The Protective Effect of Vitexin on Hypertensive Nephropathy Rats.

INTRODUCTION: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. METHODS: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured biweekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. RESULTS: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. CONCLUSION: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.

The Protective Effect of the Asystasia chelonoides Extracts on Hypertensive Nephropathy Rats.

BACKGROUND: Hypertensive nephropathy (HN) is one kind of kidney disorders caused by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In recent years, nephropathy accompanied by hypertension is becoming one of the main causes for kidney replacement therapy, but few effective treatments have been reported for HN treatment. Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear. METHODS: To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying mechanisms of AC extracts treatment in the HN rat model. RESULTS: AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFß1 and NF-кB in HN rats. CONCLUSION: The finding of the article demonstrated that AC extracts had the better therapeutic effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.

Betaine Inhibits NLRP3 Inflammasome Hyperactivation and Regulates Microglial M1/M2 Phenotypic Differentiation, Thereby Attenuating Lipopolysaccharide-Induced Depression-Like Behavior.

Depression is one of the most important mental illnesses and is closely related to inflammation. Betaine is a natural product with an anti-inflammatory and antioxidant activities. However, the mechanism by which betaine ameliorates depression-like behaviors induced by lipopolysaccharide (LPS) is poorly understood. The purpose of this study was to investigate the neuroprotective effect of betaine on LPS-induced depression-like behavior in mice and its mechanism of action. ICR mice were randomly divided into four groups: the control group, the LPS model group (0.83 mg/kg), the positive drug group (MIDO, 50 mg/kg), and the betaine group (5% and 1% in drinking water). The betaine group was administered for 21 days, and on the 22nd day, except for the blank group, LPS (0.83 mg/kg) was intraperitoneally injected to establish a lipopolysaccharide-induced mice depression-like model. Twenty-four hours after LPS injection, the tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT) were performed to evaluate the effect of betaine on LPS-induced depressive behavior in mice. After the behavioral study, the mouse brain, hippocampus, and serum were taken for detection. The expressions of cytokines and inflammatory mediators were detected by ELISA, HE staining, immunofluorescence, immunohistochemistry, and western blotting. Western blotting was used to detect the protein expression levels of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, and ASC, the protein expression levels of the microglial polarization markers COX-2, inducible nitric oxide synthase (iNOS), and CD206. The results showed that betaine significantly ameliorated the depression-like behavior in LPS-induced mice, significantly attenuated the production of proinflammatory cytokines and increased the release of an anti-inflammatory cytokines. Betaine decreased the expression of the NLRP3 inflammasome, decreased the expression of M1 polarization markers, tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), COX-2, and iNOS and promoted the expression of M2 polarization marker CD206. Our study suggests that betaine may promote the transition of microglia from the M1 to the M2 phenotype by inhibiting NLRP3 inflammasome activation, thereby attenuating lipopolysaccharide-induced depression-like behavior.

Pyruvate kinase M2 (PKM2) improve symptoms of post-ischemic stroke depression by activating VEGF to mediate the MAPK/ERK pathway.

PURPOSE: To evaluate and identify the effects and explore the mechanisms of pyruvate kinase M2 (PKM2) on stroke-induced post stroke depression (PSD). METHODS: Rats were separated into six different groups, including sham + saline, Stroke + saline, PSD + saline, PSD + recombinant pyruvate kinase M2 (rPKM2) (112 ng/kg), PSD + rPKM2 (224 ng/kg), and PSD + rPKM2 (224 ng/kg) + bevacizumab. Then, the body weight, sucrose preference rate, immobility time, horizontal movement, and vertical movement were determined to evaluate the effect of PKM2 on improving the depressive behavior of PSD rats. Subsequently, the proliferation of oligodendrocytes in subventricular zone (SVZ) of rats in each group was examined by western blot and immunofluorescent staining. Furthermore, the mRNA and protein expression levels of TNF-α, IL-6, and IL-1ß were also detected by qPCR and ELISA to verify the anti-inflammatory effects of PKM2 on PSD rats. In addition, the protein expression levels of MDA, LDH, and NO were tested to reveal that PKM2 can reduce oxidative stress in PSD rats. The western blot and IHC assays were employed to examine the protein expression levels of VEGF, PKM2, and ERK in PSD rats. RESULTS: In this study, the results showed that PKM2 can improve the depressive behavior and proliferation of oligodendrocytes in PSD rats. In addition, PKM2 has anti-inflammatory and anti-oxidative stress effects on PSD rats. Meanwhile, PKM2 activated the expression level of VEGF/MAPK/ERK pathway. CONCLUSION: PKM2 improves symptoms of post-ischemic stroke depression by activating VEGF-mediated MAPK/ERK pathway.

Up-regulation of SETD3 may contribute to post-stroke depression in rat through negatively regulating VEGF expression.

Post-stroke depression (PSD) is one of the most familiar complications of stroke, which refers to stroke patients who have varying degrees of depression (lasts for >2 weeks). SET domain-containing 3 (SETD3) is a conserved histone H3 methyltransferase, and the role of SETD3 in some diseases is increasingly being explored. However, the effects of SETD3 in PSD remain unclear. In this study, the PSD rat model was firstly constructed by Endothelin-1 injection combined with chronic unpredictable mild stress, and we discovered that SETD3 expression was up-regulated in PSD rat model. Additionally, SETD3 knockdown relieved the depressive symptom of PSD. Moreover, SETD3 knockdown promoted proliferation and differentiation of neural stem cells (NSCs). Due to the critical role of vascular endothelial growth factor (VEGF) in antidepressant and SETD3 can negatively regulate VEGF, we speculated that SETD3 may regulate PSD progression through VEGF. Our results demonstrated that SETD3 knockdown up-regulated VEGF expression. Furthermore, SETD3 modulated the proliferation and differentiation of NSCs through regulating VEGF expression. In conclusion, our study indicated that up-regulation of SETD3 contributed to PSD progression in rats through negatively regulating VEGF expression. The findings of this work suggest that SETD3 may be a promising target for treating PSD in the future.

Potential Genes and Mechanisms Linking Intracerebral Hemorrhage and Depression: A Bioinformatics-Based Study.

PURPOSE: The purpose of this study was to investigate the potential pathogenic mechanisms of post-intracerebral hemorrhage depression. METHODS: Profiles of gene expression in brain tissue of patients with intracerebral hemorrhage (ICH) or depression were downloaded from the Gene Expression Omnibus (GEO) database. We analyzed differentially expressed genes (DEGs) for the two diseases separately. With these DEGs, we conducted an enrichment analysis based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) as well as cross-talk analysis, then we identified hub bridge genes using integrated bridge landscape analysis. RESULTS: We found 131 DEGs for interaction between ICH and depression. In the enrichment analysis, we found 55 GO terms and KEGG pathways involving interacting genes of ICH and depression, and 10 GO terms and 10 KEGG pathways most significantly related to cross-talk between ICH and depression. In the integrated bridge landscape analysis, we identified 20 hub bridge genes. In further analysis, we found that hub bridge genes HLA-A, HMOX1, and JUN related to endocytosis, cell adhesion, and phagosomes may exert their effects through the dopamine (DA) system and the serotonergic pathway post-ICH depression. HLA-A may play a role in the occurrence and development of ICH and depression through immune mediation and cell adhesion. HMOX1 and JUN may participate in the mechanism by interacting with HLA-A. CONCLUSION: Through bioinformatics analysis, we identified potential hub bridge genes and pathways related to post-ICH depression. Our study provides references for further research on mechanisms on the pathogenesis of post-ICH depression.

Costunolide attenuates oxygen­glucose deprivation/reperfusion­induced mitochondrial­mediated apoptosis in PC12 cells.

The present study investigated the effect of costunolide (CT), a compound extracted from Aucklandia lappa Decne, to attenuate oxygen­glucose deprivation/reperfusion (OGD/R)­induced mitochondrial­mediated apoptosis in PC12 cells. The present study used molecular docking technology to detect the binding of CT with mitochondrial apoptotic protein targets. A model of oxygen­glucose deprivation for 2 h and reperfusion for 24 h in PC12 cells was used to mimic cerebral ischemic injury. Cell viability and damage were measured using the Cell Counting kit­8 and lactate dehydrogenase (LDH) cytotoxicity assay kits. Cellular apoptosis was analyzed using flow cytometry. A fluorescence microscope determined intracellular [Ca2+] and mitochondrial membrane potential. Furthermore, immunofluorescence and Western blot analyses were used to detect the expression of apoptosis­associated proteins. CT contains binding sites with Caspase­3, Caspase­9 and Caspase­7. CT markedly enhanced cell viability, inhibited LDH leakage, increased intracellular [Ca2+], stabilized the mitochondrial membrane potential, increased the expression of Bcl­2 and inhibited the expression of Apaf­1, Bax, cleaved­caspase­7, cleaved­caspase­9 and cleaved­caspase­3. CT may markedly protect PC12 cells from damage caused by OGD/R, and its mechanism is associated with blocking the calcium channel and inhibiting mitochondrial­mediated apoptosis.

Genes Induced by Panax Notoginseng in a Rodent Model of Ischemia-Reperfusion Injury.

Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN's neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery.

Using mRNA deep sequencing to analyze differentially expressed genes during Panax notoginseng saponin treatment of ischemic stroke.

Treatment with Panax notoginseng saponin (PNS) can prevent neurological damage in middle cerebral artery occlusion model rats to promote recovery after a stroke. However, the exact molecular mechanisms are unknown and require further study. In the present study, mRNA sequencing was employed to investigate differential gene expression between model and sham groups, and between model and PNS­treated groups. Enrichment of gene data was performed using Gene Ontology analysis and the Kyoto Encyclopedia of Genes and Genomes database. Hub genes were identified and networks were constructed using Cytoscape that were further verified by reverse transcription­quantitative PCR. A total of 1,104 genes of interest were found, which included 690 upregulated and 414 downregulated genes that were identified when the model was compared with the sham group. Additionally, 817 genes of interest, which included 390 upregulated and 427 downregulated genes, were identified when the PNS­treated group was compared with the model group. There were 303 overlapping genes of interest between the analysis of model to sham groups, and the analysis of model to PNS­treated groups. The top 10 genes from the 303 aberrantly expressed genes of interest included ubiquitin conjugating enzyme E2 variant 2, small ubiquitin­related modifier 1, small RNA binding exonuclease protection factor La, Finkel­Biskis­Reilly murine sarcoma virus (FBR­MuSV) ubiquitously expressed, centrosomal protein 290 kDa, DNA­directed RNA polymerase II subunit K, cullin­4B, matrin­3 and vascular endothelial growth factor receptor 2. In conclusion, these genes may be important in the underlying mechanism of PNS treatment in ischemic stroke. Additionally, the present data provided novel insight into the pathogenesis of ischemic stroke.

Panax notoginseng Saponins Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Human SH-SY5Y Cells by Regulating the Expression of Inflammatory Factors through miR-155.

Panax notoginseng saponins (PNS) have been widely used in China to treat stroke. Accumulating evidence has found that microRNA (miR)-155 plays critical roles in the pathology of ischemic stroke. Here we investigated whether PNS plays a protective effect against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced focal inflammation and injury in SH-SY5Y cells by regulating miR-155 expression. Treatment with PNS at a concentration less than 160 µg/mL had no effect on the proliferation of SH-SY5Y cell. In OGD/R-induced SH-SY5Y cells, 160 µg/mL PNS treatment promoted cell proliferation and cell cycle progression, as well as decreased inhibited apoptosis and miR-155 expression. However, overexpression of miR-155 attenuated the promotion effects of PNS on cell proliferation and cell cycle, apoptosis inhibition in OGD/R-induced SH-SY5Y cells. Moreover, 160 µg/mL PNS treatment decreased the levels of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) in OGD/R-induced SH-SY5Y cells, whereas overexpression of miR-155 reversed PNS-induced decreases in the levels of IL-1ß, IL-6, and TNF-α in OGD/R-treated SH-SY5Y cells. In conclusion, PNS attenuated OGD/R-induced injury in human undifferentiated SH-SY5Y cells by regulating the expression of inflammatory factors through miR-155.

[Association of single nucleotide polymorphisms of rs3819024 and rs8193037 loci of IL-17A gene with the risk of ischemic stroke].

OBJECTIVE: To assess the association of polymorphisms of rs3819024 and rs8193037 loci in the promoter region of IL-17A gene with the risk of ischemic stroke (IS) among ethnic Han Chinese from Guangxi. METHODS: The polymorphisms of rs3819024 and rs8193037 loci were detected by a SNaPshot assay and DNA sequencing among 392 IS patients and 443 healthy controls with matched age and gender. RESULTS: The genotypes, dominant model, recessive model, and alleles of rs3819024 polymorphisms showed no significant difference between the two groups, with the P values calculated as 0.150, 0.227, 0.125, 0.594 and 0.202, respectively, and OR (95% CI) as 1.27(0.92-1.74), 1.28(0.86-1.91), 1.27(0.94-1.72), 1.10(0.78-1.54), and 1.13(0.94-1.38), respectively. The genotypes, dominant model, recessive model, and alleles of rs8193037 polymorphisms also showed no significant difference between the two groups, with the P values calculated as 0.722, 0.352, 0.863, 0.345 and 0.969, respectively, and OR (95% CI) as 0.94(0.65-1.35), 2.25(0.41-12.35), 0.97(0.68-1.38), 2.27(0.41-12.48), and 1.01(0.72-1.40), respectively. CONCLUSION: Polymorphisms of the rs3819024 and rs8193037 loci of the IL-17A gene are not associated with the susceptibility to IS among ethnic Han Chinese from Guangxi.

Clinical effects and safety of electroacupuncture for the treatment of post-stroke depression: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: The aim of this systematic review was to assess the efficacy/effectiveness and safety of electroacupuncture (EA) in the treatment of post-stroke depression (PSD). METHODS: A comprehensive literature search in the Pubmed, Embase, CENTRAL, ISI Web of Science, CNKI and Wanfang databases was conducted, and all relevant randomised controlled trials (RCTs) were screened for eligibility by two independent reviewers. The Cochrane Collaboration's tool and Jadad score were used to assess the risk of bias of included studies, and only RCTs scoring ≥3 were included in a meta-analysis. RESULTS: 18 RCTs involving a total of 813 participants (mean age 61.6 years) in the EA groups and 723 participants (mean age 61.9 years) in the control groups were included. The included studies had an average 3 point Jadad score. PSD was diagnosed according to the Chinese Classification of Cerebrovascular Disease (CCCD) and the Chinese Classification of Mental Disease (CCMD) criteria. There was no significant difference between EA and antidepressants (fluoxetine 10-40 mg/day, citalopram 20 mg/day, sertraline 50 mg/day) in terms of the Hamilton Depression Rating Scale (HAMD) scores at week 4 after treatment (standardised mean difference (SMD) -0.11, 95% CI -0.31 to 0.10), at week 6 after treatment (SMD 0.04, 95% CI -0.43 to 0.51) or at week 8 after treatment (SMD -0.01, 95% CI -0.23 to 0.22). However, the combined incidence of adverse events in the EA groups was significantly lower than in the antidepressant groups (RR 0.21, 95% CI 0.14 to 0.33). CONCLUSION: There was no significant difference between EA and antidepressants in the severity of depression, however EA caused fewer adverse events than antidepressants. Additional larger scale RCTs with rigorous study design are required.

A SNP in 5' untranslated region of CD40 gene is associated with an increased risk of ischemic stroke in a Chinese population: a case-control study.

Cluster of differentiation 40 (CD40), the receptor for CD154, is a member of the tumor necrosis factor (TNF) receptor superfamily. Several studies have been conducted to investigate the effect of the CD40 rs1883832 polymorphism on atherosclerotic disease in different population; however, inconsistent results were obtained. In this study, we investigated the association of four polymorphisms (rs1883832, rs13040307, rs752118 and rs3765459) of CD40 gene and their effect on CD40 expression with the risk of ischemic stroke (IS) in a Chinese population. Three hundred and eighty patients with IS and 450 control subjects were included in the study. The CD40 polymorphisms were discriminated by Snapshot SNP genotyping assay. Serum soluble CD40 (sCD40) levels were detected by ELISA. We found that the rs1883832CT and rs1883832TT genotypes were associated with an increased risk of IS compared with the rs1883832CC genotype (OR = 1.42, 95% CI: 1.03-1.95, p = 0.030 and OR = 1.91, 95% CI: 1.29-2.82, P = 0.001, respectively), and the rs1883832T allele was associated with a significantly increased risk of IS compared with rs1883832C allele (OR = 1.40, 95% CI: 1.15-1.70, P = 0.001). Elevated serum sCD40 levels were observed in patients with IS compared with the control gropu (P < 0.01). Individuals carrying the rs1883832TT or rs1883832CT genotypes showed significantly higher sCD40 levels compared with the rs1883832CC genotype in the IS group [(64.8 ± 25.4 pg/mL, TT = 94); (63.9 ± 24.3 pg/mL, CT = 185) vs (53.3 ± 22.5 pg/mL, CC = 101), P < 0.01]. The TCCA haplotype was associated with an increased risk of IS compared with the control group (OR = 2.10, 95% CI: 1.23-3.58, p = 0.005). However, we did not find a significant association between the other three polymorphisms and IS risk. In conclusion, after a comprehensive comparison with other studies, we confirmed that the rs1883832T allele but not the rs1883832C allele is associated with an increased risk of IS. The rs1883832 polymorphism may exert influences on abnormal CD40 expression in IS patients among the Chinese population.

A SNP in 5′ untranslated region of CD40 gene is associated with an increased risk of ischemic stroke in a Chinese population: a case-control study

Abstract Cluster of differentiation 40 (CD40), the receptor for CD154, is a member of the tumor necrosis factor (TNF) receptor superfamily. Several studies have been conducted to investigate the effect of the CD40 rs1883832 polymorphism on atherosclerotic disease in different population; however, inconsistent results were obtained. In this study, we investigated the association of four polymorphisms (rs1883832, rs13040307, rs752118 and rs3765459) of CD40 gene and their effect on CD40 expression with the risk of ischemic stroke (IS) in a Chinese population. Three hundred and eighty patients with IS and 450 control subjects were included in the study. The CD40 polymorphisms were discriminated by Snapshot SNP genotyping assay. Serum soluble CD40 (sCD40) levels were detected by ELISA. We found that the rs1883832CT and rs1883832TT genotypes were associated with an increased risk of IS compared with the rs1883832CC genotype (OR = 1.42, 95% CI: 1.03-1.95, p = 0.030 and OR = 1.91, 95% CI: 1.29-2.82, P = 0.001, respectively), and the rs1883832T allele was associated with a significantly increased risk of IS compared with rs1883832C allele (OR = 1.40, 95% CI: 1.15-1.70, P = 0.001). Elevated serum sCD40 levels were observed in patients with IS compared with the control gropu (P < 0.01). Individuals carrying the rs1883832TT or rs1883832CT genotypes showed significantly higher sCD40 levels compared with the rs1883832CC genotype in the IS group [(64.8 ± 25.4 pg/mL, TT = 94); (63.9 ± 24.3 pg/mL, CT = 185) vs (53.3 ± 22.5 pg/mL, CC = 101), P < 0.01]. The TCCA haplotype was associated with an increased risk of IS compared with the control group (OR = 2.10, 95% CI: 1.23-3.58, p = 0.005). However, we did not find a significant association between the other three polymorphisms and IS risk. In conclusion, after a comprehensive comparison with other studies, we confirmed that the rs1883832T allele but not the rs1883832C allele is associated with an increased risk of IS. The rs1883832 polymorphism may exert influences on abnormal CD40 expression in IS patients among the Chinese population.

Cognitive deficits are ameliorated by reduction in amyloid ß accumulation in Tg2576/p75(NTR+/-) mice.

AIMS: Amyloid ß (Aß) is considered to be an important mediator of the development and progression of Alzheimer's disease (AD). Its direct binding to p75(NTR), not TrkA, induces apoptosis, which is thought to be the most relevant feature of p75(NTR) regarding AD. In the present study we explored the regulation of p75(NTR) on Aß production and accumulation during AD pathology. MATERIALS AND METHODS: We generated Tg2576/p75(NTR+/-) mice by crossing the transgenic AD mice (Tg2576) with p75(NTR-/-) mice to lower the p75(NTR) level. Under these conditions, we evaluated cognitive function using the Morris water maze, pathology and process by which two types of Aß (Aß40 and Aß42) are produced, by enzyme-linked immunosorbent assay and Western blotting. KEY FINDING: The results showed that cognitive deficits were rescued in Tg2576/p75(NTR+/-) mice compared with those in Tg2576 mice. This cognitive functional recovery may be a consequence of a reduction in Aß accumulation through the inhibition of ß- and γ-secretase activities, without altering α-secretase activity. SIGNIFICANCE: Here, we investigated the mechanism by which p75(NTR) regulates Aß production and accumulation. Better understanding the relationship between p75(NTR) and Aß producing may help taking insight into the AD pathology.

[Association of SNP of leukocyte differentiation antigen-CD40 gene and its serum level with ischemic stroke].

OBJECTIVE: To investigate the association of SNP of CD40 gene and its serum levels with ischemic stroke (IS). METHODS: A total of 202 IS patients from a hospital of Baise city were enrolled in case group from May 2013 to November 2014. At the same time, 109 healthy people who had physical check-ups in the outpatient department at the same hospital were enrolled in the control group. All participants were from Guangxi Zhuang Autonomous Region and unrelated to each other. 3 ml venous blood were collected on the premise of informed consent. The single nucleotide polymorphisms of CD40 gene rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A were analyzed using a Snapshot SNP genotyping assays, and the serum levels of CD40 were tested by ELISA. t-test was used to compare the serum levels of CD40 between the case and control group, and the genotypes at different locuses in case group; χ(2) test was used to compare the distribution differences of the CD40 gene locuses in different genotypes and allele between the case group and the control group; alleles was established as independent variables, the occurrence of the IS as dependent variable, and expressed relative risk with OR (95%CI) value. RESULTS: In the case group, the frequency of CC, CT and TT genotypes in CD40 gene rs1883832 C/T were 21.78% (44/202), 49.51% (100/202) and 28.71% (58/202), respectively, and 33.17% (66/199), 48.74% (97/199), 18.09% (36/199) in the control group, respectively, the differences between the two groups was significant (χ(2)=9.57, P=0.008). The CD40 serum levels were (62.7 ± 24.5) pg/ml in the case group, which was higher than that in the control group (45.3 ± 17.2) pg/ml (t=8.97, P<0.001). The serum levels of TT and CT genotypes in CD40 gene were (65.9 ± 26.3) and (64.3 ± 25.9) pg/ml, respectively, and the differences were significant when comparing with CC genotype (t equaled 5.34 and 5.03, respectively, P<0.001). The risk of developing IS was 1.56 times higher in 1883832 T allele carriers than that in rs1883832 C allele carriers (OR=1.56, 95% CI: 1.18-2.06); Combined genotype analysis displayed that CD40 gene rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A polymorphisms showed strong linkage disequilibrium, the case group TCCA haplotype was tested to be associated with a significantly increased risk of IS as compared with that in the control group(OR=2.49; 95%CI: 1.13-5.48). CONCLUSION: CD40 gene rs1883832 C/T polymorphism and its TCCA haplotype were possibly associated with ischemic stroke, and the susceptibility gene for ischemic stroke may be rs1883832 T allele.

Apolipoprotein E polymorphisms increase the risk of post-stroke depression.

Recent reports have shown that apolipoprotein E (APOE) polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study (including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction) to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These results suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.

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.

The association of L-selectin polymorphisms with L-selectin serum levels and risk of ischemic stroke.

L-selectin is a member of the selectin family of cell adhesion molecules which are important in the transient attachment of leukocytes to endothelial cells, which plays a role in inflammation processes and is one of the earliest events in the pathogenesis of atherosclerosis. No studies have examined the association of this polymorphism with ischemic stroke. Therefore, we investigated that L-selectin gene polymorphism and its soluble level are associated with ischemic stroke in Chinese population. We analyzed single nucleotide polymorphisms of L-selectin gene Pro213Ser (P213S) in 265 patients with ischemic stroke and 280 age and sex matched controls, using PCR-RFLP and DNA sequencing method, while soluble L-selectin levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of L-selectin gene P213S polymorphism between the group of patients with ischemic stroke and the control group (P < 0.05). Soluble L-selectin levels were increased in patients with ischemic stroke compared with controls (P < 0.01). Moreover, The P213S polymorphism of L-selectin was significantly associated with sL-selectin levels, the serum levels of L-selectin PP genotype carriers was significantly higher than no carriers in patients with ischemic stroke (P < 0.05). The P213S polymorphism of L-selectin and its sL-selectin levels are associated with ischemic stroke in Chinese population. Our data suggests that L-selectin gene may play a role in the development of ischemic stroke.

A novel functional polymorphism, 16974 A/C, in the interleukin-12-3' untranslated region is associated with risk of glioma.

Genetic factors are important in the development of glioma. Interleukin-12 (IL-12) is a multifunctional cytokine that induces Interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Interleukin-27 (IL-27) is a novel IL-12 family member, and the present studies demonstrate that IL-27 mediates a potent antitumor activity. The aim of this study was to investigate whether IL-12 and IL-27 gene polymorphisms and their serum levels are associated with glioma. We analyzed IL-12 gene 16974 A/C and IL-27 gene -964 A/G, 2905 T/G, and 4730 T/C polymorphisms in 210 patients with glioma and 220 matched controls, using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing methods, while serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay. Serum IL-12p40 and IL-27p28 levels were decreased in patients with glioma compared with controls (p < 0.01). There were significant differences in the genotype and allele frequencies of the IL-12 gene 16974 A/C polymorphism between the group of patients with glioma and the control group (p < 0.05). Moreover, genotypes carrying the IL-12 16974 C variant allele were associated with decreased serum IL-12p40 and IL-27p28 levels compared to the homozygous wild-type genotype in patients with glioma. The IL-12 gene 16974 A/C polymorphism may regulate expression of the serum IL-12p40 and IL-27p28, and associate with increased risk of glioma. Thus, genotypes carrying the IL-12 16974 C variant allele had a decreased ability to produce IL-12 and IL-27, which may contribute to glioma susceptibility.