The effects of smoking on blood lipids, C-reactive protein, and homocysteine in young patients with ischemic stroke

Objective:To investigate clinical significance of the effects of smoking on blood lipids, C-reactive protein,and homocysteine in young ischemic stroke patients.Methods:The clinical data of 423 young stroke patients in the department of neurology at Taihe Hospital in Shiyan City, China were retrospectively analyzed, including age,gender,drinking history,family history,and atrial fibrillation history. Patients were divided into two groups according to whether they smoked,and the blood lipids, C-reactive protein, and homocysteine were compared between groups.Results:The proportion of smokers was 41.83%.The levels of total cholesterol,triglycerides (TG), low density lipoprotein (LDL), and homocysteine were higher in patients who smoked than in those who did not(P < 0.05). High density lipoprotein (HDL) was lower in the smoking group (P < 0.05). C-reactive protein test results were divided into groups according to whether the levels exceeded the normal range or not, and no correlation was found between C-reactive protein levels and smoking(P>0.05). Conclusion:Total cholesterol, TG, LDL, HDL, and homocysteine were significantly different between stroke patients who smoked and those who did not. We therefore suggest that smoking cessation take place as soon as possible and that it be avoided entirely in order to reduce the incidence of atherosclerosis and stroke.

In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke

In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1(PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.e B-GFAP-sh PTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-sh PTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

The Role of High-sensitivity C-reactive Protein, Interleukin-6 and Cystatin C in Ischemic Stroke Complicating Atrial Fibrillation

This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy.A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited.IL-6 level was detected by using enzyme linked immunosorbent assay.Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay.The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects.Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036).The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030).After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488).It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF.Elevated cystatin C level is also indicative of the increased risk of AF.

C-reactive Protein Level,Apolipoprotein B-to-apolipoprotein A-1 Ratio,and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China

Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.

Combined Effects of A Body Shape Index and Serum C-reactive Protein on Ischemic Stroke Incidence among Mongolians in China

Objective We aimed to evaluate the combined effects of a high body shape index(ABSI) and a high serum C-reactive protein(CRP) level on the incidence of ischemic stroke in a Mongolian population in China. Methods A prospective cohort study was conducted among 2,589 participants from June 2002 to July 2012 in Inner Mongolia, China. The participants were categorized into 4 groups according to their level of ABSI and CRP. Cox proportional hazards models were used to assess the hazard ratios(HRs) and 95% confidence intervals(CIs) for ischemic stroke among all groups. Results The multivariate adjusted HRs(95% CI) of ischemic stroke for high ABSI and high CRP level were 1.46(0.89-2.39) and 1.63(0.95-2.79), respectively. Compared with the low ABSI/low CRP level group, the multivariate adjusted HRs(95% CI) of ischemic stroke in the low ABSI/high CRP, high ABSI/low CRP, and high ABSI/high CRP groups were 1.04(0.46-2.35), 1.06(0.58-1.95) and 2.52(1.27-5.00), respectively. The HR of ischemic stroke for the high ABSI/high CRP level group was the highest and most statistically significant. Conclusion We found that participants with simultaneously high ABSI and high CRP levels had the highest risk of ischemic stroke in the Mongolian population. Our findings suggest that the combination of high ABSI and high CRP levels may increase the risk of ischemic stroke.

Relationship between Levels of Serum C-Reactive Protein,Leucocyte Count and Carotid Plaque in Patients with Ischemic Stroke

In order to study the relationship between serum C-reactive protein (CRP) levels, leukocyte count and carotid plaque in patients with ischemic stroke, carotid duplex examination was performed by high-definition imaging (HDI) 5000 triplex system. Serum CRP was measured by nephelometry within 72 h after index ischemic stroke. A lesion was considered a plaque in the presence of a maximum intimal-medial wall thickness (IMT) 1.2 mm. Results of carotid ultrasonography were divided into two groups: M1, normal (IMT <1.2 mm) and M2, abnormal (IMT ≥1.2 mm). The results showed that the mean age of M2 was significantly older than that of M1 (69.7±10.4 versus 62.5±9.6, P =0.001). The patients with hypertension and diabetes mellitus (78 %, 35 % respectively)in M2 were significantly more than those (52 %, 18 % respectively) in M1 ( P <0.01, P <0.05). There were 32 (65 % ) patients with elevated CRP levels in M2, but 33 (46 %) patients with elevated CRP levels in M1, with the difference being significant between the two groups ( P <0.05). The levels of serum glucose and leukocyte count (8.1±5.5, 10.3±4.0, respectively) in abnormal CRP group were significantly higher than that of normal CRP group (6.4±2.8, 8.7±3.4) ( P <0.05, P <0.05); elevated CRP levels was found in 42 (62 %) patients with territory infarction and 23 (43 %) patients with lacunar infarction respectively, with the difference being significant between these two groups ( P <0.05). It was concluded that the elevation of CRP levels was an significant clinical index for carotid plaque in patients with acute cerebral infarction.

Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and risk of ischemic stroke in Han Chinese of eastern China

Variants of the arachidonate 5-1ipoxygenase-activating protein （ALOX5AP） gene have been suggested to play an important role in the pathogenesis of atherosclerosis and ischemic stroke. This study was aimed to explore the association of ALOX5AP variants with ischemic stroke risk in Han Chinese of eastern China. A total of 690 ischemic stroke cases and 767 controls were recruited. The subjects were further subtyped according to the Trial of Org 10172 in Acute Stroke Treatment （TOAST） criteria. On the basis of that, two polymorphisms of the ALOX5AP gene （rs10507391 and rs12429692） were determined by TaqMan genotyping assay. In addition, plasma leukotriene B4 （LTB4） levels were analyzed in these subjects. There was no evidence of association between the two variants of ALOX5AP and the risk of ischemic stroke or its TOAST-subtypes. Haplotype analysis and stratification analysis according to sex, age, body mass index, hypertension, and diabetes also showed negative association. Analysis of LTB4 levels in a subset of cases and controls revealed that LTB4 levels were significantly higher in ischemic stroke cases than in the controls （70.06± 14.75 ng/L vs 57.34±10.93 ng/L; P = 0.000） and carriers of the T allele of the rs10507391 variant were associated with higher plasma LTB4 levels （P = 0.000）. The present study suggests there is no association of the two polymorphisms in the ALOX5AP gene with ischemic stroke risk in Han Chinese of eastern China.

Elevated Homocysteine and C-reactive Protein Levels Independently Predict Worsening Prognosis after Stroke in Chinese Patients

Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known.To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic).Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period.Using the arbitrary cutoff for tHcy (【18 μmol/L and ≥18 μmol/L) and hsCRP (【1 mg/L, 1-3 mg/L and 】3 mg/L), the patients were divided into 6 groups.Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P【0.01).The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18 μmol/L) and hsCRP (】3 mg/L) compared with those with low tHcy (【18 μmol/L) and hsCRP (【1 mg/L).The increased tHcy level (≥18 μmol/L) combined with increased hsCRP level (】3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion.The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone.Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.

Latest progress in the research of protein kinase C(PKC)isoform-specific signaling and PKC-modulated autophagy in ischemic stroke

Ischemic stroke is a major cause of morbidity and mortality,and currently there is no effective treatment.The family of protein kinase C(PKCs)could phosphorylate serine or threonine residues of its substrate proteins and play a key role in the ischemia/reperfusion injury.Autophagy is essential for maintaining cell homeostasis under physiological condition and acts as a double-edged sword in the process of ischemic neuronal death.In this article,we reviewed the PKCs isoform-specific signaling pathways and PKC-modulated autophagy in ischemic stroke.

Mechanism underlying treatment of ischemic stroke using acupuncture:transmission and regulation

The inflammatory response after cerebral ischemia/reperfusion is an important cause of neurological damage and repair.After cerebral ischemia/reperfusion,microglia are activated,and a large number of circulating inflammatory cells infiltrate the affected area.This leads to the secretion of inflammatory mediators and an inflammatory cascade that eventually causes secondary brain damage,including neuron necrosis,blood-brain barrier destruction,cerebral edema,and an oxidative stress response.Activation of inflammatory signaling pathways plays a key role in the pathological process of ischemic stroke.Increasing evidence suggests that acupuncture can reduce the inflammatory response after cerebral ischemia/reperfusion and promote repair of the injured nervous system.Acupuncture can not only inhibit the activation and infiltration of inflammatory cells,but can also regulate the expression of inflammation-related cytokines,balance the effects of pro-inflammatory and anti-inflammatory factors,and interfere with inflammatory signaling pathways.Therefore,it is important to study the transmission and regulatory mechanism of inflammatory signaling pathways after acupuncture treatment for cerebral ischemia/reperfusion injury to provide a theoretical basis for clinical treatment of this type of injury using acupuncture.Our review summarizes the overall conditions of inflammatory cells,mediators,and pathways after cerebral ischemia/reperfusion,and discusses the possible synergistic intervention of acupuncture in the inflammatory signaling pathway network to provide a foundation to explore the multiple molecular mechanisms by which acupuncture promotes nerve function restoration.

Treadmill training improves neurological deficits and suppresses neuronal apoptosis in cerebral ischemic stroke rats

RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intens让ies, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3卩 signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/ protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This study was approved by the Ethics Committee of Animal Experimentation in Shanghai No. 8 Peoples Hospital, China.

δ-Opioid receptor as a potential therapeutic target for ischemic stroke

Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels.Despite having advancement in the use of thrombolytic and clot removal medicine,significant numbers of stroke patients are still left out without option for treatment.In this review,we summarize recent research work on the activation ofδ-opioid receptor as a strategy for treating ischemic stroke-caused neuronal injury.Moreover,as activation ofδ-opioid receptor by a non-peptidicδ-opioid receptor agonist also modulates the expression,maturation and processing of amyloid precursor protein andβ-secretase activity,the potential role of these effects on ischemic stroke caused dementia or Alzheimer’s disease are also discussed.

Ischemic stroke susceptibility gene in a Northern Han Chinese population

Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the –607C/A （rs1946518） polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 –137G/C （rs187238） polymorphism and the –13T/C （rs11024595） polymorphism in the 5＇-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A allele （C homozygotes） was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the –13T/C （rs11024595） polymorphism in the 5′-flanking region of serum amyloid A has no correlation with ischemic cerebrovascular disease, but the C allele of the –607C/A （rs1946518） polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.

Association of ALOX5AP with ischemic stroke in eastern Chinese

BACKGROUND：5-1ipoxygenase protein （ALOX5AP） has been recognized as a susceptibility gene for stroke and coronary artery diseases. The present study was to explore the role of this gene in the eastern Chinese patients with ischemic stroke.METHODS： Using a case-control design, we studied 658 patients with ischemic stroke and 704 unrelated population-based controls who were age- and sex-matched. The 658 patients were classified by the Trial of Org 10172 in Acute Stroke Treatment （TOAST）. Two single-nucleotide polymorphisms （SNPs） covering ALOX5AP were genotyped. RESULTS： The genotype frequencies of TG of the SNPs rs17222919 located in the promoter of the ALOX5AP gene were significantly higher in patients with ischemic stroke than in controls （OR＊=1.34, 95%C1＊=1.02-1.75）, especially in patients with ischemic stroke caused by small-artery occlusion （SAO） （OR＊=1.40, 95%C1＊=1.02-1.93）. Meanwhile, the genotype frequencies of TG and TG/ GG were higher in female patients than in the controls. After specification, the genotype frequencies of TG and TG/GG were higher in the patients than in controls with hypertension. The genotype frequencies of AG and AG/GG of the SNPs rs9579646 located in the intron of the ALOX5AP gene were higher in the controls than in the patients. After specification, the genotype frequencies of TG were higher in the controls than patients without hypertension. CONCLUSIONS： The present study suggests that sequence variants in the ALOX5AP gene are significantly associated with ischemic stroke.

Relationship between serum S-100 protein level and ischemic damage degree in patients with acute cerebral infarction

Objective: To investigate the time course of serum S-100 concentrations of patients with acute cerebral infarction,and their relation with the clinical data and the prognosis. Methods: Serum S-100 levels were serially determined in 36 patients with acute cerebral infarction within 12 h, at 24 h and day 2, 3, 4, 5, 7 and 10 after acute cerebral infarction and in 20 age- and sex-matched control subjects. An S-100 content assay was performed using a two-site radioimmunoassay technique. The clinical status was assessed using NIH Stroke Scale. The functional deficit at 4 weeks after acute cerebral infarction was scored using the modified Rankin scale. A cranial computed tomography was performed initially. Results: Elevated concentrations of S-100 (>0.2 μg/L) were observed in 29 of 36 patients with acute cerebral infarction,but none of the control subjects. The S-100 peak levels were at day 2 and 3 after acute cerebral infarction and were significantly high in those patients with severe neurological deficit at admission, with extensive infarction or with space-occupying effect of ischemic edema as compared with the rest of the populations. Conclusion: Serum S-100 level assay can be used as a peripheral marker of ischemic brain damage, and may be helpful for evaluation of therapeutic effects in acute ischemic stroke.

A study on the relationship between changes in serum hs-CRP levels and Chinese ischemic stroke subclassification

Objective: To study the relationship between changes in serum high sensitivity C-reactive protein (hs-CRP) levels and Chinese ischemic stroke subclassification (CISS), and explore the action mechanism of hs-CRP in the pathogenetic process of ischemic stroke. Methods: The serum hs-CRP level was measured in all subjects (including the healthy). As to 177 ischemic stroke patients, they were subclassified based on causes and pathogenesis to explore the relationship between the serum hs-CRP level and CISS. Results: The serum hs-CRP level in the ischemic stroke group was significantly higher than that in the control group (p < .05). The difference of the serum hs-CRP levels in different Chinese ischemic stroke subtypes was of statistical significance (p < .05). Conclusions: The level of serum hs-CRP is closely associated with the incidence of the ischemic stroke, and the difference of the serum hs-CRP levels in different Chinese ischemic stroke subtypes is of statistical significance.

Myrrh extract alleviated ROS-mediated ferroptosis through regulating TXNIP/NLRP3 axis in ischemic stroke

OBJECTIVE To investigate the neuroprotective effects and exact mechanisms of myrrh extract following cerebral ischemic stroke.METHODS Male rats were randomly divided into three groups:sham group,middle cerebral artery occlusion(MCAO)group and myrrh group.Morphological changes were assessed after 7 d of myrrh treatment.Microarray analysis with circulating mRNA was performed to identify differential gene expression profile,gene ontology and pathway enrichment analyses were carried out to predict the gene function.Gene co-expression and pathway networks were constructed to identify the potential targets.The markers of oxidative stress,inflammatory reaction and ferroptosis in the cerebral cortex were detected by ELISA assays.The identified hub pathways and genes were validated by western blotting,immunofluorescence and immunohistochemistry analyses.Neurons were exposed to transient oxygen-glucose deprivation(OGD)to model ischemia-like conditions.siRNA-TXNIP were transfected in OGD-induced neurons to explore the mechanism.RESULTS Myrrh extract significantly alleviated neurological deficits,infarct volume and histo⁃pathological damage in MCAO rats.A total of 2200 differentially expressed genes were identified among the three groups.Oxidation-reduction process,inflammatory response,ferroptosis were enriched as the significant gene ontology items.NOD-like receptor signaling were identified as the hub pathway based on the pathway relation network.TXNIP and NLRP3 were screened as the potential targets by a time sequence profile analysis.The levels of IL-1β,IL-18,TNF-α,MDA and TFR in brain tissues were increased while the CAT,SOD,GSH-px and GPX4 levels were significantly decreased in MCAO group.As expected,myrrh extract greatly reversed these changes.The similarly results were also observed in OGD treated neuron cells.The elevated expressions of TXNIP and NLRP3 induced by OGD were success⁃fully inhibited by myrrh treatment.Knockdown of TXNIP significantly alleviated OGD-induced ROS accumulation and oxidative stress,but the antioxidative effect of myrrh was impaired when TXNIP was absent in neuron cells.In addition,knockdown of TXNIP significantly decreased the expression of NLRP3 and increased the expression of GPX4 in OGDinduced neuron cells.However,myrrh treatment scarcely changed the expressions of NLRP3 and these ferroptosis markers in siRNA-TXNIP pretreated cells,compared with the siRNA-TXNIP alone treatment group.Therefore,these data demonstrated that the neuroprotective effect of myrrh extract was dependent on TXNIP-NLRP3 axis.CONCLU⁃SION Thatmyrrh extract exerts neuroprotective property through alleviated ROS-mediated ferroptosis by regulating the TXNIP/NLRP3 axis in ischemic stroke.Myrrh extract could be considered as a promising candidate for the treatment of ischemic stroke.

Study on Related Factors of Aspirin Resistance in Acute Ischemic Stroke

Objective:To study the related factors of aspirin resistance(AR)in acute ischemic stroke.Methods:A total of 138 patients with acute ischemic stroke treated in hospital affiliated to Xuzhou medical university from August 2016 to August 2018 were the study subjects,examine his medical data from the past.They were divided into the AR group(40 cases)and the non-AR group(98 cases)according to whether AR appears.Gender,disease history,biochemical indicators and etc.were compared between the two groups.The independent risk factors of AR were investigated using univariate analysis and logistic regression analysis.Results:40 cases of AR occurred in 138 patients,with an incidence rate of 28.99%.Diabetes,platelet count(PLT),microRNA-19a(m iR-19a)expression,smoking,high-sensitivity C-reactive protein(hs-CRP),Low-density lipoprotein cholesterol(LDL-C),fibrinogen(FIB)and age difference between the AR group and non-AR group was statistically significant(P<0.05).Gender,hypertension,uric acid(UA),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),homocysteine(Hcy),total cholesterol(TC),and alanine aminotransferase(ALT)between the two groups were not significantly different(P>0.05).Logistic regression analysis showed that the independent risk factors for AR in acute ischemic stroke were diabetes(OR=2.773,95%CI:1.102~5.065,P=0.025),miR-19a(OR=3.021,95%CI:1.322~6.545,P=0.021),hs-CRP(OR=2.719,95%CI:1.301~5.022,P=0.028)and smoking(OR=1.983,95%CI:1.114~3.887,P=0.040).Conclusion:The incidence of AR is higher in acute ischemic stroke.Risk factors include diabetes,miR-19a expression,hs-CRP,smoking,etc.Clinical intervention measures can be taken to reduce the risk of AR and improve acute ischemic stroke prognosis.