Papers by Venil N Sumantran
Indian Journal of Community Medicine
Background: The CRISPR-Cas (clustered regularly interspaced short palindromic repeats–CRISPR-asso... more Background: The CRISPR-Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) systems are the short DNA sequences and RNA-dependent nuclease involved in the adaptive immunity in bacteria and archaea. The type of CRISPR-Cas system influences antibiotic susceptibility in Klebsiella pneumoniae. Here, our objective was to study the diversity of CRISPR-Cas system in the genome of K. pneumoniae from the available whole genome sequencing (WGS) data. Material and Methods: We identified the CRISPR-Cas systems of K. pneumoniae using the CRISPR-CasFinder database. The complete genome sequence and its submission details were obtained from the National Center for Biotechnology Information (NCBI) database. Results: A total of 1607 K. pneumoniae whole genome sequences were analyzed. The major contributors of WGS data of K. pneumoniae were China (26.6%), United States (21.5%), Australia (10%), South Korea (8%), India (5.5%), and United Kingdom (4.9%). Out of 1607...
Multitasking proteins or moonlighting proteins (MLP) play a major role in human disease and many ... more Multitasking proteins or moonlighting proteins (MLP) play a major role in human disease and many are drug targets. MLPs have a single polypeptide with two different biochemical functions and often have different cellular localizations. Analysis of MultitaskProtDB-II and Comparative Toxicogenomics databases and Gene Ontology and STRING analysis, showed that curcumin and resveratrol regulate 3 groups of MLPs. Group 1 MLPs drive epithelial mesenchymal transition (EMT), whereas MLPs in groups 2 and 3 regulate tumour growth and suppression, respectively. The 3 groups of MLPs form a complex self-regulating network due to regulatory interactions between MLPs and the presence of transcription factors (CTNNB1, p53, NRF2) with their regulators and targets. Curcumin and/or resveratrol downregulate MLPs which drive EMT (CTNNB1, FASN, SMADs 2,3,4, MECP2, MMP2, TGFβR1, HES1) and promote growth and inflammation (MMP2, EGFR, FGF2, MDR1). Second, curcumin and/or resveratrol modulate pleiotropic, regulatory ‘hub’ MLPs (GSK3, NOTCH1, HMGB1). Third, both phytochemicals upregulate tumour suppressor CDH1, and CYCS, which triggers apoptosis. Fourth, both phytochemicals modulate p53 expression, activity, and independently downregulate tumorigenic gene targets of p53 in groups 1 and 2. This dual mechanism can permit regulation of p53 activity in cells with wild type or mutant p53. Fifth, moonlighting functions of specific MLPs can cause unpredictable effects. These results add insights into synergistic and pleiotropic anti-cancer mechanisms of curcumin and resveratrol. It has clinical relevance because both phytochemicals are chemo-preventive agents and chemosensitizers in clinical trials.
Microarray and pattern miner analysis of AXL and VIM gene networks in MDA‑MB‑231 cells, 2018
MDA-MB-231 cells represent malignant triple-negative breast cancer, which overexpress epidermal g... more MDA-MB-231 cells represent malignant triple-negative breast cancer, which overexpress epidermal growth factor receptor (EGFR) and two genes (AXL and VIM) associated with poor prognosis. The present study aimed to identify novel therapeutic targets and elucidate the functional networks for the AXL and VIM genes in MDA-MB-231 cells. We identified 71 genes upregulated in MDA-MB-231 vs. MCF7 cells using BRB-Array tool to re-analyse microarray data from six GEO datasets. Gene ontology and STRING analysis showed that 43/71 genes upregulated in MDA-MB-231 compared with MCF7 cells, regulate cell survival and migration. Another 19 novel genes regulate migration, metastases, senescence, autophagy and chemoresistance. The Pattern Miner systems biology tool uses specific genes as inputs or 'baits' to identify outputs from the NCI-60 database. Using five genes regulating cancer cell migration (AXL, VIM, EGFR, CAPN2, and COL4A1) as input 'baits', we used pattern miner to identify statistically significant, co-expressed genes from the list of 71 genes upregulated in MDA-MB-231 compared with MCF7 cells. Outputs were subsets of the 71 genes, which showed significant co-expression with one or more of the five input genes. These outputs were used to develop functional networks for AXL and VIM. Analysis of these networks verified known properties of AXL and VIM, and suggested novel functions for these two genes. Thus, genes in the AXL network promote migration, metastasis and chemoresistance, whereas the VIM gene network regulates novel tumorigenic processes, such as lipogenesis, senescence and autophagy. Notably, these two networks contain 12 genes not reported for TNBC.
Intussusceptive angiogenesis as a key therapeutic target for cancer therapy, 2020
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the author's institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are
Nitric oxide mitigates thalidomide-induced abnormalities during germination and development of fennel seeds, 2021
Thalidomide causes teratogenic effects in several animal species and in humans. Accordingly, the ... more Thalidomide causes teratogenic effects in several animal species and in humans. Accordingly, the World Health Organization banned thalidomide when mothers who took thalidomide during pregnancy delivered abnormal fetuses. After four decades, thalidomide underwent drug "re-purposing" since its antiangiogenic and immunomodulatory effects were therapeutic for multiple myeloma. There are no reports of thalidomide's effects on prokaryotes, but it showed teratogenic effects in Arabidopsis thaliana, an ancestor of the plant kingdom. This proof of concept study clearly shows that thalidomide caused a significant and reproducible decrease in germination rate, nitric oxide (NO) production, and chlorophyll content of fennel plantlets. Thalidomide also induced the formation of abnormal fennel plantlets with stunting, wrinkling, and curling of fennel shoots and leaves. Notably, quantitative analysis showed that thalidomide caused a 50% increase in the formation of abnormal fennel plantlets and that these negative effects of thalidomide showed a 2.50-to 4-fold decrease when fennel seeds were co-incubated with an NO donor (Spermine NoNoate) or a stable cGMP analog 8-bromo Guanosine 3 ,5-cyclic monophosphate (8-Bromo-cGMP). This study is important because it confirms that thalidomide's negative effects on fennel seed germination and growth are mediated by attenuation of NO and disruption of NO signaling. This reproducible model of thalidomide-induced, NO-dependent damage in a plant system can be used to further investigate the molecular mechanisms of thalidomide action in plants. Importantly, this study establishes a link between the evolution of development of higher plants and mammals.
Methods in Molecular Biology, 2011
Data on cell viability have long been obtained from in vitro cytotoxicity assays. Today, there is... more Data on cell viability have long been obtained from in vitro cytotoxicity assays. Today, there is a focus on markers of cell death, and the MTT cell survival assay is widely used for measuring cytotoxic potential of a compound. However, a comprehensive evaluation of cytotoxicity requires additional assays which -measure short and long-term cytotoxicity. Assays which measure the cytostatic effects of compounds are not less important, particularly for newer anticancer agents. This overview discusses the advantages and disadvantages of different non-clonogenic assays for measuring short and medium-term cytotoxicity. It also discusses clonogenic assays, which accurately measure long-term cytostatic effects of drugs and toxic agents. For certain compounds and cell types, the advent of high throughput, multiparameter, cytotoxicity assays, and gene expression assays have made it possible to predict cytotoxic potency in vivo.
Evidence-Based Complementary and Alternative Medicine, 2012
A recent, exciting discovery relates to the concept of “shared pathology” between cancer and meta... more A recent, exciting discovery relates to the concept of “shared pathology” between cancer and metabolic syndrome. One major pathway common to cancer and metabolic syndrome is chronic inflammation, which is a major driving force in carcinogenesis. Indeed, chronic inflammation precedes most cancers and is considered a “hallmark” of the neoplastic process. We discuss molecular and biochemical evidence which links diet, obesity, abnormal lipid metabolism, and type 2 diabetes mellitus with chronic inflammation. We also explain how each of these factors is linked with biochemical aberrations of carcinogenesis and the prevalence and risk of cancer. While there are reliable biomarkers for chronic inflammation, there are few markers for a mechanistic link between early inflammation and digestive disorders. Discovery of such a marker could lead to identification of a new subtype of patients with digestive disorders that predispose them to cancer and/or metabolic syndrome. In this context, we d...
Current Bioinformatics, 2014
Journal of the Society for Gynecologic Investigation, 1998
ABSTRACT
Journal of Ayurveda and Integrative Medicine
This 'discussion paper' raises 'provocative questions' to identify physiological systems underlyi... more This 'discussion paper' raises 'provocative questions' to identify physiological systems underlying vata dosha and candidate biomarkers for vata activity. We explained the strong correlations between survival and homeostatic functions of the parasympathetic vagus nerve, and functions governed by the five major sub-types of vata dosha (Praana, Udana, Vyaana, Samaana, and Apana). Four reasons were provided to hypothesize that vagal activity is a reliable candidate biomarker of important vata dosha functions. First, normal vata dosha and the vagus maintain neural, respiratory, and digestive homeostasis, and dysfunctions in both entities cause very similar diseases. Second, vata dosha regulates higher neural functions such as mental health and behaviour, and the 'polyvagal theory' proposes similar functions for the vagus. Third, the similar roles of vata dosha and vagus in maintaining gut homeostasis, suggest that vagal activity in the 'gut-brain' link is a candidate biomarker of pakwashaya (lower gut), a primary regulatory site for vata dosha. Fourth, the vagus is the only vital nerve whose activity can be reliably measured and manipulated. Indeed, vagal nerve stimulation is a USA-FDA approved therapy for certain ailments attributed to impaired vata dosha. No other nerve or dosha, has such multi-functional and life-sustaining properties. These arguments position vagal activity as a suitable candidate biomarker for certain functions of vata dosha.
The Indian journal of medical research, Nov 1, 2017
Proliferative vitreoretinopathy (PVR) is characterized by the presence of epiretinal membrane (ER... more Proliferative vitreoretinopathy (PVR) is characterized by the presence of epiretinal membrane (ERM), which exerts traction and detaches the retina. Epithelial to mesenchymal transition (EMT) of the retinal pigment epithelial (RPE) cells underlies ERM formation. Adjuvant therapies aimed at preventing recurrence of PVR after surgery mostly failed in clinical trials. This study was aimed to evaluate the anti-EMT properties of bio-active compounds epigallocatechin gallate (EGCG), curcumin and lycopene as inhibitors of EMT induced by transforming growth factor beta 1 (TGF-β1) in cultured ARPE-19 cells. ARPE-19 cells were treated with TGF-β1 alone or co-treated with EGCG (1-50 μM), lycopene (1-10 μM) and curcumin (1-10 μM). The mRNA and protein expression of EMT markers, alpha-smooth muscle actin, vimentin, zonula occludens-1 and matrix metalloproteinase-2 (MMP-2), were assessed by reverse transcription polymerase chain reaction/quantitative polymerase chain reaction and immunofluorescenc...
National Journal of Physiology, Pharmacy and Pharmacology
Background: Toll-like receptors (TLRs) are key sensors of microbial components and triggers signa... more Background: Toll-like receptors (TLRs) are key sensors of microbial components and triggers signals responsible for the activation of innate immune responses. Unmethylated cytosine-guanosine oligodeoxynucleotides called CpG ODNs act as a ligand for TLR9. Aims and Objectives: The present study was conducted to determine whether the presence of antimycotic amphotericin B (AmB) used in the culture medium has any profound effect on MCF-7 cells treated with CpG. Materials and Methods: MCF-7, a breast adenocarcinoma cell line, was cultured and maintained in the media with the absence of AmB (Group 1) and presence of AmB at 0.25 µg/ml (Group 2). The morphology of MCF-7 cells grown in these two groups of media was assessed, and the cytotoxicity of CpG treated in both the groups was evaluated by MTT assay. Results: Visualizing the monolayer of MCF-7 cells grown in two groups of media revealed identical morphology, growth pattern, and confluence. MCF-7 cells in Group 1 media treated with the CpG ODN at 1, 2, and 3 µM for 24 h showed a dose-dependent cytotoxicity in 13%, 18%, and 22% of the cells, respectively, whereas treatment with CpG ODN at 1, 2, and 3 µM for 48 h demonstrated a better cytotoxicity of 16%, 27%, and 37% of cells, respectively. On the other hand, MCF-7 cells in Group 2 media treated with the CpG ODN at 1, 2, and 3 µM for 24 h and 48 h showed poor cytotoxic effect. Conclusion: While comparing the effect of CpG ODN in Group 1 (AmB−) versus Group 2 (AmB+) for 24-and 48-h duration in MCF-7 cells evidenced that the response of CpG ODN was significantly different between the two groups (P < 0.01). The results strongly evidenced that the presence of AmB in culture media during the maintenance of cell line shown to decrease the cytotoxic effects of CpG ODN. Hence, the present study suggests to avoid using AmB in cell culture, particularly while conducting in vitro studies related to TLR signaling.
Reproductive Toxicology, 2017
Certain metals have been known for their toxic effects on embryos and fetal development. The vasc... more Certain metals have been known for their toxic effects on embryos and fetal development. The vasculature in early pregnancy is extremely dynamic and plays an important role in organogenesis. Nascent blood vessels in early embryonic life are considered to be a primary and delicate target for many teratogens since the nascent blood islands follow a tightly controlled program to form vascular plexus around and inside the embryo for resourcing optimal ingredients for its development. The state of the distribution of toxic metals, their transport mechanisms and the molecular events by which they notch extra-embryonic and embryonic vasculatures are illustrated. In addition, pharmacological aspects of toxic metal induced teratogenicity have also been portrayed. The work reviewed state of the current knowledge of specific role of microRNAs (miRNAs) that are differentially expressed in response to toxic metals, and how they interfere with the vasculogenesis that manifests into embryonic anomalies.
Scientific reports, Jun 27, 2016
Nitric oxide (NO), a vascular signaling molecule, is primarily produced by endothelial NO synthas... more Nitric oxide (NO), a vascular signaling molecule, is primarily produced by endothelial NO synthase. Recently, a functional endothelial NO synthase (eNOS) was described in red blood cells (RBC). The RBC-eNOS contributes to the intravascular NO pool and regulates physiological functions. However the regulatory mechanisms and clinical implications of RBC-eNOS are unknown. The present study investigated regulation and functions of RBC-eNOS under mechanical stimulation. This study shows that mechanical stimuli perturb RBC membrane, which triggers a signaling cascade to activate the eNOS. Extracellular NO level, estimated by the 4-Amino-5-Methylamino-2', 7'-Difluorofluorescein Diacetate probe, was significantly increased under mechanical stimuli. Immunostaining and western blot studies confirmed that the mechanical stimuli phosphorylate the serine 1177 moiety of RBC-eNOS, and activates the enzyme. The NO produced by activation of RBC-eNOS in vortexed RBCs promoted important endoth...
Proceedings of the National Academy of Sciences, 1995
Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. To determine th... more Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. To determine the role of these proteins in maintaining cancer cell viability, an adenovirus vector that expresses bcl-xs, a functional inhibitor of these proteins, was constructed. Even in the absence of an exogenous apoptotic signal such as x-irradiation, this virus specifically and efficiently kills carcinoma cells arising from multiple organs including breast, colon, stomach, and neuroblasts. In contrast, normal hematopoietic progenitor cells and primitive cells capable of repopulating severe combined immunodeficient mice were refractory to killing by the bcl-xs adenovirus. These results suggest that Bcl-2 family members are required for survival of cancer cells derived from solid tissues. The bcl-xs adenovirus vector may prove useful in killing cancer cells contaminating the bone marrow of patients undergoing autologous bone marrow transplantation.
Journal of Pediatric Hematology/Oncology, 2009
Journal of Biosciences, 2007
Journal of Biosciences, 2007
Commiphora mukul were known as myrrh. In Ayurvedic literature, myrrh oleoresins are referred to a... more Commiphora mukul were known as myrrh. In Ayurvedic literature, myrrh oleoresins are referred to as guggulu. Guggulu destroys ama (bodily wastes and toxins), boosts metabolism and strength, and rejuvenates the body. Excessive ama plays a major role in the aetiopathology of rheumatoid arthritis. A study reported the anti-infl ammatory activity of crystalline steroids from C. mukul resin (Arora et al 1971). In a clinical trial, C. mukul capsules administered to patients with osteoarthritis (OA) of the knee led to signifi cant improvement without side-effects (Singh et al 2003). However, there are no in vitro studies examining the chondroprotective mechanisms underlying the anti-arthritic activity of C. mukul. This study focused on Triphala guggulu (TG), a major guggulu-based formulation for the treatment of acute arthritis
Investigative Ophthalmology & Visual Science, 2010
Evidence-Based Complementary and Alternative Medicine, 2008
There is a need for effective nutraceuticals for osteoarthritis care. The fruit ofPhyllanthus emb... more There is a need for effective nutraceuticals for osteoarthritis care. The fruit ofPhyllanthus emblicais used as a powerful rejuvenator in Ayurvedic medicine. This study measured the chondroprotective potential ofP. emblica(‘Amalaki’) fruitsin vitro. We used aqueous extracts of unprocessedP. emblicafruit powder (powder A), and the powder obtained after hot water extraction and drying of powder A (powder B). Chondroprotection was measured in three different assay systems. First, we tested the effects of both fruit powders on the activities of the enzymes hyaluronidase and collagenase type 2. Second, anin vitromodel of cartilage degradation was set-up with explant cultures of articular knee cartilage from osteoarthritis patients. Cartilage damage was assayed by measuring glycosaminoglycan release from explants treated with/withoutP. emblicafruit powders. Aqueous extracts of both fruit powders significantly inhibited the activities of hyaluronidase and collagenase type 2in vitro. Third,...
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Papers by Venil N Sumantran