Publications by authors named "Nishant Jain"

100 Publications

Mutant IDH1 inhibitors activate pSTAT3-Y705 leading to an increase in BCAT1 and YKL-40 levels in mutant IDH1-expressing cells.

Biochim Biophys Acta Mol Cell Res 2021 10 28;1868(11):119114. Epub 2021 Jul 28.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

IDH1 mutations are frequent and early events in gliomas. Mutant IDH1 produces D-2HG that causes epigenetic changes by increasing histone and DNA methylations, thereby contributing to tumor growth. Mutant IDH1 rewires metabolism and endows a few therapeutic vulnerabilities in cells. But, mutant IDH1 inhibitor(s) treatments reverse these therapeutic vulnerabilities by increasing cell growth. Nevertheless, it is unclear how mutant IDH1 inhibitor(s) increases cell growth. As mutant IDH1 inhibitor(s) increase cell growth, therefore we asked whether mutant IDH1 inhibitor(s) activate oncogenes in mutant IDH1-expressing cells. To answer this question, we used allosteric mutant IDH1 inhibitors to treat mutant IDH1-expressing HT1080 cells, and examined for activation of oncogenes by assessing the levels of our read-outs: BCAT1 and YKL-40. We found that mutant IDH1 inhibitors' treatments increased BCAT1 and YKL-40 levels in HT1080 cells. Next, we observed that mutant IDH1 inhibitors activated STAT3 by phosphorylation at Tyr-705 position (pSTAT3-Y705) and its nuclear translocation. Upon examining the molecular mechanism of pSTAT3-Y705 activation in mutant IDH1 inhibitor-treated cells, we found that mutant IDH1 strongly bound STAT3, but mutant IDH1 inhibitor treatment decreased mutant IDH1-STAT3 binding. Furthermore, we observed that STAT3-knockdown and pharmacological inhibition of STAT3 attenuated the mutant IDH1 inhibitor-mediated increase in BCAT1 and YKL-40 levels, whereas STAT3 overexpression and Interleukin-6 (STAT3 activator) treatments increased BCAT1 and YKL-40 levels. We conclude that mutant IDH1 inhibitors activate the oncogenic transcription factor-STAT3 leading to an increase in BCAT1 and YKL-40 levels in mutant IDH1-expressing cells.
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http://dx.doi.org/10.1016/j.bbamcr.2021.119114DOI Listing
October 2021

APC/C CDH1 ubiquitinates IDH2 contributing to ROS increase in mitosis.

Cell Signal 2021 Oct 13;86:110087. Epub 2021 Jul 13.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

NADPH is a cofactor used by reactive oxygen species (ROS) scavenging enzymes to block ROS produced in cells. Recently, it was shown that in cancer cells, ROS progressively increases in tune to cell cycle leading to a peak in mitosis. Loss of IDH2 is known to cause severe oxidative stress in cell and mouse models as ROS increases in mitochondria. Therefore, we hypothesized that IDH2, a major NADPH-producing enzyme in mitochondria is ubiquitinated for ROS to increase in mitosis. To test this hypothesis, in cancer cells we examined IDH2 ubiquitination in mitosis and measured the ROS produced. We found that IDH2 is ubiquitinated in mitosis and on inhibiting anaphase-promoting complex/Cyclosome (APC/C) IDH2 was stabilized. Further, we observed that overexpressing APC/C coactivator CDH1 decreased IDH2, whereas depleting CDH1 decreased IDH2 ubiquitination. To understand the link between IDH2 ubiquitination and ROS produced in mitosis, we show that overexpressing mitochondria-targeted-IDH1 decreased ROS by increasing NADPH in IDH2 ubiquitinated cells. We conclude that APC/C CDH1 ubiquitinates IDH2, a major NADPH-producing enzyme in mitochondria contributing to ROS increase in mitosis. Based on our results, we suggest that mitosis can be a therapeutic window in mutant IDH2-linked pathologies.
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http://dx.doi.org/10.1016/j.cellsig.2021.110087DOI Listing
October 2021

Stimulation of dorsal hippocampal histaminergic transmission mitigates the expression of ethanol withdrawal-induced despair in mice.

Alcohol 2021 11 3;96:1-14. Epub 2021 Jul 3.

Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Koni, Bilaspur, Chhattisgarh, India. Electronic address:

Garnered literature points toward the role of the dorsal hippocampus (CA1) in ethanol withdrawal-induced responses, wherein a strong presence of the histaminergic system is also reported. Therefore, the present study investigated the effect of an enhanced CA1 histaminergic transmission on the expression of chronic ethanol withdrawal-induced despair in mice on the tail suspension test (TST). The results revealed that mice who were on an ethanol-fed diet (5.96%, v/v) for 8 days exhibited maximum immobility time on the TST, and decreased locomotion at 24 h post-ethanol withdrawal (10th day), indicating ethanol withdrawal-induced despair. Enhancement of CA1 histaminergic activity achieved by the treatment of intra-CA1 microinjection of histaminergic agents such as histamine (0.1, 10 μg/mouse, bilateral), the histamine precursor l-histidine (1, 10 μg/mouse, bilateral), the histamine neuronal releaser/H receptor antagonist thioperamide (2, 10 μg/mouse, bilateral), the histamine H receptor agonist FMPH (2, 6.5 μg/mouse, bilateral), or the H receptor agonist amthamine (0.1, 0.5 μg/mouse, bilateral) to ethanol-withdrawn mice, 10 min before the 24-h post-ethanol withdrawal time point, significantly alleviated the expression of ethanol withdrawal-induced despair in mice on the TST. On the other hand, only the pre-treatment of the histamine H receptor agonist FMPH (2, 6.5 μg/mouse, intra-CA1 bilateral) reversed the reduction in locomotor activity induced in ethanol-withdrawn mice, whereas other employed histaminergic agents were devoid of any effect on this behavior. Therefore, our findings indicate that an enhanced CA1 histaminergic transmission, probably via stimulation of CA1 postsynaptic histamine H or H receptor, could preclude the behavioral despair, while H stimulation affects motor deficit expressed after ethanol withdrawal.
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http://dx.doi.org/10.1016/j.alcohol.2021.06.002DOI Listing
November 2021

Integrated health service delivery during COVID-19: a scoping review of published evidence from low-income and lower-middle-income countries.

BMJ Glob Health 2021 06;6(6)

Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

Background: Integrated health service delivery (IHSD) is a promising approach to improve health system resilience. However, there is a lack of evidence specific to the low/lower-middle-income country (L-LMIC) health systems on how IHSD is used during disease outbreaks. This scoping review aimed to synthesise the emerging evidence on IHSD approaches adopted in L-LMIC during the COVID-19 pandemic and systematically collate their operational features.

Methods: A systematic scoping review of peer-reviewed literature, published in English between 1 December 2019 and 12 June 2020, from seven electronic databases was conducted to explore the evidence of IHSD implemented in L-LMICs during the COVID-19 pandemic. Data were systematically charted, and key features of IHSD systems were presented according to the postulated research questions of the review.

Results: The literature search retrieved 1487 published articles from which 18 articles met the inclusion criteria and included in this review. Service delivery, health workforce, medicine and technologies were the three most frequently integrated health system building blocks during the COVID-19 pandemic. While responding to COVID-19, the L-LMICs principally implemented the IHSD system via systematic horizontal integration, led by specific policy measures. The government's stewardship, along with the decentralised decision-making capacity of local institutions and multisectoral collaboration, was the critical facilitator for IHSD. Simultaneously, fragmented service delivery structures, fragile supply chain, inadequate diagnostic capacity and insufficient workforce were key barriers towards integration.

Conclusion: A wide array of context-specific IHSD approaches were operationalised in L-LMICs during the early phase of the COVID-19 pandemic. Emerging recommendations emphasise the importance of coordination and integration across building blocks and levels of the health system, supported by a responsive governance structure and stakeholder engagement strategies. Future reviews can revisit this emerging evidence base at subsequent phases of COVID-19 response and recovery in L-LMICs to understand how the approaches highlighted here evolve.
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http://dx.doi.org/10.1136/bmjgh-2021-005667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210663PMC
June 2021

Evidence of integrated health service delivery during COVID-19 in low and lower-middle-income countries: protocol for a scoping review.

BMJ Open 2021 05 3;11(5):e042872. Epub 2021 May 3.

International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

Introduction: The importance of integrated, people-centred health systems has been recognised as a central component of Universal Health Coverage. Integration has also been highlighted as a critical element for building resilient health systems that can withstand the shock of health emergencies. However, there is a dearth of research and systematic synthesis of evidence on the synergistic relationship between integrated health services and pandemic preparedness, response, and recovery in low-income and lower-middle-income countries (LMICs). Thus, the authors are organising a scoping review aiming to explore the application of integrated health service delivery approaches during the emerging COVID-19 pandemic in LMICs.

Methods And Analysis: This scoping review adheres to the six steps for scoping reviews from Arksey and O'Malley. Peer-reviewed scientific literature will be systematically assembled using a standardised and replicable search strategy from seven electronic databases, including PubMed, Embase, Scopus, Web of Science, CINAHL Plus, the WHO's Global Research Database on COVID-19 and LitCovid. Initially, the title and abstract of the collected literature, published in English from December 2019 to June 2020, will be screened for inclusion which will be followed by a full-text review by two independent reviewers. Data will be charted using a data extraction form and reported in narrative format with accompanying data matrix.

Ethics And Dissemination: No ethical approval is required for the review. The study will be conducted from June 2020 to May 2021. Results from this scoping review will provide a snapshot of the evidence currently being generated related to integrated health service delivery in response to the COVID-19 pandemic in LMICs. The findings will be developed into reports and a peer-reviewed article and will assist policy-makers in making pragmatic and evidence-based decisions for current and future pandemic responses.
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http://dx.doi.org/10.1136/bmjopen-2020-042872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098290PMC
May 2021

Nanotechnology synergized immunoengineering for cancer.

Eur J Pharm Biopharm 2021 Jun 24;163:72-101. Epub 2021 Mar 24.

Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA. Electronic address:

Novel strategies modulating the immune system yielded enhanced anticancer responses and improved cancer survival. Nevertheless, the success rate of immunotherapy in cancer treatment has been below expectation(s) due to unpredictable efficacy and off-target effects from systemic dosing of immunotherapeutic(s). As a result, there is an unmet clinical need for improving conventional immunotherapy. Nanotechnology offers several new strategies, multimodality, and multiplex biological targeting advantage to overcome many of these challenges. These efforts enable programming the pharmacodynamics, pharmacokinetics, and delivery of immunomodulatory agents/co-delivery of compounds to prime at the tumor sites for improved therapeutic benefits. This review provides an overview of the design and clinical principles of biomaterials driven nanotechnology and their potential use in personalized nanomedicines, vaccines, localized tumor modulation, and delivery strategies for cancer immunotherapy. In this review, we also summarize the latest highlights and recent advances in combinatorial therapies availed in the treatment of cold and complicated tumors. It also presents key steps and parameters implemented for clinical success. Finally, we analyse, discuss, and provide clinical perspectives on the integrated opportunities of nanotechnology and immunology to achieve synergistic and durable responses in cancer treatment.
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http://dx.doi.org/10.1016/j.ejpb.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170847PMC
June 2021

Synthesis and characterization of an injectable microparticles integrated hydrogel composite biomaterial: In-vivo biocompatibility and inflammatory arthritis treatment.

Colloids Surf B Biointerfaces 2021 May 2;201:111597. Epub 2021 Feb 2.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay (IIT Bombay), Mumbai, India. Electronic address:

Polymeric hydrogels and microparticles have been widely used for localized drug delivery applications for the treatment of arthritis. Nonetheless, owing to initial burst drug release, non-specific biodistribution and low retention time at the target site in body, these polymeric drug delivery systems have been found with low in-vivo performance. Hence, the above limitations need to be resolved by designing a smart novel drug delivery system which is the current need in biomedicine. Herein, a novel localized injectable thermoresponsive microparticles embedded hydrogel composite drug delivery system has been developed for the treatment of inflammatory arthritis. In the current study, methotrexate (MTX) loaded alginate microparticles (MTX-Microparticles) are embedded into thermoreversible hydrogel matrix (MTX-MPs-H) prepared by physical blending of sodium hyaluronate and methylcellulose (SHMC). Microparticles-hydrogel composite system exhibited appropriate in-vitro thermoreversibility (sol at 4 °C and gel at 37 °C), biocompatibility (>80 %), hemocompatibility, and controlled drug release profile. The in-vivo biocompatibility studies for 10 days revealed that composite system is non-toxic in nature. The developed MTX-MPs-H composite drug delivery system effectively decreased the swelling/ inflammation of the arthritis affected paw in wistar rats in comparison to only alginate microparticles and pure MTX up to 30 days.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111597DOI Listing
May 2021

Evidence of integrated primary-secondary health care in low-and middle-income countries: protocol for a scoping review.

Syst Rev 2020 11 9;9(1):260. Epub 2020 Nov 9.

Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Background: Integrated care is a people-centered health delivery approach that ensures the comprehensiveness, quality, and continuity of service across the settings and levels of health systems. The World Health Organization (WHO) recommends integration across levels and building-blocks of health systems as a prerequisite of Universal Health Coverage (UHC). While health systems of low- and middle-income countries (LMICs) are often fragmented and led by siloed service delivery structure, several LMICs-including India-have attempted health system integration. Several systematic reviews of evidence on healthcare integration from developed countries exist, but no synthesis from LMICs was reported to date. This review will overview the existing evidence of primary-secondary care integration (PSI) in the context of LMICs, aiming to support policy decisions for the effective integration of health delivery systems in India.

Methods: The review will be conducted following the six steps recommend by Arksey and O'Malley. Scientific and grey literature will be systematically selected from PubMed, Embase, Scopus, Web of Science, Global Index Medicus, and electronic repositories (such as WHO, World Bank, Health Policy Plus, and OpenGrey). Using a comprehensive search strategy, literature written in English and published between 2000 and 2020 will be selected, and two independent authors will screen their titles and abstracts. The result will be charted using a data extraction form and reported using tables, figures, and narrative forms.

Discussion: No ethical approval is necessary for the review. The final report will be developed with the consultation of other stakeholders and disseminated through workshops, conference papers, and peer review articles. The review will serve as a guiding tool to approach, implement, and test the PSI models in India and other LMICs. SCOPING REVIEW REGISTRATION: https://osf.io/kjhzt .
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http://dx.doi.org/10.1186/s13643-020-01514-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654598PMC
November 2020

Central histaminergic transmission modulates the expression of chronic nicotine withdrawal induced anxiety-like and somatic behavior in mice.

Behav Brain Res 2021 02 6;399:112997. Epub 2020 Nov 6.

Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, 495009, India. Electronic address:

The present study investigated the plausible modulatory role of central histaminergic transmission on the expression of nicotine withdrawal induced anxiety and somatic behavior in mice. Abrupt cessation of chronic nicotine (2 mg/kg, i.p. × 3/day) treatment for 12 days to mice, expressed increased anxiety in light & dark test and total abstinence (somatic) score at 24 h post nicotine withdrawal time. The somatic signs includes a composite score of all behaviors such as grooming, rearing, jumping, body shakes, forelimb tremors, head shakes, abdominal constrictions, scratching, empty mouth chewing or teeth chattering, genital licking, tail licking. Mice exhibited higher expression to nicotine withdrawal induced anxiety in light & dark test at 24 h post-nicotine withdrawal time on pre-treatment centrally (i.c.v) with histaminergic agents like histamine (0.1, 50 μg/mouse), histamine H receptor inverse agonist, thioperamide (2, 10 μg/mouse), histamine H receptor agonist, FMPH (2, 6.5 μg/mouse) or H receptor agonist amthamine (0.1, 0.5 μg/mouse) or intraperitoneally (i.p.) with histamine precursor, l-histidine (250, 500 mg/kg) as compared to control nicotine withdrawn animals. Furthermore, mice pre-treated with all these histaminergic agents except histamine H receptor agonist, FMPH shows exacerbated expression to post-nicotine withdrawal induced total abstinence (somatic) score in mice. On the other hand, central injection of selective histamine H receptor antagonist, cetirizine (0.1 μg/mouse, i.c.v.) or H receptor antagonist, ranitidine (50 μg/mouse, i.c.v) to mice 10 min before 24 h post-nicotine withdrawal time completely alleviated the expression of nicotine withdrawal induced anxiety and somatic behavior. Thus, it can be contemplated that the blockade of central histamine H or H receptor during the nicotine withdrawal phase could be a novel approach to mitigate the nicotine withdrawal associated anxiety-like manifestations. Contribution of endogenous histamine via H or H receptor stimulation in the nicotine withdrawal induced anxiety and somatic behavior is proposed.
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http://dx.doi.org/10.1016/j.bbr.2020.112997DOI Listing
February 2021

Mixed and Multi-Methods Protocol to Evaluate Implementation Processes and Early Effects of the Pradhan Mantri Jan Arogya Yojana Scheme in Seven Indian States.

Int J Environ Res Public Health 2020 10 26;17(21). Epub 2020 Oct 26.

Indo-German Social Security Programme (IGSSP), Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH, New Delhi 110029, India.

In September 2018, India launched Pradhan Mantri Jan Arogya Yojana (PM-JAY), a nationally implemented government-funded health insurance scheme to improve access to quality inpatient care, increase financial protection, and reduce unmet need for the most vulnerable population groups. This protocol describes the methodology adopted to evaluate implementation processes and early effects of PM-JAY in seven Indian states. The study adopts a mixed and multi-methods concurrent triangulation design including three components: 1. demand-side household study, including a structured survey and qualitative elements, to quantify and understand PM-JAY reach and its effect on insurance awareness, health service utilization, and financial protection; 2. supply-side hospital-based survey encompassing both quantitative and qualitative elements to assess the effect of PM-JAY on quality of service delivery and to explore healthcare providers' experiences with scheme implementation; and 3. process documentation to examine implementation processes in selected states transitioning from either no or prior health insurance to PM-JAY. Descriptive statistics and quasi-experimental methods will be used to analyze quantitative data, while thematic analysis will be used to analyze qualitative data. The study design presented represents the first effort to jointly evaluate implementation processes and early effects of the largest government-funded health insurance scheme ever launched in India.
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http://dx.doi.org/10.3390/ijerph17217812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663328PMC
October 2020

Arsenic adsorbent derived from the ferromanganese slag.

Environ Sci Pollut Res Int 2021 Jan 10;28(3):3230-3242. Epub 2020 Sep 10.

Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Saharanpur Campus, Saharanpur, Uttar Pradesh, 247001, India.

Arsenic-contaminated groundwater has a severe negative impact on the health of living beings. Groundwater majorly contains arsenite (As(III)) as well as arsenate (As(V)). Among these two, the arsenite species are more carcinogenic, mobile, and lethal. Hence, it is more difficult to remove by conventional water treatment methods. Ferromanganese slag, waste generated from steel industries, has been utilized in this study for the development of arsenic adsorbent. A chemical treatment method is applied to the ferromanganese slag to prepare efficient arsenic adsorbent, and it is easy to scale up. An adsorbent with the capacity for simultaneous oxidation of As(III) and adsorption of total arsenic species can be efficient for arsenic decontamination. X-ray photoelectron spectroscopy and X-ray absorption near edge spectra techniques prove the As(III) oxidation capability of the developed material is about 70 ± 5% based on initial As(III) concentration. The adsorbent not only oxidizes the As(III) species but also adsorbs both the arsenic species. The Langmuir isotherm model estimates the maximum adsorption capacities at the equilibrium concentration of 10 μg/L are 1.010 ± 0.004 mg/g and 1.614 ± 0.006 mg/g for As(III) and As(V), respectively. The rate of adsorption of As(III) was higher compared to the As(V), which was confirmed by the pseudo-second-order kinetic model. Therefore, the treated water quality meets the World Health Organization and Indian drinking water standards.
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http://dx.doi.org/10.1007/s11356-020-10745-9DOI Listing
January 2021

Synthesis and anti-proliferative activity of a novel 1,2,3-triazole tethered chalcone acetamide derivatives.

Bioorg Med Chem Lett 2020 08 4;30(16):127304. Epub 2020 Jun 4.

Fluoro-Agrochemicals Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. Electronic address:

A new series of 1,2,3-triazole tethered chalcone acetamide derivatives (7a-c &8a-r) have been synthesized in excellent yields and their structures were determined by analytical and spectral (FT-IR, H NMR, C NMR & HRMS) studies. The newly synthesized derivatives were evaluated for their cytotoxic activity against four human cancer cell lines, such as HeLa (Human cervical cancer), A549 (Human alveolar adenocarcinoma), MCF-7 (Human breast adenocarcinoma) and SKNSH (Human brain cancer). Among them, compound 7c exhibited good anti-proliferation activity with HeLa (IC 7.41 + 0.8 μM), SKNSH (IC 8.68 + 1.1 μM), MCF-7 (IC 9.76 + 1.3 μM) and MDA-MB-231, while compounds 7a and 7b showed promising anti-proliferation against above four human cancer cell lines with IC 7.95-11.62 μM, respectively, compared with the standard drug Doxorubicin. We explored the probable key active site and binding mode interactions in HDAC8 (PDB ID:3SFH) and EHMT2 (PDB ID:3K5K) proteins. The docking results are complementary to the experimental observations.
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http://dx.doi.org/10.1016/j.bmcl.2020.127304DOI Listing
August 2020

Liposomal nanotheranostics for multimode targeted in vivo bioimaging and near-infrared light mediated cancer therapy.

Commun Biol 2020 06 5;3(1):284. Epub 2020 Jun 5.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, 400076, India.

Developing a nanotheranostic agent with better image resolution and high accumulation into solid tumor microenvironment is a challenging task. Herein, we established a light mediated phototriggered strategy for enhanced tumor accumulation of nanohybrids. A multifunctional liposome based nanotheranostics loaded with gold nanoparticles (AuNPs) and emissive graphene quantum dots (GQDs) were engineered named as NFGL. Further, doxorubicin hydrochloride was encapsulated in NFGL to exhibit phototriggered chemotherapy and functionalized with folic acid targeting ligands. Encapsulated agents showed imaging bimodality for in vivo tumor diagnosis due to their high contrast and emissive nature. Targeted NFGL nanohybrids demonstrated near infrared light (NIR, 750 nm) mediated tumor reduction because of generated heat and Reactive Oxygen Species (ROS). Moreover, NFGL nanohybrids exhibited remarkable ROS scavenging ability as compared to GQDs loaded liposomes validated by antitumor study. Hence, this approach and engineered system could open new direction for targeted imaging and cancer therapy.
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http://dx.doi.org/10.1038/s42003-020-1016-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275035PMC
June 2020

Osteoporosis in Rheumatoid Arthritis -An Observational Study in Tertiary Care Hospital of Central India.

J Assoc Physicians India 2020 Jan;68(1):70

J.L.N.H.R.C., Bhilai C.G.

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January 2020

Polymeric Core-Shell Combinatorial Nanomedicine for Synergistic Anticancer Therapy.

ACS Omega 2019 Nov 11;4(22):19614-19622. Epub 2019 Nov 11.

Department of Biosciences and Bioengineering and Department of Metallurgical Engineering & Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

Core-shell nanostructures are promising platforms for combination drug delivery. However, their complicated synthesis process, poor stability, surface engineering, and low biocompatibility are major hurdles. Herein, a carboxymethyl chitosan-coated poly(lactide--glycolide) (cmcPLGA) core-shell nanostructure is prepared via a simple one-step nanoprecipitation self-assembly process. Engineered core-shell nanostructures are tested for combination delivery of loaded docetaxel and doxorubicin in a cancer-mimicked environment. The drugs are compartmentalized in a shell (doxorubicin, Dox) and a core (docetaxel, Dtxl) with loading contents of ∼1.2 and ∼2.06%, respectively. Carboxymethyl chitosan with both amine and carboxyl groups act as a polyampholyte in diminishing ζ-potential of nanoparticles from fairly negative (-13 mV) to near neutral (-2 mV) while moving from a physiological pH (7.4) to an acidic tumor pH (6) that can help the nanoparticles to accumulate and release the drug on-site. The dual-drug formulation was found to carry a clinically comparable 1.7:1 weight ratio of Dtxl/Dox, nanoengineered for the sequential release of Dox followed by Dtxl. Single and engineered combinatorial nanoformulations show better growth inhibition toward three different cancer cells compared to free drug treatment. Importantly, Dox-Dtxl cmcPLGA nanoparticles scored synergism with combination index values between 0.2 and 0.3 in BT549 (breast ductal carcinoma), PC3 (prostate cancer), and A549 (lung adenocarcinoma) cell lines, demonstrating significant cell growth inhibition at lower drug concentrations as compared to single-drug control groups. The observed promising performance of dual-drug formulation is due to the G2/M phase arrest and apoptosis.
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http://dx.doi.org/10.1021/acsomega.9b02167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881840PMC
November 2019

Synthesis and biological evaluation of bergenin-1,2,3-triazole hybrids as novel class of anti-mitotic agents.

Bioorg Chem 2019 10 31;91:103161. Epub 2019 Jul 31.

Centre for Natural Products & Traditional Knowledge, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address:

In continuation of our investigation of pharmacologically-motivated natural products, we have isolated bergenin (1) as a major compound from Mallotus philippensis, which is deployed in different Indian traditional systems of medicine. Here, a series of bergenin-1,2,3-triazole hybrids were synthesized and evaluated for their potentials against a panel of cancer cell lines. Several of the hybrid derivatives were found more potent in comparison to parent compound bergenin (1). Among them, 4j demonstrated potent activity against A-549 and HeLa cell lines with IC values of 1.86 µM and 1.33 μM, respectively, and was equipotent to doxorubicin. Cell cycle analysis showed that 4j arrested HeLa cells at G2/M phase and lead to accumulation of Cyclin B1 protein. Cell based tubulin polymerization assays and docking studies demonstrated that 4j disrupts tubulin assembly by occupying colchicine binding pocket of tubulin.
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http://dx.doi.org/10.1016/j.bioorg.2019.103161DOI Listing
October 2019

Abundance of d-2-hydroxyglutarate in G2/M is determined by FOXM1 in mutant IDH1-expressing cells.

FEBS Lett 2019 08 4;593(16):2177-2193. Epub 2019 Jul 4.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.

Isocitrate dehydrogenases (IDHs) are metabolic enzymes that are mutated in several cancers, resulting in overproduction of d-2-hydroxyglutarate (D-2HG). However, the signalling pathways and factors that regulate mutant IDHs or their metabolites remain elusive. Here, we report that in synchronized cells and cells treated with anti-mitotic agents, wild-type and mutant IDH proteins are induced maximally in G2/M. Moreover, mutant IDH1-expressing cells arrested in G2/M harbour high D2HG levels. Genetic or pharmacological perturbation of Forkhead box protein M1 (FOXM1) abrogates the levels of IDH1 mRNA, protein and D2HG in G2/M. Conversely, overexpression of FOXM1 or hyperactive FOXM1 activates the IDH1 promoter and increases the abundance of its protein levels. In summary, our results show that in G2/M, higher D2HG levels are dependent on FOXM1-mediated transcription of IDH1.
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http://dx.doi.org/10.1002/1873-3468.13500DOI Listing
August 2019

Chitosan-Fe-Al-Mn metal oxyhydroxides composite as highly efficient fluoride scavenger for aqueous medium.

Carbohydr Polym 2019 Jul 6;216:140-148. Epub 2019 Apr 6.

Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Saharanpur Campus, Saharanpur 247001, India. Electronic address:

Nano-particles are highly efficient fluoride adsorbents, but agglomerate easily due to their high surface activity and are difficult to separate from aqueous medium after use. Mixed-metals oxyhydroxides nano-particles were prepared into a natural polymeric matrix of chitosan to overcome these problems. Hydrous mixed-metal oxyhydroxides, loaded chitosan composite ([email protected]) was prepared using abundantly available laterite clay and waste from steel industry via co-precipitation method. Fluoride removal using [email protected] composite followed Freundlich isotherm model which revealed multilayer adsorption on heterogeneous surface sites. [email protected] exhibited maximum adsorption capacity of 40±0.5 mg/g, while if only the inorganic mass fraction of composite was considered; the value reached 55±0.5 mg/g. Fluoride adsorption on [email protected] followed the pseudo-second order kinetics with rapid adsorption. No significant effect of other competitive ions was observed on F adsorption using [email protected] composite. The composite adsorbent is found to be effective to produce drinking water from fluoride contaminated groundwater.
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http://dx.doi.org/10.1016/j.carbpol.2019.04.028DOI Listing
July 2019

Variability in Prices for Erectile Dysfunction Medications-Are All Pharmacies the Same?

J Sex Med 2018 12;15(12):1785-1791

University Hospitals Cleveland Medical Center, Urology Institute, Cleveland, OH, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address:

Background: Variability in prices of medications is a well-known phenomenon; however, this variability has not been quantified in the realm of erectile dysfunction (ED) medications. ED medications are ideal for this quantification, because they are often not covered by insurances; therefore, the cost is the most direct reflection of price variability among pharmacies as they affect the patients.

Aim: To evaluate the variability in cash prices for phosphodiesterase type 5 inhibitors (PDEIs) for ED. We also evaluated whether certain types of pharmacies consistently offer better pricing than others, and whether there was any correlation with demographic factors.

Methods: 331 pharmacies were contacted within a 25-mile radius of our institution to obtain the cash price for 4 commonly used ED medications with prespecified doses. After exclusion, 323 pharmacies were categorized as chain, independent, wholesale, or hospital-associated. Cash prices for the specified medications were evaluated. In addition, we identified demographic and socioeconomic factors to determine if these had an impact on median drug pricing within each zip code.

Main Outcome Measure: The main outcome was the cost for patients to fill each prescription.

Results: Independent pharmacies provided the lowest cost for 3 of 4 of the PDEIs. The largest price difference for 10 tablets of 100 mg sildenafil between all pharmacies was 38,000%. The median cost difference between independent pharmacies and chain pharmacies for sildenafil was >900%, and >1,100% for independent pharmacies vs hospital-associated pharmacies. Demographic and socioeconomic factors had no impact on the cost.

Clinical Implications: Our goal is to promote patient counseling among practitioners and to empower patients to shop for the best prices for their medications.

Strength And Limitations: A strength of the study is the large cohort that was surveyed; however, a weakness is that the large majority of the cohort was comprised of chain pharmacies. Mail pharmacies could not be evaluated as they required a valid prescription before offering prices.

Conclusion: The drastic differences in cash prices for the PDEIs give us an insight into the variability and cost-inflation of medications in the United States. These patterns hold true for other essential medications as well, and improved transparency will allow patients to make informed decisions when choosing where to purchase their medications. It may also encourage certain pharmacies to provide medications at more affordable prices. Mishra K, Bukavina L, Mahran A, et al. Variability in prices for erectile dysfunction medications-Are all pharmacies the same? J Sex Med 2018;15:1785-1791.
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http://dx.doi.org/10.1016/j.jsxm.2018.10.011DOI Listing
December 2018

Enhanced central histaminergic transmission attenuates compulsive-like behavior in mice.

Neuropharmacology 2018 08 25;138:106-117. Epub 2018 May 25.

Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chattisgarh, India. Electronic address:

Present investigation demonstrated the effect of central histaminergic transmission on the compulsive-like marble burying and spontaneous alteration behavior (SAB) in mice. Result demonstrates that on enhancement of endogenous histaminergic transmission in mice achieved by central (i.c.v.) administration of histamine or central histamine neuronal releaser, H receptor antagonist or on intraperitoneal (i.p.) administration of histamine precursor, l-histidine significantly attenuated the number of marble buried in marble burying behavior (MBB) test as well as obliterated the persistent behavior induced by 5-HT receptor agonist, 8-OH-DPAT in T-Maze test. Furthermore, central injection of histamine H receptor agonist, FMPH or H receptors agonist, amthamine also attenuated the MBB in mice. On the other hand, prior i.c.v administration of H but not H receptor antagonist attenuated the effects exhibited in MBB test on mice by all the above agents capable of enhancing the endogenous central histaminergic transmission. Thus, the results of the present investigation delineate the attenuating effect of central histaminergic transmission predominantly via H receptor on compulsive-like behavior in mice.
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http://dx.doi.org/10.1016/j.neuropharm.2018.05.031DOI Listing
August 2018

Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: Relevance in age-associated vascular dysfunction.

Biochim Biophys Acta Mol Basis Dis 2018 Apr 31;1864(4 Pt A):1115-1128. Epub 2018 Jan 31.

Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Innovative Research, Training and Development Complex, Chennai 600113, India. Electronic address:

Endothelial senescence in conjunction with mitochondrial dysfunction orchestrates age-associated cardiovascular disorders. In this study we investigated the causal link between these two processes and studied the molecular mechanisms by which metformin acts to coordinate the delay of endothelial senescence via enhancing mitochondrial biogenesis/function. AMPK activators metformin and AICAR delayed endothelial senescence via SIRT1-mediated upregulation of DOT1L, leading to increased trimethylation of H3K79 (H3K79me3). Treatment of cells with either siAMPK or siSIRT1 repressed DOT1L-mediated enhancement of H3K79me3. Moreover, the increase in SIRT3 expression and mitochondrial biogenesis/function by AMPK activators was H3K79me-dependent as H3K79N mutant or siDOT1L abrogated these effects. This was confirmed by the enrichment of H3K79me3 in the SIRT3 promoter with AMPK activation. Intriguingly, enhanced PGC-1α expression by SIRT3 via AMPK activation was responsible for increased hTERT expression and delayed endothelial senescence. In contrast, SIRT3 knockdown caused increased oxidative stress and premature senescence, possibly by depleting hTERT expression. Furthermore, a chronic low dose administration of metformin significantly attenuated vascular aging and inhibited age-associated atherosclerotic plaque formation in ApoE mice. Overall, the results of this study show a novel regulation of mitochondrial biogenesis/function, and cellular senescence by H3K79me acting through SIRT3, thus providing a molecular basis for metformin-mediated age-delaying effects.
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http://dx.doi.org/10.1016/j.bbadis.2018.01.018DOI Listing
April 2018

Role of histamine H receptor in caffeine induced locomotor sensitization.

Neurosci Lett 2018 03 5;668:60-66. Epub 2018 Jan 5.

Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, India. Electronic address:

The present study elucidated the role of histamine H receptor in the caffeine induced locomotor sensitization. Intermittent administration of caffeine (15 mg/kg, i.p.) on alternate days (induction phase) i.e. 1, 3, 5, 7, 9, 11 and 13 resulted in the development of locomotor sensitization. In addition, challenge with sub-stimulant dose of caffeine (10 mg/kg, i.p.) directly on 17 day to induction group animals resulted in expression to locomotor sensitization to caffeine. I.c.v. injection of histaminergic agents concomitantly with caffeine during induction phase i.e. histamine H receptor agonist, FMPH (6.5 μg/mouse) significantly potentiated while H receptor antagonist, cetirizine (0.1 μg/mouse) attenuated the locomotor sensitization induced by caffeine (15 mg/kg, i.p.). In addition, challenge with caffeine (10 mg/kg, i.p.) on the expression day (17) to the induction group mice on FMPH + caffeine treatment showed enhanced, while those on cetirizine + caffeine treatment exhibited lesser expression to locomotor sensitization. Therefore, a possible contributory role of the central histaminergic system via H receptor stimulation or up-regulation in the caffeine-induced locomotor sensitizing effect is proposed.
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http://dx.doi.org/10.1016/j.neulet.2018.01.002DOI Listing
March 2018

Synthesis of imidazo-thiadiazole linked indolinone conjugates and evaluated their microtubule network disrupting and apoptosis inducing ability.

Bioorg Chem 2018 02 7;76:420-436. Epub 2017 Dec 7.

Medicinal Chemistry and Biotechnology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500 007, India; Pharmacology & Toxicology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address:

A series of imidazo[2,1-b][1,3,4]thiadiazole linked indolinone conjugates were synthesized and investigated for antiproliferative activity in different human cancer cell lines by changing various substitutions at indolinone and phenyl ring systems. Among them conjugates 7, 14 and 15 were exhibited potent antiproliferative activity with GI values from 0.13 to 3.8 μΜ and evaluated for cell cycle analysis, tubulin polymerization assay and apoptosis. Treatment with 7, 14 and 15 were resulted in accumulation of cells in G2/M phase, inhibition of tubulin assembly, disruption of microtubule network. Inhibition of tubulin polymerization was further supported by Western blot analysis. In addition, the conjugates (7, 14 and 15) also showed apoptosis in HeLa cell line, detailed biological studies such as Hoechst 33,258 staining, DNA fragmentation and caspase-3 assays suggested that these compounds induce cell death by apoptosis. Docking studies revealed that these compounds (7, 14 and 15) bind with αAsn101, αThr179, αSer178, βCys241, βLys254 and βLys352 in the colchicine-binding site of the tubulin.
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http://dx.doi.org/10.1016/j.bioorg.2017.11.021DOI Listing
February 2018

Synthesis of novel tetrazole containing hybrid ciprofloxacin and pipemidic acid analogues and preliminary biological evaluation of their antibacterial and antiproliferative activity.

Mol Divers 2018 Feb 14;22(1):83-93. Epub 2017 Nov 14.

Medicinal Chemistry and Pharmacology Division, Discovery Laboratory, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.

A series of 1-substituted-1H-tetrazole-5-thiol building blocks were synthesized and introduced to the N-4 piperazinyl group at C-7 position of the quinolone core, and these novel compounds (5a-g and 8a-g) were screened for their antibacterial and antiproliferative activities. Bioactive assay studies manifested that most of new compounds exhibited significant antibacterial activity against the tested strains, including multi-drug-resistant MRSA in comparison with reference drugs ciprofloxacin, streptomycin B and pipemidic acid. Among the synthesized compounds, only ciprofloxacin (5a-g) derivatives displayed significant activity ([Formula: see text]) compared to reference drugs. In addition, these compounds were evaluated for their in vitro inhibition of human cancer cell lines viz human cervical carcinoma cell line (SiHA), breast adenocarcinoma (MDA-MB-235) and human pancreas carcinoma (PANC-1) cell lines by using the SRB assay method. Most of the target compounds showed broad potent growth inhibition activity ([Formula: see text]) against all the tested cancer cell lines compared with reference drug. The most promising active compounds in this series were 5c, 5d, 8c, 8d and 8f endowed with excellent antiproliferative activity. A new class of compounds was designed rationally by introducing tetrazole building block on N-4 piperazinyl group at C-7 position of quinolones core. The titled compounds were evaluated for their preliminary antibacterial and antiproliferative activities.
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http://dx.doi.org/10.1007/s11030-017-9795-yDOI Listing
February 2018

Potential anti-proliferative agents from 1,4-benzoxazinone-quinazolin-4(3H)-one templates.

Bioorg Med Chem Lett 2017 12 20;27(24):5481-5484. Epub 2017 Oct 20.

Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.

A novel synthetic protocol has been developed for the synthesis of 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids 7a-n by employing Pd-catalyzed CH arylation in presence of 5-10% phosphine ligand in good to excellent yields and evaluated for their anti-proliferative activity against three cancer cell lines such as A549 (lung), HeLa (cervical), MDA-MB-231 (breast). Compounds 7d, 7f, 7l and 7n exhibited promising anti-proliferative activity with GI values ranging from 0.37 to 2.73 µM respectively against A549, HeLa, and MDA-MB-231, while compound 7f showed significant activity against MDA-MB-231 with GI value 0.58 µM, 7j showed significant activity against A549 with GI value 0.32 µM and 7l showed significant activity against HeLa with GI value 0.37 µM. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids.
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http://dx.doi.org/10.1016/j.bmcl.2017.10.044DOI Listing
December 2017

Novel Gomisin B analogues as potential cytotoxic agents: Design, synthesis, biological evaluation and docking studies.

Eur J Med Chem 2017 Oct 1;139:441-453. Epub 2017 Aug 1.

Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India. Electronic address:

As part of pharmacological-phytochemical integrated studies on medicinal flora, Gomisin B (1) was isolated as major phytochemical lead from schisandra grandiflora, a plant traditionally used in different Asian systems of medicine. A series of 1,2,3-triazoles derivatives were synthesized at the C-7' position of the gomisin B core through diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reactions. All these triazolyl derivatives (5a-5q) were well characterized using modern spectroscopic techniques and evaluated for their anti-cancer activity against a panel of five human cancerous cell-lines. Among them, compound 5b exhibited the best cytotoxicity against SIHA cell (IC 0.24 μM) which was more than the standard drug doxorubicin, while the other derivatives were exhibited moderate to low activities in tested cell lines. The cell cycle analysis indicated that compound 5b stalled HeLa cells at G2/M phase. 5b promoted tubulin polymerization and this was supported by the docking studies, wherein 5b showed significant binding affinity at the colchicine binding pocket of tubulin. Overall, we identified a novel small molecule that demonstrated anticancer activity by promoting in vitro tubulin assembly.
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http://dx.doi.org/10.1016/j.ejmech.2017.07.076DOI Listing
October 2017

Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors.

Bioorg Med Chem Lett 2017 08 24;27(16):3794-3801. Epub 2017 Jun 24.

Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, Telangana, India. Electronic address:

A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, 8j showed potent activity against the cancer cell lines such as HeLa, HepG2, A549 and MCF-7 with IC 12.3±0.8, 9.6±0.4, 10.5±1.0 and 11.7±0.5μM respectively. 8j was taken up for elaborate biological studies and the cells in the cell cycle were arrested in G2/M phase. In addition, 8j was examined for its effect on the microtubule system with a tubulin polymerization assay, immunofluorescence. 8j showed remarkable inhibition of tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. The studies suggested that 8jhas a good binding affinity of -7.949 towards nocodazole binding site of tubulin while nocodazole has -7.462.
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http://dx.doi.org/10.1016/j.bmcl.2017.06.060DOI Listing
August 2017

An augmented reality tool for learning spatial anatomy on mobile devices.

Clin Anat 2017 Sep 6;30(6):736-741. Epub 2017 Jul 6.

Division of Clinical Anatomy, Department of Surgery, Stanford University School of Medicine, Stanford, California.

Augmented Realty (AR) offers a novel method of blending virtual and real anatomy for intuitive spatial learning. Our first aim in the study was to create a prototype AR tool for mobile devices. Our second aim was to complete a technical evaluation of our prototype AR tool focused on measuring the system's ability to accurately render digital content in the real world. We imported Computed Tomography (CT) data derived virtual surface models into a 3D Unity engine environment and implemented an AR algorithm to display these on mobile devices. We investigated the accuracy of the virtual renderings by comparing a physical cube with an identical virtual cube for dimensional accuracy. Our comparative study confirms that our AR tool renders 3D virtual objects with a high level of accuracy as evidenced by the degree of similarity between measurements of the dimensions of a virtual object (a cube) and the corresponding physical object. We developed an inexpensive and user-friendly prototype AR tool for mobile devices that creates highly accurate renderings. This prototype demonstrates an intuitive, portable, and integrated interface for spatial interaction with virtual anatomical specimens. Integrating this AR tool with a library of CT derived surface models provides a platform for spatial learning in the anatomy curriculum. The segmentation methodology implemented to optimize human CT data for mobile viewing can be extended to include anatomical variations and pathologies. The ability of this inexpensive educational platform to deliver a library of interactive, 3D models to students worldwide demonstrates its utility as a supplemental teaching tool that could greatly benefit anatomical instruction. Clin. Anat. 30:736-741, 2017. © 2017Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ca.22943DOI Listing
September 2017

Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors.

Bioorg Med Chem 2017 07 12;25(13):3285-3297. Epub 2017 Apr 12.

Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India; Academy of Scientific and Innovative Research, New Delhi 110 025, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad 500 037, India; Catalytic Chemistry Research Chair, Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address:

1,2,3-Triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates (5a-v) were designed, synthesized and evaluated for their cytotoxic potency against some human cancer cell lines like DU-145 (prostate), HeLa (cervical), MCF-7 (breast) HepG2 (liver) and A549 (lung). Preliminary results revealed that some of these conjugates like 5f and 5k exhibited significant antiproliferative effect against human breast cancer cells (MCF-7) with IC values of 0.60 and 0.78µM respectively. Flow cytometric analysis of the cell cycle demonstrated an increase in the percentage of cells in the G/M phase which was further authenticated by elevation of cyclin B1 protein levels. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 5f and 5k, and western blot analysis revealed that these conjugates accumulated more tubulin in the soluble fraction. Moreover, the conjugates caused apoptosis of the cells that was confirmed by mitochondrial membrane potential and Annexin V-FITC assay. Molecular docking studies indicated that these conjugates occupy the colchicine binding site of the tubulin protein.
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http://dx.doi.org/10.1016/j.bmc.2017.04.013DOI Listing
July 2017
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