Publications by authors named "Subhojit Paul"

15 Publications

  • Page 1 of 1

Understanding the SARS-CoV-2 virus to mitigate current and future pandemic(s).

Virusdisease 2021 Jun 5:1-10. Epub 2021 Jun 5.

Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences (DIPAS), Defence R&D Organization (DRDO), Lucknow Road, Timarpur, Delhi 110054 India.

Micro-organisms form the first pioneer community in the history of biological life, thought to be present in the primordial soup and evolving later with more complex life-forms. Among micro-organisms, viruses form a separate taxon of organisms. Viruses are obligate parasites, being inactive without a host and becoming active once in contact with specific hosts. Viruses, with an inherent ability to infect and hijack cellular structures, have been utilised as vectors to introduce foreign genetic material in a variety of biological species, e.g. adenoviral vectors. However, viruses have also been the root cause of many infectious diseases, most notable being HIV-AIDS, for its resistance to treatment and omnipresent occurrence. There are many families of viruses like retroviridae, picornaviridae and poxviridae. This review focuses on a specific member of the coronaviridae, the SARS-CoV-2. This virus is responsible for the current COVID-19 pandemic. This review summarises its transmission, molecular mechanism by which it causes disease, associated clinical symptoms and the strategies available to control it from sources like PubMed, Google Scholar, webservers of National Institute of Health (NIH), European Molecular Biology Laboratory (EMBL), World Health Organisation (WHO), United States Food and Drug Administration (USFDA) and Centers for Disease Control and Prevention (CDC) available as on 1st May 2021.
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http://dx.doi.org/10.1007/s13337-021-00696-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178034PMC
June 2021

Modulation of lung cytoskeletal remodeling, RXR based metabolic cascades and inflammation to achieve redox homeostasis during extended exposures to lowered pO.

Apoptosis 2021 May 17. Epub 2021 May 17.

Defence Institute of Physiology and Allied Sciences, Defence R&D Organization, Timarpur, Delhi, 110054, India.

Extended exposure to low pO has multiple effects on signaling cascades. Despite multiple exploratory studies, omics studies elucidating the signaling cascades essential for surviving extended low pO exposures are lacking. In this study, we simulated low pO (P = 40 kPa; 7620 m) exposure in male Sprague-Dawley rats for 3, 7 and 14 days. Redox stress assays and proteomics based network biology were performed using lungs and plasma. We observed that redox homeostasis was achieved after day 3 of exposure. We investigated the causative events for this. Proteo-bioinformatics analysis revealed STAT3 to be upstream of lung cytoskeletal processes and systemic lipid metabolism (RXR) derived inflammatory processes, which were the key events. Thus, during prolonged low pO exposure, particularly those involving slowly decreasing pressures, redox homeostasis is achieved but energy metabolism is perturbed and this leads to an immune/inflammatory signaling impetus after third day of exposure. We found that an interplay of lung cytoskeletal elements, systemic energy metabolism and inflammatory proteins aid in achieving redox homeostasis and surviving extended low pO exposures. Qualitative perturbations to cytoskeletal stability and innate immunity/inflammation were also observed during extended low pO exposure in humans exposed to 14,000 ft for 7, 14 and 21 days.
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http://dx.doi.org/10.1007/s10495-021-01679-9DOI Listing
May 2021

Comments on potential re-purposing of medicines against high-altitude illnesses towards SARS-CoV2: possibilities and pitfalls.

J Proteins Proteom 2021 Jan 20:1-3. Epub 2021 Jan 20.

Defence Institute of Physiology and Allied Sciences (DIPAS), Defence R and D Organization (DRDO), Timarpur, New Delhi-110054 India.

In the ongoing COVID-19 pandemic, the global fraternity of researchers has been assiduously investigating pharmacological interventions against the SARS-CoV2. This novel virus is known to gain entry through the ACE 2 receptor of pulmonary epithelial cells lining the respiratory tract. Many of its initial symptoms (e.g. difficulty breathing) resemble acute high altitude illnesses, particularly HAPE. Based on these overt symptoms, a number of high altitude researchers have speculated on repurposing of drugs used to treat acute altitude illnesses (especially HAPE). However, eminent high altitude researchers with medical expertise as well as some studies on the deeper causes underlying the overt symptoms have found that such repurposing maybe counter-productive. Other factors, (e.g. contra-indications of these drugs), make their use in COVID-19 patients hazardous. The fit-for-repurposing options maybe experimental prophylactic interventions (e.g. silymarin, curcumin) which have proven anti-oxidant and anti-inflammatory effects. Another line of thought focuses on proteomics-based investigations of such patients. However, apart from the logistical and safety issues, a targeted proteomics approach based on prior sound molecular investigations is a more logical approach instead of mere shotgun proteomics. In this commentary, we shed light on such issues associated with COVID-19.
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http://dx.doi.org/10.1007/s42485-020-00055-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815497PMC
January 2021

D4F prophylaxis enables redox and energy homeostasis while preventing inflammation during hypoxia exposure.

Biomed Pharmacother 2021 Jan 8;133:111083. Epub 2020 Dec 8.

Defence Institute of Physiology & Allied Sciences (DIPAS), Defence R&D Organization (DRDO), Timarpur, New Delhi, 110054, India. Electronic address:

Apo-A1 is correlated with conditions like hyperlipidemia, cardiovascular diseases, high altitude pulmonary edema and etc. where hypoxia constitutes an important facet.Hypoxia causes oxidative stress, vaso-destructive and inflammatory outcomes.Apo-A1 is reported to have vasoprotective, anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, effects of Apo-A1 augmentation during hypoxia exposure are unknown.In this study, we investigated the effects of exogenously supplementing Apo-A1-mimetic peptide on SD rats during hypoxia exposure. For easing the processes of delivery, absorption and bio-availability, Apo-A1 mimetic peptide D4F was used. The rats were given 10 mg/kg BW dose (i.p.) of D4F for 7 days and then exposed to hypoxia. D4F was observed to attenuate both oxidative stress and inflammation during hypoxic exposure. D4F improved energy homeostasis during hypoxic exposure. D4F did not affect HIF-1a levels during hypoxia but increased MnSOD levels while decreasing CRP and Apo-B levels. D4F showed promise as a prophylactic against hypoxia exposure.
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http://dx.doi.org/10.1016/j.biopha.2020.111083DOI Listing
January 2021

Intermittent hypoxia modulates redox homeostasis, lipid metabolism associated inflammatory processes and redox post-translational modifications: Benefits at high altitude.

Sci Rep 2020 05 13;10(1):7899. Epub 2020 May 13.

Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road, Timarpur, Delhi, 110054, India.

Intermittent hypoxia, initially associated with adverse effects of sleep apnea, has now metamorphosed into a module for improved sports performance. The regimen followed for improved sports performance is milder intermittent hypoxic training (IHT) as compared to chronic and severe intermittent hypoxia observed in sleep apnea. Although several studies have indicated the mechanism and enough data on physiological parameters altered by IH is available, proteome perturbations remain largely unknown. Altitude induced hypobaric hypoxia is known to require acclimatization as it causes systemic redox stress and inflammation in humans. In the present study, a short IHT regimen consisting of previously reported physiologically beneficial FIO2 levels of 13.5% and 12% was administered to human subjects. These subjects were then airlifted to altitude of 3500 m and their plasma proteome along with associated redox parameters were analyzed on days 4 and 7 of high altitude stay. We observed that redox stress and associated post-translational modifications, perturbed lipid metabolism and inflammatory signaling were induced by IHT exposure at Baseline. However, this caused activation of antioxidants, energy homeostasis mechanisms and anti-inflammatory responses during subsequent high-altitude exposure. Thus, we propose IHT as a beneficial non-pharmacological intervention that benefits individuals venturing to high altitude areas.
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http://dx.doi.org/10.1038/s41598-020-64848-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220935PMC
May 2020

Saliva panel of protein candidates: A comprehensive study for assessing high altitude acclimatization.

Nitric Oxide 2020 02 25;95:1-11. Epub 2019 Nov 25.

Peptide & Proteomics Division, Defence Institute of Physiology & Allied Sciences (DIPAS), Defence R&D Organization (DRDO), Timarpur, New Delhi, 110054, India. Electronic address:

Altitude acclimatization describes the processes whereby lowland humans respond to decreased partial pressure of oxygen. It refers to the changes seen as beneficial and involves a series of physiological adjustments that compensate for reduced ambient PO, as opposed to changes that are pathological. Although numerous reports document the physiological effects of exposure to hypobaric hypoxia of varying durations but an interesting aspect overlooked by many researchers is that of acclimatization related studies. As proteome, a dynamic entity responds immediately to external stimuli, protein markers and their trends can be studied to assess acclimatization status of an individual. Compared to blood, the use of saliva is advantageous because sample collection and processing are easy, minimally invasive, low cost and better tolerated by individuals. In this study, we employed iTRAQ based LC-MS/MS technique for comparing saliva samples from humans exposed to hypobaric hypoxia from 7 to 120 days with normoxic controls followed by analysis using Ingenuity Pathway Analysis software and validation by immunoassays. Nearly 67 proteins were found to be differentially expressed in the exposed groups as compared to normoxia indicating modulated canonical pathways as lipid metabolism; acute phase response signalling and proteins as carbonic anhydrase 6, alpha-enolase, albumin, and prolactin inducible protein. Collectively, this study provides the proof of concept for the non-invasive assessment of high altitude acclimatization.
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http://dx.doi.org/10.1016/j.niox.2019.11.007DOI Listing
February 2020

Plasma protein(s)-based conceptual diagnostic tool for assessing high-altitude acclimation in humans.

Funct Integr Genomics 2020 Mar 24;20(2):191-200. Epub 2019 Aug 24.

Defence R&D Organization (DRDO), Defence Institute of Physiology & Allied Sciences (DIPAS), Lucknow Road, Timarpur, New Delhi, 110054, India.

Exposure to high altitude above 3000 m leads to two outcomes-acclimation or high-altitude maladies. To reach a particular outcome, the plasma proteome is modified differentially, either in context of an acclimation response or mal-acclimation response leading to disease. This ensures that hypoxia-responsive plasma protein trends reflect acclimation in acclimated individuals when compared with their levels prior to acclimation. Such protein trends could be used to assess acclimation in an individual and any significant deviation from this trend may indicate non-acclimation, thereby preventing high-altitude illnesses before they manifest. In this study, we investigate and statistically evaluate the trendlines of various hypoxia-responsive plasma protein levels, reported significantly perturbed in our previous studies, in individuals (male; n = 20) exposed to 3520 m at high-altitude day 1 (HAD1), HAD4, and HAD7L and to 4420 m at HAD7H, HAD30, and HAD120. We observe that thioredoxin (Trx), glutathione peroxidase 3 (GPx-3), and apolipoprotein AI (Apo-AI) are statistically robust markers to assess acclimation across the exposure duration while sulfotransferase 1A1 (ST1A1) is a capable negative control whose levels increase only in cases of HAPE. We also observe exposure day-specific and resident altitude-specific proteins capable of accurately assessing acclimation when compared with baseline levels or the lower altitude zone.
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http://dx.doi.org/10.1007/s10142-019-00712-0DOI Listing
March 2020

Triple-negative breast cancer-derived microvesicles transfer microRNA221 to the recipient cells and thereby promote epithelial-to-mesenchymal transition.

J Biol Chem 2019 09 24;294(37):13681-13696. Epub 2019 Jul 24.

School of Biological Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India

The triple-negative phenotype is the most prevalent form of human breast cancer worldwide and is characterized by poor survival, high aggressiveness, and recurrence. Microvesicles (MV) are shredded plasma membrane components and critically mediate cell-cell communication, but can also induce cancer proliferation and metastasis. Previous studies have revealed that protease-activated receptor 2 (PAR2) contributes significantly to human triple-negative breast cancer (TNBC) progression by releasing nano-size MV and promoting cell proliferation, migration, and invasion. MV isolated from highly aggressive human TNBC cells impart metastatic potential to nonmetastatic cells. Over-expression of microRNA221 (miR221) has also been reported to enhance the metastatic potential of human TNBC, but miR221's relationship to PAR2-induced MV is unclear. Here, using isolated MV, immunoblotting, quantitative RT-PCR, FACS analysis, and enzymatic assays, we show that miR221 is translocated via human TNBC-derived MV, which upon fusion with recipient cells, enhance their proliferation, survival, and metastasis both and by inducing the epithelial-to-mesenchymal transition (EMT). Administration of anti-miR221 significantly impaired MV-induced expression of the mesenchymal markers Snail, Slug, N-cadherin, and vimentin in the recipient cells, whereas restoring expression of the epithelial marker E-cadherin. We also demonstrate that MV-associated miR221 targets phosphatase and tensin homolog (PTEN) in the recipient cells, followed by AKT Ser/Thr kinase (AKT)/NF-κB activation, which promotes EMT. Moreover, elevated miR221 levels in MV derived from human TNBC patients' blood could induce cell proliferation and metastasis in recipient cells. In summary, miR221 transfer from TNBC cells via PAR2-derived MV induces EMT and enhances the malignant potential of recipient cells.
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http://dx.doi.org/10.1074/jbc.RA119.008619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746455PMC
September 2019

Reverse translating SULT1A1, a potential biomarker in roentgenographically tested rat model of rapid HAPE induction.

Life Sci 2019 Jul 14;229:132-138. Epub 2019 May 14.

Defence Institute of Physiology & Allied Sciences (DIPAS), Defence R&D Organization (DRDO), Timarpur, New Delhi 110054, India. Electronic address:

Aims: HAPE remains the most common lethal high-altitude disease. Although its pathophysiology and other associated causal factors have been partially uncovered along with some potential biomarker proteins, it has not been completely elucidated. A major hindrance to improving the understanding of HAPE pathophysiology and associated molecular events has been the absence of a quick, reliable and definitive animal model of HAPE. This study is aimed at development of a rapid and reliable SD rat model of high altitude pulmonary edema (HAPE) that can be roentgenographically confirmed and be used to study protein markers of HAPE.

Main Methods: In this study, we detail the process of rapidly inducing HAPE in male SD rats within 18 h of simulated high-altitude exposure without causing high rates of mortality. Thereafter, we confirmed HAPE using roentgenography. We assessed Sulfotransferase 1A1 (SULT1A1), IL-1 beta, TNF- alpha and IFN-gamma using ELISA. Finally, H&E staining of lung tissues was also performed.

Key Findings: A roentgenographically confirmed HAPE model was demonstrated. SULT 1A1 levels are found to be highest in rats suffering HAPE, as previously confirmed in human patients. Inflammation was also assessed based on levels of inflammatory proteins like IL-1b, TNF-a, and IFN-g in addition to H&E staining of lung tissues. Inflammation and HAPE were observed to be synergistic events and not cause and effect of each other.

Significance: This rat model of HAPE will help researchers and clinicians in evaluating performance of therapies, potential biomarker and also further elucidate underlying molecular processes causing HAPE.
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http://dx.doi.org/10.1016/j.lfs.2019.05.035DOI Listing
July 2019

Diagnosis and prophylaxis for high-altitude acclimatization: Adherence to molecular rationale to evade high-altitude illnesses.

Life Sci 2018 Jun 23;203:171-176. Epub 2018 Apr 23.

Peptide & Proteomics Division, Defence Institute of Physiology & Allied Sciences (DIPAS), Defence R&D Organization (DRDO), Timarpur, New Delhi 110054, India. Electronic address:

Lack of zero side-effect, prescription-less prophylactics and diagnostic markers of acclimatization status lead to many suffering from high altitude illnesses. Although not fully translated to the clinical setting, many strategies and interventions are being developed that are aimed at providing an objective and tangible answer regarding the acclimatization status of an individual as well as zero side-effect prophylaxis that is cost-effective and does not require medical supervision. This short review brings together the twin problems associated with high-altitude acclimatization, i.e. acclimatization status and zero side-effect, easy-to-use prophylaxis, for the reader to comprehend as cogs of the same phenomenon. We describe current research aimed at preventing all the high-altitude illnesses by considering them an assault on redox and energy homeostasis at the molecular level. This review also entails some proteins capable of diagnosing either acclimatization or high-altitude illnesses. The future strategies based on bioinformatics and systems biology is also discussed.
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http://dx.doi.org/10.1016/j.lfs.2018.04.040DOI Listing
June 2018

Competing trends of ROS and RNS-mediated protein modifications during hypoxia as an alternate mechanism of NO benefits.

Biochimie 2018 May 20;148:127-138. Epub 2018 Mar 20.

Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road, Timarpur, Delhi, 110054, India. Electronic address:

Hypoxia, especially altitude associated hypoxia is known to cause severe physiological alterations and life-threatening conditions. Impaired redox balance along with oxidative stress, protein carbonylation and instigation of apoptotic events are common sub-cellular events that follow the hypoxic insult. The role of nitric oxide (NO) is very dynamic and versatile in preventing the ill effects of hypoxia vis-a-vis reacting with oxidative species and causing protein nitrosylation. Although several mechanisms of NO-mediated cytoprotection are known during hypoxic insult, limited pieces of evidence are available to support the relationship between two downstream events of oxidative stress, protein carbonylation (caused by carbonyl; CO radical) and protein nitrosylation/nitration (caused by NO/peroxynitrite; ONOO radical). In this study, we investigated an entirely new aspect of NO protection in hypoxia involving crosstalk between carbonylation and nitrosylation. Using standard NO inhibitor l-NAME and simulated hypoxic conditions in hypoxia-sensitive cell line H9c2, we evaluated the levels of radicals, cell death, mitochondrial membrane potential, levels of protein nitrosylation, protein nitration and carbonylation and glutathione content. The results were then carefully analyzed in light of NO bioavailability. Our study shows that reducing NO during hypoxia caused cell death via the increased degree of carbonylation in proteins. This provides a new aspect of NO benefits which furthers opens new possibilities to explore potential mechanisms and effects of cross-talk between nitrosylation, protein nitration and carbonylation, especially through some common antioxidant mediators such as glutathione and thioredoxin.
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http://dx.doi.org/10.1016/j.biochi.2018.03.009DOI Listing
May 2018

STAT3-RXR-Nrf2 activates systemic redox and energy homeostasis upon steep decline in pO gradient.

Redox Biol 2018 04 17;14:423-438. Epub 2017 Oct 17.

Defence Institute of Physiology & Allied Sciences (DIPAS), Defence R&D Organization (DRDO), Timarpur, New Delhi 110054, India. Electronic address:

Hypobaric hypoxia elicits several patho-physiological manifestations, some of which are known to be lethal. Among various molecular mechanisms proposed so far, perturbation in redox state due to imbalance between radical generation and antioxidant defence is promising. These molecular events are also related to hypoxic status of cancer cells and therefore its understanding has extended clinical advantage beyond high altitude hypoxia. In present study, however, the focus was to understand and propose a model for rapid acclimatization of high altitude visitors to enhance their performance based on molecular changes. We considered using simulated hypobaric hypoxia at some established thresholds of high altitude stratification based on known physiological effects. Previous studies have focused on the temporal aspect while overlooking the effects of varying pO levels during exposure to hypobaric hypoxia. The pO levels, indicative of altitude, are crucial to redox homeostasis and can be the limiting factor during acclimatization to hypobaric hypoxia. In this study we present the effects of acute (24h) exposure to high (3049m; pO: 71kPa), very high (4573m; pO: 59kPa) and extreme altitude (7620m; pO: 40kPa) zones on lung and plasma using semi-quantitative redox specific transcripts and quantitative proteo-bioinformatics workflow in conjunction with redox stress assays. It was observed that direct exposure to extreme altitude caused 100% mortality, which turned into high survival rate after pre-exposure to 59kPa, for which molecular explanation were also found. The pO of 59kPa (very high altitude zone) elicits systemic energy and redox homeostatic processes by modulating the STAT3-RXR-Nrf2 trio. Finally we posit the various processes downstream of STAT3-RXR-Nrf2 and the plasma proteins that can be used to ascertain the redox status of an individual.
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http://dx.doi.org/10.1016/j.redox.2017.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680518PMC
April 2018

The meta-analytical paradigm in an in silico hybrid: Pathways and networks perturbed during exposure to varying degrees of hypobaric hypoxia.

Proteomics Clin Appl 2017 07 21;11(7-8). Epub 2017 Mar 21.

Peptide & Proteomics Division, Defence Institute Of Physiology & Allied Sciences (DIPAS), Defence R&D Organization (DRDO), Ministry of Defence, Timarpur, New Delhi, India.

Purpose: Computational biology has opened a gateway to omics data analysis and shifted the focus from molecules to systemic molecular networks in the domain of hypobaric hypoxia (HH). Yet there are no meta-analytical investigations circumventing constraints such as organism (rat/human), HH exposure conditions (acute/chronic), and the tissues that can be investigated simultaneously in the realm of wet lab experiments.

Experimental Design: We analyzed 154 differentially expressed proteins upon HH exposure using Ingenuity Pathway Analysis (IPA) tool, without the constraint of using a single organism or tissue type, to determine the most significant pathways and networks that are perturbed across a range of HH conditions.

Results: We found acute phase response signaling, farsenoid X receptor/retinoid X receptor activation, liver X receptor/retinoid X receptor activation, clathrin-mediated endocytosis signaling, mitochondrial dysfunction, production of nitric oxide and ROS in macrophages, and integrin signaling to be the most significant universally perturbed pathways. Unique protein-function relationships have also been highlighted.

Conclusion And Clinical Relevance: This meta-analysis provides a list of specific pathways and networks across two model organisms that are perturbed due to HH exposure irrespective of its duration/intensity. Thus, it will be a map of important pathways and proteins to look at when exploring effects of HH exposure irrespective of tissue/organism chosen, particularly in the context of prophylactic/therapeutic targets.
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http://dx.doi.org/10.1002/prca.201600160DOI Listing
July 2017

Size restricted silymarin suspension evokes integrated adaptive response against acute hypoxia exposure in rat lung.

Free Radic Biol Med 2016 07 20;96:139-51. Epub 2016 Apr 20.

Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO), Ministry of Defence, Lucknow Road, Timarpur, Delhi 110054, India. Electronic address:

Despite its extraordinary antioxidant capacity, the clinical usage of silymarin has remained restricted to amelioration of hepatic pathology. Perhaps its low bioavailability and uneven bio-distribution, owing to its poor aqueous solubility, are two main causes that have dampened the clinical applicability and scope of this preparation. We took these two challenges and suggested an unexplored application of silymarin. Apart from liver, two of the most susceptible vital organs at the highest risk of oxidative stress are brain and lung, especially during reduced oxygen saturation (hypoxia) at anatomical level. Hypoxia causes excess generation of radicals primarily in the lungs as it is the first organ at the interphase of atmosphere and organism making it the most prone and vulnerable to oxidative stress and the first responder against hypobaric hypoxia. As our first objective, we improved the silymarin formulation by restricting its size to the lower threshold and then successfully tested the prophylactic and therapeutic action in rat lung challenged with simulated hypobaric hypoxia. After dose optimization, we observed that 50mg/kg BW silymarin as size restricted and homogenous aqueous suspension successfully minimized the reactive oxygen species and augmented the antioxidant defense by significant upregulation of catalase and superoxide dismutase and reduced glutathione. Moreover, the well-established hypoxia markers and proteins related to hypoxia adaptability, hif1a and VEGF were differentially regulated conferring significant reduction in the inflammation caused by hypobaric hypoxia. We therefore report,the unexplored potential benefits of silymarin for preventing high altitude associated pathophysiology further paving its road to clinical trials.
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http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.020DOI Listing
July 2016

Revisiting cobalt chloride preconditioning to prevent hypobaric hypoxia-induced damage: identification of global proteomic alteration and key networks.

Funct Integr Genomics 2016 May 16;16(3):281-95. Epub 2016 Feb 16.

Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road Timarpur, Delhi, 110054, India.

Several studies have supported the hypoxia mimetic roles and cytoprotective properties of cobalt chloride in vitro and in vivo. However, a clear understanding of biological process-based mechanism that integrates the available information remains unknown. This study was aimed to explore the potential mechanism of cobalt chloride deciphering its benefits and well-known physiological challenge caused by hypobaric hypoxia that reportedly affects nearly 24 % of the global population. In order to explore the mechanism of CoCl2, we used global proteomic and systems biology approach in rat model to provide a deeper insight into molecular mechanisms of preconditioning. Furthermore, key conclusions were drawn based on biological network analysis and their enrichment with ontological overlaps. The study was further strengthened by consistent identification of validation of proteins using immunoblotting. CoCl2-pretreated animals exposed to hypoxia showed two significant networks, one lipid metabolism and other cell cycle associated, with a total score of 23 and eight focus molecules. In this study, we delineated two primary routes: one, by direct modulation of reactive oxygen species metabolism and, second, by regulation of lipid metabolism which was not known until now. The previously known benefits of cobalt chloride during physiological challenge by hypobaric hypoxia are convincing and could be explained by some basic set of metabolic and molecular reorganization within the hypoxia model. Interestingly, we also observed some of the completely unknown roles of cobalt chloride such as regulation of lipid that could undulate the translational roles of cobalt chloride supplementation beyond hypoxia preconditioning.
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http://dx.doi.org/10.1007/s10142-016-0483-2DOI Listing
May 2016