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OBJECTIVE@#To assess the predictors and outcomes of acute kidney injury (AKI) among patients with coronavirus disease 2019 (COVID-19).@*OBJECTIVE@#This retrospective observational study was conducted among patients with a confirmed diagnosis of COVID-19 admitted to Hankou Hospital between January, 5 and March 8, 2020. We evaluated the association of AKI with the demographic and biochemical parameters and clinical outcomes of the patients using univariate regression analysis.@*OBJECTIVE@#Atotal of 287 COVID-19 patients, including 55 with AKI and 232 without AKI, were included in the analysis. Compared with the patients without AKI, the patients with AKI were older, predominantly male, and were more likely to have hypoxia and pre-existing hypertension and cerebrovascular diseases. The patients with AKI also had higher levels of white blood cells, D-dimer, aspartate aminotransferase, total bilirubin, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, a higher prevalence of hyperkalemia, lower lymphocyte counts, and higher chest computed tomographic scores. The incidence of stage 1 AKI was 14.3% and that of stage 2 or 3 AKI was 4.9%. The patients with AKI had much higher mortality rate than those without AKI.@*OBJECTIVE@#AKI is an important complication of COVID-19. An older age, a male gender, multiple pre- existing comorbidities, lymphopenia, increased infection indicators, elevated D-dimer, and impaired heart and liver functions are all potential risk factors ofAKI. COVID- 19 patients with AKI that progresses into stages 2 or 3 AKI have a high mortality rate. Prevention of AKI and monitoring kidney function is critical in the care of COVID-19 patients.
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Aged , Humans , Male , Acute Kidney Injury/epidemiology , COVID-19 , China/epidemiology , Retrospective Studies , SARS-CoV-2ABSTRACT
[ ABSTRACT] Myosin light chain kinase ( MLCK) activates the regulatory light chain of myosin II, and the phos-phorylated myosin light chain leads to actomyosin contractile activity, as well as the cell contraction and increasing intercel-lular gap, which finally results in endothelial barrier dysfunction.MLCK-dependent hyperpermeability occurs in response to multiple cell signaling molecules and signaling pathways, including Ca2+, Src, PKC, NO, cGMP and mitogen activated protein kinases ( MAPK) .In this review, different mechanisms of endothelial hyperpermeability mediated by MLCK are discussed.
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<p><b>OBJECTIVE</b>To investigate the role of Fas pathway in H(2)O(2)-induced apoptosis of L02 human hepatocytes and the effect of schisandrin B on Fas pathway.</p><p><b>METHODS</b>Real-time quantitative PCR was used to detect the expressions of FAS, fas associated death domain protein (FADD) and caspase-8 mRNA in L02 cells exposed to H(2)O(2). Flow cytometry was employed to assess the cell apoptosis. ELISA, Western blotting and spectrophotometric assay were performed to determine the expressions of FAS protein, FADD protein and caspase-8 activity.</p><p><b>RESULTS</b>Within the dose range of 5-15 mol/L, schisandrin B dose-dependently inhibited FAS and FADD expressions and caspase-8 activation.</p><p><b>CONCLUSION</b>Schisandrin B can partially inhibit H(2)O(2)-induced L02 cell apoptosis possibly by affecting the FAS-FADD-caspase-8 pathway.</p>
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Humans , Apoptosis , Caspase 8 , Metabolism , Cell Line , Cyclooctanes , Pharmacology , Fas-Associated Death Domain Protein , Metabolism , Flow Cytometry , Hepatocytes , Metabolism , Hydrogen Peroxide , Lignans , Pharmacology , Polycyclic Compounds , Pharmacology , Signal Transduction , fas Receptor , MetabolismABSTRACT
In recent years, researchers have made some breakthroughs on human embryonic stem cells, in particular, on reprogramming differentiated cell (such as human skin fibroblast) into human embryonic stem cell. Induced pluripotent stem cells could be generated from human skin fibroblasts by inducting into four transcription factors known as OCT3/4, SOX2, C-MYC and KLF4. This approach enables better understanding the pathogenesis of diseases from the perspective of genetic component and promising in the treatment of related diseases. This article introduces the latest advancement of those researches.
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The effects of advanced glycation end products(AGE)on phosphorylation of ezrin/radixin/ moesin(ERM)protein in human umbilical vein endothelial ceils were detected by immunofluorescence cytochemistry and its mechanism was explored.AGE stimulated the phosphorylation of ERM protein in dose-and time-dependent manners(all P<0.05),which was involved in AGE receptor,Rho kinase,and p38 mitogen-activated protein kinase pathways.
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Objective To study the role of P38 mitogen-activated protein kinase(P38 MAPK) activation in high level glucose-induced microvascular hyperpermeability.Methods Rats were induced to diabetis by intraperitoneal injection of streptozotocin(STZ).The rats were divided into 5 groups,including normal,diabetes,control,MKK6b(A) and MKK6b(E) groups.The permeability coefficient to albumin(Pa) was measured in venules of in vivo mesenterium using a fluorescence ratio technique;Morphological changes of microvascular endothelial cell were monitored by observing fluorescence of F-actin stained with rhodamine-phalloidin.Results The permeability of diabetic rats was obviously increased.The activation of P38 MAPK by MKK6b(E) could increase microvascular permeability in normal rats,and the inhibition of P38 MAPK by MKK6b(A) could inhibit hyperpermeability of diabetic rats.Conclusion The activation of P38 MAPK induced by hyperglycemia may play a role in diabetic microvascular hyperpermeability.
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Objective To gain a higher quality of pathophysiology experiment teaching of students studying abroad.Methods To improve greatly in knowing the characteristics of students studying abroad,preparation before class, teaching method and effect judgement.Results We have a conspicuous improvement in the quality and effect of pathophysiology experiment teaching. Conclusions To gain a higher quality of pathophysiology experiment teaching of students studying abroad,we should improve greatly in knowing the characteristics of students studying abroad,preparation before class,teaching method and effect judgement.
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AIM: To study the effect of microelement powder (MP) on membrane potential of vascular endothelial and smooth muscle cells of rats in order to elucidate the mechanism of microcirculation improvement by MP. METHODS: Cultured pulmonary vascular endothelial cells (EC) and aortic smooth muscle cells (SMC) of rats and detecting the changes of cellular membrane potentials by using potential-sensitive fluorescent probe and laser jet confocal microscope. RESULTS: MP hyperpolarized SMCs significantly. Glybenclamide (2 μmol/L), a blocker of KATP channel, which had no effect on membrane potential of SMCs, reversed the hyperpolarization of MP completely; MP hyperpolarized ECs slightly, but the effect was unaffected by glybenclamide. CONCLUSION: MP hyperpolarizes SMCs by activating KATP channels and leads to dilation of microvessels and improvement of microcirculation.
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As a powerful intervention to protect ischemic tissues,ischemic preconditioning (IPC) has been a hot spot due to its greatly potential clinical values throughout the past decades.From the triggers and cell-membrane receptors to intracellular signal molecules and mitochondrial signal chains,we inquire in this review the common points and relativities on the signaling transduction of IPC by conferring the cardio-and neuro-protection mechanisms of IPC.
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AIM: To investigate the effect of advanced glycosylation end products(AGEs) modified protein on morphological changes of actin cytoskeleton in primary endothelial cells and the role of MAPK signaling pathways in this pathological procedure.METHODS: Human umbilical vein endothelial cells(HUVECs) were incubated with AGEs modified human serum albumin(AGE-HSA) at concentrations of 12.5,25,50,and 100 mg/L,respectively,for 2,4,8,12 and 24 hours.The cells were treated with different chemical compounds of inhibitors,or adenoviral deliver approach(either dominant positive or negative adenoviral constructs) of MAP kinases to specifically block or activate certain signal transduction pathways under above situations.As control,HSA of the same concentration was administered to cells at the same time.The treated cells were incubated with FITC-phalloidin to stain F-actin.RESULTS: F-actin in HUVECs was rearranged greatly by AGEs in a concentration and time-dependent manners.The unmodified HSA did not influence Factin distributions.The AGEs-induced changes were blocked by pretreatment with SB203580,PD98059 for 30 min,or pre-infection with recombinant virus of dominant negative form of MKK 6b [MKK6b(A)],MEK1 [MEK1(A)] for 24 h,while SP600125 and dominant negative form of MKK7 [MKK7(A)] failed to inhibit the effects of AGEs.Furthermore,the infection of recombinant virus of constitutive active form of MKK6b [MKK6b(E)] or MEK1 [MEK1(E)] could also induced re-arrangement of F-actin,respectively,while the effect elicited by [MKK6b(E)] was abolished by co-infection with recombinant adeno-virus of dominant negative p38?. CONCLUSION: AGEs-induced morphological changes of F-actin in endothelial cells are mediated by p38-and ERK MAPK signal pathways.
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AIM: To study the effect of cGMP-dependent protein kinase (PKG) on the pathogenesis of burn shock. METHODS: Confluent endothelial cells were disintegrated and centrifugated to obtain cell lysates after being treated with 10% burn serum or PKG activator 8-Br-cGMP. PKG activity of lysates was measured with radioactive isotope label method in a reaction system of phosphorylation of specific substrate H2B by PKG, and the shape and the distribution of intracellular filamentous actin were detected by specific fluorescence staining. For the control study, the PKG specific inhibitor KT5823 were used to pretreat the endothelial cells before the administration of burn serum or PKG activator 8-Br-cGMP. RESULTS: Exposures to burn serum and 8-Br-cGMP led to a rapid time-dependent increase in endothelial PKG activity and the polar distribution of intracellular filamentous actin, and preincubation with KT5823 abolished those effects. CONCLUSIONS: The results suggest that burn serum induces PKG activation and the stress variety of filamentous actin in the vascular endothelial cells, which probably contributes to the endothelial hyperpermeability after burn shock. [
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AIM: To investigate whether small GTPase RhoA's downstream effector Rho kinase mediates burn serum-induced endothelial hyperpermeability. METHODS: Primary cultured rat dermal microvascular endothelial cells (DMECs) were exposed to serum isolated from burned or sham burn rats for 6 hours and 8 hours, respectively, and did or didn't pretreated or post-treated with Y-27632 (30 ?mol/L), a specific inhibitor of Rho kinase. ECs were then prepared for routine scanning electron microscopy observation, or stained with rhodamine-phalloidin for F-actin visualization. Permeability to FITC-albumin was evaluated using EC monolayers. RESULTS: Stimulation with 15% burn serum for 6 h changed the ultrastructure on cellular surface of DMECs with appearance of ripple marks instead of microvillus. The small protuberances at cellular lateral were shorten and the gaps were seen between adjacent cells. Post-treatment of Y-27632 reversed the changes of ultrastructure on the cellular surface. Burn serum induced a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity of the peripheral filament bands and formation of the long and thick stress fibers, lamellipodia and filopodia. The stress fibers were diminished by pretreatment or post-treatment of Y-27632. But lamellipodia and filopodia were not influenced by pretreatment or post-treatment of Y-27632. Pre-treatment of Y-27632 also attenuated significantly the increase in EC monolayer permeability stimulated by burn serum for 6 h. However, post-treatment of Y-27632 could not attenuated burn serum-induced endothelial hyperpermeability response although their Pa values were lower than simple burn serum group's. CONCLUSION: These findings indicate that Rho kinase is involved in the mediation of burn serum-induced endothelial actin cytoskeleton reorganization and early stage of barrier dysfunction. [
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AIM: To study the change of intercellular adhesion molecule-1(ICAM-1) expression in intestine tissues of mice induced by LPS and regulatory effect of p38 mitogen-activated protein kinase (p38 MAPK) on ICAM-1 expression. METHODS: Protein and mRNA of ICAM-1 were measured using Western blotting and RT-PCR respectively in intestine tissue of BALB/c mice treated by lipopolysaccharide(LPS) or LPS plus SB203580, a specific inhibitor of p38 MAPK. RESULTS: Compared with control group, the expression of ICAM-1 protein and mRNA was increased significantly by LPS stimulation in dose- and time-dependent manner. ICAM-1 expression reached peak value at 12-36 h after LPS stimulation. 20.0 mg/kg of LPS could induce the maximum of ICAM-1 expression. Pretreatment of mice with SB203580 for 30 min could inhibit significantly LPS-induced expression of ICAM-1 protein and mRNA expression in mouse intestine tissues. CONCLUSIONS: These data highlight that LPS could up-regulate ICAM-1 protein and mRNA expression in intestine tissue of mice in dose- and time-dependent manner, and p38 MAPK signal pathway plays an important role in ICAM-1 expression induced by LPS. It suggests that inhibition of p38 MAPK might be a useful principle for the prevention and treatment of intestine damage of endotoxic shock.
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Protein kinase C pathway is an important intracellular signal transduction pathway.A growing number of evidences showes that activation of PKC influences endothelial cell permeability.In this review,we briefly summarize the effects and regulating pathways of protein kinase C in modulation of vascular endothelium permeability.
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AIM: To study the effect of microelement powder (MP) on membrane potential of vascular endothelial and smooth muscle cells of rats in order to elucidate the mechanism of microcirculation improvement by MP. METHODS: Cultured pulmonary vascular endothelial cells (EC) and aortic smooth muscle cells (SMC) of rats and detecting the changes of cellular membrane potentials by using potential-sensitive fluorescent probe and laser jet confocal microscope. RESULTS: MP hyperpolarized SMCs significantly. Glybenclamide (2 ?mol/L), a blocker of K ATP channel, which had no effect on membrane potential of SMCs, reversed the hyperpolarization of MP completely; MP hyperpolarized ECs slightly, but the effect was unaffected by glybenclamide. CONCLUSION: MP hyperpolarizes SMCs by activating K ATP channels and leads to dilation of microvessels and improvement of microcirculation.
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Endogenous carbon monoxide (CO) is proposed to be an intracellular signaling molecule. As a new gaseous messenger, CO shares with nitric oxide (NO) the ability of modulating neuroendocrine function and inducing vasorelaxation, mainly by stimulating soluble guanylate cyclase and regulating the level of cGMP. This review emphasized the endogenous source of CO and the interaction of CO- and NO-generating systems. It also discussed the biological effects of CO and the underlying mechanisms.
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Theincreasedmicrovascularpermeabilityappearsmainlyinvenuleduringinflammation , shock ,andburns .Endothelialcellsplayanimportantroleinvenulepermeabilityenhancement.Therearetwo kindsofpathwayformacromoleculeextravasation .Oneisparacellularpathwayandanotheristranscellular pathway ,whicharerelatedtotheformationofendothelialgaportranscellularopeningsseperately .Thealter ationofintercellularrelatedprotein ,suchasoccludin ,claudin ,zonaoccludens (ZO) ,junctionaladhesion molecule (JAM) ,VE -cadherin ,catenin ,integrin ,etc ,andthealterationofendothelialcytoskeleton ,such asrearrangementofactinfilament,formationofstressfiberandfocaladhesion ,etc ,involveinthepathogenesis ofincreasedmicrovascularpermeability . [
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AIM: To study I_ to channel function in severe burn and its contribution to cardiac dysfunction induced by severe burn. METHODS: CHO-K1 cells were transfected with human Kv4.3, the major subunit of human I_ to channel. The expressed Kv4.3 channels were recorded by whole-cell patch clamp and the effects of rat burn serum on Kv4.3 current densities and kinetics were observed. RESULTS: Kv4.3 channels expressed in CHO-K1 cells were endowed with the characterization of fast activation and inactivation, which was quite similar to that of native I_ to channels in cardiomyocytes. Rat's burn serum at the concentration of 2% decreased the current density significantly. At +40 mV, the current density in control group was (67.6?15.1) pA/pF, in contrast to (32.3?9.7)pA/pF in burn serum-treated group (P
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AIM: This experiment is to investigate the effects of LPS on the organization and localization of VE-cadherin and F-actin in cultured human umbilical endothelial cells.METHODS: The human umbilical vein endothelial cell lines ECV-304 were incubated with LPS at different concentrations for 30 min. VE-cadherin was detected by immunofluorescence with primary mAb of VE-cadherin and FITC-conjugated secondary antibody. F-actin was detected with fluorescence staining with rodamine-phalloidin. RESULTS: At high concentration, LPS could induce reorganization of VE-cadherin with the formation of serrata cellular border and enlargement of intercellular gaps, which were apparently different from that in normal conditions with the high fluorescence intensity at cell-cell junction. F-actin depolymerization could also be induced by LPS at high concentration with the formation of stress fiber and filopodia. CONCLUSION: LPS(300 ?g/L) could induce reorganization of VE-cadherin and F-actin in human umbilical vein endothelial cells.