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Objective:To investigate the mechanism by which glycoprotein non-transferable melanin B(GPNMB)regulates microglia M2 polarization to reduce nerve damage after cerebral ischemic stroke(CIS).Methods:SD rats were used for establishment of middle cerebral artery occlusion(MCAO)model.Neurons,astrocytes and microglia were cultured under oxygen and glucose depri-vation(OGD)conditions,and the expression of GPNMB in tissues and cells were measured by Western blot.Gpnmb wrapped with adeno-associated virus(AAV)or shRNA-Gpnmb were injected into rat brain tissues for overexpression or inhibition of GPNMB,modified neurological deficit score(mNSS),Rotarod fatigue test and tape removal test were used to evaluate rat nerve function,the proportion of cerebral infarction was determined by TTC staining,microglia M1/M2 polarization markers were detected by immunofluorescence and RT-PCR,and the expression of Phosphatidylinositol 3-kinase(PI3K)/Serine/threonine kinase(Akt)pathway was determined by Western blot.Microglia was cultured under OGD conditions in vitro,Gpnmb was overexpressed and PI3K expression were inhibited by LY294002,and M1/M2 polarization markers were measured.Results:Compared with normal rats or normal cultured cells,the expres-sion of GPNMB in MCAO model or OGD-intervened microglia was up-regulated(P<0.05);when Gpnmb was overexpressed in the brain tissue of MCAO rats,the mNSS score decreased,the Rotarod time of latency to fall lengthened,the contact time and removal time shortened in the tape removal test,the proportion of cerebral infarction decreased,the M1 polarization level of microglia decreased while the M2 polarization level increased,PI3K/Akt pathway activated,and these difference were statistically significant(P<0.05);inhibition of PI3K reversed the effect of overexpression of Gpnmb on promoting M2 polarization of microglia in vitro(P<0.05).Conclusion:GPNMB promotes M2 polarization of microglia by activating the PI3K/Akt pathway,thereby reducing nerve damage after CIS.
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Infection by SARS-CoV2 provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled by in vitro co-culture the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV2-specific inflammatory gene cluster distinct from that seen in influenza-A or Ebola virus-infected co-cultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV2 proteins (Spike and some non-structural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age-dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV2 induces in epithelia.
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Viral myocarditis (VMC) is a disease characterized by inflammation of myocardial cells caused by viral infection. Since the pathogenesis mechanism of VMC has not been fully elucidated, the diagnosis and treatment of this disease remains extremely challenging. Non-coding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. An increasing number of studies have shown that ncRNAs are involved in regulating the occurrence and development of VMC, thus providing potential new targets for the treatment and diagnosis of VMC. This review summarizes the possible roles of ncRNAs in the pathogenesis and diagnosis of VMC revealed recently.
Assuntos
Humanos , Infecções por Coxsackievirus , Enterovirus Humano B , Inflamação , Miocardite/genética , Viroses/genéticaRESUMO
Enterovirus 71 (EV71) is a major pathogen causing severe hand, foot and mouth disease (HFMD) in infants under five years old. It can cause central nervous system damageand even death in severe cases. Considering the high mortality and disability rate of HFMD, this review focused on the most recent developments in vaccines and treatments against EV71 infection.
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AIM: To establish a RP-HPLC method for simultaneous determination of the dl-tetrahydropalmatine and imperatorin in Yuanhu Zhitong Prescription (Rhizoma Corydalis, Radix Angelicae Dahuricae). METHODS: dl- tetrahydropalmatine and imperatorin were extracted with ether and determined by HPLC using a BDS C 18 column(5?m,4.6?250mm),phosphate buffer(pH6.6)-methanol(39∶61) as a mobile phase. The mobile rate was at 1mL?min -1 and detection wavelength was at 280nm. RESULTS: The relationship between the concentration and the peak area of dl-tetrahydropamaltine and imperatorin were good linear relation, respectively. Either of correlation coefficient approached 0.999. CONCLUSION: This method can be used to determine the concentration of dl-tetrahydropalmatine and imperatorin in the preparation of Yuanhu Zhitong Prescription.