Aldehyde Dehydrogenase Isoform 1 Predicts a Poor Prognosis of Acute Cerebral Infarction.

To investigate the prognostic potential of serum aldehyde dehydrogenase isoform 1 (ALDH1) level in acute cerebral infarction, and the molecular mechanism in mediating neurological deficits, a total of 120 acute cerebral infarction cases within 72 h of onset were retrospectively analyzed. Serum ALDH1 level in them was detected by qRT-PCR. Receiver operating characteristic (ROC) and Kaplan-Meier curves were depicted for assessing the diagnostic and prognostic potentials of ALDH1 in acute cerebral infarction, respectively. An in vivo acute cerebral infarction model in rats was established by performing MCAO, followed by evaluation of neurological deficits using mNSS and detection of relative levels of ALDH1, Smad2, Smad4, and p21 in rat brain tissues. Pearson's correlation test was carried out to verify the correlation between ALDH1 and mNSS and relative levels of Smad2, Smad4, and p21. Serum ALDH1 level increased in acute cerebral infarction patients. A high level of ALDH1 predicted a poor prognosis of acute cerebral infarction patients. In addition, ALDH1 was sensitive and specific in distinguishing acute cerebral infarction cases, presenting a certain diagnostic potential. mNSS was remarkably higher in acute cerebral infarction rats than that of controls. Compared with sham operation group, relative levels of ALDH1, Smad2, and Smad4 were higher in brain tissues of modeling rats, whilst p21 level was lower. ALDH1 level in brain tissues of modeling rats was positively correlated to mNSS, and mRNA levels of Smad2 and Smad4, but negatively correlated to p21 level. Serum ALDH1 level is a promising prognostic and diagnostic factor of acute cerebral infarction, which is correlated to 90-day mortality. Increased level of ALDH1 in the brain of cerebral infarction rats is closely linked to neurological function, which is associated with the small mothers against decapentaplegic (Smad) signaling and p21.

Relationship between adiponectin multimer levels and subtypes of cerebral infarction.

AIM: Serum adiponectin levels are decreased in patients with cerebral infarction. Adiponectin in circulation exists in three isoforms: high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW) adiponectin. We measured serum levels of total adiponectin and adiponectin multimers (HMW, MMW, and LMW) in patients with cerebral infarction and compared the serum levels of the three adiponectin multimers in stroke subtypes. We also evaluated the clinical value of adiponectin multimer levels as a biomarker for cerebral infarction. METHODS: We assessed a total of 132 patients with cerebral infarctions. The serum levels of total and adiponectin multimers were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The total and HMW adiponectin levels were significantly lower in atherothrombotic infarction (AI) than in cerebral embolism (CE) (total, p < 0.05; HMW, p < 0.05). In male patients, the MMW adiponectin level was significantly lower in the lacunar infarction (LI) group than in the AI group (p < 0.05). The LMW adiponectin level was significantly lower in the AI group than in the LI and CE groups (LI, p < 0.001; CE, p = 0.001). However, there were no significant differences in adiponectin multimer levels among the stroke subtypes in female subjects. Additionally, in female patients with AI and LI, the LMW adiponectin levels were negatively associated with C-reactive protein (CRP; AI, p < 0.05; LI, p < 0.05). CONCLUSION: These findings suggest that a decrease in adiponectin is associated with AI and that serum LMW adiponectin level represents a potential biomarker for AI.

Predictive serum biomarkers of patients with cerebral infarction.

OBJECTIVES: Stroke is the third most common cause of death and also causes seizures and disability. Biomarkers are abnormal signal indicators at the biological level that are present before the organism is seriously affected and are more sensitive to early diagnosis than are traditional imaging methods. Early diagnosis of stroke can prevent the progression of the disease. However, there are currently no widely accepted biomarkers for stroke that have been applied clinically. METHODS: A serum metabonomics method based on ultra-high-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF/MS) was used to identify potential biomarkers and metabolic pathways of cerebral infarction. The receiver-operating characteristic (ROC) curve was used to verify the diagnostic and classification abilities of the biomarkers, and a support vector machine (SVM) model was developed for the prediction of cerebral infarction. RESULTS: Principal component analysis revealed a clear separation between the normal and cerebral infarction groups. A total of 13 potential serum biomarkers were identified, which were mainly involved in linoleic acid metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; tyrosine metabolism; arachidonic acid metabolism; and fatty acid biosynthesis. The ROC curve analysis showed that the potential biomarkers had high specificity and sensitivity for the diagnosis of cerebral infarction. The SVM model had good diagnostic ability and could accurately distinguish the control group from the cerebral infarction group. DISCUSSION: The metabonomics approach may be a useful bioanalytical method for understanding the pathophysiology of cerebral infarction and may provide an experimental basis for the development of clinical biomarkers for stroke.

Adenosine A1R/A3R (Adenosine A1 and A3 Receptor) Agonist AST-004 Reduces Brain Infarction in a Nonhuman Primate Model of Stroke.

BACKGROUND AND PURPOSE: Treatment with A1R/A3R (adenosine A1 and A3 receptor) agonists in rodent models of acute ischemic stroke results in significantly reduced lesion volume, indicating activation of adenosine A1R or A3R is cerebroprotective. However, dosing and timing required for cerebroprotection has yet to be established, and whether adenosine A1R/A3R activation will lead to cerebroprotection in a gyrencephalic species has yet to be determined. METHODS: The current study used clinical study intervention timelines in a nonhuman primate model of transient, 4-hour middle cerebral artery occlusion to investigate a potential cerebroprotective effect of the dual adenosine A1R/A3R agonist AST-004. Bolus and then 22 hours intravenous infusion of AST-004 was initiated 2 hours after transient middle cerebral artery occlusion. Primary outcome measures included lesion volume, lesion growth kinetics, penumbra volume as well as initial pharmacokinetic-pharmacodynamic relationships measured up to 5 days after transient middle cerebral artery occlusion. Secondary outcome measures included physiological parameters and neurological function. RESULTS: Administration of AST-004 resulted in rapid and statistically significant decreases in lesion growth rate and total lesion volume. In addition, penumbra volume decline over time was significantly less under AST-004 treatment compared with vehicle treatment. These changes correlated with unbound AST-004 concentrations in the plasma and cerebrospinal fluid as well as estimated brain A1R and A3R occupancy. No relevant changes in physiological parameters were observed during AST-004 treatment. CONCLUSIONS: These findings suggest that administration of AST-004 and combined A1R/A3R agonism in the brain are efficacious pharmacological interventions in acute ischemic stroke and warrant further clinical evaluation.

Therapeutic effect of Danhong injection on diabetic patients with cerebral infarction and its influence on vascular endothelial function and hemodynamics.

To investigate the therapeutic effect of Danhong injection on diabetic patients with cerebral infarction and its influence on vascular endothelial function and hemodynamic level. A total of 100 diabetic patients with cerebral infarction admitted to our hospital from November 2019 to November 2020 were identified as the research subjects and randomly divided into a control group given routine treatment and a study group treated with Danhong injection, with 50 cases in each group. The efficiency of the two groups on vascular endothelial function, blood glucose level, National Institute of Health Stroke Scale (NIHSS) score, the incidence of adverse reactions, and hemodynamic indicators were compared. Most (98%) of patients in the study group displayed effective outcomes, which was significantly better than that in the control group. The study group outperformed the control study group in the vascular endothelial function, blood glucose level, NIHSS score and hemodynamic indicators (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Danhong injection obtains a promising therapeutic effect on diabetic patients with cerebral infarction, as it significantly improves the vascular endothelial function and hemodynamic level.

Early-stage serum Stanniocalcin 1 as a predictor of outcome in patients with aneurysmal subarachnoid hemorrhage.

ABSTRACT: Stanniocalcin-1 (STC1) takes part in anti-inflammatory and anti-oxidative processes, thus demonstrating neuroprotective properties. Early brain injuries associated with initial subarachnoid hemorrhage typically led to secondary cerebral infarction and poor outcomes. This retrospective study aimed to clarify the clinical significance of serum STC1 level in patients with subarachnoid hemorrhage.We collected demographic information, comorbidities, neurological status in detail. All blood samples were collected on admission. Enzyme-linked immunosorbent assay kits were used to detect the serum level of STC1. Spearman analysis was used to explore the relationship between STC1 and clinical severity. Multivariate logistic regression was used to investigate the prognostic role of STC1 in patients with aneurysmal subarachnoid hemorrhage (aSAH). Receiver operating characteristic curve was performed to investigate the power of STC1 in predicting outcome in aSAH patients.Serum STC1 concentration was significantly higher in aSAH patients than in healthy individuals. Serum concentration of STC1 positively correlated with Hunt-Hess grade (r = 0.62, P < .01) and Fisher grade (r = 0.48, P < .01), and negatively correlated with Glasgow Coma Scale on admission (r = -0.45, P < .01). Patients with delayed cerebral ischemia (DCI) had higher level of serum STC1 than those without DCI (13.12 ±â€Š1.44 vs 8.56 ±â€Š0.31, P < .01). Moreover, patients with poor outcome had higher concentration of STC1 than patients with good outcome (11.82 ±â€Š0.62 vs 8.21 ±â€Š0.35,P < 0.01). Results of univariate and multivariate logistic analysis revealed that Hunt-hess III-IV, DCI, and high STC1 level were independent risk factors associated with poor outcome of patients with aSAH. Further analysis revealed that combination of STC1 with Hunt-hess grade was more superior to 2 indicators alone in predicting clinical outcome of aSAH patients.STC1 can be used as a novel biomarker in predicting outcome of patients with aSAH, especially when combined with Hunt-hess grade.

Serum anti-SERPINE1 antibody as a potential biomarker of acute cerebral infarction.

The presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.

The Prognostic Value of Serum Uric Acid in Hospitalized Patients with Acute Cerebral Infarction.

BACKGROUND: Previous studies reported that the level of serum uric acid (SUA) was an important risk factor for acute cerebral infarction (ACI). However, the prognostic value of SUA levels in hospitalized patients with ACI has not been fully elucidated. The aim of this study was to investigate whether the SUA level on admission was associated with subsequent mortality in hospitalized patients with ACI. METHODS: The clinical data of ACI patients obtained from December 2017 to December 2019 were retrospectively reviewed. χ 2 and Kaplan-Meier methods were used to compare the clinical differences and overall survival between patients with or without hyperuricemia, respectively. Univariate and multivariate analyses were used to identify independent prognoses. RESULTS: In the total population, the in-hospital mortality of the hyperuricemia group was significantly higher than that of the normal uric acid group (P = 0.006). In the abnormal renal function group, the in-hospital mortality among the hyperuricemia group was significantly higher than the normal uric acid group (P = 0.002). However, there was no statistical difference of in-hospital mortality between the two groups in the normal renal function group (P = 0.321). Univariate and multivariate analyses showed that a previous history of diabetes (P = 0.018), hyperuricemia (P = 0.001), and National Institutes of Health Stroke Scale (NIHSS) score on admission (P ≤ 0.001) were independent factors for all samples. The hyperuricemia (P = 0.003) on admission were independent factors for patients with abnormal renal function. CONCLUSIONS: In ACI patients with abnormal renal function, hyperuricemia may be associated with higher in-hospital mortality than patients with normal uric acid, and hyperuricemia may be an independent associated factor for in-hospital death in the subgroup patients.

Analysis of Brain Natriuretic Peptide Levels after Traumatic Acute Subdural Hematoma and the Risk of Post-Operative Cerebral Infarction.

Traumatic acute subdural hematoma (aSDH) is associated with a high mortality rate caused by post-operative cerebral infarction. Recently, brain natriuretic peptide (BNP) was considered a reliable biomarker in the acute phase of traumatic brain injuries. We therefore aimed in this study to analyze BNP levels on admission, identify the predictors of their elevation, and assess the relationship between BNP and the risk of post-operative cerebral infarction. Patients with isolated, unilateral, traumatic aSDH who were admitted to our department between July 2017 and May 2020 were enrolled in this study. On admission, cranial computer tomography (CCT) and BNP sampling were simultaneously performed. Additionally, the time between head trauma and BNP sampling (TTS) was assessed. Admission radiographic variables included hematoma volumes, midline shift, and degree of brain edema. Cerebral infarction was detected on postoperative CCT. In total, 130 patients were included in this study. Surgical treatment was performed in 82.3% (n = 107) of cases. The multiple regression analysis showed that larger hematoma volumes (p = 0.032) and advanced age (p = 0.005) were independent predictors of elevated BNP when TTS <24 h. The binomial logistical regression analysis identified BNP with a cutoff value of <29.4 pg/mL (TTS = 3-12 h, adjusted odds ratio [aOR] = 16.5, p = 0.023) as an independent predictor of post-operative cerebral infarction. Elevated BNP levels in the first 24 h post-trauma were related to larger hematoma volumes and advanced age. Further, an increased risk of post-operative cerebral infarction was identified in patients with lower BNP levels in the post-traumatic period 3-12 h.

A Single-Center Clinical Study to Evaluate Shenxiong Glucose Injection Combined with Edaravone in the Treatment of Acute Large-Area Cerebral Infarction.

OBJECTIVES: To investigate the clinical efficacy and safety of Shenxiong glucose injection combined with edaravone in the treatment of acute large-area cerebral infarction. METHODS: 156 patients with acute large-area cerebral infarction admitted to our hospital from July 2015 to January 2017 were included in the analysis. The patients were randomly divided into experimental (78 cases) and control (78 cases) groups. Patients in the experimental group were given a 30 mg injection of edaravone in 100 ml of 0.9% sodium chloride solution by intravenous drip, twice a day within 30 minutes and a daily 200 ml injection of Shenxiong glucose by intravenous drip. Patients in the control group were given a 30 mg edaravone injection in 100 ml of 0.9% sodium chloride solution by intravenous drip, twice a day, and the drip was completed within 30 minutes. Patients in both groups were treated for 2 weeks. The levels of fibrinogen (FIB), D-dimer, interleukin 6 (IL-6), P-selectin (CD62P), and hypersensitive C-reactive protein (hs-CRP) were evaluated in the two groups of patients. Neurological disability was evaluated using the modified Rankin scale (mRS) and the neurological deficit score (National Institute of Health Stroke Scale, NIHSS). Adverse reactions to the treatments were also recorded. RESULTS: No significant differences in age, gender, medical histories, and blood biochemical indices were observed between the two groups before treatment (P > 0.05). After treatment, the levels of FIB, D-dimer, IL-6, CD62P, and hs-CRP were significantly lower following treatment and compared to the control group (P < 0.05). Also, the mRS and NIHSS scores were significantly lower after treatment and compared with the control group (P < 0.05). The total effective rate of the treatment in the experimental group was significantly higher compared to the control group (P < 0.05). During the treatment period, no obvious adverse reactions were observed in the two groups of patients. CONCLUSIONS: In addition to the routine basic treatment of acute large-area cerebral infarction, the addition of Shenxiong glucose injection combined with edaravone injection can improve platelet aggregation and reduce inflammation by affecting P-selectin, D-dimer, and FIB. This treatment approach promotes the recovery of nerve defect function without obvious adverse reactions in patients with acute large-area cerebral infarction.

Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction.

BACKGROUND: Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. METHODS: In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991-1993) were also examined. RESULTS: The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case-control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. CONCLUSIONS: ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.

The relation between aortic arch branching types and the location of large vessel occlusion in cardioembolic stroke.

Cardiac embolism is the leading etiology of ischemic strokes. There are arguments about the left-right propensity of cardioembolic strokes.This study aimed to reveal the relationship between the different aortic arch types and the location of large vessel occlusion (LVO) in cardioembolic stroke.We retrospectively identified all patients with acute ischemic stroke admitted to our comprehensive stroke center who had medium- to high-risk cardioembolicsources according to the TOAST classification.Only those with LVO and available images of the aortic arch were included. Patients were classified into 3 groups according to the aortic arch types: Type I (n = 44), Type II (n = 105), Type III (n = 36).The thrombus was divided into large thrombus or small thrombus based on the location of LVO.Overall, left-sided strokes (50.8%) were almost equal to right-sided (49.2%). There was a growing tendency for the percentage of left-sided infarcts with advancement of the aortic arch types either in the total cases or in the atrial fibrillation cases, with no statistical difference between the 3 aortic arch types.In type III aortic arch, left-sided strokes (69.0%) were twice than right-sided (31%) in large thrombus (P < 0.05), while right-sided strokes (85.7%) were more common than left-sided (14.3%) in small thrombus (P < 0.05).Conversely, in type Ⅰ and II aortic arches, left-sided strokes were more common than right-sided in small thrombus, while right-sided strokes were more common than left-sided in large thrombus (P < 0.05). The left-right propensity of cardioembolic stroke is related to the proximity of clot lodging in different aortic arch types.

Predictive Value of Degranulating Factors of Neutrophils in Massive Cerebral Infarction.

Massive cerebral infarction (MCI) is a life-threatening disease and may lead to cerebral herniation. Neutrophil degranulation contributes to ischemic injury in the early stage. To investigate whether neutrophil degranulating factors can predict cerebral herniation and the long-term prognosis of patients with MCI and to investigate the relationship between neutrophil degranulation and blood brain barrier (BBB) damage. In this case-control study of 14 MCI patients, we divided the patients into a cerebral hernia group and no cerebral hernia group according to whether they developed cerebral herniation within 5 days. The prognosis of MCI patients was assessed using the Modified Rankin Scale (mRS) score at 6 months, which was the primary end point. The composition of white blood cells (WBC) and degranulating factors for neutrophils in the plasma of MCI patients was determined on days 2 and 4. Baseline characteristics were comparable in both groups. The neurological functional scores and long-term prognosis showed no difference between patients with or without cerebral herniation, while the mortality rate of the cerebral hernia group in the short term was higher (P < 0.05). The WBC count, neutrophil to lymphocyte ratio (NLR) and plasma myeloperoxidase (MPO) levels of patients with cerebral hernia were significantly higher than those of patients without cerebral hernia (all P < 0.05). MPO is a better predictor of cerebral herniation, and the NLR showed superior predictive value in the prognosis of MCI patients. neutrophil degranulation may play an important role in malignant cerebral hernia during MCI. These data suggest that, MPO and the NLR might be predictive factors for cerebral herniation and the prognosis of MCI patients.

The Value of Combined Detection of D-dimer and CD62p in Judging the Severity of Acute Cerebral Infarction and Short-Term Prognosis.

OBJECTIVE: To explore the value of combined detection of peripheral blood P-selectin (CD62p) and D-dimer (D-dimer) in the judgment of acute cerebral infarction severity and short-term prognosis. METHODS: 268 patients with acute cerebral infarction from February 2015 to February 2019 were selected as the observation group. According to the National Institute of Health stroke scale, there were 90 cases (SCI group), 88 cases (MOCI group), and 90cases (MICI group) in the severe, moderate, and mild cerebral infarction groups, respectively. In the same period, 80 cases of healthy people served as the Normal group. Use flow cytometry to detect CD62p in peripheral blood and magnetic bead method to detect D-dimer level within 24 hours of onset. Logistic regression was used to analyze whether the two are factors affecting the short-term prognosis of acute cerebral infarction, and the ROC curve was drawn to evaluate the value of the combined detection of the two in the short-term prognosis of patients with acute cerebral infarction. RESULTS: Peripheral blood D-dimer and CD62p levels (2.95 ± 0.76 ng/l, 34.03 ± 5.29 ng/l) in the SCI group were higher than those in the MOCI group (2.30 ± 0.51 ng/l, 27.58 ± 5.56 ng/l) and the MICI group (1.87 ± 0.40 ng/l, 19.60 ± 3.98 ng/l); the difference between the groups was statistically significant (P < 0.05). Logistic regression analysis showed that D-dimer and CD62p were independent risk factors affecting the poor prognosis of patients with acute cerebral infarction (OR values were 3.752 and 1.213, and 95% CI were 1.612-7.934 and 1.093-1.342, respectively, both P < 0.05). The AUC of D-dimer combined with CD62p for predicting poor prognosis of acute cerebral infarction is 0.859, which is better than D-dimer and CD62p alone. CONCLUSION: Peripheral blood D-dimer combined with CD62p detection is helpful for the risk stratification and short-term prognosis assessment of patients with acute cerebral infarction. Clinical detection is of great significance for the prevention and monitoring of disease development.

Serum Exosomal microRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ.

Acute cerebral infarction (ACI) possesses high mortality. Exosomes present in serum have potential application value in ACI diagnosis. This study investigated the mechanism of serum exosomes in ACI. Serum exosomes isolated from ACI patients and normal people were identified and then injected into the established middle cerebral artery occlusion (MCAO) rat model to evaluate cerebral injury and inflammation. Exosomal microRNA (miR)-27-3p expression was detected and interfered to analyze rat cerebral inflammation. The binding relationship between miR-27-3p and PPARγ was predicted and verified. The lipopolysaccharide (LPS)-treated microglia model was established and intervened with miR-27-3p to detect PPARγ, Iba-1, and inflammation-related factor expressions. After overexpressing PPARγ, rat cerebral inflammation was evaluated. The clinical significance of serum exosomal miR-27-3p in ACI was evaluated. Serum exosomes from ACI patients caused exacerbated MCAO rat cerebral injury and poor behavior recovery, as well as promoted cerebral inflammation. Serum exosomal miR-27-3p deepened rat brain inflammation. miR-27-3p targeted PPARγ to promote microglia activation and inflammation-related factor expressions in MCAO rats, and overexpressing PPARγ attenuated MCAO rat cerebral inflammation. Serum exosomal miR-27-3p promised to be a biomarker for ACI. We proved that serum exosomes from ACI patients aggravated ACI patient cerebral inflammation via the miR-27-3p/PPARγ axis.

Influence of butyphthalide combined with urinary kallikrein in ACI treatment on neuro-cytokines and vascular endothelial function and its clinical effect.

Objective: To study the influence of butyphthalide combined with urinary kallikrein in acute cerebral infarction (ACI) treatment on neuro-cytokines and indicators of vascular endothelial function, observe the curative effect and adverse effects, and discuss its safety and feasibility.Method: 110 ACI patients were chosen as the objects, and classified into observation group (55 cases) and control group (55 cases) according to the method of random number table. Butyphthalide injection combined with urinary kallikrein was adopted for the observation group based on conventional treatment, while cinepazide maleate injection combined with alprostadil injection was applied for the control group based on conventional treatment. The following indicators of both groups were compared before and after treatment: neurotrophic factor (NTF), nerve growth factor (NGF), neuron specific enolase (NSE); content of CXC chemotactic factor ligand 16 (CXCL16), soluble CD ligand (CD40L), Fibulin-5 and high mobility group box B1 (HMGB1); the content of indicators of vascular endothelial function including plasma endothelin -1 (ET-1) and no therapeutic effects and adverse effects were recorded.Results: NSE of both groups after treatment decreased obviously, and the content of NTF and NGF increased obviously. NSE content of observation group was lower than that of control group. NTF content and NGF content of observation group were higher than those of control group. The differences had statistical significance (p < 0.05). The levels of CXCL16, CD40L, Fibulin-5 and HMGB1 declined obviously, compared with pre-treatment, and the levels of observation groups were significantly lower than those of control grip. The differences had statistical significance (p < 0.05). ET-1 level rose significantly after treatment, and NO level declined obviously after treatment. ET-1 level of observation group was significantly higher than that of control group, and NO level of observation group was significantly lower than that of control group. The difference had statistical significance (p < 0.05). Clinical effect of observation group was significantly higher than that of control group. The difference had statistical significance (p < 0.05). The comparison difference of both groups in the occurrence rate of adverse effects had no statistical significance (p > 0.05).Conclusion: The application of butyphthalide combined with urinary kallikrein in ACI treatment can effectively inhibit secretion and release of neuro-cytokines, and improve patients' vascular endothelial function, with significant treatment effect and high safety. Therefore, it deserves to be promoted clinically.

Relationship between cobalt transporter II gene rs9606756 site mutant and serum homocysteine level and recurrent cerebral infarction in young and middle-aged people.

BACKGROUND: This study aimed to investigate the effect of cobalt transporter II gene (rs1801198, rs2301957, rs9606756) polymorphism on serum homocysteine level and its correlation with young and middle recurrent cerebral infarction. METHODS: A total of 348 young and middle-aged patients with cerebral infarction admitted to The Third Affiliated Hospital of Qiqihar Medical University from January 2017 to March 2018 were enrolled. The patients were divided into recurrent and non-recurrent groups according to follow-up. DNA was extracted from the peripheral blood of patients, and the DNA samples were genotyped by IlluminaBeadArray technology to detect the gene polymorphisms of cobalt transporter II (TCN2) sites (rs1801198, rs2301957, rs9606756), and the homocysteine (hcy) level was determined by cyclic enzymatic method. VitB12 and folate levels were measured by chemiluminescence immunoassay, and holo transcobalamin (holoTC) expression levels were detected by enzyme-linked immunosorbent assay. RESULTS: The frequency of alleles of rs9606756 mutation in the recurrent group was higher than that in the non-recurrent group (P<0.05), and the Hcy level in rs9606756 locus genotype AG+GG was significantly higher than the AA genotype in the recurrent group (P=0.031). Pearson correlation analysis showed that Hcy levels were associated with different genotypes of rs9606756 in the recurrent group (r=0.483, P=0.0003). The rs9606756 allele AA in SH-SY5Y cells was replaced with GG by point mutation experiment. The Hcy metabolism levels of wild and mutant cells were detected. The accumulation level of Hcy in the mutant group was significantly increased (P=0.007). The holoTC in the supernatant was significantly reduced in the mutant (P=0.032). CONCLUSIONS: The TCN2 gene rs9606756 mutation is closely related to the level of Hcy metabolism in young and middle-aged patients, which may affect the recurrence of cerebral infarction. It is of great significance to further understand the pathogenesis, prevention and treatment of recurrent cerebral infarction in young and middle-aged patients.

Hypocaloric Diet Initiated Post-Ischemia Provides Long-Term Neuroprotection and Promotes Peri-Infarct Brain Remodeling by Regulating Metabolic and Survival-Promoting Proteins.

Calorie restriction confers post-ischemic neuroprotection, when administered in a defined time window before ischemic stroke. How a hypocaloric diet influences stroke recovery when initiated after stroke has not been investigated. Male C57BL6/j mice were exposed to transient intraluminal middle cerebral artery occlusion. Immediately post-ischemia, mice were randomized to two groups receiving moderately hypocaloric (2286 kcal/kg food) or normocaloric (3518 kcal/kg) diets ad libitum. Animals were sacrificed at 3 or 56 days post-ischemia (dpi). Besides increased low density lipoprotein at 3 days and reduced alanine aminotransferase and increased urea at 56 days, no alterations of plasma markers were found in ischemic mice on hypocaloric diet. Body weight mildly decreased over 56 dpi by 7.4%. Hypocaloric diet reduced infarct volume in the acute stroke phase at 3 dpi and decreased brain atrophy, increased neuronal survival and brain capillary density in peri-infarct striatum and reduced motor coordination impairment in tight rope tests in the post-acute stroke phase over up to 56 dpi. The abundance of brain-derived neurotrophic factor, the NAD-dependent deacetylase and longevity protein sirtuin-1, the anti-oxidant glutathione peroxidase-3, and the ammonium detoxifier glutamine synthetase in the peri-infarct brain tissue was increased by hypocaloric diet. This study shows that a moderately hypocaloric diet that is initiated after stroke confers long-term neuroprotection and promotes peri-infarct brain remodeling.

Plasma miR-409-3p promotes acute cerebral infarction via suppressing CTRP3.

Abnormal expression of miR-409-3p has been found in several neurodevelopmental disorders, but whether it is dysregulated in the patients with acute cerebral infarction (ACI) has not been evaluated. The current study mainly focused on the clinical significance and the underlying mechanism of plasma miR-409-3p in the progression of ACI. The level of plasma miR-409-3p was determined in ACI patients (n = 80) and healthy controls (n = 30). Pearson correlation assay was performed to evaluate the association and cardiovascular risk factors. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of plasma miR-409-3p levels in patients with ACI. Dual luciferase reporter assay and western blot were performed to determine the possible target gene of miR-409-3p. Our data showed that the expression of plasma miR-409-3p in the ACI group was higher than that in the healthy controls. Furthermore, Pearson correlation analysis indicated a positive correlation between plasma miR-409-3p and the NIHSS score. ROC analysis indicated that plasma miR-409-3p could differentiate plasma miR-409-3p in ACI patients from healthy controls. Then, we explored the possible target genes of miR-409-3p. Interestingly, C1q and TNF-related 3 (CTRP3), a novel adipose tissue-derived secreted factor, was found to be a target gene of miR-409-3p. We found that knockdown of CTRP3 significantly induced PC12 cell apoptosis, even in PC12 cells transfected with miR-409-3p inhibitor. These data suggested that miR-409-3p induced PC12 cell apoptosis by targeting CTRP3. Altogether, elevated plasma miR-409-3p is correlated with disease severity and may be efficient for the early diagnosis of ACI.