Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments

The coronavirus disease 2019(COVID-19)pandemic has been a serious threat to global health for nearly 3 years.In addition to pulmonary complications,liver injury is not uncommon in patients with novel COVID-19.Although the prevalence of liver injury varies widely among COVID-19 patients,its incidence is significantly increased in severe cases.Hence,there is an urgent need to understand liver injury caused by COVID-19.Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes.Liver function tests,computed tomography scans,and ultrasound can help evaluate liver injury.Risk factors for liver injury in patients with COVID-19 include male sex,preexisting liver disease including liver transplantation and chronic liver disease,diabetes,obesity,and hypertension.To date,the mechanism of COVID-19-related liver injury is not fully understood.Its pathophysiological basis can generally be explained by systemic inflammatory response,hypoxic damage,ischemia-reperfusion injury,and drug side effects.In this review,we systematically summarize the existing literature on liver injury caused by COVID-19,including clinical features,underlying mechanisms,and potential risk factors.Finally,we discuss clinical management and provide recommendations for the care of patients with liver injury.

A new peptide,VD11,promotes structural and functional recovery after spinal cord injury

The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury.Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue.While amphibians have a pronounced ability to regenerate the spinal cord,few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury.Here we report for the first time the successful identification and isolation of a new polypeptide,VD11(amino acid sequence:VDELWPPWLPC),from the spinal cord of an endemic Chinese amphibian(Odorrana schmackeri).In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide,as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia.In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury,alleviated pathological damage,and promoted axonal regeneration.Furthermore,RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways.In summary,we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.

A finTRIM member 100 (FTR100) is unique to Otomorpha fish for constitutive regulation of IFN response

Vertebrate interferon(IFN)expression is fine-tuned in order to avoid excessive tissue injury under normal conditions and during virus infection.FinTRIM(fish novel TRIM,FTR)proteins are reported to regulate the fish IFN response.Here,we identify a novel finTRIM gene from yellow catfish(Pelteobagrus fulvidraco),which is sequentially named PfFTR100 according to the nomenclature rule in zebrafish.Genome-wide analyses reveal that FTR100 is unique to Otomorpha fish,with a single copy in spite of additional genome duplication in some fish species.Considering that few of the 99 finTRIM genes identified in zebrafish are conserved in main fish branches and most,such as FTR100,are unique to distinct branches due to lineage-specific expansion of finTRIM genes,we develop a nomenclature for newly cloned finTRIM genes from different fish species.PfFTR100 mRNA is not induced by virus infection,with a relatively high expression level comparable to that of cellular IFN and some IFN-stimulated genes(ISGs)in virally-infected tissues.However,ectopically-expressed PfFTR100 protein is attenuated in virally-infected cells through the proteasomal-dependent pathway.Overexpression of PfFTR100 promotes SVCV replication by downregulating the constitutive and inducible IFN response via a mechanism by which PfFTR100 targets IRF3 and IRF7 to attenuate their mRNA levels rather than their protein levels.Our results indicate that yellow catfish FTR100 is essential for homeostatic regulation of fish tonic IFN response.