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1.
Environmental and Molecular Mutagenesis ; 63:16, 2022.
Article in English | EMBASE | ID: covidwho-2059389

ABSTRACT

Genome instability mechanisms that characterize cancer initiation and subsequent therapy resistance are still less well understood. Recent evidence suggests that the REV1-dependent translesion synthesis (TLS) is the cornerstone for new mutation formation that primes genome instability, including intrinsic and acquired resistance to therapy. Remarkably, REV1 inhibition also switches the biology of cisplatin-dependent cell death response from apoptosis to senescence, suggesting that REV1 functions beyond a DNA damage polymerase. Furthermore, we discovered two unexpected phenotypes of REV1 TLS polymerase: a) REV1 inhibition triggers autophagy that associated with radioresistance. b) By means of striking preliminary data we show that REV1 inhibition limits SARS-CoV-2 RNA virus propagation, which we recently reported to cause hostcell DNA damage response and telomere instability. These new observations add to the repertoire of REV1- dependent genome instability pathways significant to understanding a wide repertoire of human diseases, including cancer pathogenesis.

2.
Chemical Biology Letters ; 9(4), 2022.
Article in English | Scopus | ID: covidwho-1958111

ABSTRACT

The evolution of lipid nanoparticles (LNPs) has been remarkably interesting and in beneficent directions for food and health industries working towards human well being. Since the discovery of the first-generation lipid based self-assembled nanostructures, i.e., liposomes in the 1960s, it has witnessed significant advances in their development and distinctive potential in different application domains. Based on the composition and structure, these lipid-based structures have varied from liposome to lipid nanoparticles, e.g., solid lipid nanoparticles (SLNs) & nanostructured lipid carriers (NLCs) to overcome certain limitation pertaining to their use in different fields. The outstanding application of LNPs as therapeutic delivery systems has made them key players to treat different human disorders including the fatal cancers. Their life-saving global contribution has recently been witnessed in the form of mRNA vaccines against deadly COVID-19. They have also significantly served purpose in other domains such as biomedical imaging, cosmetics, nutrition, and agriculture. Their prominent role is in the area of anticancer therapy as delivery vectors for nucleic acids and drugs. Some issues with respect to the cellular delivery of drugs and genes, such as circulation time and stability have been somewhat resolved, but the unmet goal of site-specific substantial delivery remains the main focus in LNPs development research. Despite the promise shown by LNPs in animal studies and the fact that technological advances in LNPs research have made the approval possible of a few formulations, therapeutic outcomes in human are not satisfactory. The LNPs technology has managed to survive due to possible tailoring of their properties by virtue of the possibility of altering the composition and modifying the surface. Therefore, enormous scientific endeavours are on the rise to transform lipid structures, composition along with tinkering with surface of LNPs. The alternative methods to guide LNPs coupled with advances in small molecule nucleic acid therapeutics and drug development technology to make the entry possible to specific cells may be effective in cancer therapy. The development is very promising;however enduring efforts are required till the goal is reached. © ScienceIn Publishing.

3.
Journal of Association of Physicians of India ; 69(10):17-23, 2021.
Article in English | Scopus | ID: covidwho-1469268

ABSTRACT

Background: There is more than twofold rise in prevalence of mucormycosis cases in India during the COVID-19 pandemic which needs to be evaluated. Aims: The study aimed to document the spectrum of cases of mucormycosis seen at our Institute during COVID-19 times. Methods: The study is a retrospective observational study carried out at our Institute from May 2021 to mid-June 2021. All patients with biopsy-proven mucormycosis were enrolled in the study. The patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were treated with a multidisciplinary approach with antifungal therapy as well as surgical intervention when needed. Results: Ten patients (n=10) were seen, with a mean age of 50.3 years. The major risk factors included recent use of steroids, uncontrolled diabetes, and CKD. The most common presentation was swelling of unilateral eye and ptosis, followed by loss of vision. Inflammatory marker (CRP) and d-dimer were raised at presentation in all cases. Imaging showed the spread of infection from paranasal sinus to orbit and brain via cavernous sinus, which was a poor prognostic factor. Intravenous Amphotericin-B was given to all patients for at least 4 weeks. Two patients were discharged after completion of treatment and mortality was seen in three patients. Conclusion: We present an array of COVID-associated-mucormycosis (CAM) cases from Eastern India. CAM is presenting with rhino-orbito-cerebral involvement. There is poor outcome with cerebral involvement and high incidence of adverse effects with deoxycholate formulation of amphotericin-B. The causal association of COVID-19 with mucormycosis needs to be unearthed but possible preventive role of anticoagulation should be evaluated. © 2021 Journal of Association of Physicians of India. All rights reserved.

4.
Journal of the Indian Medical Association ; 118(9):61-63, 2020.
Article in English | EMBASE | ID: covidwho-875238

ABSTRACT

The COVID 19 pandemic is taking its toll on humanity in more ways than readily discernable. The number of recoveries inspires hope but it needs to be ensured that apart from physical recovery a holistic rehabilitation of the sufferer is contemplated.

5.
Journal of the Indian Medical Association ; 118(5):34-36, 2020.
Article in English | EMBASE | ID: covidwho-681552

ABSTRACT

We present three patients of COVID19 who presented to the emergency with neurological derangements. On admission fever, cough, sorethroat or contact history were notably absent in the first two that led to initial confusion about the diagnosis. We hereby stress on keeping SARSCoV2 infection in the differential diagnosis if patients present during this pandemic with neurological symptoms.

6.
Journal of the Indian Medical Association ; 118(4):44-46, 2020.
Article in English | EMBASE | ID: covidwho-678610

ABSTRACT

Hydroxychloroquine is a safer derivative of chloroquine that is being used in the treatment and prophylaxis of COVID19. Evidence of its efficacy is sparse, two small studies demonstrating clinical, radiological and serological improvement. However, scarcity of available treatment options has projected this drug into prominence. Drug interactions and risk of QT prolongation are to be kept in mind during use.

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