Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Biochanin A attenuates spinal cord injury in rats during early stages by inhibiting oxidative stress and inflammasome activation

Previous studies have shown that Biochanin A,a flavonoid compound with estrogenic effects,can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury;howeve r,its effect on spinal cord injury is still unclea r. In this study,a rat model of spinal cord injury was established using the heavy o bject impact method,and the rats were then treated with Biochanin A(40 mg/kg) via intrape ritoneal injection for 14 consecutive days.The res ults showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal co rd tissue injury,reduced inflammation and oxidative stress in spinal cord neuro ns,and reduced apoptosis and pyroptosis.In addition,Biochanin A inhibited the expression of inflammasome-related proteins(ASC,NLRP3,and GSDMD)and the Toll-like receptor 4/nuclear factor-κB pathway,activated the Nrf2/heme oxygenase 1 signaling pathway,and increased the expression of the autophagy markers LC3 Ⅱ,Beclin-1,and P62.Moreove r,the therapeutic effects of Biochanin A on early post-s pinal cord injury were similar to those of methylprednisolone.These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways.These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

Lactobacillus plantarum AR113 attenuates liver injury in D-galactose-induced aging mice via the inhibition of oxidative stress and endoplasmic reticulum stress

Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.

Mechanisms and Research Progress of Traditional Chinese Medicine Regulating NF-κB in the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring the relevance of NF-κB and the pathogenesis of this disease,it was found that this disease was mainly associated with inflammation,dysfunction of the endothelial barrier,oxidative stress,impaired clearance of alveolar fluid,and coagulation disorders.Traditional Chinese medicine(TCM)has the characteristics of multitargeting,multipathway effects,and high safety,which can directly or indirectly affect the treatment of ALI/ARDS.This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS.It provides an overview from the perspectives of Chinese herbal monomers,TCM couplet medicines,TCM injections,Chinese herbal compounds,and Chinese herbal preparations,offering insights into the prevention and treatment of ALI/ARDS with TCM.

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Oxidative stress mediates glycidol-induced endothelial injury and its protection by 6-C-(E-2-fluorostyryl)naringenin

Glycidol is a common lipid-derived foodborne toxicant mainly presents in refined oils and related foodstuffs.Vascular endothelial cells may be potential targets of the deleterious effects associated with glycidol exposure.In human umbilical vein endothelial cells(HUVECs),we found that glycidol treatment promoted endothelialto-mesenchymal transition(EndMT)at a lower concentration(0.5 mmol/L),while induced apoptosis and inflammation at a higher concentration(1 mmol/L).These harmful effects were achieved by the activation of NF-κB/MAPK signaling pathway and were mediated by reactive oxygen species(ROS).In addition,the protective potential of 6-C-(E-2-fluorostyryl)naringenin(6-CEFN)against glycidol was evaluated and compared with naringenin.HUVECs pre-treated with 6-CEFN,but not naringenin,displayed resistance to endothelial dysfunction caused by glycidol.

Protective effect of camellia oil on H_(2)O_(2)-induced oxidative stress injury in H9C2 cardiomyocytes of rats

Objective: To explore the protective effect of camellia oil against H2O2-induced oxidative stress injury in rat H9C2 cardiomyocytes. Methods: CCK8 method was used to detect the cell survival rate of H9C2 cardiomyocytes treated with different concentrations of H2O2. Normal cultured cells were used as the blank control group, and the cells were treated with 200 μmol/L H2O2 for 24 h. An oxidative stress injury model was constructed as the model group. The cells were pretreated with 1%, 0.1% and 0.01% camellia oil for 24 h, and then H2O2 was added for 24 h as the experimental group. The β-galactosidase senescence staining assay, mitochondrial membrane potential assay, EdU cell proliferation staining assay and scratch assay were used to observe the changes of cell senescence, mitochondrial membrane potential, proliferation, apoptosis and migration in each group. The superoxide dismutase (SOD) activity, lactate dehydrogenase (LDH) activity, and malondialdehyde (MDA) content of the cells in each group were detected by using the kit. Results: The cell viability of H9C2 cardiomyocytes treated with different concentrations of H2O2 was inhibited and positively correlated with the concentration of H2O2 (P<0.01). Compared with the blank control group, the positive rate of cell senescence, MDA content and LDH activity increased in the H2O2 model group (P<0.01);mitochondrial membrane potential, cellular value-added rate, migration rate and SOD activity decreased (P<0.01). Compared with the H2O2 model group, the positive rate of cellular senescence (P<0.01 or P<0.05), MDA content and LDH activity decreased (P< 0.01 or P<0.05);mitochondrial membrane potential increased, cell proliferation rate and migration rate increased (P<0.01 or P<0.05) in the experimental group. Conclusion: Camellia oil can significantly inhibit oxidative stress injury in H9C2 cells and exert cardiomyocyte protective effects.

Inhibiting tau protein improves the recovery of spinal cord injury in rats by alleviating neuroinflammation and oxidative stress

After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.

Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure

BACKGROUND Stress granules(SGs)could be formed under different stimulation to inhibit cell injury.AIM To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure(ALF)by reducing endoplasmic reticulum stress(ERS)mediated apoptosis.METHODS The agonist of SGs,arsenite(Ars)was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models.Further,the siRNA of activating transcription factor 4(ATF4)and SGs inhibitor anisomycin was then used to intervene in cell models.RESULTS With the increase of hypoxia time from 4 h to 12 h,the levels of HIF-1α,ERS and apoptosis gradually increased,and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased.Compared with the hypoxia cell model group and ALF mice model,the levels of HIF-1α,apoptosis and ERS were increased in the Ars intervention group.After siRNA-ATF4 intervention,the level of SGs in cells increased,and the levels of HIF-1α,ERS and apoptosis decreased.Compared with the siRNA-ATF4 group,the levels of G3BP1 in the siRNAATF4+anisomycin group were decreased,and the levels of HIF-1α,ERS and apoptosis were increased.Moreover,compared with the ALF group,the degree of liver injury and liver function,the levels of HIF-1α,ERS and apoptosis in the Ars intervention group were decreased,the level of SGs was increased.CONCLUSION SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERSmediated apoptosis.

Hydralazine Promotes Central Nervous System Recovery after Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation through Macrophage Regulation

Objective:This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury(SCI)in the central nervous system(CNS)and its mechanism in promoting the structural and functional recovery of the injured CNS.Methods:A compressive SCI mouse model was utilized for this investigation.Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein,acrolein-induced inflammation-related factors,and macrophages at the injury site and within the CNS.Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase(PI3K)/AKT pathway to study macrophage regulation.The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67(GAD65/67),vesicular glutamate transporter 1(VGLUT1),paw withdrawal response,and Basso Mouse Scale score.Nissl staining and Luxol Fast Blue(LFB)staining were performed to investigate the structural recovery of the injured CNS.Results:Hydralazine downregulated the levels of acrolein,IL-1β,and TNF-αin the spinal cord.The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway,leading to M2 macrophage polarization,which protected neurons against SCI-induced inflammation.Additionally,hydralazine promoted the structural recovery of the injured spinal cord area.Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression.Furthermore,hydralazine facilitated motor function recovery following SCI.Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.Conclusion:Hydralazine,an acrolein scavenger,significantly mitigated SCI-induced inflammation and oxidative stress in vivo,modulated macrophage activation,and consequently promoted the structural and functional recovery of the injured CNS.

Periplaneta Americana Extract Ameliorates LPS-induced Acute Lung Injury Via Reducing Inflammation and Oxidative Stress

Objective Acute lung injury(ALI)is an acute clinical syndrome characterized by uncontrolled inflammation response,which causes high mortality and poor prognosis.The present study determined the protective effect and underlying mechanism of Periplaneta americana extract(PAE)against lipopolysaccharide(LPS)-induced ALI.Methods The viability of MH-S cells was measured by MTT.ALI was induced in BALB/c mice by intranasal administration of LPS(5 mg/kg),and the pathological changes,oxidative stress,myeloperoxidase activity,lactate dehydrogenase activity,inflammatory cytokine expression,edema formation,and signal pathway activation in lung tissues and bronchoalveolar lavage fluid(BALF)were examined by H&E staining,MDA,SOD and CAT assays,MPO assay,ELISA,wet/dry analysis,immunofluorescence staining and Western blotting,respectively.Results The results revealed that PAE obviously inhibited the release of proinflammatory TNF-α,IL-6 and IL-1βby suppressing the activation of MAPK/Akt/NF-κB signaling pathways in LPS-treated MH-S cells.Furthermore,PAE suppressed the neutrophil infiltration,permeability increase,pathological changes,cellular damage and death,pro-inflammatory cytokines expression,and oxidative stress upregulation,which was associated with its blockage of the MAPK/Akt/NF-κB pathway in lung tissues of ALI mice.Conclusion PAE may serve as a potential agent for ALI treatment due to its anti-inflammatory and anti-oxidative properties,which correlate to the blockage of the MAPK/NF-κB and AKT signaling pathways.

Mental stress, atheroma, myocardial ischaemia and injury: the link is inflammation

Increasing observational and experimental trial data have shownthat mental stress can lead toan increase in adverse clinical cardiovascular events.Mental stress affects the heart by inducing ischaemia and precipitating myocardial infarction(MI)or direct myocardial injury.Mental stress leads to systemic inflammation.Inflammation is known to cause rapid atheromatous plaque progression,instability and thrombosis—the classic type 1 MI.Inflammation can also lead to type 2 MI or myocarditis and injury.The published data linking systemic inflammation,mental stress and cardiovascular disease will be reviewed to establish the linkage between mind and heart,thereby highlighting the importance of holistically managing the patient,not only addressing separate organ systems.Finally,recent trial evidence showing the value of anti-inflammatory drugs in cardiovascular and mental conditions will be briefly considered.

Melatonin treatment alleviates chilling injury in mango fruit 'Keitt' by modulating proline metabolism under chilling stress

Mangoes often suffer from low temperature-induced chilling injury (CI) during postharvest cold storage.Therefore,advanced techniques are crucial and in high demand to solve the chilling stress of mango fruit for a higher value.This study addresses chilling stress modulation by investigating the effects of melatonin treatment on CI,proline metabolism,and related gene expressions of ‘Keitt’ mango during cold storage after dipped in 0 (control),0.1 (MT1),and 0.2 mmol L^(-1)(MT2) melatonin solution for 30 min.The results revealed that melatonin treatment in MT1 significantly reduced CI development and increased proline content in mango fruit during cold storage compared to the control.These changes were along with increases in the activity of critical enzymes as well as the expression of encoding genes involved in proline biosynthesis,such as pyrroline-5-carboxylate synthetase (P5CS),pyrroline-5-carboxylate reductase (P5CR),ornithine D-aminotransferase (OAT),P5CS2,P5CR2,and OAT3.Additionally,proline dehydrogenase (PDH) activity and the expression of the PDH3 gene associated with proline dehydrogenation were lower in MT1-treated mangoes than the controlled group.Thus,melatonin treatment has regulated proline metabolism resulting in the accumulation of proline,subsequently contributing to enhancing the chilling tolerance of‘Keitt’mango fruit.

Inhibition of endoplasmic reticulum stress alleviates secondary injury after traumatic brain injury

Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal（1 mg/kg）, by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.

Stress and strain analysis on the anastomosis site sutured with either epineurial or perineurial sutures after simulation of sciatic nerve injury

The magnitude of tensile stress and tensile strain at an anastomosis site under physiological stress is an important factor for the success of anastomosis following suturing in peripheral nerve injury treatment. Sciatic nerves from fresh adult cadavers were used to create models of sciatic nerve injury. The denervated specimens underwent epineurial and perineurial suturing. The elastic modulus （40.96 ＋ 2.59 MPa） and Poisson ratio （0.37 ＋ 0.02） of the normal sciatic nerve were measured by strain electrical measurement. A resistance strain gauge was pasted on the front, back left, and right of the edge of the anastomosis site after suturing. Strain electrical measurement results showed that the stress and strain values of the sciatic nerve following perineurial suturing were lower than those following epineurial suturing. Scanning electron microscopy revealed that the sciatic nerve fibers were disordered following epineurial compared with perineurial suturing. These results indicate that the effect of perineurial suturing in sciatic nerve injury repair is better than that of epineurial suturing.

Urinary Kidney Injury Molocule-1 Level in Preterm Neonates with Respiratory Distress Syndrome

Background: Despite recent advances in perinatal and neonatal care in respiratory distress syndrome (RDS) prevention and treatment, a considerable number of these neonates suffer from acute kidney injury (AKI), and it is associated with poor outcome as an independent risk factor. KIM-1 mRNA and protein are expressed at a low level in normal kidney but are increased in post ischemic kidney. Aim: The aim is to detect the value of urinary KIM-1 measurement as an early predictor marker of acute kidney injury in preterm neonates with respiratory distress syndrome. Patients and methods: The study included 30 preterm newborn with (RDS) ≤36 weeks during the period from October 2014 to March 2015. Also the study included 30 apparently healthy newborn ≤36 weeks as controls. They were selected from NICU of Manshiate Elbakry hospital Cairo, Egypt. uKIM-1 along with serum creatinine levels and eGFR were assessed in days 1 of life for both groups and in day 3 for cases. Results: In day one of life, we found a significant increase in uKIM-1 levels in preterm newborn with RDS compared to their controls (2.88 ± 1.01 ng/ml and 0.95 ± 0.52 ng/ml respectively (p = 0.001)). There is no significant difference between both groups regarding serum creatinine and eGFR. In day 3 of life, preterm with RDS had significant decrease in uKIM-1 levels compared to day 1 of life with significant increase in non-survivor compared to survivor group ( 2.30 ± 1.56 ng/ml and 1.30 ± 0.90 ng/ml respectively (p = 0.03)). The sensitivity and specificity of uKIM-1 and serum creatinine was calculated (100.00%, 86.67% and 33.33%;95.00%) respectively. Conclusion: Preterm neonate with RDS is at high risk of developing AKI. Early and serial uKIM-1 measurements can be used as a non-invasive indicator of kidney injury in premature newborn with RDS.

Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities

Acute myocardial infarction(AMI) is the leading cause of death worldwide. Its associated mortality, morbidity and complications have significantly decreased with the development of interventional cardiology and percutaneous coronary angioplasty(PCA) treatment, which quick-ly and effectively restore the blood flow to the area previously subjected to ischemia. Paradoxi-cally, the restoration of blood flow to the ischemic zone leads to a massive production of reactive oxygen species(ROS) which generate rapid and severe damage to biomolecules, generating a phenomenon called myocardial reperfusion injury(MRI). In the clinical setting, MRI is associated with multiple complications such as lethal reperfusion, no-reflow, myocardial stunning, and reperfusion arrhythmias. Despite significant advances in the understanding of the mechanisms accounting for the myocardial ischemia reperfusion injury, it remains an unsolved problem. Although promising results have been obtained in experimental studies(mainly in animal models), these benefits have not been translated into clinical settings. Thus, clinical trials have failed to find benefits from any therapy to prevent MRI. There is major evidence with respect to the contribution of oxidative stress to MRI in cardiovascular diseases. The lack- of consistency between basic studies and clinical trials is not solely based on the diversity inherent in epidemiology but is also a result of the methodological weak-nesses of some studies. It is quite possible that pharmacological issues, such as doses, active ingredients, bioavailability, routes of administration, co-therapies, startup time of the drug intervention,and its continuity may also have some responsibility for the lack- of consistency between different studies. Furthermore, the administration of high ascorbate doses prior to reperfusion appears to be a safe and rational therapy against the development of oxidative damage associated with myocardial reperfusion. In addition, the association with N-acetylcysteine(a glutathione donor) and deferoxamine(an iron chelator) could improve the antioxidant cardioprotection by ascorbate, mak-ing it even more effective in preventing myocardial reperfusion damage associated with PCA following AMI.