouped into 16 distinct clusters by using nonhierarchical Euclidean cluster analysis. Cluster VI contained maximum 36 genotypes followed by cluster IV (31 genotypes), cluster I (25 genotypes), cluster II and XIV having 22 genotypes. The most diverse clusters were cluster XV and IX (34.444) followed by clusters XV and X (30.886), which indicated maximum diversity between the genotypes of these clusters. Cluster IX characterized by high number of secondary branches/plant, number of pods/plant, early maturity and most of the yield related traits, while cluster XV was represented by genotype having extra bold seeded group. The promising genotypes (GM-53, GM-40, L-316, L-6-416, R/5-18, GM-28, GM-212, GM-11, L-324) for seed yield/plant, biological yield, harvest index, number of pods/plant, number of secondary branches/plant and early maturing were identified from different cluster on the basis of better performance, which could be utilized for hybridization programme to produce better recombinants for development of high yielding varieties.
Pepsin Assisted Doxorubicin Delivery from Mesoporous Silica Nanoparticles Downsizes Solid Tumor Volume and Enhances Therapeutic Efficacy in Experimental Murine Lymphoma
(American Chemical Society, 2018) Prateek Srivastava; Sumit Kumar Hira; Uttam Gupta; Vivek Kumar Singh; Ranjeet Singh; Pankaj Pandey; Divesh Narayan Srivastava; Ram Adhar Singh; Partha Pratim Manna
Pepsin, a digestive enzyme, plays an important role in the metabolism of protein products in the stomach. The pH is regarded as the most pivotal criteria in appraising the pepsin's enzymatic activity. Pepsin is idle at the physiological pH (7.4) but dynamic in the acidic environments of the stomach (pH 2.0-4.0). Inspired by such pH regulatory actions, we have used pepsin as an enhancer, which is attached to silica nanoparticles for the doxorubicin release in the acidic tumor environment. Pepsin enzyme is transitional between the doxorubicin loaded silica nanoparticles and the biotin-avidin cap system, which intercedes the pores. The formed nanoplatform is poised at the physiological pH. However, when switched to low pH simulated conditions, the pepsin become vibrant and cleaves the avidin, rendering the clearance of the path for the diffusion of the drug. This design strategy augmented the drug bioavailability deep inside the solid tumor with enhanced uptake and apoptosis of the tumor cells in experimental lymphoma. Copyright © 2018 American Chemical Society.
Pseudotumor Cerebri Syndrome (PTCS), Clinico-Radiological Profile: A Prospective Study
(Wolters Kluwer Medknow Publications, 2022) Ranjeet Singh; Anand Kumar; Varun Singh; Abhishek Pathak; Rameshwar Chaurasia; Vijaya Mishra; Deepika Joshi
Objectives: The aim of the study was to classify patients of Pseudotumor Cerebri Syndrome (PTCS) on the basis of newer classification along with its clinico-radiological correlations. Patients and Methods: A prospective study was conducted at a tertiary care teaching hospital. A total of 25 consecutive patients who fulfilled the new diagnostic criteria for PTCS were enrolled after taking informed written consent. A thorough clinical history, neurological examination and neuroimaging was carried out. Patients were classified into Primary and Secondary PTCS followed by Definite, Probable and Suggested as per new nomenclature. Results: Out of 25 patients, there were 9 patients in the primary PTCS group and 16 in the secondary PTCS group. Mean duration of symptoms was 40.84 ± 45.68 days. Primary PTCS group patients were significantly overweight and had higher BMI as compared to the secondary group with significant number of patients reporting recent rapid weight gain. The CSF pressure and protein were non-significantly higher in the primary PTCS group. We could classify 17 (68%) patients in our study as definite PTCS, 7 (28%) as probable PTCS and suggested PTCS in one patient. In secondary PTCS group there were 16 (64%) patients. APLA positivity was found to be the most common etiology for secondary PTCS with statistical significance (P = 0.025). Conclusions: Early recognition along with appropriate classification and prompt treatment can prevent vision loss in PTCS. Apart from obesity, recent weight gain is also closely related with primary PTCS. © 2022 Neurology India, Neurological Society of India.
Reactive oxygen species in cancer progression and its role in therapeutics
(Open Exploration Publishing Inc, 2022) Ranjeet Singh; Partha Pratim Manna
The redox status in pathogenesis is critically regulated by careful balance between the generation of reactive oxygen species (ROS) and their elimination. Increased ROS level above the cellular tolerability threshold results in apoptotic or necrotic cell death. ROS belongs to a group of highly reactive compounds that have evolved to play key roles in cellular signaling pathways. It’s widely assumed that a reasonable amount of ROS is essential for a variety of biological processes. Elevated levels of ROS are known to cause various pathologic conditions like neurological disorders, cardiovascular conditions, inflammation, autoimmunity, and cancer. ROS is well known to initiate and assist in progression of tumor by promoting proliferation and survival of cancer cells and thus facilitates pro-tumorigenic signaling in tumor microenvironment. As cancer cells become more resilient to the effects of ROS manipulating drugs, increased antioxidant capacity attenuates their susceptibility to cancer treatment. Excessive environmental stress, on the other hand, can cause cancer cells to die. This review summarizes various molecular mechanisms including the role of checkpoint inhibitors that can be harnessed to develop effective therapeutic strategies for targeting ROS related signaling in cancer. © The Author(s) 2022.