Publications by authors named "Kiran Meena"

8 Publications

  • Page 1 of 1

Nuclear receptor subfamily 5 group A member 2 (NR5A2): role in health and diseases.

Mol Biol Rep 2021 Oct 13. Epub 2021 Oct 13.

Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Rishikesh, Rishikesh, Uttarakhand, India.

Nuclear receptors are the regulatory molecules that mediate cellular signals as they interact with specific DNA sequences. NR5A2 is a member of NR5A subfamily having four members (Nr5a1-Nr5a4). NR5A2 shows involvement in diverse biological processes like reverse cholesterol transport, embryonic stem cell pluripotency, steroidogenesis, development and differentiation of embryo, and adult homeostasis. NR5A2 haploinsufficiency has been seen associated with chronic pancreatitis, pancreatic and gastrointestinal cancer. There is a close relationship between the progression of pancreatic cancer from chronic pancreatitis, NR5A2 serving a common link. NR5A2 activity is regulated by intracellular phospholipids, transcriptional coregulators and post-translational modifications. The specific ligand of NR5A2 is unknown hence called an orphan receptor, but specific phospholipids such as dilauroyl phosphatidylcholine and diundecanoyl phosphatidylcholine act as a ligand and they are established drug targets in various diseases. This review will focus on the NR5A2 structure, regulation of its activity, and role in biological processes and diseases. In future, need more emphasis on discovering small molecule agonists and antagonist, which act as a drug target for therapeutic applications.
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http://dx.doi.org/10.1007/s11033-021-06784-1DOI Listing
October 2021

COVID-19 and Gut Microbiota: A Potential Connection.

Indian J Clin Biochem 2021 Jan 21:1-12. Epub 2021 Jan 21.

Department of Biochemistry, AIIMS Rishikesh, Uttarakhand, 249203 India.

Currently, world is facing a global outbreak causing a pandemic threat known as COVID-19. This infectious disease is triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Gut microbiota harbours multi species community with a strong impact on host immune homeostasis. However, our knowledge about this gut microbiota and its symbiotic relationship with immune activation in association with SARS-CoV-2 is limited. Unbalanced bacterial flora with too many opportunistic infections can shift immune system towards a cascade of inflammatory responses leading to multi organ damage. This review will highlight immune-regulation via various mechanisms in SARS-CoV-2 infection. Diet has an unbelievable influence on gut microbiome that allows a new state of homeostasis to be reached through timing, frequency and duration of intake. This review article focuses on gut, lung microbiota and immunomodulation with specific attention on immune activation by gut microbiota.
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http://dx.doi.org/10.1007/s12291-020-00948-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818076PMC
January 2021

Nicotinamide combined with gemcitabine is an immunomodulatory therapy that restrains pancreatic cancer in mice.

J Immunother Cancer 2020 11;8(2)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA

Background: Treatments for pancreatic ductal adenocarcinoma are poorly effective, at least partly due to the tumor's immune-suppressive stromal compartment. New evidence of positive effects on immune responses in the tumor microenvironment (TME), compelled us to test the combination of gemcitabine (GEM), a standard chemotherapeutic for pancreatic cancer, with nicotinamide (NAM), the amide form of niacin (vitamin B), in mice with pancreatic cancer.

Methods: Various mouse tumor models of pancreatic cancer, that is, orthotopic Panc-02 and KPC (Kras, p53, Pdx1-Cre) grafts, were treated alternately with NAM and GEM for 2 weeks, and the effects on efficacy, survival, stromal architecture and tumor-infiltrating immune cells was examined by immunohistochemistry (IHC), flow cytometry, Enzyme-linked immunospot (ELISPOT), T cell depletions in vivo, Nanostring analysis and RNAscope.

Results: A significant reduction in tumor weight and number of metastases was found, as well as a significant improved survival of the NAM+GEM group compared with all control groups. IHC and flow cytometry showed a significant decrease in tumor-associated macrophages and myeloid-derived suppressor cells in the tumors of NAM+GEM-treated mice. This correlated with a significant increase in the number of CD4 and CD8 T cells of NAM+GEM-treated tumors, and CD4 and CD8 T cell responses to tumor-associated antigen survivin, most likely through epitope spreading. In vivo depletions of T cells demonstrated the involvement of CD4 T cells in the eradication of the tumor by NAM+GEM treatment. In addition, remodeling of the tumor stroma was observed with decreased collagen I and lower expression of hyaluronic acid binding protein, reorganization of the immune cells into lymph node like structures and CD31 positive vessels. Expression profiling for a panel of immuno-oncology genes revealed significant changes in genes involved in migration and activation of T cells, attraction of dendritic cells and epitope spreading.

Conclusion: This study highlights the potential of NAM+GEM as immunotherapy for advanced pancreatic cancer.
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http://dx.doi.org/10.1136/jitc-2020-001250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646363PMC
November 2020

Occurrence of Mycoplasma genitalium in the peritoneal fluid of fertile and infertile women with detailed analysis among infertile women.

Microb Pathog 2019 Apr 5;129:183-186. Epub 2019 Feb 5.

Department of Zoology, University of Rajasthan, Jaipur, Rajasthan, India. Electronic address:

Objective: To determine the frequency of occurrence of Mycoplasma genitalium infection in the peritoneal fluid of infertile women as compared to fertile women.

Materials And Methods: We have selected 162 infertile women aged 22-40 years as study subject and 162 women posted for elective caesarean section, were taken as control. Peritoneal fluid of the infertile women and control samples was obtained by suction during diagnostic laparoscopy and M. genitalium infection was diagnosed by PCR method.

Results: The genetic material of M. genitalium was detected in the peritoneal fluid of 10 subjects in the infertile group and in 1 from the control group. High prevalence was found in cases with unexplained (13.3%) and primary infertility (6.7%) in comparison to explained (4.5) and secondary infertility (4.5%). Consistent relationship was reported between past obstetric history and presence of M. genitalium infection in infertile subjects. M. genitalium infection was two times more common in women with cervicitis (8.6%) and with blocked fallopian tubes (8.4%). Out of the 101 cases with normal looking uterus, 7 had M. genitalium infection, while 3 out of 61 cases with a congested uterus had infection. The fallopian tubes appeared normal in about 53% cases whereas, inflammation, hydrosalpinx, peritubular adhesions and endometriotic patches were noted in 11.7%, 4.3%, 19.7% and 11.1% of cases respectively.

Conclusion: Present study shows association between M. genitalium infection and infertility. We suggest routine screening and early treatment of this pathogen because prolonged inflammation of upper genital tract sites may lead to significant reproductive morbidity and infertility.
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http://dx.doi.org/10.1016/j.micpath.2019.02.006DOI Listing
April 2019

Differential anti-microbial secondary metabolites in different ESKAPE pathogens explain their adaptation in the hospital setup.

Infect Genet Evol 2018 12 15;66:57-65. Epub 2018 Sep 15.

Department of Biochemistry, Central University of Rajasthan, Bandarsindri, Ajmer, -305817, India.

Nosocomial infections are caused by ESKAPE (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. cloacae) pathogens, and their co-existence is associated with their ability to survive in the hospital setup. They may produce molecules, which helps in the better survival of one ESKAPE pathogens over other. We have identified all secondary metabolite gene clusters in six ESKAPE pathogens and predicted antimicrobial and anti-biofilm properties of their product secondary metabolites. To validate our model, we have taken the secondary metabolites of ESKAPE pathogens and studied their interaction with diguanylate cyclase (involved in quorum sensing) and biofilm-associated protein (involved in biofilm formation) of Acinetobacter baumannii. Results suggest the presence of differential secondary metabolites in all ESKAPE pathogens with only three common non-antimicrobial secondary metabolites. Out of twenty-three antimicrobial secondary metabolites, TP-1161, nosiheptide and meilingmycin, showed the best antimicrobial activity and nineteen showed high anti-biofilm activity. Interaction study showed that secondary metabolites produced by other ESKAPE pathogens (non-Acinetobacter) have very good interaction with diguanylate cyclase and biofilm-associated protein of A. baumannii. This concludes that better survival of these ESKAPE pathogens in hospital setup can be correlated with differential production of antimicrobial secondary metabolites. The present study also investigates the molecular mechanism of the competition of different pathogens living in similar hospital setup (similar habitat). Therefore, the present study will initiate research that might lead to the discovery of antibiotics from one ESKAPE pathogen that controls the infection of other ESKAPE pathogens or other pathogens.
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http://dx.doi.org/10.1016/j.meegid.2018.09.010DOI Listing
December 2018

Cholesterol ester transfer protein and apolipoprotein E gene polymorphisms in hyperlipidemic Asian Indians in North India.

Mol Cell Biochem 2011 Jun 6;352(1-2):189-96. Epub 2011 Mar 6.

Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

We determined the distribution of the polymorphic variants of CETP TaqIB and ApoE genes and their association with lipid and anthropometric parameters in hyperlipidemic and normolipidemic Asian Indians in North India. CETP TaqIB and ApoE polymorphism were assayed by PCR-RFLP in hyperlipidemic (n = 220) and normolipidemic (n = 367) subjects. Plasma lipids levels were estimated using commercially available kits from Randox (USA). The distribution of CETP TaqIB genotypes and alleles did not differ between the two groups. The frequency of ApoE ε4 allele was significantly higher in hyperlipidemic than normolipidemic subjects. Serum lipid levels were comparable between subjects with the different CETP TaqIB and ApoE genotypes in the two groups. Multivariate analysis after adjusting for age, sex, BMI, WHR, and total skinfold thickness showed that subjects with the Ε3Ε4 genotype and ε4 allele carriers were at significantly higher odds to develop hyperlipidemia [2.07 (1.29-3.30) and 2.05 (1.30-3.24), respectively] as compared to the other genotypes. ApoE ε4 allele and E3E4 genotype emerged as important genetic markers for hyperlipidemia in this study population.
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http://dx.doi.org/10.1007/s11010-011-0753-1DOI Listing
June 2011

Apolipoprotein E polymorphism in cerebrovascular & coronary heart diseases.

Indian J Med Res 2010 Oct;132:363-78

Department of Environmental Sciences, Bharathiar University, Coimbatore, India.

The role of apolipoprotein E (apo E) in lipid metabolism and cholesterol transport is well established. About 14 per cent of the variation in plasma cholesterol levels is attributed to polymorphisms in APO E gene (APO E). APO E consists of three common alleles, designated as ε2, ε3 and ε4 which code for E2, E3 and E4 proteins respectively resulting in three homozygous (E2/E2, E3/E3, E4/E4) and three heterozygous (E3/E2, E4/E2 and E4/E3) phenotypes. Different populations studied worldwide inherit variable frequencies of the APO E alleles and genotypes, with the most frequent allele being ε3.The ε4 allele has been consistently shown to be associated with Alzheimer's disease, coronary heart disease and cerebrovascular disorders. In this review, we have discussed the role of APO E polymorphisms in cerebrovascular and coronary heart diseases. The status of APO E polymorphisms and their disease associations in Asian Indians besides, other populations has also been discussed. Further, studies elucidating the pathophysiology of apo E deficiency conducted in knock-out mice have been reviewed.
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October 2010
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