ORCID Profile
0000-0003-4478-7581
Current Organisation
University of Tasmania
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Publisher: Cold Spring Harbor Laboratory
Date: 23-12-2019
DOI: 10.1101/2019.12.22.883728
Abstract: Excessive tumor necrosis factor (TNF) is known to cause significant pathology. Paradoxically, deficiency in TNF (TNF -/- ) also caused significant pathology during respiratory ectromelia virus (ECTV) infection, a surrogate mouse model for smallpox. TNF -/- mice succumbed to fulminant disease whereas wild-type mice, and those expressing only transmembrane TNF, recovered. TNF deficiency did not affect viral load or leukocyte recruitment but caused severe lung pathology and excessive production of the cytokines IL-6, IL-10, TGF-β, and IFN-γ. Blockade of these cytokines reduced lung pathology concomitant with induction of protein inhibitor of activated STAT3 (PIAS3) and/or suppressor of cytokine signaling 3 (SOCS3), factors that inhibit STAT3 activation. Short-term inhibition of STAT3 activation in ECTV-infected TNF -/- mice with an inhibitor reduced lung pathology. TNF is essential for regulating inflammation and its deficiency exacerbates ECTV infection as a consequence of significant lung pathology caused by dysregulation of inflammatory cytokine production, in part via overactivation of STAT3.
Publisher: Public Library of Science (PLoS)
Date: 12-01-2017
Publisher: Proceedings of the National Academy of Sciences
Date: 12-10-2020
Abstract: Viruses have coevolved with their hosts and developed strategies to d en, evade, or subvert the host immune response to provide an advantage to the virus. We show that ectromelia virus (ECTV) encodes a TNF receptor (TNFR) homolog, which provides an advantage to the host and virus by d ening TNF levels and inflammation. Infection of ECTV-resistant mice with a mutant virus lacking viral TNFR (vTNFR) caused significant lung pathology and death due to secretion of excessive levels of TNF and other inflammatory cytokines. In vitro, recombinant vTNFR from ECTV and other orthopoxviruses bound to membrane-associated TNF and down-regulated inflammatory gene expression through reverse signaling. vTNFR benefits the host by enabling survival, potentially facilitating virus spread, which should advantage the virus.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/305241
Abstract: Objectives . To assess cardiovascular risk factors in Nepalese population with subclinical hypothyroidism as compared to age and sex matched controls. Materials and Methods . A case control study was conducted among 200 subjects (100 subclinical hypothyroid and 100 euthyroid) at B.P. Koirala Institute of Health Sciences, Dharan, Nepal. Demographic and anthropometric variables including systolic and diastolic blood pressure (BP) were taken. Blood s les were assayed for serum free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and high sensitivity C reactive protein (hs-CRP). Results . Subclinical hypothyroid patients had significantly higher diastolic BP, total cholesterol, LDL cholesterol, and hs-CRP than controls. The odds ratio of having hypercholesterolemia ( mg/dL), low HDL cholesterol ( mg/dL), undesirable LDL-cholesterol ( mg/dL), high hs-CRP ( mg/L), and high diastolic BP ( mmHg) and being overweight (BMI ≥ 23 Kg/m 2 ) in subclinical hypothyroidism was 2.29 (95% CI 1.2–4.38, p = 0.011 ), 1.73 (95% CI 0.82–3.62, p = 0.141 ), 3.04 (95% CI 1.66–5.56, p 0.001 ), 2.02 (95% CI 1.12–3.64, p = 0.018 ), 3.35 (95% CI 1.72–6.55, p 0.001 ), and 0.9 (95% CI 0.48–1.67, p = 0.753 ), respectively, as compared to controls. Conclusion . Subclinical hypothyroid patients are associated with higher risk for cardiovascular disease than euthyroid subjects.
Publisher: Cold Spring Harbor Laboratory
Date: 10-02-2022
DOI: 10.1101/2022.02.09.479486
Abstract: Pneumonia is a severe complication caused by inflammation of the lungs following infection with seasonal and pandemic strains of influenza A virus (IAV) that can result in lung pathology, respiratory failure and death. There is currently no treatment available for severe disease and pneumonia caused by IAV. Antivirals are available, but they are far from satisfactory if treatment is not initiated within 48 hours of symptoms onset. Influenza complications and mortality are often associated with high viral load and excessive lung inflammatory cytokine response. Therefore, we simultaneously targeted IAV with the antiviral drug oseltamivir and inflammation with the anti-inflammatory drug etanercept, targeting TNF after the onset of clinical signs to treat IAV pneumonia effectively. The combined treatment effectively reduced lung viral load, lung pathology, morbidity and mortality during respiratory IAV infection in mice, contemporaneous with significant downregulation of the inflammatory cytokines TNF, IL-1β, IL-6, IL-12p40, chemokines CCL2, CCL5 and CXCL10 and d ened STAT3 activation. Consequently, combined therapy with oseltamivir and a STAT3 inhibitor also effectively reduced clinical disease and lung pathology. Combined treatment using either of the anti-inflammatory drugs and oseltamivir d ened an overlapping set of cytokines. Thus, combined therapy targeting a specific cytokine or cytokine signaling pathway plus an antiviral drug provides an effective treatment strategy for ameliorating IAV pneumonia. Effective treatment of IAV pneumonia required multiple doses of etanercept and a high dose of oseltamivir. This approach might apply to the treatment of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Antivirals against influenza A virus (IAV) are ineffective in treating pneumonia if administered 48 h after onset of disease symptoms. The host inflammatory response and tissue damage caused by IAV are responsible for lung pathology. We reasoned that targeting both virus and inflammation would be more effective in reducing lung pathology and pneumonia, morbidity and mortality. The simultaneous treatment with an anti-inflammatory drug targeting TNF or STAT3, combined with the anti-IAV antiviral drug, oseltamivir, significantly improved clinical disease, reduced lung viral load and pathology, and protected mice from severe pneumonia. The combined treatment suppressed multiple pro-inflammatory cytokines and cytokine signaling pathways. Thus, after the onset of disease symptoms, both virus and inflammation must be targeted to treat IAV pneumonia effectively.
Publisher: Proceedings of the National Academy of Sciences
Date: 17-02-2022
Abstract: Antivirals are ineffective in treating viral pneumonia if administered after 48 h post onset of disease symptoms. Lung pathology during respiratory viral infections is triggered by the host inflammatory response and tissue damage caused by replicating virus. Therefore, targeting both virus and inflammation would be more effective in treating pneumonia. Simultaneous treatment with an anti-inflammatory drug targeting TNF or STAT3 combined with an antiviral drug significantly improved clinical disease, reduced lung viral load and pathology and protected mice from severe pneumonia caused by respiratory ectromelia virus infection. The combined treatment suppressed multiple proinflammatory cytokines and cytokine-signaling pathways, including NF-κB and STAT3. Late after onset of symptoms, antiviral treatment alone cannot ameliorate viral pneumonia, as it cannot reduce inflammation effectively.
Publisher: Wiley
Date: 08-03-2022
DOI: 10.1111/FEBS.15782
Abstract: Pneumonia is a serious complication associated with inflammation of the lungs due to infection with viral pathogens. Seasonal and pandemic influenza viruses, variola virus (agent of smallpox) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 agent of COVID‐19) are some leading ex les. Viral pneumonia is triggered by excessive inflammation associated with dysregulated cytokine production, termed ‘cytokine storm’. Several cytokines have been implicated but tumour necrosis factor (TNF) plays a critical role in driving lung inflammation, severe lung pathology and death. Despite this, the exact role TNF plays in the aetiology and pathogenesis of virus infection‐induced respiratory complications is not well understood. In this review, we discuss the pathological and immunomodulatory roles of TNF in contributing to immunopathology and resolution of lung inflammation, respectively, in mouse models of influenza‐ and smallpox (mousepox)‐induced pneumonia. We review studies that have investigated d ening of inflammation on the outcome of severe influenza and orthopoxvirus infections. Most studies on the influenza model have evaluated the efficacy of treatment with anti‐inflammatory drugs, including anti‐TNF agents, in animal models on the day of viral infection. We question the merits of those studies as they are not transferable to the clinic given that in iduals generally present at a hospital only after the onset of disease symptoms and not on the day of infection. We propose that research should be directed at determining whether d ening lung inflammation after the onset of disease symptoms will reduce morbidity and mortality. Such a treatment strategy will be more relevant clinically.
Publisher: Proceedings of the National Academy of Sciences
Date: 22-06-2020
Abstract: Excessive tumor necrosis factor (TNF) production during some respiratory viral infections is associated with lung pathology and death. We show here that deficiency in TNF also causes significant pathology during respiratory poxvirus infection of mice but has no effect on viral load. TNF deficiency causes increased production of interleukin (IL)-6, IL-10, transforming growth factor beta, and interferon gamma and overactivation of STAT3 signaling. Cytokine blockade, or STAT3 inactivation, ameliorates lung pathology in TNF-deficient mice. The membrane form of TNF alone is necessary and sufficient for regulating inflammation and the prevention of lung pathology. Targeting specific cytokines or cytokine signaling pathways to can ameliorate lung inflammation during respiratory viral infections but the timing and duration of the interventive measures are critical.
Publisher: Cold Spring Harbor Laboratory
Date: 25-02-2020
DOI: 10.1101/2020.02.24.963520
Abstract: Ectromelia virus (ECTV) causes mousepox, a surrogate mouse model for smallpox caused by variola virus in humans. Both viruses encode tumor necrosis factor receptor (TNFR) homologs termed cytokine response modifier (Crm) proteins, containing a TNF-binding domain and a chemokine-binding domain termed smallpox virus-encoded chemokine receptor (SECRET) domain. Infection of ECTV-resistant C57BL/6 mice with an ECTV CrmD deletion mutant resulted in uniform mortality due to excessive TNF secretion and dysregulated inflammatory cytokine production but viral load was not affected. CrmD d ened lung pathology, leukocyte recruitment and inflammatory cytokines including TNF, IL-6, IL-10 and IFN-γ. Blockade of IL-6, IL-10R or TNF function with monoclonal antibodies reduced lung pathology and provided 60-100% protection from an otherwise lethal infection. IFN-γ caused lung pathology only when both the TNF-binding and SECRET domains were deleted but it was neither necessary nor sufficient to cause pathology when only the CrmD SECRET domain was expressed by virus.
Publisher: Biotechnology Society of Nepal
Date: 31-12-2016
Abstract: The main objective of this study was to determine the prevalence of non-albicans Candida among the patients attending a tertiary care hospital in Kathmandu, Nepal. Candida spp. isolated from different clinical s les (sputum, urine, vaginal swab, blood, endotracheal (ET) secretion, pus) from 250 patients between the period of February 2013 and December 2015 were included in the study. Of those 250 patients, 20% were immunocompromised. Sabouraud dextrose agar was used for the isolation of Candida spp. and the identification was performed on the basis of colony morphology, Gram’s stain, India ink preparation, germ tube test, temperature tolerance test, characteristic color change in CHROMagar, chlamydospore production, sugar fermentation test and sugar assimilation test.Out of total 300 Candida spp., majority were isolated from sputum (43.33%) followed by urine (40%) and vaginal swab (6.67%). Of total 151 (50.33%) non-albicans Candida, the most common species isolated were C. tropicalis (62.25%) followed by C. glabrata (23.84%). High prevalence of non-albicans Candida among the patients attending a hospital in Kathmandu, Nepal was noted.
Location: Nepal
No related grants have been discovered for Pratikshya Pandey.