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Article ; Online: Fenofibrate mediated activation of PPARα negatively regulates trophoblast invasion.

Singh, Sunil / Dhar, Ruby / Karmakar, Subhradip

2022 Volume 126, Page(s) 140–149

Abstract: The Peroxisome Proliferator-Activated Receptor-alpha (PPARα) is a member of the ligand-dependent nuclear receptor superfamily known for their crucial role in lipid metabolism. The expression and role of PPARα in trophoblast cells are not very well known. ...

Abstract	The Peroxisome Proliferator-Activated Receptor-alpha (PPARα) is a member of the ligand-dependent nuclear receptor superfamily known for their crucial role in lipid metabolism. The expression and role of PPARα in trophoblast cells are not very well known. Trophoblast invasion is one of the most critical processes required for successful implantation of the developing embryo into the maternal endometrium. Defects in this process are associated with adverse pregnancy outcomes such as FGR(Fetal Growth Restriction), Preeclampsia, and choriocarcinoma. In this present study, we investigated the role of the ligand-activated transcription factor, Peroxisome proliferator-activated receptor (PPARα) in regulating trophoblast cell invasion using cell lines and explants-based models. Immunohistological localization of PPARα in human placental tissues showed a gestational variation with relatively low expression at term as compared to early trimester. PCR and Western Blot also confirmed this. Further to delineate the effect of PPAR alpha on trophoblast invasion, EVT derived HTR8/SVneo cell lines were stimulated with PPARα agonist, i.e., fenofibrate (FF). Fenofibrate stimulation led to an increased activation and nuclear translocation of PPARα, followed by reduced migration and invasion of these cells in a matrigel invasion assay (Boyden chamber). PPAR alpha stimulation also led to a reduced MMP-2/9 expression following our previous observation. Thus, we may conclude that PPARα to be playing a very important regulatory role in orchestrating the invasive trophoblast programme and hence it seems plausible for it to be associated with PE, which is often characterized by a shallow trophoblast invasion.
MeSH term(s)	Cell Movement/physiology ; Female ; Fenofibrate/metabolism ; Fenofibrate/pharmacology ; Humans ; Ligands ; PPAR alpha/metabolism ; Placenta/metabolism ; Pregnancy ; Trophoblasts/metabolism
Chemical Substances	Ligands ; PPAR alpha ; Fenofibrate (U202363UOS)
Language	English
Publishing date	2022-06-14
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603951-0
ISSN	1532-3102 ; 0143-4004
ISSN (online)	1532-3102
ISSN	0143-4004
DOI	10.1016/j.placenta.2022.05.015
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Article: Fault Lines in India's COVID-19 Management: Lessons Learned and Future Recommendations.

Dhar, Ruby / Pethusamy, Karthikeyan / Jee, Babban / Karmakar, Subhradip

Risk management and healthcare policy

2021 Volume 14, Page(s) 4379–4392

Abstract: With about 0.4-0.5 million COVID cases diagnosed every single day in a row over the past three weeks back in May 2021, India was at the epicenter of the global viral rampage. The catastrophe of this crisis was unprecedented, pushing the health care ... ...

Abstract	With about 0.4-0.5 million COVID cases diagnosed every single day in a row over the past three weeks back in May 2021, India was at the epicenter of the global viral rampage. The catastrophe of this crisis was unprecedented, pushing the health care system to its breaking point. Although significant progress has been made in identifying these highly transmissible variants, what is somewhat lacking is the competence to exploit this information for risk mitigation and effective disease management through an integrated nationwide coordinated approach. With a positivity rate of 15-20% (April-May 2021) and the healthcare system pushed to its limit, accompanied by increased mortality, the situation was rather grim then. Though the central command scrambled all its resources and logistics to streamline the supply chain, the efforts were insufficient in response to the ongoing crisis due to a disproportionate rise in the case. We examined the current scenario emerging from this 2nd COVID wave and identified the possible lacunae. We also suggested few recommendations that may be adopted to avoid similar failures in the future.
Language	English
Publishing date	2021-10-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2495128-6
ISSN	1179-1594
ISSN	1179-1594
DOI	10.2147/RMHP.S320880
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Article: Heat Shock Proteins and Their Role in Pregnancy: Redefining the Function of "Old Rum in a New Bottle".

Jee, Babban / Dhar, Ruby / Singh, Sunil / Karmakar, Subhradip

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 648463

Abstract: Pregnancy in humans is a multi-step complex physiological process comprising three discrete events, decidualization, implantation and placentation. Its overall success depends on the incremental advantage that each of the preceding stages passes on to ... ...

Abstract	Pregnancy in humans is a multi-step complex physiological process comprising three discrete events, decidualization, implantation and placentation. Its overall success depends on the incremental advantage that each of the preceding stages passes on to the next. The success of these synchronized sequels of events is an outcome of timely coordination between them. The pregnancy events are coordinated and governed primarily by the ovarian steroid hormones, estrogen and progesterone, which are essentially ligand-activated transcription factors. It's well known that intercellular signaling of steroid hormones engages a plethora of adapter proteins that participate in executing the biological functions. This involves binding of the hormone receptor complex to the DNA response elements in a sequence specific manner. Working with
Language	English
Publishing date	2021-04-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.648463
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Article: Balancing Healthcare and Economy Amidst the COVID-19 Pandemic: An Indian Experience.

Dhar, Ruby / Jee, Babban / Karmakar, Subhradip

Risk management and healthcare policy

2021 Volume 14, Page(s) 827–833

Abstract: With its 1.3 billion population and faced with the COVID-19 pandemic, India is at the junction of two crucial decisions, balancing healthcare and the economy. To prevent the community spread of the virus, the Indian Government imposed a nationwide ... ...

Abstract	With its 1.3 billion population and faced with the COVID-19 pandemic, India is at the junction of two crucial decisions, balancing healthcare and the economy. To prevent the community spread of the virus, the Indian Government imposed a nationwide lockdown. Though initially successful to some extent in containing the disease spread, the extended lockdown eventually leads to a spiraling out effect resulting in the slowdown of the economy, which, in turn, lead to widespread consequences affecting the lives of millions of people, mostly those at the base of the social pyramid. We investigated the implications of few government policies taken during this pandemic and their impact on society, thereby suggesting short-term crisis management with long-term solutions. Here, we present a comprehensive account of Indian policy in dealing with the COVID-19 crisis, balancing both economic and public health. We also explored a future contingency plan for risk mitigation along with few recommendations. This viewpoint will be useful for effective healthcare management and the economy in Asia's populous nation in the COVID-19 and prepare for a future crisis of this nature.
Language	English
Publishing date	2021-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2495128-6
ISSN	1179-1594
ISSN	1179-1594
DOI	10.2147/RMHP.S291084
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Article ; Online: Applications of Quantum Dots in Preventive Oncology.

Sarkar, Sajib / Srivastava, Tryambak Pratap / Sahoo, Om Saswat / Shankar, Abhishek / Rai, Avdhesh / Pethusamy, Karthikeyan / Dhar, Ruby / Karmakar, Subhradip

Asian Pacific journal of cancer prevention : APJCP

2024 Volume 25, Issue 3, Page(s) 747–756

Abstract: QDs are semiconductor nanocrystalline materials with distinct optical and electronic characteristics due to their microscopic size and quantum mechanical properties. They are often composed of materials such as cadmium selenide (CdSe), cadmium telluride ( ...

Abstract	QDs are semiconductor nanocrystalline materials with distinct optical and electronic characteristics due to their microscopic size and quantum mechanical properties. They are often composed of materials such as cadmium selenide (CdSe), cadmium telluride (CdTe), or indium phosphide (InP) and are typically in the size range of 2 to 10 nanometers in diameter. These tiny particles are used in various scientific and technological applications. Some key characteristics and applications of quantum dots are size-dependent Optical Properties with tunable emission. The color of light emitted by quantum dots highly depends on their size. Smaller QDs emit blue or green light, while larger ones emit red or near-infrared light. This tunability makes them valuable in various applications, especially in molecular medicine and oncology research. Quantum dots can exhibit a high quantum yield, meaning they efficiently emit light when excited, making them excellent fluorescent probes for non-invasive imaging. This review discusses the applications of QDs and their role in biomedical research and patient care, focusing on non-invasive imaging and preventive oncology.
MeSH term(s)	Humans ; Quantum Dots/chemistry ; Cadmium Compounds/chemistry ; Tellurium ; Nanoparticles/chemistry
Chemical Substances	cadmium telluride (STG188WO13) ; Cadmium Compounds ; Tellurium (NQA0O090ZJ)
Language	English
Publishing date	2024-03-01
Publishing country	Thailand
Document type	Review ; Journal Article
ZDB-ID	2218955-5
ISSN	2476-762X ; 1513-7368
ISSN (online)	2476-762X
ISSN	1513-7368
DOI	10.31557/APJCP.2024.25.3.747
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Article ; Online: Covid-19: research methods must be flexible in a crisis.

Karmakar, Subhradip / Dhar, Ruby / Jee, Babban

BMJ (Clinical research ed.)

2020 Volume 370, Page(s) m2668

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Research Design ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-07-06
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.m2668
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Article ; Online: The issues and challenges with cancer biomarkers.

Purkayastha, Kakali / Dhar, Ruby / Pethusamy, Karthikeyan / Srivastava, Tryambak / Shankar, Abhishek / Rath, Goura Kishor / Karmakar, Subhradip

Journal of cancer research and therapeutics

2023 Volume 19, Issue Supplement, Page(s) S20–S35

Abstract: A biomarker is a measurable indicator used to distinguish precisely/objectively either normal biological state/pathological condition/response to a specific therapeutic intervention. The use of novel molecular biomarkers within evidence-based medicine ... ...

Abstract	A biomarker is a measurable indicator used to distinguish precisely/objectively either normal biological state/pathological condition/response to a specific therapeutic intervention. The use of novel molecular biomarkers within evidence-based medicine may improve the diagnosis/treatment of disease, improve health outcomes, and reduce the disease's socio-economic impact. Presently cancer biomarkers are the backbone of therapy, with greater efficacy and better survival rates. Cancer biomarkers are extensively used to treat cancer and monitor the disease's progress, drug response, relapses, and drug resistance. The highest percent of all biomarkers explored are in the domain of cancer. Extensive research using various methods/tissues is carried out for identifying biomarkers for early detection, which has been mostly unsuccessful. The quantitative/qualitative detection of various biomarkers in different tissues should ideally be done in accordance with qualification rules laid down by the Early Detection Research Network (EDRN), Program for the Assessment of Clinical Cancer Tests (PACCT), and National Academy of Clinical Biochemistry. Many biomarkers are presently under investigation, but lacunae lie in the biomarker's sensitivity and specificity. An ideal biomarker should be quantifiable, reliable, of considerable high/low expression, correlate with the outcome progression, cost-effective, and consistent across gender and ethnic groups. Further, we also highlight that these biomarkers' application remains questionable in childhood malignancies due to the lack of reference values in the pediatric population. The development of a cancer biomarker stands very challenging due to its complexity and sensitivity/resistance to the therapy. In past decades, the cross-talks between molecular pathways have been targeted to study the nature of cancer. To generate sensitive and specific biomarkers representing the pathogenesis of specific cancer, predicting the treatment responses and outcomes would necessitate inclusion of multiple biomarkers.
MeSH term(s)	Child ; Humans ; Biomarkers, Tumor/metabolism ; Neoplasms/diagnosis ; Biomarkers/metabolism ; Cost-Effectiveness Analysis
Chemical Substances	Biomarkers, Tumor ; Biomarkers
Language	English
Publishing date	2023-05-08
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2187633-2
ISSN	1998-4138 ; 0973-1482
ISSN (online)	1998-4138
ISSN	0973-1482
DOI	10.4103/jcrt.jcrt_384_22
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Article: SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.

William, Jonahunnatha Nesson George / Dhar, Ruby / Gundamaraju, Rohit / Sahoo, Om Saswat / Pethusamy, Karthikeyan / Raj, A F P Allwin Mabes / Ramasamy, Subbiah / Alqahtani, Mohammed S / Abbas, Mohamed / Karmakar, Subhradip

Frontiers in oncology

2024 Volume 14, Page(s) 1288501

Abstract: SKP2 (S-phase kinase-associated protein 2) is a member of the F-box family of substrate-recognition subunits in the SCF ubiquitin-protein ligase complexes. It is associated with ubiquitin-mediated degradation in the mammalian cell cycle components and ... ...

Abstract	SKP2 (S-phase kinase-associated protein 2) is a member of the F-box family of substrate-recognition subunits in the SCF ubiquitin-protein ligase complexes. It is associated with ubiquitin-mediated degradation in the mammalian cell cycle components and other target proteins involved in cell cycle progression, signal transduction, and transcription. Being an oncogene in solid tumors and hematological malignancies, it is frequently associated with drug resistance and poor disease outcomes. In the current review, we discussed the novel role of SKP2 in different hematological malignancies. Further, we performed a limited in-silico analysis to establish the involvement of SKP2 in a few publicly available cancer datasets. Interestingly, our study identified
Language	English
Publishing date	2024-03-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2024.1288501
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Article: TETology: Epigenetic Mastermind in Action

Seethy, Ashikh / Pethusamy, Karthikeyan / Chattopadhyay, Indranil / Sah, Ramkishor / Chopra, Anita / Dhar, Ruby / Karmakar, Subhradip

Applied biochemistry and biotechnology. 2021 June, v. 193, no. 6

2021

Abstract: Cytosine methylation is a well-explored epigenetic modification mediated by DNA methyltransferases (DNMTs) which are considered “methylation writers”; cytosine methylation is a reversible process. The process of removal of methyl groups from DNA remained ...

Abstract	Cytosine methylation is a well-explored epigenetic modification mediated by DNA methyltransferases (DNMTs) which are considered “methylation writers”; cytosine methylation is a reversible process. The process of removal of methyl groups from DNA remained unelucidated until the discovery of ten-eleven translocation (TET) proteins which are now considered “methylation editors.” TET proteins are a family of Fe(II) and alpha-ketoglutarate-dependent 5-methyl cytosine dioxygenases—they convert 5-methyl cytosine to 5-hydroxymethyl cytosine, and to further oxidized derivatives. In humans, there are three TET paralogs with tissue-specific expression, namely TET1, TET2, and TET3. Among the TETs, TET2 is highly expressed in hematopoietic stem cells where it plays a pleiotropic role. The paralogs also differ in their structure and DNA binding. TET2 lacks the CXXC domain which mediates DNA binding in the other paralogs; thus, TET2 requires interactions with other proteins containing DNA-binding domains for effectively binding to DNA to bring about the catalysis. In addition to its role as methylation editor of DNA, TET2 also serves as methylation editor of RNA. Thus, TET2 is involved in epigenetics as well as epitranscriptomics. TET2 mutations have been found in various malignant hematological disorders like acute myeloid leukemia, and non-malignant hematological disorders like myelodysplastic syndromes. Increasing evidence shows that TET2 plays an important role in the non-hematopoietic system as well. Hepatocellular carcinoma, gastric cancer, prostate cancer, and melanoma are some non-hematological malignancies in which a role of TET2 has been implicated. Loss of TET2 is also associated with atherosclerotic vascular lesions and endometriosis. The current review elaborates on the role of structure, catalysis, physiological functions, pathological alterations, and methods to study TET2, with specific emphasis on epigenomics and epitranscriptomics.
Keywords	5-methylcytosine ; DNA ; DNA methylation ; DNA methyltransferase ; RNA ; biotechnology ; catalytic activity ; endometriosis ; epigenetics ; hepatoma ; melanoma ; myeloid leukemia ; oxidation ; prostatic neoplasms ; stomach neoplasms
Language	English
Dates of publication	2021-06
Size	p. 1701-1726.
Publishing place	Springer US
Document type	Article
Note	NAL-AP-2-clean ; Review
ZDB-ID	392344-7
ISSN	0273-2289
ISSN	0273-2289
DOI	10.1007/s12010-021-03537-5
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Article ; Online: TETology: Epigenetic Mastermind in Action.

Seethy, Ashikh / Pethusamy, Karthikeyan / Chattopadhyay, Indranil / Sah, Ramkishor / Chopra, Anita / Dhar, Ruby / Karmakar, Subhradip

Applied biochemistry and biotechnology

2021 Volume 193, Issue 6, Page(s) 1701–1726

Abstract: Cytosine methylation is a well-explored epigenetic modification mediated by DNA methyltransferases (DNMTs) which are considered "methylation writers"; cytosine methylation is a reversible process. The process of removal of methyl groups from DNA remained ...

Abstract	Cytosine methylation is a well-explored epigenetic modification mediated by DNA methyltransferases (DNMTs) which are considered "methylation writers"; cytosine methylation is a reversible process. The process of removal of methyl groups from DNA remained unelucidated until the discovery of ten-eleven translocation (TET) proteins which are now considered "methylation editors." TET proteins are a family of Fe(II) and alpha-ketoglutarate-dependent 5-methyl cytosine dioxygenases-they convert 5-methyl cytosine to 5-hydroxymethyl cytosine, and to further oxidized derivatives. In humans, there are three TET paralogs with tissue-specific expression, namely TET1, TET2, and TET3. Among the TETs, TET2 is highly expressed in hematopoietic stem cells where it plays a pleiotropic role. The paralogs also differ in their structure and DNA binding. TET2 lacks the CXXC domain which mediates DNA binding in the other paralogs; thus, TET2 requires interactions with other proteins containing DNA-binding domains for effectively binding to DNA to bring about the catalysis. In addition to its role as methylation editor of DNA, TET2 also serves as methylation editor of RNA. Thus, TET2 is involved in epigenetics as well as epitranscriptomics. TET2 mutations have been found in various malignant hematological disorders like acute myeloid leukemia, and non-malignant hematological disorders like myelodysplastic syndromes. Increasing evidence shows that TET2 plays an important role in the non-hematopoietic system as well. Hepatocellular carcinoma, gastric cancer, prostate cancer, and melanoma are some non-hematological malignancies in which a role of TET2 has been implicated. Loss of TET2 is also associated with atherosclerotic vascular lesions and endometriosis. The current review elaborates on the role of structure, catalysis, physiological functions, pathological alterations, and methods to study TET2, with specific emphasis on epigenomics and epitranscriptomics.
MeSH term(s)	5-Methylcytosine/analogs & derivatives ; 5-Methylcytosine/metabolism ; Animals ; DNA Methylation ; Dioxygenases/genetics ; Dioxygenases/metabolism ; Epigenesis, Genetic ; Humans
Chemical Substances	5-hydroxymethylcytosine (1123-95-1) ; 5-Methylcytosine (6R795CQT4H) ; Dioxygenases (EC 1.13.11.-)
Language	English
Publishing date	2021-03-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	392344-7
ISSN	1559-0291 ; 0273-2289
ISSN (online)	1559-0291
ISSN	0273-2289
DOI	10.1007/s12010-021-03537-5
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