COVID-19-related liver injury:Focus on genetic and drug-induced perspectives

BACKGROUND Empirical use of potentially hepatotoxic drugs in the management of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is considered as one of the major etiopathogenetic factors for liver injury.Recent evidence has shown that an underlying genetic factor may also occur.Hence,it is important to understand the host genetics and iatrogenic-based mechanisms for liver dysfunction to make timely remedial measures.AIM To investigate drug-induced and genetic perspectives for the development of coronavirus disease 2019(COVID-19)-related liver injury.METHODS Reference Citation Analysis,PubMed,Google Scholar and China National Knowledge Infrastructure were searched by employing the relevant MeSH keywords and pertaining data of the duration,site and type of study,sample size with any subgroups and drug-induced liver injury outcome.Genetic aspects were extracted from the most current pertinent publications.RESULTS In all studies,the hepatic specific aminotransferase and other biochemical indices were more than their prescribed upper normal limit in COVID-19 patients and were found to be significantly related with the gravity of disease,hospital stay,number of COVID-19 treatment drugs and worse clinical outcomes.In addition,membrane bound O-acyltransferase domain containing 7 rs641738,rs11385942 G>GA at chromosome 3 gene cluster and rs657152 C>A at ABO blood locus was significantly associated with severity of livery injury in admitted SARS-CoV-2 patients.CONCLUSION Hepatic dysfunction in SARS-CoV-2 infection could be the result of individual drugs or due to drug-drug interactions and may be in a subset of patients with a geneticpropensity. Thus, serial estimation of hepatic indices in hospitalized SARS-CoV-2 patients shouldbe done to make timely corrective actions for iatrogenic causes to avoid clinical deterioration.Additional molecular and translational research is warranted in this regard.

Growth differentiation factor 15 as an emerging novel biomarker in SARS-CoV-2 infection

BACKGROUND Growth differentiation factor(GDF)-15 is a member of a transforming growth factor-βcytokine superfamily that regulates metabolism and is released in response to inflammation,hypoxia and tissue injury.It has evolved as one of the most potent cytokines for predicting the severity of infections and inflammatory conditions,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To investigate the utility of GDF-15 in predicting the severity of SARS-CoV-2 infection.METHODS PubMed,Reference Citation Analysis,CNKI,and Goggle Scholar were explored by using related MeSH keywords and data such as the first author’s name,study duration,type and place of study,sample size and subgroups of participants if any,serum/plasma GDF-15 level in pg/mL,area under the curve and cut-off value in receiver operating characteristic analysis,method of measurement of GDF-15,and the main conclusion were extracted.RESULTS In all studies,the baseline GDF-15 level was elevated in SARS-CoV-2-infected patients,and it was significantly associated with severity,hypoxemia,viral load,and worse clinical consequences.In addition,GDF-15 levels were correlated with C-reactive protein,D-dimer,ferritin and procalcitonin,and it had superior discriminatory ability to detect severity and in-hospital mortality of SARS-CoV-2 infection.Hence,GDF-15 might be used to predict the severity and prognosis of hospitalized patients with SARS-CoV-2.CONCLUSION Serial estimation of GDF-15 levels in hospitalized patients with SARS-CoV-2 infection appeared to have useful prognostic value and GDF-15 can be considered a clinically prominent sepsis biomarker for SARS-CoV-2 infection.

Antioxidative study of Cerium Oxide nanoparticle functionalised PCL-Gelatin electrospun fibers for wound healing application

Skin wound healing involves a coordinated cellular response to achieve complete reepithelialisation.Elevated levels of reactive oxygen species(ROS)in the wound environment often pose a hindrance in wound healing resulting in impaired wound healing process.Cerium oxide nanoparticles(CeNPs)have the ability to protect the cells from oxidative damage by actively scavenging the ROS.Furthermore,matrices like nanofibers have also been explored for enhancing wound healing.In the current study CeNP functionalised polycaprolactone(PCL)-gelatin nanofiber(PGNPNF)mesh was fabricated by electrospinning and evaluated for its antioxidative potential.Wide angle XRD analysis of randomly oriented nanofibers revealed^2.6 times reduced crystallinity than pristine PCL which aided in rapid degradation of nanofibers and release of CeNP.However,bioactive composite made between nanoparticles and PCLgelatin maintained the fibrous morphology of PGNPNF upto 14 days.The PGNPNF mesh exhibited a superoxide dismutase(SOD)mimetic activity due to the incorporated CeNPs.The PGNPNF mesh enhanced proliferation of 3T3-L1 cells by^48%as confirmed by alamar blue assay and SEM micrographs of cells grown on the nanofibrous mesh.Furthermore,the PGNPNF mesh scavenged ROS,which was measured by relative DCF intensity and fluorescence microscopy;and subsequently increased the viability and proliferation of cells by three folds as it alleviated the oxidative stress.Overall,the results of this study suggest the potential of CeNP functionalised PCL-gelatin nanofibrous mesh for wound healing applications.

Tapered Optical Fiber-Based LSPR Biosensor for Ascorbic Acid Detection

The ascorbic acid(AA)is a biomarker that can be used to detect the symptoms of severe disorders such as scurvy,Parkinson’s,Alzheimer’s,and cardiovascular diseases.In this work,a simple and effective sensor model is developed to diagnose the presence of AA samples.To develop the sensor,a tapered single-mode optical fiber has been used with the well-known phenomenon of localized surface plasmon resonance(LSPR).For LSPR,the tapered region is immobilized with synthesized gold nanoparticles(AuNPs)and zinc oxide nanoparticles(ZnO-NPs)whose absorbance peak wavelengths appear at 519nm and 370nm,respectively.On the basis of nanoparticles(NPs)configurations,two different biosensor probes are developed.In the first one,the sensing region is immobilized with AuNPs and named Probe I.In the second probe,the immobilized layer of AuNPs is further coated with a layer of ZnO-NPs,and a resultant probe is termed as Probe II.The characterizations of synthesized AuNPs and developed fiber probes are done by the ultraviolet-visible(UV-vis)spectrophotometer,high-resolution transmission electron microscope(HR-TEM),atomic force microscopy(AFM),and scanning electron microscope(SEM).To enhance the selectivity,a sensing region of probes is functionalized with ascorbate oxidase enzyme that oxidizes the AA in the presence of oxygen.The response of developed sensor probes is authenticated by sensing the samples of AA in the range from 500 nM to 1 mM,which covers the range of AA found in human bodies,i.e.,40μM-120μM.The performance analysis of the developed sensor probes has been done in terms of their stability,reproducibility,reusability,and selectivity.To observe the stability of AA,a pH-test has also been done that results in a better solubility of AA molecules in phosphate-buffered saline(PBS)solution.