Publications by authors named "N K Ganguly"

687 Publications

Neem leaf glycoprotein salvages T cell functions from Myeloid-derived suppressor cells-suppression by altering IL-10/STAT3 axis in melanoma tumor microenvironment.

Melanoma Res 2021 Feb 18. Epub 2021 Feb 18.

Department of Immunoregulation and Immunodiagnostics Department of Clinical Biochemistry, Chittaranjan National Cancer Institute Department of Botany, Ramakrishna Mission Vivekananda Centenary College, Rahara, Kolkata, India.

Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune functions. We have observed that an immunomodulator, neem leaf glycoprotein (NLGP), inhibits tumor-resident MDSCs and enhances antitumor CD8+ T cell immunity. NLGP inhibits the number as well as functions of tumor-resident MDSCs (Gr1±CD11b±) and enhances antitumor CD8± T cell immunity by downregulating arginase 1 and inducible nitric oxide synthase production in MDSCs. Accordingly, decreased T cell anergy and helper to regulatory T cell conversion have been observed in the presence of NLGP, which ultimately augments T cell functions. Mechanistically, NLGP-mediated rectification of T cell suppressive functions of MDSCs was primarily associated with downregulation of the interleukin (IL)-10/signal transducer and activator of transcription 3 (STAT3) signaling axis within the tumor microenvironment, as confirmed by knockdown of STAT3 (by STAT3-siRNA) and using IL-10-/- mice. Thus, NLGP-mediated suppression of MDSC functions in tumor hosts is appeared to be another associated effective mechanism for the eradication of murine melanoma by NLGP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CMR.0000000000000721DOI Listing
February 2021

Role of long non‑coding RNAs and related epigenetic mechanisms in liver fibrosis (Review).

Int J Mol Med 2021 Mar 26;47(3). Epub 2021 Jan 26.

Department of Pathology and Laboratory Medicine, University of Western Ontario, London, ON N6A 5C1, Canada.

Liver fibrosis is one of the major liver pathologies affecting patients worldwide. It results from an improper tissue repair process following liver injury or inflammation. If left untreated, it ultimately leads to liver cirrhosis and liver failure. Long non‑coding RNAs (lncRNAs) have been implicated in a wide variety of diseases. They can regulate gene expression and modulate signaling. Some of the lncRNAs promote, while others inhibit liver fibrosis. Similarly, other epigenetic processes, such as methylation and acetylation regulate gene transcription and can modulate gene expression. Notably, there are several regulatory associations of lncRNAs with other epigenetic processes. A major mechanism of action of long non‑coding RNAs is to competitively bind to their target microRNAs (miRNAs or miRs), which in turn affects miRNA availability and bioactivity. In the present review, the role of lncRNAs and related epigenetic processes contributing to liver fibrosis is discussed. Finally, various potential therapeutic approaches targeting lncRNAs and related epigenetic processes, which are being considered as possible future treatment targets for liver fibrosis are identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijmm.2021.4856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846421PMC
March 2021

Role of Extracellular Vesicles in Glioma Progression: Deciphering cellular biological processes to clinical applications.

Curr Top Med Chem 2020 Dec 6. Epub 2020 Dec 6.

Gachon Institute of Pharmaceutical Science and Department of Pharmacy, College of Pharmacy, Gachon University, Incheon. Korea.

Glioma predominantly targets glial cells in the brain and spinal cord. There are grade I, II, III, and IV gliomas with anaplastic astrocytoma and glioblastoma multiforme as the most severe forms of the disease. Current diagnostic methods are limited in their data acquisition and interpretation, markedly affecting treatment modalities and patient outcomes. Circulating extracellular vesicles (EVs) or "magic bullets" contain bioactive signature molecules such as DNA, RNA, proteins, lipids, and metabolites. These secretory "smart probes" participate in myriad cellular activities, including glioma progression. EVs are released by all cell populations and may serve as novel diagnostic biomarkers and efficient nanovehicles in the targeted delivery of encapsulated therapeutics. The present review describes the potential of EVbased biomarkers for glioma management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568026620666201207100139DOI Listing
December 2020

A comprehensive overview of proteomics approach for COVID 19: new perspectives in target therapy strategies.

J Proteins Proteom 2020 Nov 2:1-10. Epub 2020 Nov 2.

Department of Research, Sir Ganga Ram Hospital, New Delhi, 110060 India.

World Health Organisation declared COVID-19 a pandemic on March 11, 2020. It was temporarily named as 2019-nCoV then subsequently named as COVID-19 virus. A coronavirus is a group of viruses, known to be zoonotic, causing illness ranging from acute to mild respiratory infections. These are spherical or pleomorphic enveloped particles containing positive sense RNA. The virus enters host cells, its uncoated genetic material transcribes, and translates. Since it has started spreading rapidly, protective measures have been taken all over the world. However, its transmission has been proved to be unstoppable and the absence of an effective drug makes the situation worse. The scientific community has gone all-out to discover and develop a possible vaccine or a competent antiviral drug. Other domains of biological sciences that promise effective results and target somewhat stable entities that are proteins, could be very useful in this time of crisis. Proteomics and metabolomics are the vast fields that are equipped with sufficient technologies to face this challenge. Various protein separation and identification techniques are available which facilitates the analysis of various types of interactions among proteins and their evolutionary lineages. The presented review aims at confronting the question: 'how proteomics can help in tackling SARS-CoV-2?' It deals with the role of upcoming proteome technology in these pandemic situations and discusses the proteomics approach towards the COVID-19 dilemma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s42485-020-00052-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605460PMC
November 2020

Differential transcriptome analysis in HPV-positive and HPV-negative cervical cancer cells through CRISPR knockout of miR-214.

J Biosci 2020 ;45

Cancer Biology Lab, School of Biotechnology, KIIT University, Bhubaneswar, India.

In this study we have investigated the effects of a tumour suppressor microRNA, miR-214, on gene expression in HPV-positive (CaSki) and HPV-negative cervical cancer cells (C33A) by RNA sequencing using next generation sequencing. The HPV-positive and HPV-negative cervical cancer cells were either miR-214- knocked-out or miR-214-overexpressed. Gene expression analysis showed that a total of 904 genes were upregulated and 365 genes were downregulated between HPV-positive and HPV-negative cervical cancer cells with a fold change of +/- 2. Furthermore, 11 differentially expressed and relevant genes which showed a fold change of +/-5 were selected to confirm by real-time PCR. This study represents the first report of miR-214 on global gene expression in the context of HPV.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2020

Intestinal microbiota and vaccine efficacy in children from resource poor settings - potential impact for the usefulness of probiotics?

Benef Microbes 2020 Aug 28;11(4):319-328. Epub 2020 Jul 28.

Institute of Liver and Biliary Science, New Delhi, India.

Developing countries continue to contribute significantly to the global burden of childhood mortality due to infectious diseases. Infections leading to diseases like diarrhoea, pneumonia and meningitis account for millions of deaths annually. Most of these diseases are preventable by vaccination and therefore global vaccination rates have risen substantially with clear benefits. But paradoxically, the vaccines have demonstrated lower immunogenicity in developing countries as compared to their industrialised counterparts. Malnutrition in resource poor settings along with repeated polymicrobial infections at early age are some of the reasons for the differences in vaccine efficacy in different settings. Recent studies indicate that the gastrointestinal microbiota possibly influences maturation of immune system as well as vaccine efficacy. In this review we discuss evidences from , animal and human studies showing that probiotics can positively modulate gut microbiota composition and exert immunomodulatory effects on the host. We also discuss how they should be evaluated for their ability to improve vaccine performance especially in low resource settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3920/BM2019.0155DOI Listing
August 2020

Neem leaf glycoprotein reverses tumor-induced and age-associated thymic involution to maintain peripheral CD8 T cell pool.

Immunotherapy 2020 Aug 22;12(11):799-818. Epub 2020 Jul 22.

Department of Immunoregulation & Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, SP Mukherjee Road, Kolkata 700026, India.

As tumor causes atrophy in the thymus to target effector-T cells, this study is aimed to decipher the efficacy of neem leaf glycoprotein (NLGP) in tumor- and age-associated thymic atrophy. Different thymus parameters were studied using flow cytometry, reverse transcriptase PCR and immunocyto-/histochemistry in murine melanoma and sarcoma models. Longitudinal NLGP therapy in tumor hosts show tumor-reduction along with significant normalization of thymic alterations. NLGP downregulates intrathymic IL-10, which eventually promotes Notch1 to rescue blockade in CD25CD44c-KitDN2 to CD25CD44c-KitDN3 transition in T cell maturation and suppress Ikaros/IRF8/Pu.1 to prevent DN2-T to DC differentiation in tumor hosts. The CD5TCRαβ DP3 population was also increased to endorse CD8 T cell generation. NLGP rescues tumor-induced altered thymic events to generate more effector T cells to restrain tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt-2019-0168DOI Listing
August 2020

Tumor Arrests DN2 to DN3 Pro T Cell Transition and Promotes Its Conversion to Thymic Dendritic Cells by Reciprocally Regulating Notch1 and Ikaros Signaling.

Front Immunol 2020 5;11:898. Epub 2020 Jun 5.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), Kolkata, India.

Tumor progression in the host leads to severe impairment of intrathymic T-cell differentiation/maturation, leading to the paralysis of cellular anti-tumor immunity. Such suppression manifests the erosion of CD4CD8 double-positive (DP) immature thymocytes and a gradual increase in CD4CD8 double negative (DN) early T-cell progenitors. The impact of such changes on the T-cell progenitor pool in the context of cancer remains poorly investigated. Here, we show that tumor progression blocks the transition of LinThy1.2CD25CD44c-KitDN2b to LinThy1.2CD25CD44c-KitDN3 in T-cell maturation, instead leading to DN2-T-cell differentiation into dendritic cells (DC). We observed that thymic IL-10 expression is upregulated, particularly at cortico-medullary junctions (CMJ), under conditions of progressive disease, resulting in the termination of IL-10R DN2-T-cell maturation due to dysregulated expression of Notch1 and its target, CCR7 (thus restricting these cells to the CMJ). Intrathymic differentiation of T-cell precursors in IL-10 mice and fetal thymic organ cultures revealed that IL-10 promotes the interaction between thymic stromal cells and Notch1 DN2-T cells, thus facilitating these DN2-T cells to differentiate toward CD45CD11cMHC-II thymic DCs as a consequence of activating the Ikaros/IRF8 signaling axis. We conclude that a novel function of thymically-expressed IL-10 in the tumor-bearing host diverts T-cell differentiation toward a DC pathway, thus limiting the protective adaptive immune repertoire.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.00898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292239PMC
June 2020

CRISPR-mediated knockdown of miR-214 modulates cell fate in response to anti-cancer drugs in HPV-negative and HPVpositive cervical cancer cells.

J Biosci 2020 ;45

Cancer Biology Lab, School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar 751 024, India.

Cervical cancer is the fourth most common cause of mortality in women worldwide. In this study we investigated the effect of a tumour suppressor microRNA miR-214 in modulating the cell death against chemotherapeutic drugs like Doxorubicin, Cisplatin and Paclitaxel. CRISPR-facilitated knockdown and plasmid-based overexpression of miR-214 was performed in cervical cancer cell lines HeLa, C33A and CaSki. It was observed that knocking out miR-214 resulted in reduced apoptosis and cell migration upon drug treatments; while overexpression of miR-214 resulted in marginal increase in apoptosis and cell migration when treated with drugs. However, miR-214 had very little effect on production of reactive oxygen species. Our results also indicate that Doxorubicin was least effective and Paclitaxel most effective in inducing cell death. A combination of miR-214 overexpression and Paclitaxel treatment was found to be most effective in inducing cell death in cervical cancer cells. Analysis of cell cycle phases followed by apoptotic markers also showed that miR-214 overexpression along with Paclitaxel treatment caused an increase in PARP and decline of PI-3 kinase/Akt levels. Therefore, miR-214 levels determine the fate of the cancer cell during chemotherapeutic treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2020

Neem Leaf Glycoprotein Restrains VEGF Production by Direct Modulation of HIF1α-Linked Upstream and Downstream Cascades.

Front Oncol 2020 6;10:260. Epub 2020 Mar 6.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), Kolkata, India.

Neem Leaf Glycoprotein (NLGP) is a natural immunomodulator, have shown sustained tumor growth restriction as well as angiogenic normalization chiefly by activating CD8 T cells. Here, we have investigated the direct role of NLGP as a regulator of tumor microenvironmental hypoxia and associated vascular endothelial growth factor (VEGF) production. We observed a significant reduction in VEGF level in both murine tumor and cancer cells (B16Mel, LLC) and macrophages after NLGP treatment. Interestingly, NLGP mediated VEGF downregulation in tumor cells or macrophages within hypoxic chamber was found at an early 4 h and again at late 24 h in mRNA level. Our data suggested that NLGP prevented hypoxia-induced strong binding of HIF1α with its co-factors, CBP/p300 and Sp3, but not with Sp1, which eventually limit the binding of HIF1α-transcriptional complex to hypoxia responsive element of VEGF promoter and results in restricted early VEGF transcription. On the otherhand, suppressed phosphorylation of Stat3 by NLGP results reduction of HIF1α at 24 h of hypoxia that further support sustained VEGF down-regulation. However, NLGP fails to regulate VHL activity as observed by both and studies. Therefore, this study for the first time reveals a mechanistic insight of NLGP mediated inhibition of angiogenesis by suppressing VEGF, which might help in vascular normalization to influence better drug delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067891PMC
March 2020

NLGP Attenuates Murine Melanoma and Carcinoma Metastasis by Modulating Cytotoxic CD8 T Cells.

Front Oncol 2020 10;10:201. Epub 2020 Mar 10.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata, India.

Neem leaf glycoprotein (NLGP), a natural immunomodulator, attenuates murine carcinoma and melanoma metastasis, independent of primary tumor growth and alterations in basic cellular properties (cell proliferation, cytokine secretion, etc.). Colonization event of invasion-metastasis cascade was primarily inhibited by NLGP, with no effect on metastasis-related invasion, migration, and extravasation. High infiltration of interferon γ (IFN-γ)-secreting cytotoxic CD8 T cells [CD44, CD69, GranB, IFN-γ, and interleukin 2] was documented in the metastatic site of NLGP-treated mice. Systemic CD8 T cell depletion abolished NLGP-mediated metastasis inhibition and reappeared upon adoptive transfer of NLGP-activated CD8 T cells. Interferon γ-secreting from CD8 T cells inhibit the expression of angiogenesis regulatory vascular endothelial growth factor and transforming growth factor β and have an impact on the prevention of colonization. Neem leaf glycoprotein modulates dendritic cells (DCs) for proper antigen presentation by its DC surface binding and upregulation of MHC-I/II, CD86, and CCR7. Neem leaf glycoprotein-treated DCs specifically imprint CXCR3 and CCR4 homing receptors on activated CD8 T cells, which helps to infiltrate into metastatic sites to restrain colonization. Such NLGP's effect on DCs is translation dependent and transcription independent. Studies using ovalbumin, OVA, and crude B16F10 antigen indicate MHC-I upregulation depends on the quantity of proteasome degradable peptide and only stimulates CD8 T cells in the presence of antigen. Overall data suggest NLGP inhibits metastasis, in conjunction with tumor growth restriction, and thus might appear as a promising next-generation cancer immunotherapeutic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076076PMC
March 2020

Typhoid fever: Control & challenges in India.

Indian J Med Res 2019 11;150(5):437-447

Policy Center for Biomedical Research, Translational Health Science & Technology Institute, Faridabad, Haryana, India.

Enteric fever is a common but serious disease that affects mostly children and adolescents in the developing countries. Salmonella enterica serovar Typhi remains responsible for most of the disease episodes; however, S. Paratyphi A has also been reported as an emerging infectious agent of concern. The control measures for the disease must encompass early diagnosis, surveillance and vaccine to protect against the disease. Sanitation and hygiene play a major role in reducing the burden of enteric diseases as well. The current status of diagnostics, the surveillance practices in the recent past and the vaccine development efforts have been taken into account for suggesting effective prevention and control measures. However, the challenges in all these aspects persist and cause hindrance in the implementation of the available tools. Hence, an integrative approach and a comprehensive policy framework are required to be in place for the prevention, control and elimination of typhoid fevers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijmr.IJMR_411_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977362PMC
November 2019

Potentials of "stem cell-therapy" in pancreatic cancer: An update.

Pancreatology 2019 Dec 1;19(8):1034-1042. Epub 2019 Oct 1.

Department of Research, Sir Ganga Ram Hospital, Room No. 1258, Rajinder Nagar, New Delhi, 110060, India.

In recent times, cell-therapies like T-activated cells, dendritic cells and natural killer cells have shown increasing promise in treating cancers as evidenced by both animal and human studies in the literature. In addition, stem cells are also being considered as potent anti-cancer agents since they act through multi-pronged approaches (chemokines, cytokines, paracrine action). In this review, we have attempted to discuss the inferences of studies that have used different sub-types of stem cells namely mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs) and neural stem cells (NSCs) in in-vitro/in-vivo mice and/or human studies as a treatment modality for pancreatic cancer. Pancreatic cancers are diagnosed in late/metastatic stages hence limiting its progress to partial/disease-free status. Recent literature supports evidences of stem cell therapy in pancreatic cancer with promising results; yet their impact remains inconclusive due to limited studies in human subjects. With reference to the treatment options for pancreatic cancer, the most studied sub-type of stem cells was HSCs as evident from the available clinical trials. The suggested mechanism of the HSC-transplantation is presumably via the graft-versus-tumor effect that elicits an anti-tumor immune response activated by the T-cell repertoires. On the other hand, the property of MSCs like tropism, migration to tumor site and activation of host immune cells by its secretome, appear to be able to regulate pancreatic tumor microenvironment. Further, drug delivery potential could be mediated via engineered MSCs to enhance the bioavailability of drug/prodrug at tumor site. Conclusively, stem cells have shown great potentials as next-generation therapeutic options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pan.2019.09.016DOI Listing
December 2019

CAR T cell therapy: A new era for cancer treatment (Review).

Oncol Rep 2019 Dec 24;42(6):2183-2195. Epub 2019 Sep 24.

Cancer Biology Laboratory, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) University, Bhubaneswar, Odisha 751024, India.

Cancer has recently been identified as the leading cause of mortality worldwide. Several conventional treatments and cytotoxic immunotherapies have been developed and made available to the market. Considering the complex behavior of tumors and the involvement of numerous genetic and cellular factors involved in tumorigenesis and metastasis, there is a need to develop a promising immunotherapy that targets tumors at both the cellular and genetic levels. Chimeric antigen receptor (CAR) T cell therapy has emerged as a novel therapeutic T cell engineering practice, in which T cells derived from patient blood are engineered in vitro to express artificial receptors targeted to a specific tumor antigen. These directly identify the tumor antigen without the involvement of the major histocompatibility complex. The use of this therapy in the last few years has been successful, with a reduction in remission rates of up to 80% for hematologic cancer, particularly for acute lymphoblastic leukemia (ALL) and non‑Hodgkin lymphomas, such as large B cell lymphoma. Recently, anti‑CD19 CAR therapy, or UCART19, has been shown to be efficacious in treating relapsed/refractory hematologic cancer. Several other cell surface tumor antigens, such as CD20 and CD22, found in the majority of leukemias and lymphomas are considered potential targets by pharmaceutical companies and research organizations, and trials have been ongoing in this direction. Although this therapeutic regimen is currently confined to treating hematologic cancer, the increasing involvement of several auxiliary techniques, such as bispecific CAR, Tan‑CAR, inhibitory‑CAR, combined antigens, the clustered regularly interspaced short palindromic repeats gene‑editing tool and nanoparticle delivery, may substantially improve its overall anticancer effects. CAR therapy has the potential to offer a rapid and safer treatment regime to treat non‑solid and solid tumors. The present review presents an insight into the advantages and the advances of CAR immunotherapy and presents the emerging discrepancy of CAR therapy over usual forms of therapy, such as chemotherapy and radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2019.7335DOI Listing
December 2019

NLGP counterbalances the immunosuppressive effect of tumor-associated mesenchymal stem cells to restore effector T cell functions.

Stem Cell Res Ther 2019 09 23;10(1):296. Epub 2019 Sep 23.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata, 700026, India.

Background: A dynamic interaction between tumor cells and its surrounding stroma promotes the initiation, progression, metastasis, and chemoresistance of solid tumors. Emerging evidences suggest that targeting the stromal events could improve the efficacies of current therapeutics. Within tumor microenvironment (TME), stromal progenitor cells, i.e., MSCs, interact and eventually modulate the biology and functions of cancer and immune cells. Our recent finding disclosed a novel mechanism stating that tumor-associated MSCs inhibit the T cell proliferation and effector functions by blocking cysteine transport to T cells by dendritic cells (DCs), which makes MSCs as a compelling candidate as a therapeutic target. Immunomodulation by nontoxic neem leaf glycoprotein (NLGP) on dysfunctional cancer immunity offers significant therapeutic benefits to murine tumor host; however, its modulation on MSCs and its impact on T cell functions need to be elucidated.

Methods: Bone marrow-derived primary MSCs or murine 10 T1/2 MSCs were tumor-conditioned (TC-MSCs) and co-cultured with B16 melanoma antigen-specific DCs and MACS purified CD4 and CD8 T cells. T cell proliferation of T cells was checked by Ki67-based flow-cytometric and thymidine-incorporation assays. Cytokine secretion was measured by ELISA. The expression of cystathionase in DCs was assessed by RT-PCR. The STAT3/pSTAT3 levels in DCs were assessed by western blot, and STAT3 function was confirmed using specific SiRNA. Solid B16 melanoma tumor growth was monitored following adoptive transfer of conditioned CD8 T cells.

Results: NLGP possesses an ability to restore anti-tumor T cell functions by modulating TC-MSCs. Supplementation of NLGP in DC-T cell co-culture significantly restored the inhibition in T cell proliferation and IFNγ secretion almost towards normal in the presence of TC-MSCs. Adoptive transfer of NLGP-treated TC-MSC supernatant educated CD8 T cells in solid B16 melanoma bearing mice resulted in better tumor growth restriction than TC-MSC conditioned CD8 T cells. NLGP downregulates IL-10 secretion by TC-MSCs, and concomitantly, pSTAT3 expression was downregulated in DCs in the presence of NLGP-treated TC-MSC supernatant. As pSTAT3 negatively regulates cystathionase expression in DCs, NLGP indirectly helps to maintain an almost normal level of cystathionase gene expression in DCs making them able to export sufficient amount of cysteine required for optimum T cell proliferation and effector functions within TME.

Conclusions: NLGP could be a prospective immunotherapeutic agent to control the functions and behavior of highly immunosuppressive TC-MSCs providing optimum CD8 T cell functions to showcase an important new approach that might be effective in overall cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-019-1349-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757425PMC
September 2019

Genetic characterization of group-A rotaviruses among children in eastern India during 2014-2016: Phylodynamics of co-circulating genotypes.

Vaccine 2019 10 19;37(45):6842-6856. Epub 2019 Sep 19.

ICMR-National Institute of Cholera and Enteric Diseases (ICMR-NICED), Kolkata, India. Electronic address:

Background: Group-A human rotaviruses (GARV) are among the major cause of childhood diarrhea worldwide. In lieu of monitoring the circulatory GARV strains and underscoring the burden of GARV related hospitalization, a systematic surveillance was conducted in three hospitals of eastern India. In this hospital-based diarrheal disease surveillance (2014-2016), GARV was the most common cause of acute infantile gastroenteritis. The strains were genotyped and characterized to understand their prevalence and phylodynamics prior to the introduction of vaccine in eastern India.

Materials And Methods: A total of 3652 stool samples were screened from children (≤5 years) hospitalized with acute diarrhea during 2014-2016. Initial screening for VP6 antigen was done by ELISA. GARV positive samples were genotyped by multiplex semi-nested PCR and DNA sequencing and phylogenetic analyses were based on the capsid proteins VP4 and VP7.

Results: Of 3652 samples, 1817 (49.8%) were GARV positive. G1, G2, G3 and G9 in conjunction with P[4], P[6]and P[8]genotypes were seen to co-circulate in the population. A sharp deflection from G1 to G3 occurred since 2016; upsurge of G9 strains was seen in alternate years, whereas G2 strains had a low frequency. All the circulating genotypes depicted a low phylogenetic relatedness to the vaccine strains. Differences in antigenic epitopes of VP4 and VP7 proteins in local strains were seen when compared to the vaccine strains. A significant difference in the degree of dehydration, duration of mean hospital stay and frequency of vomiting/24 h between GARV positive and negative children was evident.

Conclusion: The study provides a relevant set of base-line data on high burden of rotaviral gastroenteritis and the varied genotypic diversity among children prior to the introduction of GARV vaccine in this endemic region. Continuous monitoring during post-vaccination era will be required to assess the impact of vaccination in this region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2019.06.062DOI Listing
October 2019

Innovations for the elimination and control of visceral leishmaniasis.

PLoS Negl Trop Dis 2019 09 19;13(9):e0007616. Epub 2019 Sep 19.

Apollo Hospitals Educational and Research Foundation, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752755PMC
September 2019

Transcriptomic analyses of gene expression by CRISPR knockout of miR-214 in cervical cancer cells.

Genomics 2020 03 26;112(2):1490-1499. Epub 2019 Aug 26.

Cancer Biology Lab, School of Biotechnology, KIIT University, Bhubaneswar, India. Electronic address:

In this study, we investigate the effect of one such micro RNA, miR-214 which is frequently down-regulated in cervical cancer. In this study, we either CRISPR knocked out or overexpressed miR-214 in cervical cancer cells and analyzed the global mRNA expression by Next Generation Sequencing (NGS) It was observed that a total of 108 genes were upregulated and 178 downregulated between the samples, above and below the baseline respectively. Gene Ontology and KEGG pathway analysis reveal distinct biological processes and pathways. Analysis of gene regulatory networks also gave different network patterns in the two samples. We confirmed the RNA sequencing data for 10 genes; IFIF27, SMAD3, COX11, TP53INP1, ABL2, FGF8, TNFAIP3, NRG1, SP3 and MDM4 by Real-time PCR. This is the first report on the effect of miR-214 on global mRNA profile in cervical cancer cells. This study also reports new biomarkers for cervical cancer prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2019.08.020DOI Listing
March 2020

Artificial Intelligence and Deep Learning: The Future of Medicine and Medical Practice.

J Assoc Physicians India 2019 Apr;67(4):71-73

Formerly Director General of ICMR, Director, PGIMER and President of JIPMER, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana.

Abstract: Artificial Intelligence (AI) and access to "Big Data" together with the evolving techniques in biotechnology will change the medical practice a big way. Many diseases such as type II diabetes will no longer be considered as a single disease. Many familiar cancers such as cancer of liver or pancreas will have hundreds of subtypes whose management will be very different. The way we think about diseases will change. It will no longer be possible for clinicians to make a diagnosis, remember the names of diseases, the names of drugs or management protocols without the help of computers. As computer intelligence becomes more important than human intelligence in deciding diagnosis and treatment there will be a paradigm in the role of doctors. Internet, computers and social media will become more important than individuals in decision making. As a result, medicine will go more and more egalitarian ("wiki") with increasing community participation in health decision making and management. A socialistic pattern will evolve over time globally as an adaptive reaction to the pressures put by artificial intelligence. This is because the individual differences in knowledge or intellect between human beings will become less apparent compared to the super powers of artificial intelligence. Qualities which are unique for humans such as compassion, empathy and emotional care will decide the professional success of future physicians even more than today. Today we are using artificial intelligence in diagnosis and prediction to help clinicians. Clinical algorithms and human experience cannot be replaced by machines. It will take many years to completely merge or replace humans with machines. However, we need to modify our medical education system in order to prepare the medical community and sensitize the society well in advance for a smooth transition.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2019

Trials of the killed oral cholera vaccine (Shanchol) in India and Bangladesh: Lessons learned and way forward.

Vaccine 2020 02 10;38 Suppl 1:A127-A131. Epub 2019 Jul 10.

Translational Health Science and Technology Institute, India.

Cholera has been endemic in India and Bangladesh for the greater part of recorded history, giving this region the reputation of being the 'homeland of cholera'. The causative organism Vibrio cholerae O1 has been responsible for large epidemics and pandemics. Bangladesh and India have conducted several sequential studies of Oral Cholera Vaccine (OCV) to ascertain its safety, efficacy, effectiveness, field feasibility and acceptance in high-risk urban populations. The objective of this article is to illustrate the experience of OCV use in these endemic settings, its major challenges, and how policymakers can grant vaccine licenses as well as implement its use in the national immunization programme. The relevant aspects of the OCV studies, such as boosting the effect of vaccine, single-dose versus double-dose trials and thermal stability of the vaccine during delivery have generated strong evidence for recommendation of vaccine use in these settings. Studies have shown that a single dose is effective for children of five years of age and older age groups. The locally manufactured vaccine in India is thermostable and can be delivered in field settings without use of cold chain. The vaccine delivery is feasible and the protective efficacy (PE) of this vaccine above five years of age against cholera was 53-65%. Administration of an OCV boosting regimen elicits an immune response similar to those who received a two-dose vaccine five years back. OCV can be used as a preemptive measure in endemic settings, in natural calamities and during political instability when there is total disruption as well as collapse of safe water supply, sanitation and hygiene (WASH) facilities and other control measures. Clear identification of areas and target population (who will gain benefit from the OCVs) is required to be developed in endemic settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2019.06.082DOI Listing
February 2020

Opportunities and challenges for cholera control in India.

Vaccine 2020 02 29;38 Suppl 1:A25-A27. Epub 2019 Jun 29.

Policy Center for Biomedical Research, Translational Health Science and Technology Institute, NCR Biotech Bioscience Cluster, Faridabad Gurgaon Expressway, Faridabad 121001, India. Electronic address:

The Indo Gangetic delta is homeland for cholera for almost two centuries now and there is evidence of global spread from this area. With migration of people to more urban areas within the country and increase in international travel, it is time for action against cholera in India, given its capacity to present itself in epidemic proportions. The Global roadmap to end cholera by 2030 was launched by the WHO Global Task force for Cholera Control which has led to renewed vigor and convergence of stakeholders across the world against the disease. There is also an emphasis on cleanliness and improved sanitation by the current government. The article discusses the unique opportunity for India in the current scenario, to act against diseases like cholera and challenges that are anticipated in deployment of interventions due to suboptimal surveillance and shortage of vaccines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2019.06.032DOI Listing
February 2020

Malaria control in India: A national perspective in a regional and global fight to eliminate malaria.

J Vector Borne Dis 2019 Jan-Mar;56(1):41-45

WorldWide Antimalarial Resistance Network; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Department of Genome Sciences, University of Washington, Seattle, WA, USA.

Since the declaration of the vision of malaria eradication in 2007, the overall burden of malaria has been reduced substantially in many countries in the endemic world. This progress has, however, recently slowed worldwide and even an increase of morbidity and mortality has been observed in some regions. That reality has led to reflection on the strategy for malaria elimination, noting that focusing only on low transmission sites has competed with the efforts in countries that still have foci with high malaria burdens. This opinion piece outlines the collaboration of the ICMR-National Institute of Malaria Research (ICMR-NIMR) and other partner Institutions in India with the WorldWide Antimalarial Resistance Network (WWARN), one part of a global effort to manage the spread of Plasmodium falciparum parasites associated with antimalarial resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0972-9062.257773DOI Listing
August 2019

Immunogenicity and lot-to-lot consistency of a ready to use liquid bovine-human reassortant pentavalent rotavirus vaccine (ROTASIIL - Liquid) in Indian infants.

Vaccine 2019 05 4;37(19):2554-2560. Epub 2019 Apr 4.

Serum Institute of India Pvt. Ltd., Pune, India. Electronic address:

Background: A lyophilized bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, Rotasiil®) was licensed in 2016. A liquid formulation of this vaccine (LBRV-PV, Rotasiil - Liquid) was subsequently developed and was tested for non-inferiority to Rotasiil® and for lot-to-lot consistency.

Methods: This Phase II/III, open label, randomized study was conducted at seven sites across India from November 2017 to June 2018. Participants were randomized into four arms; Lots A, B, and C of LBRV-PV and Rotasiil® in 1:1:1:1 ratio. Three doses of study vaccines were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. Non-inferiority of LBRV-PV to Rotasiil was proven if the lower limit two-sided 95% confidence interval (CI) of geometric mean concentration (GMC) ratio was at least 0.5. Lot-to-lot consistency was proven if 95% CI of the GMC ratios of three lots were between 0.5 and 2. Solicited reactions were collected by using diary cards.

Results: Of the 1500 randomized infants, 1436 infants completed the study. The IgA GMC ratio of LBRV-PV to Rotasiil® was 1.19 (95% CI 0.96, 1.48). The corresponding IgA seropositivity rates were 60.41% (57.41, 63.35) and 52.75% (47.48, 57.97). The IgA GMC ratios among the three LBRV-PV lots were: Lot A versus Lot B: 1.34 (1.03, 1.75); Lot A versus Lot C: 1.22 (0.93, 1.60); and Lot B versus Lot C: 0.91 (0.69, 1.19). The 95% CIs for the GMC ratios were between 0.69 and 1.75. The incidence of solicited reactions was comparable across the four arms. Only one serious adverse event of gastroenteritis event in the Rotasiil® group was causally related.

Conclusion: The immunological non-inferiority of LBRV-PV against Rotasiil® as well as lot-to-lot consistency of LBRV-PV was demonstrated. LBRV-PV had safety profile similar to Rotasiil®.

Trial Registration Number: Clinical Trials.Gov [NCT03474055] and Clinical Trial Registry of India [CTRI/2017/10/010104].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2019.03.067DOI Listing
May 2019

Cholera prevention and control in Asian countries.

BMC Proc 2018 7;12(Suppl 13):62. Epub 2018 Dec 7.

26World Health Organization, New Delhi, India.

Cholera remains a major public health problem in many countries. Poor sanitation and inappropriate clean water supply, insufficient health literacy and community mobilization, absence of national plans and cross-border collaborations are major factors impeding optimal control of cholera in endemic countries. In March 2017, a group of experts from 10 Asian cholera-prone countries that belong to the Initiative against Diarrheal and Enteric Diseases in Africa and Asia (IDEA), together with representatives from the World Health Organization, the US National Institutes of Health, International Vaccine Institute, Agence de médecine préventive, NGOs (Save the Children) and UNICEF, met in Hanoi (Vietnam) to share progress in terms of prevention and control interventions on water, sanitation and hygiene (WASH), surveillance and oral cholera vaccine use. This paper reports on the country situation, gaps identified in terms of cholera prevention and control and strategic interventions to bridge these gaps.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12919-018-0158-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284268PMC
December 2018

Early Initiation of Steroid-sparing Drugs in Idiopathic Pulmonary Hemosiderosis.

Indian Pediatr 2019 01;56(1):73-74

Department of Pediatrics, Institute of Child Health, Kolkata, West Bengal, India.

Idiopathic pulmonary hemosiderosis is conventionally treated with steroids, prolonged usage of which maybe deleterious and disease often recurs on tapering. We initiated hydroxy-chloroquine and azathioprine early in treatment along with steroids in seven children with idiopathic pulmonary hemosiderosis, and observed that early introduction of second line immunosuppressants helped in reducing disease flare and steroid toxicity without serious adverse effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2019

Can India lead the way in neglected diseases innovation?

BMJ 2019 Jan 22;364:k5396. Epub 2019 Jan 22.

Apollo Hospitals Educational and Research Foundation, New Delhi, India

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.k5396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340354PMC
January 2019

A Phase III open-label, randomized, active controlled clinical study to assess safety, immunogenicity and lot-to-lot consistency of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants.

Vaccine 2018 12 9;36(52):7943-7949. Epub 2018 Nov 9.

PATH, USA.

Background: A heat-stable bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was developed in India. In this study, the vaccine was tested for safety, immunogenicity and clinical lot-to-lot consistency.

Methods: This was a Phase III, open label, randomized, equivalence design study. The primary objective was to demonstrate lot-to-lot consistency of BRV-PV. Subjects were randomized into four arms, three arms received Lots A, B, and C of BRV-PV and the control arm, received Rotarix®. Three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. The three lots of BRV-PV were equivalent if the 95% Confidence Intervals (CIs) of the geometric mean concentration (GMC) ratios were between 0.5 and 2. Solicited reactions were collected by using diary cards.

Results: The study was conducted in 1500 randomized infants, of which 1341 infants completed the study. The IgA GMC ratios among the three lots were around 1 (Lot A versus Lot B: 1.07; Lot A versus Lot C: 1.06; and Lot B versus Lot C: 0.99). The 95% CIs for the GMC ratios were between 0.78 and 1.36. The IgA GMCs were: BRV-PV group 19.16 (95% CI 17.37-21.14) and Rotarix® group 10.92 (95% CI 9.36-12.74) (GMC ratio 1.75; 90% CI 1.51-2.04). Seropositivity rates were 46.98% (95% CI 43.86-50.11) and 31.12% (95% CI 26.17-36.41). The incidence of solicited reactions was comparable across the four arms. No serious adverse events were associated with the study vaccines, except two gastroenteritis events in the BRV-PV groups.

Conclusion: Lot-to-lot consistency of BRV-PV was demonstrated in terms of GMC ratios of IgA antibodies. The vaccine safety and immunogenicity profiles were similar to those of Rotarix®. Clinical Trials.Gov [NCT02584816] and Clinical Trial Registry of India [CTRI/2015/07/006034].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288065PMC
December 2018

A Retrospective Review of Hospital-Based Data on Enteric Fever in India, 2014-2015.

J Infect Dis 2018 11;218(suppl_4):S206-S213

Sabin Vaccine Institute, Washington, D. C., Georgia.

Background: Enteric fever remains a threat to many countries with minimal access to clean water and poor sanitation infrastructure. As part of a multisite surveillance study, we conducted a retrospective review of records in 5 hospitals across India to gather evidence on the burden of enteric fever.

Methods: We examined hospital records (laboratory and surgical registers) from 5 hospitals across India for laboratory-confirmed Salmonella Typhi or Salmonella Paratyphi cases and intestinal perforations from 2014-2015. Clinical data were obtained where available. For laboratory-confirmed infections, we compared differences in disease burden, age, sex, clinical presentation, and antimicrobial resistance.

Results: Of 267536 blood cultures, 1418 (0.53%) were positive for S. Typhi or S. Paratyphi. Clinical data were available for 429 cases (72%); a higher proportion of participants with S. Typhi infection were hospitalized, compared with those with S. Paratyphi infection (44% vs 35%). We observed resistance to quinolones among 82% of isolates, with cases of cephalosporin resistance (1%) and macrolide resistance (9%) detected. Of 94 participants with intestinal perforations, 16 (17%) had a provisional, final, or laboratory-confirmed diagnosis of enteric fever.

Discussion: Data show a moderate burden of enteric fever in India. Enteric fever data should be systematically collected to facilitate evidence-based decision-making by countries for typhoid conjugate vaccines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiy502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226629PMC
November 2018

Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine ROTASIIL® with the immunogenicity of infant vaccines in comparison with a licensed rotavirus vaccine.

Vaccine 2018 09 10;36(37):5519-5523. Epub 2018 Aug 10.

Serum Institute of India Pvt. Ltd., Pune, India. Electronic address:

Background: A newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India.

Methods: In this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate - pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was >10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was >0.5.

Results: A total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19].

Conclusion: BRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2018.07.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143481PMC
September 2018