Browsing by Author "Shruti Mishra"

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Arsenite treatment induces oxidative stress, upregulates antioxidant system, and causes phytochelatin synthesis in rice seedlings
(2011) Shruti Mishra; A.B. Jha; R.S. Dubey
The effects of arsenite treatment on generation of reactive oxygen species, induction of oxidative stress, response of antioxidative system, and synthesis of phytochelatins were investigated in two indica rice (Oryza sativa L.) cvs. Malviya-36 and Pant-12 grown in sand cultures for a period of 5-20 days. Arsenite (As 2O 3 25 and 50 μM) treatment resulted in increased formation of superoxide anion (O 2 .-), elevated levels of H 2O 2 and thiobarbituric acid reactive substances, showing enhanced lipid peroxidation. An enhanced level of ascorbate (AA) and glutathione (GSH) was observed irrespective of the variation in the level of dehydroascorbate (DHA) and oxidized glutathione (GSSG) which in turn influenced redox ratios AA/DHA and GSH/GSSG. With progressive arsenite treatment, synthesis of total acid soluble thiols and phytochelatins (PC) increased in the seedlings. Among antioxidative enzymes, the activities of superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), total ascorbate peroxidase (APX, EC 1.11.1.11), chloroplastic ascorbate peroxidase, guaiacol peroxidase (EC 1.11.1.7), monodehydroascorbate reductase (EC 1.6.5.4), and glutathione reductase (EC 1.6.4.2) increased in arsenite treated seedlings, while dehyroascorbate reductase (EC 1.8.5.1) activity declined initially during 5-10 days and increased thereafter.Results suggest that arsenite treatment causes oxidative stress in rice seedlings, increases the levels of many enzymatic and non-enzymatic antioxidants, and induces synthesis of thiols and PCs, which may serve as important components in mitigating arsenite-induced oxidative damage. © 2010 Springer-Verlag.
Changes in phosphate content and phosphatase activities in rice seedlings exposed to arsenite
(2008) Shruti Mishra; R.S. Dubey
The effect of arsenite (As2O3) in situ on the level of the phosphate pool and activities of phosphohydrolytic enzymes was examined in rice (Oryza sativa L.) seedlings grown for 5-20 d in sand cultures. The effects were manifested via a decline in phosphate content and inhibition of the activities of key phosphatases. Application of 50 μM As2O 3 in situ resulted in 34 to 77% inhibition of acid phosphatase activity in roots and about 38 to 50% inhibition of activity in shoots of 15-20-d-old seedlings. Similarly, alkaline phosphatase activity was inhibited in shoots under in situ As (III) toxicity. Varietal as well as organ specific differences were observed in the response of inorganic pyrophosphatase activity to in situ As (III) treatment. A moderately toxic in situ As2O 3 level of 25 μM as well as a highly toxic level of 50 μM inhibited mitochondrial-ATPase activity whereas 25 μM As (III) stimulated the chloroplastic isoform of ATPase but at a higher level (50 μM) As (III) was inhibitory. The results suggest that exposure of rice plants to arsenite leads to lowering of the phosphate pool and alteration in the activities of key phosphohydrolytic enzymes which might contribute to metabolic perturbations and decreased growth of rice plants in an As (III) polluted environment.
Comparison of flowcytometry-based scoring system for the diagnosis of early T precursor-acute lymphoblastic leukemia
(John Wiley and Sons Inc, 2023) Deepak Marballi Basavaraju; Shruti Mishra; Gaurav Chhabra; Sudarshan Chougule
Background: Early T cell precursor-acute lymphoblastic leukemia (ETP-ALL) is a hematolymphoid malignancy where the blasts demonstrate T cell differentiation markers along with stem cell and myeloid antigen expression. The differential diagnosis of ETP-ALL from non-ETP ALL and mixed phenotype acute leukemia is often challenging due to its overlapping immunophenotypic picture with co-expression of myeloid antigens. In this study, we endeavored to describe the immune-phenotype profile of ETP-ALL in our patients and compared the utility of four different scoring systems for better discrimination of these entities. Methods: This retrospective analysis included 31 ETP-ALL out of 860 acute leukemia cases consecutively diagnosed at the two tertiary care centers. Flowcytometry-based immunophenotype was reviewed for all the cases, and the utility of four flow-based objective scorings was assessed for the diagnosis of ETP-ALL. Receiver operating curves were drawn to compare the different flow-based scoring systems. Results: The prevalence of ETP-ALL was 40% (n = 31/77 T-ALL) in our study group, comprised mainly of adults with a median age of 20 years. The five-marker scoring system had the maximum area under the curve, followed by the seven-marker scoring system. A cut-off of ≥2.5 was more specific (sensitivity: 91%; specificity: 100%), while a score of ≥1.5 was more sensitive but slightly less specific (sensitivity: 94%, specificity: 96%). Conclusion: The WHO criteria for the diagnosis of ETP-ALL should be followed across all laboratories to avoid confusion and for better treatment stratification. Flow-based scoring systems can be objectively employed for better detection of cases. © 2023 International Clinical Cytometry Society.
Curcuma raktakanda induces apoptosis and suppresses migration in cancer cells: Role of reactive oxygen species
(MDPI AG, 2019) Shruti Mishra; Sumit Singh Verma; Vipin Rai; Nikee Awasthee; Jayadev S. Arya; Kaustabh K. Maiti; Subash C. Gupta
Although over 100 species of Curcuma are reported, only Curcuma longa is extensively studied. Curcuma raktakanda, a poorly studied species, is most commonly distributed in the Kerala state of India. For the first time, we examined the efficacy of different fractions (acetone, hexane, and ethyl acetate) of C. raktakanda against glioma, cervical, and breast cancer cell lines. As determined by mitochondrial reductase activity assay, the viability of cancer cells was decreased in a concentration-dependent manner by the three fractions. The half maximal inhibitory concentration (IC-50) values after the treatment of C-6 glioma cells for 48 h was found to be 32.97 μg/mL (acetone extract), 40.63 μg/mL (hexane extract), and 51.65 μg/mL (ethyl acetate extract). Of the three fractions, the acetone fraction was more effective. The long-term colony formation of cancer cells was significantly suppressed by the acetone fraction. Analyses using DAPI (4′,6- diamidino-2-phenylindole) staining, AO/PI (acridine orange/propidium iodide) staining, DNA laddering, and sub-G1 population revealed that the acetone extract induced apoptosis in glioma cells. The extract induced reactive oxygen species generation and suppressed the expression of cell survival proteins. The migration of cancer cells was also suppressed by the acetone extract. The gas chromatography-mass spectrometry (GC-MS) analysis indicated that tetracontane, dotriacontane, hexatriacontane, pentacosane, hexacosane, and eicosane are the major components in the acetone extract. Collectively, the extract from C. raktakanda exhibited anti-carcinogenic activities in cancer cells. We are exploring whether the phytoconstituents, individually, or collectively contribute to the anti-cancer activities of C. raktakanda. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Evaluation of antioxidant, anti-inflammatory and anticancer activities of diosgenin enriched Paris polyphylla rhizome extract of Indian Himalayan landraces
(Elsevier Ireland Ltd, 2021) Debmalya Das Gupta; Shruti Mishra; Sumit Singh Verma; Anusmita Shekher; Vipin Rai; Nikee Awasthee; Tridip J. Das; Dipayan Paul; Sanjib K. Das; Hui Tag; Subash Chandra Gupta; Pallabi K. Hui
Ethnopharmacological relevance: Traditional medicinal plants have gained attention as a potential therapeutic agent to combat cancer and inflammation. Diosgenin rich fresh extracts of Paris polyphylla rhizome from Indian Himalaya is traditionally used as wound healing, anti-bleeding, anti-inflammatory and anti-cancer agent by the folk healers. Aim of the study: Present study was aimed to prepare two types of extracts from Paris polyphylla rhizome of Indian Himalayan landraces – 1. ethanolic extract of Paris polyphylla rhizome (EEPPR) and 2. Diosgenin enriched Paris polyphylla rhizome extract (DPPE), quantification of diosgenin content, and to evaluate their in vitro anti-oxidant, in vivo anti-inflammatory and in vitro cytotoxicity and anti-cancer activities of the DPPE. Materials and methods: Diosgenin content of EEPPR was quantified through GC-MS while diosgenin content of DPPE was quantified through HPTLC, and the diosgenin yield from EEPPR and DPPE were compared. In vitro antioxidant activities of DPPE were performed using DPPH, NOD, RP and SOD assay while in vivo anti-inflammatory activity of DPPE were evaluated in dextran induced hind paw edema in rats. In vitro cytotoxicity and anti-cancer activities of DPPE were evaluated in human breast cancer cell lines (MCF-7, MDA-MB-231), cervical cancer cell lines (HeLa) and Hep-2 cell lines. Results: EEPPR obtained through cold extraction method using 70% ethanol showed maximum diosgenin content of 17.90% quantified through GC-MS while similar compounds pennogenin (3.29%), 7β-Dehydrodiosgenin (1.90%), 7-Ketodiosgenin acetate (1.14%), and 7 β-hydroxydiosgenin (0.55%) were detected in low concentration, and thus confirmed diosgenin as major and lead phytochemical. However, DPPE obtained through both cold and repeated hot extraction with the same solvent (70% ethanol) showed diosgenin content of 60.29% which is significantly higher (p < 0.001) than the diosgenin content in EEPPR. DPPE demonstrated significant in vitro antioxidant activities by dose-dependently quenched (p < 0.001) SOD free radicals by 76.66%, followed by DPPH (71.43%), NOD (67.35%), and RP (63.74%) at a max concentration of 2 μg/μl of ascorbic acid and test drugs with remarkable IC50 values (p < 0.01). Further, DPPE also showed potent anti-inflammatory activities by dose-dependently suppressed dextran induced paw edema in rats (p < 0.01) from 2 h to 4 h. DPPE suppressed the proliferation of MCF-7, MDA-MB-231, Hep-2 and HeLa cell lines. Maximum activity was observed in MCF-7 cells. The DPPE also induced apoptosis in MCF-7 cell lines as measured by AO/PI and DAPI staining, as well as DNA laddering, cell cycle analysis and phosphatidylserine externalization assay. The growth-inhibitory effect of DPPE on MCF-7 breast cancer cells was further confirmed from the colony-formation assay. DPPE upregulated expression of Bax and downregulated Bcl-2 and survivin mRNA transcripts. Conclusion: DPPE obtained through both cold and repeated hot extraction using ethanol showed significantly higher content of diosgenin than the diosgenin content detected in EEPPR. However, diosgenin yield of both the extracts (EEPPR & DPPE) clearly confirmed diosgenin as major and lead phytochemical of Paris polyphylla rhizome of Indian Himalayan landraces. Further, DPPE also demonstrated potent in vitro anti-oxidative and in vivo anti-inflammatory activities and showed in vitro cytotoxicity and significant anti-cancer (apoptosis) effects in MCF-7 breast cancer cells. © 2021
FtsZ phosphorylation brings about growth arrest upon DNA damage in Deinococcus radiodurans
(John Wiley and Sons Inc, 2023) Reema Chaudhary; Shruti Mishra; Ganesh K. Maurya; Yogendra S. Rajpurohit; Hari S. Misra
The polymerization/depolymerization dynamics of FtsZ play a pivotal role in cell division in the majority of the bacteria. Deinococcus radiodurans, a radiation-resistant bacterium, shows an arrest of growth in response to DNA damage with no change in the level of FtsZ. This bacterium does not deploy LexA/RecA type of DNA damage response and cell cycle regulation, and its genome does not encode SulA homologues of Escherichia coli, which attenuate FtsZ functions in response to DNA damage in other bacteria. A radiation-responsive Ser/Thr quinoprotein kinase (RqkA), characterized for its role in radiation resistance in this bacterium, could phosphorylate several cognate proteins, including FtsZ (drFtsZ) at Serine 235 (S235) and Serine 335 (S335) residues. Here, we reported the detailed characterization of S235 and S335 phosphorylation effects in the regulation of drFtsZ functions and demonstrated that the phospho-mimetic replacements of these residues in drFtsZ had grossly affected its functions that could result in cell cycle arrest in response to DNA damage in D. radiodurans. Interestingly, the phospho-ablative replacements were found to be nearly similar to drFtsZ, whereas the phospho-mimetic mutant lost the wild-type protein's signature characteristics, including its dynamics under normal conditions. The kinetics of post-bleaching recovery for drFtsZ and phospho-mimetic mutant were nearly similar at 2 h post-irradiation recovery but were found to be different under normal conditions. These results highlighted the role of S/T phosphorylation in the regulation of drFtsZ functions and cell cycle arrest in response to DNA damage, which is demonstrated for the first time, in any bacteria. © 2022 The Authors. FASEB BioAdvances published by Wiley Periodicals LLC on behalf of The Federation of American Societies for Experimental Biology.
Heavy metal toxicity induced alterations in photosynthetic metabolism in plants
(CRC Press, 2005) Shruti Mishra; R.S. Dubey
Agricultural plants are exposed to various environmental stresses from planting to marketing. Growing plants require a balanced soil environment in which all components should be present in a definite ratio. The stressful conditions of the environment such as water stress, soil salinity, heat, chilling, anaerobiosis, pathogenesis, wounding, gaseous pollutants, heavy metals, etc. drastically affect plant growth and metabolism and in turn limit crop productivity. In the present-day situation, the stress factors have multiplied in an exponential manner with the advent of modern agricultural and industrial practices. © 2005 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business.
Implementation of flow cytometry testing on rare matrix samples: Special considerations and best practices when the sample is unique or difficult to obtain
(John Wiley and Sons Inc, 2025) Katherine A. Devitt; Wolfgang Kern; Małgorzata A. Kajstura; Eda K. Holl; Amanda L. Hays; Benjamin D. Hedley; Christèle Gonneau; Evan R. Jellison; Thomas W. McCloskey; Shruti Mishra; Jennifer Rebeles; Madhu M. Ouseph
The publication of Clinical and Laboratory Standards Institute's guideline H62 has provided the flow cytometry community with much-needed guidance on development and validation of flow cytometric assays (CLSI, 2021). It has also paved the way for additional exploration of certain topics requiring additional guidance. Flow cytometric analysis of rare matrices, or unique and/or less frequently encountered specimen types, is one such topic and is the focus of this manuscript. This document is the result of a collaboration subject matter experts from a diverse range of backgrounds and seeks to provide best practice consensus guidance regarding these types of specimens. Herein, we define rare matrix samples in the setting of flow cytometric analysis, address validation implications and challenges with these samples, and describe important considerations of using these samples in both clinical and research settings. © 2024 The Author(s). Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.
Inhibition of ribonuclease and protease activities in arsenic exposed rice seedlings: Role of proline as enzyme protectant
(Elsevier GmbH, 2006) Shruti Mishra; Rama Shanker Dubey
When seedlings of two rice (Oryza sativa L.) cvs. Malviya-36 and Pant-12 were raised under 25 and 50 μM As2O3 in the medium an increase in the level of RNA, proteins and proline accompanied with a decline in the level of free amino acid pool was observed under arsenic supplementation compared to controls. In situ As3+ treatment caused a marked inhibition in activities of ribonuclease (RNase, EC 3.1.27.1), protease and leucine aminopeptidase (LAP, EC 3.4.11.1) whereas the activity level of carboxypeptidase (EC 3.4.16.5) was enhanced. In vitro supply of As2O3 in the enzyme assay medium beyond 400 μM resulted in gradual inhibition of RNase and beyond 5 μM inhibition of LAP activities. Addition of 1 M proline in the assay medium significantly restored the loss in RNase activity due to in vitro arsenic treatment or due to osmotic stress created by incorporation of polyethylene glycol (PEG). Isoform pattern of RNase extracted from As3+-exposed seedlings showed a significant alteration compared to its pattern in unexposed seedlings. Results suggest that arsenic exposure impairs hydrolysis of RNA and proteins in rice seedlings due to inhibition of RNase and proteases activities and that proline accumulating under As3+ toxicity appears to serve as enzyme protectant. © 2005 Elsevier GmbH. All rights reserved.
Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases
(Springer Science and Business Media Deutschland GmbH, 2019) Shruti Mishra; Sumit S. Verma; Vipin Rai; Nikee Awasthee; Srinivas Chava; Kam Man Hui; Alan Prem Kumar; Kishore B. Challagundla; Gautam Sethi; Subash C. Gupta
The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. The common lncRNAs known to be modulated by phytochemicals include ROR, PVT1, HOTAIR, MALAT1, H19, MEG3, PCAT29, PANDAR, NEAT1, and GAS5. The phytochemicals such as curcumin, resveratrol, sulforaphane, berberine, EGCG, and gambogic acid have been examined against lncRNAs. In some cases, formulation of phytochemicals has also been used. The disease models where phytochemicals have been demonstrated to modulate lncRNAs expression include cancer, rheumatoid arthritis, osteoarthritis, and nonalcoholic fatty liver disease. The regulation of lncRNAs by phytochemicals can affect multi-steps of tumor development. When administered in combination with the conventional drugs, phytochemicals can also produce synergistic effects on lncRNAs leading to the sensitization of cancer cells. Phytochemicals target lncRNAs either directly or indirectly by affecting a wide variety of upstream molecules. However, the potential of phytochemicals against lncRNAs has been demonstrated mostly by preclinical studies in cancer models. How the modulation of lncRNAs by phytochemicals produce therapeutic effects on cancer and other chronic diseases is discussed in this review. © Springer Nature Switzerland AG 2019.
Molecular Diagnostics in Pancreatic Cancer
(Springer Singapore, 2019) Shruti Mishra; Vipin Rai; Abhai Kumar; Sushil Kumar Aggarwal; Subash Chandra Gupta
[No abstract available]
Moringin, an isothiocyanate modulates multiple cellular signalling molecules in breast cancer cells
(Elsevier Inc., 2024) Ankit Srivastava; Shruti Mishra; Avadhesh; Anusmita Shekher; Vipin Rai; Anupam Dhasmana; Jayanta Das; Daniele Perenzoni; Renato Iori; Subash C. Gupta
Prohibitin (PHB) is a pleiotropic molecule with a variety of known functions and subcellular locations. PHB's function in breast cancer is poorly understood. Herein, we report that PHB is expressed in cancer types of diverse origin including breast cancer. The cancer patients with changes in PHB were reported to have significantly reduced ‘overall survival’ in comparison to the cases without alterations in PHB. The expression of PHB was increased by H2O2 and also by Moringin (MG), which is an isothiocyanate derived from the seeds of Moringa oleifera. MG interacted with PHB, DRP1, and SLP2 and inhibited the growth of MCF-7 and MDAMB-231 cells. The isothiocyanate triggered apoptosis in breast cancer cells as revealed by AO/PI assay, phosphatidylserine externalization, cell cycle analysis and DAPI staining. MG induced proapoptotic proteins expression such as cytochrome c, p53, and cleaved caspase-7. Further, cell survival proteins such as survivin, Bcl-2, and Bcl-xL were suppressed. A depolarization of membrane potential suggested that the apoptosis was triggered through mitochondria. The isothiocyanate suppressed the cancer cell migration and interacted with NF-κB subunits. MG suppressed p65 nuclear translocation induced by TNF-α. The reactive oxygen species generation was also induced by the isothiocyanate in breast cancer cells. MG also modulated the expression of lncRNAs. Collectively, the functions of PHB in breast cancer growth is evident from this study. The activities of MG against breast cancer might result from its ability to modulate multiple cancer-related targets. © 2023
Navigating Lineage Ambiguity: A Diagnostic Pitfall Between ETP-ALL and MPAL
(Springer, 2025) Induparkavi Murugesan; Shruti Mishra; Deepa Rani; Venkat Raj
[No abstract available]
Oxidative Stress and Cancer Development: Are Noncoding RNAs the Missing Links?
(Mary Ann Liebert Inc., 2020) Leonard Clinton D'Souza; Shruti Mishra; Anirban Chakraborty; Anusmita Shekher; Anurag Sharma; Subash Chandra Gupta
Significance: It is now clear that genetic changes underlie the basis of cancer, and alterations in functions of multiple genes are responsible for the process of tumorigenesis. Besides the classical genes that are usually implicated in cancer, the role of noncoding RNAs (ncRNAs) and reactive oxygen species (ROS) as independent entitites has also been investigated. Recent Advances: The microRNAs and long noncoding RNAs (lncRNAs), two main classes of ncRNAs, are known to regulate many aspects of tumor development. ROS, generated during oxidative stress and pathological conditions, are known to regulate every step of tumor development. Conversely, oxidative stress and ROS producing agents can suppress tumor development. The malignant cells normally produce high levels of ROS compared with normal cells. The interaction between ROS and ncRNAs regulates the expression of multiple genes and pathways implicated in cancer, suggesting a unique mechanistic relationship among ncRNA-ROS-cancer. The mechanistic relationship has been reported in hepatocellular carcinoma, glioma, and malignancies of blood, breast, colorectum, esophagus, kidney, lung, mouth, ovary, pancreas, prostate, and stomach. The ncRNA-ROS regulate several cancer-related cell signaling pathways, namely, protein kinase B (AKT), epidermal growth factor receptor (EGFR), forkhead box O3 (FOXO3), kelch-like ECH-associated protein 1 (Keap1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), p53, phosphatase and tensin homologue (PTEN), and wingless-related integration site (Wnt)/glycogen synthase kinase-3 beta (GSK3β). Critical Issues: To date, most of the reports about ncRNA-oxidative stress-carcinogenesis relationships are based on cell lines. The mechanistic basis for this relationship has not been completely elucidated. Future Directions: Attempts should be made to explore the association of lncRNAs with ROS. The significance of the ncRNA-oxidative stress-carcinogenesis interplay should also be explored through studies in animal models. © 2020, Mary Ann Liebert, Inc., publishers.
PD-L1, inflammation, non-coding RNAs, and neuroblastoma: Immuno-oncology perspective
(Academic Press, 2018) Palanisamy Nallasamy; Srinivas Chava; Sumit S. Verma; Shruti Mishra; Santhi Gorantla; Don W. Coulter; Siddappa N. Byrareddy; Surinder K. Batra; Subash C. Gupta; Kishore B. Challagundla
Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system. Chronic inflammation is involved in the recruitment of leukocytes, production of cytokines and chemokines that in turn, lead to survival, metastasis, and angiogenesis in neuroblastoma tumors. The miRNAs and long non-coding (lnc) RNAs have emerged as a novel class of non-coding RNAs that can regulate neuroblastoma associated cell-signaling pathways. The dysregulation of PD-1/PD-L1, inflammatory pathways, lncRNAs, and miRNAs have been reported in clinical and experimental samples of neuroblastoma. These signaling molecules are currently being evaluated for their potential as the biomarker and therapeutic targets in the management of neuroblastoma. A monoclonal antibody called dinutuximab (Unituxin) that attaches to a carbohydrate molecule GD2, on the surface of many neuroblastoma cells, is being used as an immunotherapy drug for neuroblastoma treatment. Atezolizumab (Tecentriq), an engineered monoclonal antibody against PD-L1, are currently in clinical trial for neuroblastoma patients. The lncRNA/miRNA-based therapeutics is being developed to deliver tumor suppressor lncRNAs/miRNAs or silencing of oncogenic lncRNAs/miRNAs. The focus of this review is to discuss the current knowledge on the immune checkpoint molecules, PD-1/PD-L1 signaling, inflammation, and non-coding RNAs in neuroblastoma. © 2017 Elsevier Ltd
Piperlongumine, a piper alkaloid, enhances the efficacy of doxorubicin in breast cancer: involvement of glucose import, ROS, NF-κB and lncRNAs
(Springer, 2022) Nikee Awasthee; Anusmita Shekher; Vipin Rai; Sumit S. Verma; Shruti Mishra; Anupam Dhasmana; Subash C. Gupta
Piperlongumine (PL, piplartine) is an alkaloid derived from the Piper longum L. (long pepper) roots. Originally discovered in 1961, the biological activities of this molecule against some cancer types was reported during the last decade. Whether PL can synergize with doxorubicin and the underlying mechanism in breast cancer remains elusive. Herein, we report the activities of PL in numerous breast cancer cell lines. PL reduced the migration and colony formation by cancer cells. An enhancement in the sub-G1 population, reduction in the mitochondrial membrane potential, chromatin condensation, DNA laddering and suppression in the cell survival proteins was observed by the alkaloid. Further, PL induced ROS generation in breast cancer cells. While TNF-α induced p65 nuclear translocation, PL suppressed the translocation in cancer cells. The expression of lncRNAs such as MEG3, GAS5 and H19 were also modulated by the alkaloid. The molecular docking studies revealed that PL can interact with both p65 and p50 subunits. PL reduced the glucose import and altered the pH of the medium towards the alkaline side. PL also suppressed the expression of glucose and lactate transporter in breast cancer cells. In tumor bearing mouse model, PL was found to synergize with doxorubicin and reduced the size, volume and weight of the tumor. Overall, the effects of doxorubicin in cancer cells are enhanced by PL. The modulation of glucose import, NF-κB activation and lncRNAs expression may have contributory role for the activities of PL in breast cancer. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Rapid screening of dengue fever using research parameters from new generation hematological analyzers
(John Wiley and Sons Inc, 2022) Gaurav Chhabra; Bismay Das; Shruti Mishra; Baijayantimala Mishra
Introduction: The early diagnosis of dengue fever and its differentiation from other causes of acute febrile illness is essential for a better outcome. The new generation automated hematology analyzers provide parameters like high fluorescence lymphocyte count (HFLC) and leukocyte cell population data (CPD) representing various leukocytes. We tried to analyze the utility of these parameters in the rapid screening of dengue fever. Methods: The HFLC and the leukocytic CPD from the Sysmex XN1000 analyzer were obtained for 299 cases presenting with acute febrile illness, which included 97 dengue-positive and 202 cases dengue-negative controls. Additionally, 100 healthy controls were also included. The Receiver operative curves (ROC) were drawn to obtain a cut-off value for these parameters for discriminating among the dengue-positive and dengue-negative subgroups and healthy controls. Results: The dengue-positive cases showed a significantly increased HFLC among the different groups of controls. The median (range) HFLC% was 1.9(0.30–6.55), 0.20(0.10–0.70), and 0.10(0.0–0.30) in the cases that were positive for dengue, negative for dengue, and healthy controls, respectively. The ROC analysis revealed HFLC% at a cut-off value of 1.75 which can discriminate between dengue-positive and dengue-negative patients, with 52% sensitivity, 90% specificity, 72% positive predictive value (PPV), and 80% negative predictive value (NPV). The regression analysis revealed LY-X, LY-Z, Ly-WX, LY-WZ, and MO-X as independent predictors for dengue fever. Conclusion: The HFLC and CPD obtained from Sysmex XN1000 hematology analyzer are valuable tools in rapidly screening dengue infection from other febrile illnesses in routine practice. © 2022 John Wiley & Sons Ltd.