ChemR23 signaling ameliorates brain injury via inhibiting NLRP3 inflammasome-mediated neuronal pyroptosis in ischemic stroke.

BACKGROUND: Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemia. ChemR23 signaling is involved in the pathophysiology of various inflammatory diseases. Nevertheless, the role of ChemR23 signaling in ischemic stroke remains largely unknown. METHODS: Permanent ischemic stroke mouse model was accomplished by middle cerebral artery occlusion (MCAO). Resolvin E1 (RvE1) or chemerin-9 (C-9), the agonists of ChemR23, were administered by intracerebroventricular (i.c.v) injection before MCAO induction. Then, analysis of neurobehavioral deficits and brain sampling were done at Day 1 after MCAO. The brain samples were further analyzed by histological staining, immunofluorescence, RNA sequencing, ELISA, transmission electron microscope, and western blots. Furthermore, oxygen-glucose deprivation (OGD) was employed in SH-SY5Y to mimic MCAO in vitro, and ChemR23 signaling pathway was further studied by overexpression of ChemR23 or administration of related agonists or antagonists. Analysis of cell death and related pathway markers were performed. RESULTS: ChemR23 expression was upregulated following MCAO. Under in vitro and in vivo ischemic conditions, ChemR23 deficiency or inhibition contributed to excessive NLRP3-mediated maturation and release of IL-1ß and IL-18, as well as enhanced cleavage of GSDMD-N and neuronal pyroptosis. These influences ultimately aggravated brain injury and neuronal damage. On the other hand, ChemR23 activation by RvE1 or C-9 mitigated the above pathophysiological abnormalities in vivo and in vitro, and overexpression of ChemR23 in SH-SY5Y cells also rescued OGD-induced neuronal pyroptosis. Blockade of NLRP3 mimics the protective effects of ChemR23 activation in vitro. CONCLUSION: Our data indicated that ChemR23 modulates NLRP3 inflammasome-mediated neuronal pyroptosis in ischemic stroke. Activation of ChemR23 may serve as a promising potential target for neuroprotection in cerebral ischemia.

Excessive apoptosis of Rip1-deficient T cells leads to premature aging.

In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.

In situ gel-forming oil as rectally delivering platform of hydrophobic therapeutics for ulcerative colitis therapy.

Because of their poor water-soluble properties and non-specific distribution, most hydrophobic therapeutics had limited benefit for patients with ulcerative colitis. Herein, an in-situ oil-based gel has been developed as a rectal delivery vehicle for these therapeutics. In situ gel-forming oil (BBLG) was composed of soybean phosphatidyl choline (40%, w/w), glyceryl dioleate (50%, w/w), and ethanol (10%, w/w). The hydrophobic laquinimod (LAQ) as a model drug was easily dissolved in gel-forming oil and its solubility was reaching to 7 ± 0.1 mg/mL. Importantly, upon contact with the colonic fluids, the gel-forming oil was quickly transited to a semi-solid gel, adhering to the inflamed colon mucosa and forming a protective barrier. Transmission Electron Microscopy showed that the gel network was arranged by the connected lipid spheres and LAQ was non-crystally encapsulated into the lipid spheres. Moreover, the universal adhesive test showed that the adhesive force and the adhesive energy of BBLG toward fresh colon tissues were 711 ± 12 mN and 25 ± 2 J/m2, which was 2.14-fold and 5-fold higher than that of the marketed Poloxamer 407 gel, respectively. Meanwhile, in vivo imaging confirmed that the retention time of BBLG in the colon lumen was more than 8 h after rectal administration. In vivo animal studies showed that BBLG also greatly enhanced the therapeutic impact of LAQ on TNBS-treated rats with ulcerative colitis, as evidenced by reduced disease activity index (DAI) scores and weight loss. Moreover, the colonic inflammation was significantly alleviated and the goblet cells were obliviously restored after treatment. Importantly, the gut mucosa barrier was largely repaired without any formation of fibrosis remodeling. Conclusively, in situ liquid gel may be a potential delivery system of hydrophobic medicines for ulcerative colitis.

Polydopamine-cladded montmorillonite micro-sheets as therapeutic platform repair the gut mucosal barrier of murine colitis through inhibiting oxidative stress.

Montmorillonite (MMT), a layered aluminosilicate, has a mucosal nutrient effect and restores the gut barriers integrity. However, orally administrating MMT is not effective to combat the reactive oxygen species (ROS) and alleviate the acute inflammatory relapse for colitis patients. Herein, polydopamine-doped montmorillonite micro-sheets (PDA/MMT) have been developed as a therapeutic platform for colitis treatment. SEM and EDS analysis showed that dopamine monomer (DA) was easily polymerized in alkaline condition and polydopamine (PDA) was uniformly cladded on the surface of MMT micro-sheets. The depositing amount of PDA was reaching to 2.06 â€‹± â€‹0.08%. Moreover, in vitro fluorescence probes experiments showed that PDA/MMT presented the broad spectra of scavenging various ROS sources including •OH, •O2-, and H2O2. Meanwhile, the intracellular ROS of Rosup/H2O2 treated Caco-2 â€‹cell was also effectively scavenged by PDA/MMT, which resulted in the obvious improvement of the cell viability under oxidative stress. Moreover, most of orally administrated PDA/MMT was transited to the gut and form a protective film on the diseased colon. PDA/MMT exhibited the obvious therapeutic effect on DSS-induced ulcerative colitis mouse. Importantly, the gut mucosa of colitis mouse was well restored after PDA/MMT treatment. Moreover, the colonic inflammation was significantly alleviated and the goblet cells were obliviously recovered. The therapeutic mechanism of PDA/MMT was highly associated with inhibiting oxidative stress. Collectively, PDA/MMT micro-sheets as a therapeutic platform may provide a promising therapeutic strategy for UC treatment.

miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke.

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke. Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke. miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model, while its effect on ischemic stroke remains elusive. In this study, we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell proliferation and enhanced angiogenesis. In rat models of focal cerebral ischemia, overexpression of miR-181b reduced infarction volume, promoted angiogenesis in ischemic penumbra, and improved neurological function. We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3'-UTR of phosphatase and tensin homolog (PTEN) mRNA to induce PTEN downregulation, leading to activation of the protein kinase B (Akt) pathway, upregulated expression of vascular endothelial growth factors, down-regulated expression of endostatin, and promoted angiogenesis. Taken together, these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stroke through activating the PTEN/Akt signal pathway and promoting angiogenesis.

Understanding college students' continuous usage intention of asynchronous online courses through extended technology acceptance model.

Asynchronous online learning has gained great popularity in higher education, especially due to the recent COVID-19 pandemic. However, few studies have investigated how to maintain students' continuous usage intention of asynchronous online courses in the context of higher education. This study incorporated four key factors (intrinsic motivation, extrinsic motivation, perception of multiple sources, and cognitive engagement) associated with students' continuous usage intention of asynchronous online courses into technology acceptance model (TAM) to identify the influencing factors on students' continuous usage intention. A survey with 325 college students was conducted to explore their continuous usage intention of asynchronous online courses and structural equation modeling analysis was carried out to analyze the relationships between the key influencing factors and students' continuous usage intention. The results showed that cognitive engagement was the only factor that directly related to continuous usage intention. Intrinsic motivation, extrinsic motivation, and perception of multiple sources indirectly correlated with students' continuous usage intention through different pathways. The results of the study have several theoretical and practical implications. Theoretically, the study verified what key learning factors incorporated into TAM and in what way they relate to the continuous usage intention of asynchronous online courses. Practically, the present study indicated that it is required to take intrinsic motivation, extrinsic motivation, perception of multiple sources, cognitive engagement and TAM into consideration when designing and conducting asynchronous online learning courses to ensure college students' continuous usage intention of asynchronous online courses.

Analyses on safety and efficacy of non-standard dose of r-tPA in intravenous thrombolysis-treated AIS patients.

Background: Intravenous 0.9 mg/kg recombinant tissue plasminogen activator (r-tPA) is one of the most effective treatments in acute ischemic stroke patients. Practically, the dose of r-tPA is still a topic that is constantly being discussed. Methods: For this observational study, data were obtained from 537 patients who received r-tPA thrombolysis at Shanghai Sixth People's Hospital stroke center over 5 years (2014-2019). Patients were divided into two groups: a non-standard dose group (0.6 mg/kg ≤ dose < 0.9 mg/kg) and a standard dose group (0.9 mg/kg). Different outcomes were observed: efficacy: 3 months mRS 0-1 (3m-mRS0-1); safety: symptomatic intracranial hemorrhage within 24 h (24h-sICH) and 3 months mortality (3m-death). We also observed the effect of r-tPA dose coefficient on outcomes in different age groups and baseline National Institute of Health stroke scale (NIHSS) score subgroups. Results: There were 265 patients who gave the standard dose treatment and 272 gave the nonstandard dose. There was no significant difference between the non-standard dose group and the standard dose group in 3m-mRS0-1, 3m-death, and 24h-sICH (p = 0.567, 0.327, and 0.415, respectively). The dose coefficient presents a significant negative correlation (p = 0.034, B = -4.290) with 3m-death in NIHSS < 16 sub-group. Door-to-needle time (DNT) is the most important independent outcome-influential factor (MIOIF) in the NIHSS ≥16 sub-group. The diabetes history and baseline NIHSS score were the MIOIF in the age ≥80-year sub-group. Conclusions: The non-standard dose group (0.6 mg/kg ≤ dose < 0.9 mg/kg) shows no difference in safety and effectiveness than the standard dose group (0.9 mg/kg) in our study. The standard dose should be considered first according to current evidence and Guidelines, but the non-standard dose (0.6 mg/kg ≤ dose < 0.9 mg/kg) might be an option in the actual diagnosis and treatment process considering the patient's clinical profile and financial condition.

ChemR23 signaling ameliorates cognitive impairments in diabetic mice via dampening oxidative stress and NLRP3 inflammasome activation.

Diabetes mellitus is associated with cognitive impairment characterized by memory loss and cognitive inflexibility. Recent studies have revealed that ChemR23 is implicated in both diabetes mellitus and Alzheimer's disease. However, the impact of ChemR23 on diabetes-associated cognitive impairment remains elusive. In this study, we explored the longitudinal changes of ChemR23 expression and cognitive function in STZ-induced type 1 diabetic mice and leptin receptor knockout type 2 diabetic mice at different ages. We also treated diabetic mice with ChemR23 agonists RvE1 or chemerin-9 to explore whether ChemR23 activation could alleviate diabetes-associated cognitive impairment. The underlying mechanism was further investigated in diabetic mice with genetic deletion of ChemR23. The results showed that ChemR23 expression was decreased along with aging and the progression of diabetes, suggesting that abnormal ChemR23 signaling may be involved in diabetes-associated cognitive impairment. Administration of RvE1 or chemerin-9 ameliorated oxidative stress and inhibited NLRP3 inflammasome activation through Nrf2/TXNIP pathway, and ultimately alleviated cognitive impairment in diabetic mice. Depletion of ChemR23 in diabetic mice abolished the beneficial effects of RvE1 and chemerin-9, and exacerbated cognitive impairment via increasing oxidative stress and activating NLRP3 inflammasome. Collectively, our data highlight the crucial role of ChemR23 signaling in diabetes-associated cognitive impairment via regulating oxidative stress and NLRP3 inflammasome, and targeting ChemR23 may serve as a promising novel strategy for the treatment of diabetes-associated cognitive impairment.

Star Sensor Denoising Algorithm Based on Edge Protection.

Single-pixel noise commonly appearing in a star sensor can cause an unexpected error in centroid extraction. To overcome this problem, this paper proposes a star image denoising algorithm, named Improved Gaussian Side Window Filtering (IGSWF). Firstly, the IGSWF algorithm uses four special triangular Gaussian subtemplates for edge protection. Secondly, it exploits a reconstruction function based on the characteristic of stars and noise. The proposed IGSWF algorithm was successfully verified through simulations and evaluated in a star sensor. The experimental results indicated that the IGSWF algorithm performed better in preserving the shape of stars and eliminating the single-pixel noise and the centroid estimation error (CEE) value after using the IGSWF algorithm was eight times smaller than the original value, six times smaller than that after traditional window filtering, and three times smaller than that after the side window filtering.

ADAMTS13 ameliorates inflammatory responses in experimental autoimmune encephalomyelitis.

BACKGROUND: ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) plays a vital role in preventing microvascular thrombosis and inflammation. Reduced ADAMTS13 levels in plasma have been detected in multiple sclerosis (MS) patients. In the present study, we have determined the role of ADAMTS13 in the disease progression of MS using a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: Female C57BL/6 mice were immunized with MOG35-55 peptide and then treated with ADAMTS13 or vehicle in preventive and therapeutic settings. Mice were analyzed for clinical deficit, white matter demyelination and inflammatory cell infiltration. To explore the underlying mechanism, VWF expression and blood-spinal cord barriers (BSCB) were determined. RESULTS: Plasma ADAMTS13 activity was suppressed in EAE mice. ADAMTS13-treated EAE mice exhibited an ameliorated disease course, reduced demyelination, and decreased T lymphocyte, neutrophil and monocyte infiltration into the spinal cord. Consistently, ADAMTS13 treatment reduced VWF levels and inhibited BSCB breakdown in the spinal cords of EAE mice. However, leukocytes in the blood and spleen of EAE mice remained unaffected by ADAMTS13 administration. CONCLUSION: Our results demonstrate that ADAMTS13 treatment ameliorates inflammatory responses, demyelination and disease course in EAE mice. Therefore, our study suggests that ADAMTS13 may represent a potential therapeutic strategy for MS patients.

Verapamil Ameliorates Motor Neuron Degeneration and Improves Lifespan in the SOD1G93A Mouse Model of ALS by Enhancing Autophagic Flux.

Amyotrophic lateral sclerosis (ALS) is a progressive, paralytic disorder caused by selective degeneration of motor neurons in the brain and spinal cord. Our previous studies indicated that abnormal protein aggregation and dysfunctional autophagic flux might contribute to the disease pathogenesis. In this study, we have detected the role of the Ca2+ dependent autophagic pathway in ALS by using the L-type channel Ca2+ blocker, verapamil. We have found that verapamil significantly delayed disease onset, prolonged the lifespan and extended disease duration in SOD1G93A mice. Furthermore, verapamil administration rescued motor neuron survival and ameliorated skeletal muscle denervation in SOD1G93A mice. More interestingly, verapamil significantly reduced SOD1 aggregation and improved autophagic flux, which might be mediated the inhibition of calpain 1 activation in the spinal cord of SOD1G93A mice. Furthermore, we have demonstrated that verapamil reduced endoplasmic reticulum stress and suppressed glia activation in SOD1G93A mice. Collectively, our study indicated that verapamil is neuroprotective in the ALS mouse model and the Ca2+-dependent autophagic pathway is a possible therapeutic target for the treatment of ALS.

The effect of lithium chloride on the attenuation of cognitive impairment in experimental hypoglycemic rats.

BACKGROUND: Hypoglycemia is the most common complication in the treatment of diabetes mellitus. Accumulating evidence indicated that severe hypoglycemia could induce cognitive impairment. However, the molecular mechanism of regulating this progress is largely unknown. METHODS: We established a model of insulin-induced recurrent hypoglycemia in adult male Wistar rats (n = 40). Lithium chloride was injected after hypoglycemia once a day for consecutive 30 days. The loss of cognition function was evaluated by water maze test in these hypoglycemic rats. Glial cells activation and Wnt and inflammatory cytokines IL-1ß, IL-6, IL-4, IL-10, TGFß and TNFα expression were further examined to determine the mechanism of cognitive function impairment. RESULTS: Hypoglycemia could induce impairment of cognitive function in rats and administration of lithium chloride could partly attenuate cognitive impairment compared to the control (p < 0.05). Lithium chloride could significantly up-regulate Wnt signaling and reduce hypoglycemia-induced neuronal death, glial cells activation and inflammatory response in the hippocampus of rats compared to the control (p < 0.05). The efficacy of lithium chloride could be reversed by injecting canonical Wnt signaling antagonist the dickkopf homolog 1. CONCLUSION: Lithium chloride attenuated hypoglycemia-induced cognitive function impairment in rats; and it was associated with Wnt signaling up-regulation and reduction of inflammatory response. Our results suggested that activating Wnt signaling pathways and inhibiting inflammatory response were the therapeutic potential to prevent hypoglycemia-induced neurological damage.

Aquaporin-4 deletion ameliorates hypoglycemia-induced BBB permeability by inhibiting inflammatory responses.

BACKGROUND: Severe hypoglycemia induces brain edema by upregulating aquaporin-4 (AQP4) expression and by degrading tight junctions. Acute severe hypoglycemia induces a proinflammatory environment that may contribute to a disruption in the epithelial barrier by decreasing tight junction protein expression. Interestingly, the altered AQP4 expression has been considered to play a critical role in neuroinflammation during acute brain injury. It has been shown that AQP4 deletion reduces brain inflammation in AQP4-null mice after intracerebral LPS injection. However, the effect of AQP4 deletion regarding protection against hypoglycemia-induced blood-brain barrier (BBB) breakdown is unknown. METHODS: An acute severe hypoglycemic stress model was established via injection of 4 unit/kg body weight of insulin. Evans blue (EB) staining and water measurement were used to assess BBB permeability. Western blot, reverse transcription polymerase chain reaction, and immunofluorescence were used to detect the expression of related proteins. The production of cytokines was assessed via enzyme-linked immunosorbent assay. RESULTS: Hypoglycemia-induced brain edema and BBB leakage were reduced in AQP4-/- mice. AQP4 deletion upregulated PPAR-γ and inhibited proinflammatory responses. Moreover, knockdown of aquaporin-4 by small interfering RNA in astrocytes co-cultured with endothelial cells effectively reduced transendothelial permeability and degradation of tight junctions. Treatment with PPAR-γ inhibitors showed that upregulation of PPAR-γ was responsible for the protective effect of AQP4 deletion under hypoglycemic conditions. CONCLUSIONS: Our data suggest that AQP4 deletion protects BBB integrity by reducing inflammatory responses due to the upregulation of PPAR-γ expression and attenuation of proinflammatory cytokine release. Reduction in AQP4 may be protective in acute severe hypoglycemia.

Clinical significance of changes in serum neuroglobin and HIF-1α concentrations during the early-phase of acute ischemic stroke.

BACKGROUND: Neuroglobin (NGB) has been described as a neuroprotective agent in cerebral ischemia, hypoxia inducible factor (HIF) has shown an important role in modulating hypoxic and ischemic injury, and therefore they have the potential to impact outcomes after acute ischemic stroke (AIS). Thus, we investigated early changes in the concentrations of serum NGB and HIF-1α after AIS and evaluated the relations of both NGB and HIF-1α to stroke severity and prognosis. METHODS: We prospectively measured the serum concentrations of NGB and HIF-1α in 40 patients with AIS at 24, 48, 72, and 96h after stroke. Correlation combined with infarct size and National Institutes of Health Stroke Scale (NIHSS) score of the patients was analyzed. Receiver operating characteristic (ROC) curve was used to appraise their value in predicting the 90-day outcome after AIS. RESULTS: Serum NGB concentrations increased and peaked at 72h after AIS, whereas serum concentrations of HIF-1α increased for 48h. Peak serum NGB concentration correlated significantly with both infarct size (R2=0.484, p<0.001) and admission NIHSS score (R2=0.578, p<0.001), while serum HIF-1α concentration was only correlated to a patient's infarct size (R2=0.394, p<0.001). ROC curve analysis suggested that the serum NGB concentration had a significantly better predictive power for poor outcome. CONCLUSIONS: NGB level increased in serum after AIS accompanied by increases in serum HIF-1α, and was suggested as a predictor of stroke severity and poor prognosis.

Uric acid is associated with vascular dementia in Chinese population.

OBJECTIVE: Mounting evidence suggests that oxidative stress is involved in the pathogenesis of vascular dementia (VD). Uric acid (UA) has long been implicated as a critical cause of cardiovascular disease. Nevertheless, UA was also expected to play an important role in antioxidant and neuroprotection recently. We hypothesized that UA may have a protective role against VD. The aim of this study was to investigate the link between serum UA and cognitive dysfunction in VD. MATERIALS AND METHODS: There were altogether 127 VD subjects and 81 nondemented controls enrolled in our study. Serum UA, demographic, and clinical characteristics were recorded at baseline, and all participants underwent Mini-Mental State Examination (MMSE) at the beginning of the trial. RESULTS: The VD group showed lower MMSE scores and serum UA levels than nondemented controls and there was significant statistical difference between the two groups (p < .05). Demographic and clinical characteristics such as age, gender, education, body mass index (BMI), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), blood urea nitrogen (BUN), and serum creatinine (Scr) did not differ dramatically between groups (p > .05). In VD subjects, there was a positive correlation between serum UA and MMSE scores (r = .32, p < .05), and this correlation was independent of demographic and clinical characteristics (ß = .272, p < .05). CONCLUSIONS: VD subjects have dramatically lower serum UA levels in comparison to nondemented controls. Lower serum UA levels are linked to cognitive dysfunction and could serve as a potential predictor for VD.

Protective effect of lithium chloride against hypoglycemia-induced apoptosis in neuronal PC12 cell.

Hypoglycemia is defined by an arbitrary plasma glucose level lower than 3.9mmol/L and is a most common and feared adverse effect of treatment of diabetes mellitus. Emerging evidences demonstrated that hypoglycemia could induce enhanced apoptosis. Lithium chloride (LiCl), a FDA approved drug clinically used for treatment of bipolar disorders, is recently proven having neuroprotection against various stresses in the cellular and animal models of neural disorders. Here, we have established a hypoglycemia model in vitro and assessed the neuroprotective efficacy of LiCl against hypoglycemia-induced apoptosis and the underlying cellular and molecular mechanisms. Our studies showed that LiCl protects against hypoglycemia-induced neurotoxicity in vitro. Exposure to hypoglycemia results in enhanced apoptosis and the underlying cellular and molecular mechanisms involved inhibition of the canonical Wnt signaling pathway by decreasing wnt3a levels, ß-catenin levels and increasing GSK-3ß levels, which was confirmed by the use of Wnt-specific activator LiCl. Hypoglycemia-induced apoptosis were significantly reversed by LiCl, leading to increased cell survival. LiCl also alters the expression/levels of the Wnt pathway genes/proteins, which were reduced due to exposed to hypoglycemia. Overall, our results conclude that LiCl provides neuroprotection against hypoglycemia-induced apoptosis via activation of the canonical Wnt signaling pathway.

Association between Helicobacter pylori infection and carotid atherosclerosis in patients with vascular dementia.

BACKGROUND AND PURPOSE: Accumulating evidence indicates that various infections contribute to the pathogenesis of atherosclerosis. Helicobacter pylori (Hp) has been implicated as a risk factor of atherosclerosis for stroke and other cardiovascular disease, but limited data exist regarding vascular dementia (VD). This study aimed to investigate the relationship between Hp infection and carotid atherosclerosis in patients with VD. METHODS: A total of 354 patients who were diagnosed with VD were enrolled. Patients were divided into Hp positive VD group (n=208) and Hp negative VD group (n=156) using the (13)C-urea breath test ((13)C-UBT). Serum YKL-40, a marker for inflammation, were analyzed by ELISA. Traditional atherosclerotic risk factors including age, gender, body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting blood glucose (FBG) were collected or detected. Carotid intima-media thickness (CIMT) was determined by color Doppler ultrasound. RESULTS: CIMT values and serum YKL-40 significantly increased in Hp positive VD group in comparison with Hp negative VD group (p<0.05). In Hp positive VD group, serum YKL-40 was positively correlated with CIMT (r=0.412, p<0.05), and the association was independent of traditional atherosclerotic risk factors (ß=0.381, p<0.001). CONCLUSIONS: CIMT and serum YKL-4 were significantly higher in Hp positive patients than Hp negative patients. Hp-induced inflammation may be a risk factor for atherosclerosis in patients with VD.

Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.

Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.

Serum neuron specific enolase level as a predictor of prognosis in acute ischemic stroke patients after intravenous thrombolysis.

OBJECTIVE: Serum neuron specific enolase (NSE) concentrations are significantly correlated with stroke severity and clinical outcome in ischemic stroke patients. We aimed to determine whether the serum levels of neuron specific enolase in acute ischemic stroke (AIS) patients after intravenous thrombolysis are associated with stroke severity, and indicative of favorable outcome. METHODS: We prospectively analyzed the serum neuron specific enolase levels with for 67 subjects with AIS patients treated with intravenous recombinant tissue type plasminogen activator (rtPA) within 4.5h from symptom onset. Neurologic deficit was assessed by the National Institutes of Health Stroke Scale. Clinical outcome was assessed after 90days according to the modified Rankin Scale. RESULTS: Neuron specific enolase levels correlated with National Institutes of Health Stroke Scale score 24h after rtPA bolus (R=0.342, p=0.005). Regarding the 67 included patients, 32 (47.8%) reached favorable outcome. They had a lower NIHSS score on admission (p=0.000) and at 24h after rtPA bolus (p=0.000), and had lower levels of neuron specific enolase (p=0.006). But only NIHSS score at 24h after rtPA bolus rather than neuron specific enolase level was an independent predictor for favorable outcome. CONCLUSION: We found that after treatment with intravenous rtPA therapy, lower serum neuron specific enolase levels were associated with favorable outcome, which may be confounded by the link to NIHSS score.

The accuracy of magnetic resonance imaging for preoperative deep myometrium assessment in endometrial cancer.

OBJECTIVE: To evaluate the accuracy of preoperative magnetic resonance imaging (MRI) to detect deep myometrial invasion in patients with endometrial cancer. MATERIALS AND METHODS: We retrospectively reviewed 66 cases of women with endometrial cancer, who underwent preoperative MRI assessment and surgical staging between January 2006 and October 2010. The MRI findings were then compared with the pathology results. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI in detecting deep myometrium invasion were evaluated. RESULTS: The sensitivity, specificity, accuracy, PPV, and NPV results of MRI for the detection of deep myometrium invasion were 92.52%, 74.35%, 81.81%,71.42%, and 93.54%, respectively, with a kappa of 0.64. In the postmenopausal group, the values were 100%, 55.5%, 74.19%, 61.9%, and 100%. In the premenopausal women, they improved to 85.7%, 90.47%, 88.57%, 88.71%, and 90.47%. The sensitivity (100%) was better than the specificity (55.56%) in the postmenopausal women. The predictive value was markedly higher in the premenopausal women than the postmenopausal women (85.7% vs. 61.9%). CONCLUSION: In patients with endometrial cancer, a preoperative MRI contributes to accurate staging, allowing planning for the scale of surgery and preoperative counseling. In our study, the pretreatment identification of myometrium invasion provided the opportunity for small-scale surgery in the premenopausal women with early endometrial cancer. However, for the postmenopausal patients, the standard surgical procedure is indicated even if the degree of myometrium invasion is low.