Ultrasensitive PD-L1-Expressing Exosome Immunosensors Based on a Chemiluminescent Nickel-Cobalt Hydroxide Nanoflower for Diagnosis and Classification of Lung Adenocarcinoma.

Programmed death ligand-1 (PD-L1)-expressing exosomes are considered a potential marker for diagnosis and classification of lung adenocarcinoma (LUAD). There is an urgent need to develop highly sensitive and accurate chemiluminescence (CL) immunosensors for the detection of PD-L1-expressing exosomes. Herein, N-(4-aminobutyl)-N-ethylisopropanol-functionalized nickel-cobalt hydroxide (NiCo-DH-AA) with a hollow nanoflower structure as a highly efficient CL nanoprobe was synthesized using gold nanoparticles as a "bridge". The resulting NiCo-DH-AA exhibited a strong and stable CL emission, which was ascribed to the exceptional catalytic capability and large specific surface area of NiCo-DH, along with the capacity of AuNPs to facilitate free radical generation. On this basis, an ultrasensitive sandwich CL immunosensor for the detection of PD-L1-expressing exosomes was constructed by using PD-L1 antibody-modified NiCo-DH-AA as an effective signal probe and rabbit anti-CD63 protein polyclonal antibody-modified carboxylated magnetic bead as a capture platform. The immunosensor demonstrated outstanding analytical performance with a wide detection range of 4.75 × 103-4.75 × 108 particles/mL and a low detection limit of 7.76 × 102 particles/mL, which was over 2 orders of magnitude lower than the reported CL method for detecting PD-L1-expressing exosomes. Importantly, it was able to differentiate well not only between healthy persons and LUAD patients (100% specificity and 87.5% sensitivity) but also between patients with minimally invasive adenocarcinoma and invasive adenocarcinoma (92.3% specificity and 52.6% sensitivity). Therefore, this study not only presents an ultrasensitive and accurate diagnostic method for LUAD but also offers a novel, simple, and noninvasive approach for the classification of LUAD.

Epidemiological and Clinical Characteristics of Sporadic Creutzfeldt-Jakob Disease: A Retrospective Study in Eastern China.

Objective: We aimed to characterize the epidemiological and clinical characteristics of sporadic Creutzfeldt-Jakob disease (sCJD) in eastern China in this retrospective study. Methods: This study enrolled 67 patients with sCJD hospitalized in a grade-A tertiary hospital in eastern China from January 2010 to January 2020. Demographic data, clinical symptoms, brain magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid (CSF) 14-3-3 protein test, polymerase chain reaction (PCR), and DNA sequence determination of genes were collected and analyzed. Results: There were 62 patients with probable sCJD and 5 patients with possible sCJD. Male (28 cases) to female (39 cases) ratio was 1:1.39. Mean age at disease onset was 64.42 ± 9.00 years (range: 29-88 years), and mean survival time was 9.39 ± 12.58 months (range: 1-60 months for patients who received the follow-ups). The most common onset symptoms were dementia (49.25%), movement disorder (44.78%), and visual disturbance (22.39%), while the most frequent clinical manifestations were language disorders (74.63%), ataxia (70.15%), and myoclonus (70.15%). The positive rates of brain MRI abnormalities, 14-3-3 protein in CSF, and periodic sharp wave complexes (PSWCs) on EEG were 84.90, 68.00, and 46.03%, respectively. The 14-3-3 protein positive (p = 0.033) and PSWCs on EEG (p = 0.020) acted as the favorable and unfavorable factor for over 1 year of survival time, respectively. Conclusions: There were some differences in epidemiological and clinical characteristics among patients in China and those of other countries. The prognosis and its influencing factors were relatively unexplored in China. The mean survival time of Chinese patients was longer than that of Caucasian patients but shorter than that of Japanese patients. The 14-3-3 protein in CSF and PSWCs on EEG were both closely related to the survival time. It is necessary to promote autopsy or biopsy to better understand sCJD in China.

Painful Diabetic Peripheral Neuropathy Study of Chinese Outpatients (PDNSCOPE): A Multicentre Cross-Sectional Registry Study of Clinical Characteristics and Treatment in Mainland China.

INTRODUCTION: This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices. METHODS: A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded. RESULTS: The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350). CONCLUSION: Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.

miR­183­5p attenuates cerebral ischemia injury by negatively regulating PTEN.

Cerebral ischemia is a common cerebrovascular disease caused by the occlusion of a cerebral blood vessel. MicroRNAs (miRNAs/miRs) are emerging regulators of various human diseases, including cerebral ischemia. Upregulation of miR­183­5p has been reported to alleviate liver injury induced by ischemia­reperfusion (I/R). However, the effect of miR­183­5p on cerebral ischemia injury remains unknown. The present study evaluated the effects of miR­183­5p on ischemia injury using ischemic models of mouse brains exposed to transient middle cerebral artery occlusion and Neuro­2A (N2A) neuroblastoma cells exposed to oxygen­glucose­deprivation (OGD) and subsequently reoxygenated. Ischemia was evaluated in mice using neurological function scores, cerebral edema, 2,3,5­triphenyltetrazoliumchloride, Nissl and Fluoro­Jade B staining assays. In addition, miR­183­5p expression, N2A cell viability and the expression levels of apoptosis­associated proteins were detected by quantitative PCR, Cell Counting Kit­8 assay, flow cytometry and western blotting. The association between miR­183­5p and phosphatase and tensin homolog (PTEN) was also confirmed by a luciferase reporter assay. The results revealed that miR­183­5p expression was decreased and brain damage was increased in ischemic mice compared with the sham group. Additionally, miR­183­5p levels were reduced, and apoptosis was increased in N2A cells exposed to ischemia compared with the control group. Following transfection with agomiR­183­5p, cerebral ischemic injury and apoptosis levels were reduced in the in vivo I/R stroke model and OGD­induced N2A cells. In addition, PTEN was determined to be a target of miR­183­5p following elucidation of a direct binding site. Overexpression of PTEN reversed the miR­183­5p­induced N2A cell apoptosis inhibition and survival after OGD. The results of the present study suggested that miR­183­5p reduced ischemic injury by negatively regulating PTEN, which may aid the development of a novel therapeutic strategy for cerebral ischemia.

AJAP1 affects behavioral changes and GABABR1 level in epileptic mice.

Adherens junction-associated protein-1 (AJAP1), also called SHREW1, was first discovered as a novel component of adherens junctions in 2004. In later studies, AJAP1 was found to suppress invasion and predict recurrence of some tumors. Apart from its function as a putative tumor suppressor, AJAP1 is still poorly understood. Schwenk et al. recently found that AJAP1 was tightly associated with the γ-Aminobutyric acid type B receptor subunit 1(GABABR1). It is well known that GABABR plays a vital role in epilepsy as an inhibitory transmitter receptor. Structurally adjacent, possibly functionally interacting, therefore, we hypothesize that AJAP1 participates in the onset and progression of epilepsy. We designed this experiment to investigate the expression and location of AJAP1 in temporal lobe epilepsy (TLE) patients and kainic acid(KA)-induced epilepsy animal models by immunofluorescence and Western blot analyses. We overexpressed and inhibited AJAP1 through lentiviruses in KA-induced models and observed the corresponding effects on epileptic animals. Double-label immunofluorescence showed that AJAP1 was expressed mainly in neurons. Western blot analysis revealed that AJAP1 expression was downregulated in the neocortex of TLE patients and the hippocampus and neocortex of epileptic animal models. The overexpression of AJAP1 can reduce the frequency of spontaneous seizures, whereas the inhibition of AJAP1 expression can increase the incidence rate. Our study demonstrated that AJAP1 may be involved in the pathogenic process of epilepsy and may represent a novel antiepileptic target.

Impaired Cerebral Autoregulation in Alzheimer's Disease: A Transcranial Doppler Study.

BACKGROUND: Vasculature changes have been observed in Alzheimer's disease (AD). AD-related vascular pathology might impair cerebral autoregulation (CA). OBJECTIVE: This study was designed to evaluate CA of AD patients by using transcranial doppler (TCD). METHODS: A total of 61 participants were included in the study, including 31 AD patients and 30 controls. The trend curves of cerebral blood flow velocities (CBFV), pulsatility index, and resistance index were obtained using TCD during supine-to-standing posture changes. CA was measured by the changes of CBFV curves during supine-to-standing test. RESULTS: There were two spikes named X spike and W spike that appeared in the CBFV curve when the subjects stood abruptly. The slope of the X spike descending branch, the slope of the W spike ascending branch, and the angle between X and W spikes (α angle), showed significant differences between the experimental and control groups (2.34±0.99 versus 3.15±1.61 cm/s2, p = 0.021; 2.31±0.81 versus 3.38±1.18 cm/s2, p < 0.001; and 52.71±20.26 versus 41.4±12.87 degrees, p = 0.012, respectively). ROC analysis showed that AUCαangle is 0.664 (p = 0.028) and that AUCSAB and AUCadjustedSAB are 0.775 and 0.738, respectively (both p < 0.001). CONCLUSIONS: Our study demonstrated that supine-to-standing TCD test is a valuable tool for the evaluation of CA in AD patients. Impaired CA in AD patients manifested as decreased efficiency of changes in the CBFV curve. Neurovascular units were involved in the pathogenesis of AD.

rs1234313 and rs45454293 are risk factors of cerebral arterial thrombosis, large artery atherosclerosis, and carotid plaque in the Han Chinese population: a case-control study.

BACKGROUND: Ischemic stroke is a leading cause of mortality and morbidity worldwide. Stenosis or blockage of an artery from atherosclerosis can cause insufficient cerebral blood supply, which leads to ischemic stroke. It has been reported that the polymorphisms of TNFSF4 (tumor necrosis factor super family member 4) are associated with multiple autoimmune diseases. However, it is still unclear whether TNFSF4 gene polymorphisms are associated with ischemic stroke in the Han Chinese population. Here we analyzed the association between TNFSF4 single nucleotide polymorphisms (SNPs) and cerebral arterial thrombosis in the Han Chinese population. METHOD: We consecutively recruited 481 patients with cerebral arterial thrombosis and 538 healthy controls. Neck ultrasonography and magnetic resonance imaging (MRI) were used to evaluate large artery atherosclerosis (LAA) and small vessel disease (SVD), as well as the thickness and calcification of carotid artery. DNA was purified from the peripheral blood samples. TNFSF4 SNPs, rs1234313 and rs45454293, were genotyped using PCR. RESULTS: rs1234313 SNP had a significant correlation with the LAA and SVD subtypes in allelic (G vs A), dominate (GG/GA vs AA) and genotypic (GA vs AA; GG vs AA) models, as well as with the calcification of carotid plaque in dominant (GG/GA vs AA, p = 0.022) and genotypic (GA vs AA, p = 0.01) models. rs45454293 SNP had a significant correlation with the LAA and SVD subtypes in allelic (G vs A) and genotypic models, as well as with the thick carotid plaque in allelic (G vs A, p = 0.01) model. CONCLUSION: TNFSF4 SNPs, rs1234313 and rs45454293, are associated with the risk of specific subtypes of cerebral arterial thrombosis in the Han Chinese population.

Clinical study on minimally invasive liquefaction and drainage of intracerebral hematoma in the treatment of hypertensive putamen hemorrhage.

OBJECTIVE: This study aims to compare the curative effect of different treatment methods of hypertensive putamen hemorrhage, in order to determine an ideal method of treatment; and to explore the curative effect of the application of soft channel technology-minimally invasive liquefaction and drainage of intracerebral hematoma in the treatment of hypertensive putamen hemorrhage. METHODS: Patients with hypertensive cerebral hemorrhage, who were treated in our hospital from January 2015 to January 2016, were included into this study. Patients were divided into three groups: minimally invasive drainage group, internal medical treatment group and craniotomy group. In the minimally invasive drainage group, puncture aspiration and drainage were performed according to different hematoma conditions detected in brain CT, the frontal approach was selected for putamen and intracerebral hemorrhage, and drainage was reserved until the hematoma disappeared in CT detection. Drug therapy was dominated in the internal medical treatment group, while surgery under general anesthesia was performed to remove the hematoma in the craniotomy group. RESULTS: Post-treatment neurological function defect scores in minimally invasive drainage group and internal medical group were 16.14 ± 11.27 and 31.43 ± 10.42, respectively; and the difference was remarkably significant (P< 0.01). Post-treatment neurological function defect scores in the minimally invasive drainage group and craniotomy group were 16.14 ± 11.27 and 24.20 ± 12.23, respectively; and the difference was statistically significant (P< 0.05). There was a remarkable significant difference in ADL1-2 level during followed-up in survival patients between the minimally invasive drainage group and internal medical treatment group (P< 0.01), and there was a significant difference in followed-up mortality between these two groups (P< 0.01). CONCLUSION: Clinical observation and following-up results revealed that minimally invasive drainage treatment was superior to internal medical treatment and craniotomy.

Protective effects and mechanism of TPX2 on neurocyte apoptosis of rats in Alzheimer's disease model.

We investigated the protective effects and mechanism of TPX2 on apoptosis of rat neurocytes. A total of 90 SD rats were randomly divided into the drug group, the control group and the blank group, with 30 rats in each group. The rats in the drug group and in the blank group were anesthetized with 10% chloral hydrate (at the dose of 0.5 ml/100 g) and Aß1-42, with the concentration of 5 µl (1 µg/µl), was injected in the exact position of bilateral hippocampal areas of rats to establish the model. The configured TPX2 inhibitors and edible benne oil were mixed and made into a suspension. After model establishment, the rats were given different treatment methods; the rats in the drug group were given gavage administration in the proportion of 75 mg/kg once a day. The rats in the control group were given intragastric administration with the same proportion of physiological saline once a day. The blank group was the normal healthy group and the rats in this group did not undergo any surgery or drug treatment. Brain tissue in rats were divided into two parts, one part was fixed, dehydrated, paraffin-embedded and made into slices of approximately 5 µm. TUNEL staining was used to examine the apoptosis of brain tissue, H&E staining was used to observe the brain tissue cells of each group, and western blotting for detecting the MAPK, Erk and expression levels of p38 and RT-polymerase chain reaction method was employed to examine mRNA expression levels of MAPK, Erk and p21. After one week, TUNEL staining showed that apoptosis of brain tissue in the drug group was significantly greater than those of the control and blank groups. The protein expression levels of MAPK, Erk and p38 were significantly higher than those of the control group and the normal healthy group; the differences were statistically significant (P<0.05). Western blotting showed that the protein expression levels of MAPK, Erk and p38 of the drug group were significantly lower than those of the control group but higher than those of the normal healthy group; the differences were statistically significant (P<0.05). TPX2 has a protective effect on the apoptosis of brain tissue processed by Aß1-42, which plays its role through the inhibition of the protein expression levels of MAPK, Erk and p38.

Chronic Estradiol Administration During the Early Stage of Alzheimer's Disease Pathology Rescues Adult Hippocampal Neurogenesis and Ameliorates Cognitive Deficits in Aß1-42 Mice.

Alzheimer's disease (AD) is the leading cause of dementia and has become an important public health concern. Accumulating evidence indicates that estradiol can both facilitate and impair memory-related processes and, as a result, the precise nature of the role that estradiol plays during AD pathology remains elusive. Therefore, the present study established a mouse model of AD using stereotactic brain injection of Aß1-42 in which the mice were bilaterally ovariectomized to investigate the effects of 17ß-estradiol (E2) treatment during different stages of the AD process (early and late stages). The cognitive deficits associated with this AD model were significantly ameliorated, and there was a significant increase in hippocampal neurogenesis in Aß1-42 mice that received E2 treatment during the early stage of AD pathology. On the other hand, Aß1-42 mice that received E2 treatment during the late stage of AD pathology did not exhibit any improvements in cognitive function or hippocampal neurogenesis. To reveal the mechanisms, underlying these effects, levels of oxidative stress, activity in death-associated pathways, gliosis, and synaptic function were assessed in the hippocampus. The Aß1-42 mice that received E2 treatment during the early stage of AD pathology exhibited significant reductions in the production of nitric oxide (NO) and reactive oxygen species (ROS), a marked decrease in the activation of Cytochrome-c/Bax/Bcl-2/caspase-3 pathway, a notable decrease in the level of gliosis a significant increase in the number of synapses (ultrastructural investigation), and a marked upregulation in synaptic function-related proteins compared to mice that received E2 treatment during the late stage of AD pathology. Taken together, these findings indicate that E2 treatment during the early stage of AD pathology might be an efficient approach to ameliorate the development of this disease.

Clinical Comparison of Outcomes of Early versus Delayed Carotid Artery Stenting for Symptomatic Cerebral Watershed Infarction due to Stenosis of the Proximal Internal Carotid Artery.

The aim of this study was to compare the clinical outcomes of early versus delayed carotid artery stenting (CAS) for symptomatic cerebral watershed infarction (sCWI) patients due to stenosis of the proximal internal carotid artery. We retrospectively collected clinical data of those who underwent early or delayed CAS from March 2011 to April 2014. The time of early CAS and delayed CAS was within a week of symptom onset and after four weeks from symptom onset. Clinical data such as second stroke, the National Institutes of Health Stroke Scale (NHISS) score, and modified Rankin Scale (mRS) score and periprocedural complications were collected. The rate of second stroke in early CAS group is lower when compared to that of delayed CAS group. There was no significant difference regarding periprocedural complications in both groups. There was a significant difference regarding mean NHISS score 90 days after CAS in two groups. Early CAS group had a significant better good outcome (mRS score ≤ 2) than delayed CAS group. We suggest early CAS for sCWI due to severe proximal internal carotid artery stenosis as it provides lower rate of second stroke, comparable periprocedural complications, and better functional outcomes compared to that of delayed CAS.

Early Carotid Artery Stenting for Cerebral Watershed Infarction Is Safe and Effective: A Retrospective Study.

BACKGROUND: With carotid artery stenosis, infarcts can occur in the cortical or internal watershed areas, or both. The timing of carotid artery stenting (CAS) after a cerebral watershed infarction (CWI) is not yet codified. In this retrospective study, we analyzed the safety and clinical effect of early CAS for CWI patients due to carotid artery stenosis. METHODS: Between March 2011 and April 2014, 120 CWI patients with ipsilateral carotid artery stenosis were recruited. Of these 120 patients, 63 received CAS within 7 days of the symptom onset (group 1) and 57 received standard medical treatment at the symptom onset (group 2). Periprocedural complications were analyzed in group 1 to evaluate the safety of early CAS. Clinical effects were analyzed by evaluating National Institutes of Health Stroke Scale (NIHSS) score as well as modified Ranking Scale (mRS) score of pre- and post-treatment in 2 groups. RESULTS: There was no significant difference in pre-treatment NIHSS score between the 2 groups (8.52 ± 2.46 and 7.84 ± 2.64, p = 0.15). However, group 1 had lower post-treatment NIHSS score as compared to group 2 (3.03 ± 1.44 and 3.84 ± 1.73, p = 0.006). In both groups, NIHSS score after treatment was significantly reduced (p < 0.05). Treatment effect in group 1 was larger compared to group 2 (-5.49 ± 2.12 and -4.00 ± 1.98, p < 0.05). Before the treatment, both groups had similar patient numbers with mRS score ≤2; however, after 30 days of surgery, group 1 had more number of patients with mRS score ≤2 than group 2. CONCLUSION: This study suggested that early CAS for CWI can be performed without significant risk. More importantly, early CAS for CWI can improve the prognosis.

Plasma homocysteine involved in methylation and expression of thrombomodulin in cerebral infarction.

Homocysteine (Hcy) regulates endothelial injury and methylation status of key genes in cerebral ischemia. Thrombomodulin (TM) may be protective against cerebral ischemia by downregulating coagulation. However, it remains unclear whether Hcy involved in methylation and expression of TM in cerebral infarction (CI). Here, we find patients with cerebral infarction had a higher TM methylation level than controls (74.2% vs 47.5%, X(2) = 14.724, P = 0.00), which are positively correlated with plasma levels of tHcy (r = 0.701, P = 0.00) and negatively related to mRNA expression of TM (r = -0.711, P = 0.00). Plasma levels of tHcy (t = 7.566, P = 0.00) and sTM (t = 17.268, P = 0.00) are significantly higher in cases than in controls. Our data indicate hyperhomocysteine leads to hypermethylation of the TM gene and further induces TM gene silencing, which may play an important role in the occurrence and development of CI. Plasma higher concentrations of sTM in cases are not caused by TM expression and may be only a result of Hcy induced endothelial injury.

Rhabdomyolysis induced by antiepileptic drugs: characteristics, treatment and prognosis.

INTRODUCTION: Rhabdomyolysis syndrome refers to a variety of factors that affect the striated muscle cell membrane, the membrane channels and its energy supply. Most cases of rhabdomyolysis are due to direct trauma. However, infection, toxins, drugs, muscle ischemia, electrolyte imbalance, metabolic diseases, genetic diseases and abnormal body temperature can also lead to rhabdomyolysis. Epilepsy is one of the most common chronic neurological diseases. The primary long-term treatment is antiepileptic drugs (AEDs), which may cause rhabdomyolysis. This article summarizes the characteristics, treatment methods and prognosis of patients with rhabdomyolysis that is induced by antiepileptic drugs. AREAS COVERED: This review is based on PubMed, EMBASE and MEDLINE searches of the literature using the keywords "epilepsy", "antiepileptic drugs","status epilepticus","rhabdomyolysis", and "antiepileptic drugs and rhabdomyolysis syndrome" as well as extensive personal clinical experience with various antiepileptic drugs. Potential relationships between antiepileptic drugs and rhabdomyolysis are discussed. EXPERT OPINION: Worldwide, there are approximately 50 million epilepsy patients, most of whom are treated with drugs. Reports have indicated that the majority of antiepileptic drugs on the market can cause rhabdomyolysis. Although rhabdomyolysis induced by antiepileptic drugs is a rare condition with a low incidence, this condition has serious consequences and merits attention from clinicians.

Estradiol prevents Aß 25 35-inhibited long-term potentiation induction through enhancing survival of newborn neurons in the dentate gyrus.

AIM AND METHODS: Estradiol (E2) is reported to attenuate ß-amyloid (Aß) accumulation and slow the progression of Alzheimer's disease (AD). This study explored the beneficial effect of E2 in AD using histological examination and electrophysiological recording technique in AD model mice created by intracerebroventricular injection of ß-amyloid 25-35 (Aß 25-35). RESULTS: Infusion of Aß 25-35 reduced the number of newborn neurons in the 2nd week after birth, a critical period for neurite growth, and impaired high-frequency stimulation-dependent long-term potentiation (LTP) induction in perforant path-granular synapses of hippocampal dentate gyrus (DG). Administration of E2 from the 2nd to 4th week after cell birth in Aß 25-35-mice ameliorated the impairment of newborn neurons and LTP induction in DG. Acute application of E2 failed to increase the newborn neurons and rescue LTP induction in the DG of Aß 25-35-mice. CONCLUSIONS: The effect of E2 in Aß 25-35-impaired LTP induction depends on its neuroprotection improvement.

SNCA rs3822086 C>T Polymorphism Increases the Susceptibility to Parkinson's Disease in a Chinese Han Population.

OBJECTIVE: Protofibrils of alpha-synuclein mediate neuronal cell death and propagate Parkinson's disease (PD). In this study, we investigated the relationship between the rs3822086 C>T polymorphism located in the fourth intron of the alpha-synuclein (SNCA) gene and susceptibility to PD in a Chinese Han population. METHODS: 146 PD patients and 144 sex- and age-matched healthy individuals (control group) were selected for this study. The SNCA rs3822086 polymorphism was examined in all 300 study subjects by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The genotype and allele frequencies of the SNCA rs3822086 polymorphism showed significant differences between the PD group and control group (TT: 25.3% vs. 18.8%, p=0.035; CT+TT: 77.4% vs. 66.0%, p=0.031; T allele: 51.4% vs. 42.4%, p=0.030; respectively). Stratified analyses based on gender indicated that male PD patients exhibited higher genotype and allele frequencies of the SNCA rs3822086 polymorphism compared to healthy male controls (TT: 26.7% vs. 13.2%, p=0.011; CC+CT: 73.3% vs. 86.8%, p=0.024; T allele: 51.2% vs. 37.9%, p=0.012; respectively). Age-stratified analyses indicated that the genotype and allele frequencies of the SNCA rs3822086 polymorphism were significantly higher in PD patients older than 60 years in comparison to healthy controls (TT: 32.2% vs. 20.5%, p=0.014; CT+TT: 77.0% vs. 60.2%, p=0.017; T allele: 54.6% vs. 40.3%, p=0.008; respectively). CONCLUSION: Our findings demonstrate that the SNCA rs3822086 C>T polymorphism correlates with increased susceptibility to PD among the Chinese Han population.

Change of MicroRNA-134, CREB and p-CREB expression in epileptic rat.

OBJECTIVE: To To investigate the changes of MicroRNA-134, CREB and p-CREB expression in epileptic rat brains in order to elucidate the molecular mechanisms of epilepsy, providing new ideas for clinical treatment. METHODS: Sixty-four Spraque-Dawley (SD) rats were divided into groups randomly, including control group, six hours after seizure group, 24-hour group, three-day group, one-week group, two-week group, four-week group, and eight-week group. All groups were placed under a pilocarpine-induced epilepsy model except the control group, and all rats were decapitated in different points of time. Brain specimens were taken for quantitative PCR experiments, immunohistochemistry and Western blot experiments. The results of the epilepsy model groups and the control group were compared. RESULTS: There were no significant differences between the six hours after seizure group, the 24-hour group and the control group about the MicroRNA-134 levels. MicroRNA-134 in the hippocampus tissue of the three-day group significantly reduced compared with the control group; same result was observed with the one-week, two-week, four-week and eight-week groups. The CREB and p-CREB levels in the three-day group's rat hippocampus significantly increased compared with the control group; and the high levels of CREB and p-CREB were constantly maintained in the one-week, two-week, four-week and eight-week groups. CONCLUSIONS: The MicroRNA-134 level of the epileptic rat hippocampus is significantly lower than normal after three days, and continues to maintain a low level; while CREB and p-CREB levels are rsignificantly increased after three days, and continue to remain at a high level. MicroRNA-134 plays a role in inhibiting synaptic plasticity by inhibiting CREB and p-CREB expressions.

Quantification of microRNA-210 in the cerebrospinal fluid and serum: Implications for Alzheimer's disease.

The aim of the present study was to investigate the potential clinical application of the genetic marker microRNA (miRNA)-210 in the cerebrospinal fluid (CSF) and serum of patients with Alzheimer's disease (AD). The enrolled patients were divided into the mild cognitive impairment (MCI) and AD groups. Healthy individuals were used as the controls. The mRNA and protein expression of vascular endothelial growth factor (VEGF) in the CSF and serum samples was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The expression of miRNA-210 in the CSF and serum was detected by RT-qPCR. The results revealed that the mRNA and protein expression levels of VEGF in the CSF and serum were decreased in the MCI and AD groups compared with those in the control group. The greater the severity of the dementia, the lower the mRNA and protein expression of VEGF. Similar to the trend observed for VEGF, the miRNA-210 expression in the CSF and serum decreased as the severity of the AD increased. miRNA-210 is thus not only indicative of AD pathogenesis, but may also provide novel insights into the prevention and treatment of the disease.

A feasible strategy for focal cerebral ischemia-reperfusion injury: remote ischemic postconditioning.

It is difficult to control the degree of ischemic postconditioning in the brain and other ischemia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperfusion injury model was established using three cycles of remote ischemic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the infarct area and attenuated brain edema. In addition, inflammatory nuclear factor-κB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the cerebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.

Adipose stem cells-conditioned medium blocks 6-hydroxydopamine-induced neurotoxicity via the IGF-1/PI3K/AKT pathway.

Previous studies suggest that the delivery of neurotrophic factors secreted from adipose stromal cells (ASC) protect the brain from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. However, it remains unclear which secreted neurotrophic factor has an important role in protecting 6-OHDA-treated neurons. Through the use of antibodies in this study, we demonstrated that specific neutralization of IGF-1 activity in ASC conditioned media (ASC-CM) significantly blocks ASC-CM-induced neuroprotection against 6-OHDA neurotoxicity. Consistently, this neuroprotection was mostly attributed to the activation of the AKT-mediated signaling pathway. In contrast, brain derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in ASC-CM did not play a role in ASC-CM-induced neuroprotection against 6-OHDA.