Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance

BACKGROUND： Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions.DATA SOURCES： The data of mouse hepatic models and rele- vant human liver diseases presented in this review are system- atically collected from PubMed, ScienceDirect and the Web of Science databases published in English. RESULTS： The hepatotoxic liver injury in mice induced by the metabolites of CC14, acetaminophen or alcohol represent ne- crotic cell death with activation of cytochrome pathway, for- mation of reactive oxygen species （ROS） and mitochondrial damage. The Fas or TNF-a induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrat- ed the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The a-GalCer-induced liver injury was mediated by TNF-a. The LPS-induced hepatitis involved TNF-a, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly（I：C） induced liver injury was mediated by natural killer cells and TNF-a signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune ceils and cell death mediators in viral hepatitis （HBV, HCV）, drug-induced liver injury, non-alcohol- ic fatty liver disease and alcoholic liver disease in human were discussed. CONCLUSIONS： The mouse animal models of hepatitis provide a parallel approach for the study of human liver pathology. Blocking or stimulating the pathways associated with liver cell death could unveil the novel therapeutic strategies in the management of liver diseases.

COVID-19 and comorbidities of hepatic diseases in a global perspective

The worldwide outbreak of coronavirus disease 2019(COVID-19) has challenged the priorities of healthcare system in terms of different clinical management and infection transmission, particularly those related to hepatic-disease comorbidities. Epidemiological data evidenced that COVID-19 patients with altered liver function because of hepatitis infection and cholestasis have an adverse prognosis and experience worse health outcomes. COVID-19-associated liver injury is correlated with various liver diseases following a severe acute respiratory syndrome-coronavirus type 2(SARS-CoV-2) infection that can progress during the treatment of COVID-19 patients with or without pre-existing liver disease. SARS-CoV-2 can induce liver injury in a number of ways including direct cytopathic effect of the virus on cholangiocytes/hepatocytes, immune-mediated damage, hypoxia, and sepsis. Indeed, immediate cytopathogenic effects of SARSCoV-2 via its potential target, the angiotensin-converting enzyme-2 receptor, which is highly expressed in hepatocytes and cholangiocytes, renders the liver as an extra-respiratory organ with increased susceptibility to pathological outcomes. But, underlying COVID-19-linked liver disease pathogenesis with abnormal liver function tests(LFTs) is incompletely understood. Hence, we collated COVID-19-associated liver injuries with increased LFTs at the nexus of pre-existing liver diseases and COVID-19, and defining a plausible pathophysiological triad of COVID-19, hepatocellular damage, and liver disease. This review summarizes recent findings of the exacerbating role of COVID-19 in pre-existing liver disease and vice versa as well as international guidelines of clinical care, management, and treatment recommendations for COVID-19 patients with liver disease.

The circulation of unique reassortment strains of infectious bursal disease virus in Pakistan

Infectious bursal disease(IBD),caused by IBD virus(IBDV),is one of the most devastating and immunosuppressive diseases of the poultry and has been a constraint on the sustainable poultry production around the globe including Pakistan.While the disease is threatening the poulty industry,the nature of predominant strains of IBDV in Pakistan remained l-defined.In this study,an epidemiology survey was conducted in the main chicken-farming regions of Pakistan.The batch of Pakistan IBDVs genes simultaneously covering both VP1 and VP2 were amplified,sequenced,and analyzed.The unique segment-reassortant IBDVs(vv-A/Uniq-B),carrying segmentA from vvIBDV and segment B from one unique ancestor,were identifed as one important type of circulating strains in Pakistan.The data also discovered the characteristic molecular features of Pakistan IBDVs,which will contribute to scientific vaccine selection and effective prevention of the disease.

Tuning structural,electrical,dielectric and magnetic properties of Mg-Cu-Co ferrites via dysprosium(Dy^(3+))doping

In current research work,Dy3+substituted Mg0.5Cu0.25Co0.25Fe2-xDyxO4(0.0≤x≤0.04 with the step interval of 0.01)soft ferrites were synthesized by the sol-gel auto combustion method.The prepared samples were characterized by the techniques using X-ray diffraction(XRD),scanning electron microscopy(SEM),energy dispersive X-ray spectroscopy(EDS),Fourier transform infrared(FTIR)spectroscopy,curre nt-voltage(Ⅰ-Ⅴ)measurement,LCR meter,vibrating sample magnetometer(VSM)and Raman.XRD data reveal that the average crystallite size is 49.71 nm and the lattice constant is 0.83703 nm for sample x=0.03.The non-uniform grain growth was demonstrated by micrographs and impurity-free elemental composition was observed from EDX analysis.The DC resistivity has an increasing and decreasing trend in ferromagnetic and paramagnetic regions with an increase in temperature.Moreover,the high resistivity is observed with the order of 1010Ω·cm,and the activation energy is 0.944 eV for samples x=0.03.The dielectric parameters including dielectric constant,dielectric losses,and impedance gradually decrease with the increase in frequency from 8 Hz to 8 MHz.The minimum dielectric loss at high frequency is found for sample x=0.03.The coercivity(Hc)and saturation magnetization(Ms)are found in the ranges of 520.82-544.02 Oe and 20.5841-21.1473 emu/g,respectively.These observations confirm that dysprosium(x=0.03)doped MCC-soft ferrites may be applicable in transformer cores,microwave absorbance,and telecommunication devices.