High-Temperature Metal-Free Molecular Ferroelectrics with Large Spontaneous Polarization.

In the past two decades, numerous molecular ferroelectrics have been reported. However, metal-free molecular ferroelectrics with high working temperatures and large spontaneous polarizations are still uncommon. Herein, we present two metal-free molecular ferroelectrics prepared from monoprotonated hexamethylenetetramine (HMTA), namely (HMTAH)Cl and (HMTAH)Br, which crystallize in a polar point group of 3m. In these crystals, the polar HMTAH+ organic cations can be reoriented 180° along the polar axis because of the quasispherical molecular geometry. As a result of the large shift of the positively charged protonated N atoms, these compounds demonstrate large spontaneous polarizations with values of 8.3 and 8.1 µC cm-2 and high working temperatures of 390 and 435 K, respectively. The ferroelectric property of these compounds is characterized with second-harmonic generation, ferroelectric hysteresis loop, and pyroelectric current measurements.

Inversion of Molecular Chirality Associated with Ferroelectric Switching in a High-Temperature Two-Dimensional Perovskite Ferroelectric.

Controlling molecular chirality by external stimuli is of great significance in both fundamental research and technological applications. Herein, we report a high-temperature (384 K) molecular ferroelectric of a Cu(II) complex whose spontaneous polarization can be switched associated with flipping of molecular chirality. In this two-dimensional perovskite structure, the inorganic layer is separated by (NH3(CH2)2SS(CH2)2NH3)2+ organic cations skewed in a chiral conformation (P- or M-helicity in an individual crystal). As the stereodynamic disulfide bridge determines the molecular dipole moment along the polar axis, the chiral organic cation can be converted to its enantiomer as a consequence of an electric field-induced shift of the S-S moiety relative to its screw axis during the ferroelectric switching. The variation of the molecular chirality is examined with single-crystal X-ray diffraction and circular dichroism spectra. The simultaneous switching of molecular chirality and spontaneous polarization in this perovskite ferroelectric may lead to novel chiral electronic phenomena.

Associations of Abdominal Visceral Fat Content and Plasma Adiponectin Level With Intracranial Atherosclerotic Stenosis: A Cross-Sectional Study.

Background: Abdominal obesity and adipocytokines are closely related to atherosclerosis, and adiponectin level is considered one of the important clinical indicators. This study aimed to analyze the associations of abdominal visceral fat content and adiponectin level with intracranial atherosclerotic stenosis (ICAS). Methods: A total of 186 patients were enrolled in this study. Patients were distributed into ICAS and non-ICAS by the degree of artery stenosis. Plasma adiponectin levels and the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) were measured. The related factors of intracranial atherosclerotic stenosis were determined using multivariable logistic regression analysis. Results: The VAT/SAT ratio (OR, 26.08; 95% CI, 5.92-114.83; p < 0.001) and adiponectin (OR, 0.61; 95% CI, 0.44-0.84; p = 0.002) were found to be the independent predictors of ICAS in a multivariable logistic regression analysis. The prevalence of ICAS increased (T1: 27.4%; T2: 50.0%; T3: 75.8%) as the VAT/SAT ratio tertile increased (p < 0.001). The prevalence of ICAS decreased (T1: 72.6%; T2: 54.8%; T3: 25.8%) as the adiponectin tertile increased (p < 0.001). In ROC curves analysis, VAT/SAT ratio had a sensible accuracy for the prediction of ICAS. The optimal cut-off value of VAT/SAT ratio to predict ICAS in this study was 1.04 (AUC: 0.747; p < 0.001; sensitivity: 67.4%; specificity: 74.7%). The optimal adiponectin cutoff was 3.03 ug/ml (AUC: 0.716; p < 0.001; sensitivity:75.8%; specificity: 61.5%). Conclusion: Higher VAT/SAT ratio and lower plasma adiponectin levels were closely related to the increased risk of intracranial atherosclerotic stenosis.

Reverse Hofmann-Type Spin-Crossover Compound Showing a Multichannel Controllable Color Change in an Ambient Environment.

Materials that demonstrate a multichannel controllable color change in response to external stimuli are fascinating for their potential applications in sensoring and displaying devices. Herein we report a FeII spin-crossover (SCO) compound that exhibits both solvatochromism and thermochromism under an ambient environment. This Hofmann-type compound possesses two different pores where the solvent guests can be removed in a two-step process. Because the loss of solvent guests modifies the spin state of magnetic centers, an unusual yellow-red-yellow two-step color change of crystals was detected. Moreover, because of the strong cooperativity of the spin centers, a dramatic red-to-yellow color change of crystals in response to a minute thermal perturbation around 303 K is triggered by an abrupt spin transition of the metal centers. The multichannel controllable dramatic color change demonstrated in the present compound highlights the sensoring and displaying roles of SCO materials.

Ferulic Acid Ameliorates Isoproterenol-Induced Heart Failure by Decreasing Oxidative Stress and Inhibiting Cardiocyte Apoptosis via Activating Nrf2 Signaling Pathway in Rats.

Ferulic acid (FA) has potential therapeutic effects in multiple diseases including cardiovascular diseases. However, the effect and molecular basis of FA in heart failure (HF) has not been thoroughly elucidated. Herein, we investigated the roles and mechanisms of FA in HF in isoproterenol (ISO)-induced HF rat model. Results found that FA ameliorated cardiac dysfunction, alleviated oxidative stress, reduced cell/myocardium injury-related enzyme plasma level, inhibited cardiocyte apoptosis in ISO-induced HF rat models. Moreover, FA reduced the co-localization of Keap1 and nuclear factor-E2-related factor 2 (Nrf2) in heart tissues of ISO-induced HF rats, and FA alleviated the inhibitory effects of ISO on expressions of p-Nrf2, heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1). Additionally, Nrf2 signaling pathway inhibitor ML385 showed adverse effects. FA weakened the effects of ML385 in ISO-induced HF rat models. Collectively, FA ameliorated HF by decreasing oxidative stress and inhibiting cardiocyte apoptosis via activating Nrf2 pathway in ISO-induced HF rats. Our data elucidated the underling molecular mechanism and provided a novel insight into the cardioprotective function of FA, thus suggested the therapeutic potential of FA in HF treatment.

In reply to the letter to the editor regarding "TGM6 variants in Parkinson's disease: clinical findings and functional evidence".

No abstract present.

Predictors of urinary tract infection in acute stroke patients: A cohort study.

Patients with stroke have a high risk of infection which may be predicted by age, procalcitonin, interleukin-6, C-reactive protein, National Institute of Health stroke scale (NHSS) score, diabetes, etc. These prediction methods can reduce unfavourable outcome by preventing the occurrence of infection.We aim to identify early predictors for urinary tract infection in patients after stroke.In 186 collected acute stroke patients, we divided them into urinary tract infection group, other infection type groups, and non-infected group. Data were recorded at admission. Independent risk factors and infection prediction model were determined using Logistic regression analyses. Likelihood ratio test was used to detect the prediction effect of the model. Receiver operating characteristic curve and the corresponding area under the curve were used to measure the predictive accuracy of indicators for urinary tract infection.Of the 186 subjects, there were 35 cases of urinary tract infection. Elevated interleukin-6, higher NIHSS, and decreased hemoglobin may be used to predict urinary tract infection. And the predictive model for urinary tract infection (including sex, NIHSS, interleukin-6, and hemoglobin) have the best predictive effect.This study is the first to discover that decreased hemoglobin at admission may predict urinary tract infection. The prediction model shows the best accuracy.

GPNMB contributes to a vicious circle for chronic obstructive pulmonary disease.

Osteoporosis (OP) is significant and debilitating comorbidity of chronic obstructive pulmonary disease (COPD). We hypothesize that genetic variance identified with OP may also play roles in COPD. We have conducted a large-scale relation data analysis to explore the genes implicated with either OP or COPD, or both. Each gene linked to OP but not to COPD was further explored in a mega-analysis and partial mega-analysis of 15 independently collected COPD RNA expression datasets, followed by gene set enrichment analysis (GSEA) and literature-based pathway analysis to explore their functional linked to COPD. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in COPD. At the first step of the analysis, we have identified 918 genes associated with COPD, 581 with OP, and a significant overlap (P<2.30e-140; 210 overlapped genes). Partial mega-analysis showed that, one OP gene, GPNMB presented significantly increased expression in COPD patients (P-value = 0.0018; log fold change = 0.83). GPNMB was enriched in multiple COPD pathways and plays roles as a gene hub formulating multiple vicious COPD pathways included gene MMP9 and MYC. GPNMB could be a novel gene that plays roles in both COPD and OP. Partial mega-analysis is valuable in identify case-specific genes for COPD.

Donepezil Improves Gait Performance in Patients with an Acute Cerebral Infarction: A Prospective Observational Cohort Study.

BACKGROUND: Hemiplegia is a common symptom after acute cerebral infarction. OBJECTIVE: This study aimed to explore the influence factors of gait performance and investigate whether donepezil could improve gait performance in patients with an acute cerebral infarction. METHODS: A total of 107 patients who experienced unilateral paresis after an acute cerebral infarction incident were enrolled in this prospectively observational study. Participants underwent a 3- month assessment. At the study's conclusion, patients were divided into 2 groups-those who received donepezil daily (observation Group) and those who did not (Control Group). RESULTS: There was a significant difference (t=3.269, P=0.001) of Wisconsin Gait Scale (WGS) score between single site infarction (27.11±6.65) and multiple sites infarction (31.54±6.42). For gender, smoking, drinking, hypertension, hyperlipidemia and diabetes, there was no difference in WGS scores between subgroups (P>0.05), respectively. The patient's admission National Institute of Health Stroke Scale(NIHSS) score had a strongly positive correlation with WGS score (r=0.850, P<0.001). Besides, age (r=0.218, P=0.024), glycosylated hemoglobin (r=0.274, P=0.004), MMSE (r=-0.261, P=0.007) and Montreal Cognitive Assessment (MoCA) (r=-0.272, P=0.005) had a weak correlation with WGS scores. Multivariate analysis showed age (95% CI: 0.042~0.188, P=0.002), admission NIHSS score (95% CI: 2.405~3.137, P<0.001) and multiple sites infarction (95% CI: 0.044~2.983, P=0.044) were independent risk factors of WGS scores. WGS scores of both observation and control groups gradually decreased after admission (P<0.001). At 3 months after admission, WGS score of the observation group was significantly lower than the control group (t=2.468, P=0.015). There were no significant differences between observation and control group at admission and 1 month after admission (P>0.05) and WGS scores of both single site and multiple sites infarction gradually decreased at one month and three months after admission (P<0.001), while there was no significant difference between two groups (P>0.05). CONCLUSION: Admission NIHSS score, age and multiple sites infarction were independent risk factors of WGS score. Donepezil could improve gait performance in patients with acute cerebral infarction.

TGM6 variants in Parkinson's disease: clinical findings and functional evidence.

TGM6 encodes transglutaminase 6, which catalyzes the covalent crosslinking of proteins through transamination reactions. Variants in TGM6 have been identified as the cause of spinocerebellar ataxia type 35. However, we found 12 TGM6 variants of low frequency among 308 patients with Parkinson's disease using next-generation sequencing technologies and multiple ligation-dependent probe amplification, including two variants TGM6 p.R111C and p.L517W, which have been reported to affect functions of transglutaminase 6 in spinocerebellar ataxia type 35 cases. The characteristics of these TGM6 carriers were summarized. To clarify the role of TGM6 variants in Parkinson's disease, we constructed the plasmids of wild-type TGM6 and TGM6 p.R111C, p.P359L, p.L517W to transfect A53T-SH-SY5Y cells and conducted transglutaminase assay, western blots, immunofluorescence, and cell viability assay. Results revealed that the distribution and expression levels of transglutaminase 6 were not affected by TGM6 variants. However, the variants showed lower transglutaminase activity than wild-type transglutaminase 6. The overexpression of wild-type TGM6 was proved to relieve the cell damage, down-regulate the level of α-synuclein and enhance autophagy. These effects were weakened in cells transfected with mutant TGM6 plasmids. Our results suggested that there may be some relationship between TGM6 and Parkinson's disease. TGM6 carriers in Parkinson's disease patients presented with typical parkinsonism but progressed slower. The high expression level of wild-type transglutaminase 6 may protect cells by decreasing α-synuclein and enhancing autophagy.

Giant Single-Crystal Shape Transformation with Wide Thermal Hysteresis Actuated by Synergistic Motions of Molecular Cations and Anions.

Manipulating the collective molecular movements to implement macroscopic mechanical response of bulk material is attractive and challenging. Here, an organic-inorganic hybrid single crystal is synthesized, which exhibits a giant macroscopic shape transformation with a remarkable thermal hysteretic feature. The colossal anisotropic shape change, which manifests as an abrupt elongation of ca. 9 % along the crystallographic c-axis and a concomitant contraction of ca. 9 % in a perpendicular direction, is induced by a significant reorientation of imidazolium, accompanied with a substantial configurational variation in CuBr4 2- complex anions. The synergistic motions of both the molecular cations and anions engender a remarkable large thermal hysteresis (>30 K) in the shape transformation of the single crystal, implying that this material may play a role in alternating memory media. Furthermore, due to the stable crystal lattice, a single crystal that demonstrates naked-eye detectable large shape transformation was used as a thermal actuator to spontaneously control an electric circuit by temperature variation.

Pilot testing the caregiver self-management intervention for caregivers of relatives with dementia.

This study was designed to examine the feasibility of a caregiving self-management support program developed for caregivers of relatives with dementia in Shanghai. A total of 41 caregivers were recruited for a quasi-experimental study. The experimental group of 26 participants attended six bi-weekly social support group sessions. The control group of 15 participants received three monthly telephone instructions. All of participants received an illustrated caregiver educational booklet and three educational presentations during a six-month follow-up period. The results demonstrated a stronger sense of self-efficacy regarding the gathering of information about dementia care in both study groups compared to the baseline data. Caregivers participating in the group sessions reported better health-related quality of life, improved responses to behavioral disturbances, and efficacy in the management of stress than those who received telephone instructions. This study provided some preliminary information regarding ways to improve self-management for the target population in mainland China.

Long noncoding RNA KCNQ1OT1 promotes apoptosis in neuroblastoma cells by regulating miR-296-5p/Bax axis.

Long noncoding RNAs (lncRNAs) are emerging as important regulators of multiple cellular processes such as cell invasion, growth, apoptosis and differentiation. LncRNAs can function as competing endogenous RNAs (ceRNAs) which sponge and sequester microRNA (miRNA) to regulate specific targets. Previously, we found that the target genes of several miRNAs, including FADD, Fas, Casp and Bax, are related to neuronal apoptosis and form a regulatory network. Among several factors, microRNA-296-5p expression was found to be negatively correlated with caspase activity and apoptosis. Here, we aimed to investigate the role of miR-296-5p in neuroblastoma (NB) cells. By performing quantitative real-time PCR (qRT-PCR), western blot and flow cytometry assays we analysed the expression of apoptotic markers in NB cells transfected with miR-296-5p mimics or inhibitor. Pathway-specific PCR array allowed us to identify the target genes of miR-296-5p. Using LncBase online tool, we predicted lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) as an upstream regulator of miR-296-5p. The binding of KCNQ1OT1 and miR-296-5p was validated via RNA immunoprecipitation and Biotin pull-down assays. We also demonstrate that miR-296-5p suppresses apoptosis of NB cells in vitro and in vivo. Mechanistically, miR-296-5p directly bound the 3'UTR of Bax mRNA, thus repressing Bax at the mRNA and protein level. Moreover, through bioinformatic analysis and molecular experiments, we showed that KCNQ1OT1 sponged miR-296-5p and impaired its effect on NB cell apoptosis. In summary, KCNQ1OT1 is a potent promoting factor of cell apoptosis, which acts by sponging miR-296-5p and upregulating Bax. Our findings identify a regulatory axis of cell fate in NB cells.

Elevated Tumor Necrosis Factor-a-induced Protein 8-like 2 mRNA from Peripheral Blood Mononuclear Cells in Patients with Acute Ischemic Stroke.

Background: Tumor necrosis factor-a-induced protein 8-like 2 (TIPE2) is a novel regulator of immunity and protects against experimental stroke. However, the expression and function of TIPE2 in patients with acute ischemic stroke has not been well demonstrated. Methods: A total of 182 consecutive patients with acute ischemic stroke and 40 healthy controls were included during November 2015 to June 2016. The mRNA levels of TIPE2, interleukin(IL)-1ß, IL-10, IL-6, nuclear factor(NF)-κß, activator protein(AP)-1, interferon(IFN)-γ and tumor necrosis factor(TNF)-α from peripheral blood mononuclear cells were determined using real time quantitative reverse transcriptase polymerase chain reaction. The severity of stroke was assessed using the National Institutes of Health Stroke Scale (NIHSS) score. Results: The median mRNA levels of TIPE2, TNF-α, AP-1, IFN-γ and NF-κß in patients with acute ischemic stroke were significantly higher than healthy controls (all P<0.001, respectively). Of note, TIPE2 mRNA showed an increasing trend on a time-dependent manner after the onset of stroke. Furthermore, TIPE2 mRNA was negatively associated with lesion volumes (r=-0.23, P<0.01), NIHSS(r=-0.15, P<0.05), TNF-α(r=-0.33,P<0.001), AP-1(r=-0.28,P<0.001), IFN-γ (r=-0.16, P<0.05) and NF-κß (r=-0.13, P<0.05), but positively associated with IL-6(r=0.14, P<0.05) and IL-10(r=-0.31, P<0.001). Hierarchy cluster analysis showed that TIPE2 mRNA has nearest membership with TNF-α, followed by IL-6, NF-κß, AP-1, IL-10, IL-1ß and IFN-γ. In addition, TIPE2 mRNA in survivals (n=149) was significantly higher than nonsurvivals (n=33) (P<0.001), and showed a great odd ratio (0.52, 95% confidence interval: 0.349-0.760, P<0.001) on 3-month mortality. Conclusions: TIPE2 mRNA contributed to the immune response of stroke and might be a potential biomarker for the mortality of acute ischemic stroke.

Homocysteine is Associated with Exaggerated Morning Blood Pressure Surge in Patients with Acute Ischemic Stroke.

BACKGROUND: Considerable researches suggest that high level of homocysteine (Hcy) is associated with the risk of ischemic stroke. Ambulatory blood pressure monitoring (ABPM) parameters have also been confirmed associated with cardio-cerebrovascular events. However, the relationship between Hcy and ABPM parameters remains unclear in patients with acute ischemic stroke. In this study, we aim to investigate the association between Hcy level and ABPM parameters in patients with acute ischemic stroke. METHODS: We enrolled 60 patients with acute ischemic stroke who received ABPM. We calculated ABPM parameters like morning blood pressure surge (MBPS), ambulatory arterial stiffness index, blood pressure variability, and night dipping patterns. RESULTS: Multivariate logistic regression analysis indicated that patients in the top quartile of Hcy level tended to have a higher level of prewaking and sleep-trough MBPS compared with patients in the lower 3 quartiles after adjusted for age and gender (P = .028 and P = .030, respectively). When treating Hcy as a continuous variable, the linear regression showed the association between Hcy level and both MBPS parameters remained significant (prewaking MBPS, r = .356, P = .022; sleep-trough MBPS, r = .365, P = .017, respectively). However, there is no association between Hcy level and ambulatory arterial stiffness index, blood pressure variability or night dipping patterns (P = .635, P = .348 and P = .127 respectively). CONCLUSIONS: There is a relationship between the 2 major cerebrovascular risk factors: MBPS and Hcy.

Effect of marital status on survival in glioblastoma multiforme by demographics, education, economic factors, and insurance status.

The relationship between marital status and glioblastoma multiforme (GBM) has not been addressed in depth. Here, we aimed to investigate the association between marital status and survival in GBM. We searched the Surveillance, Epidemiology, and End Results (SEER) database and extracted the data of eligible patients diagnosed with GBM after 2004. Marital status was classified as married, divorced/separated, widowed, and single. A Kaplan-Meier test was conducted to compare the survival curves of different groups. Multivariate Cox regression was performed to evaluate overall survival (OS) and cause-specific survival (CSS) in different groups. Subgroup analysis was applied according to demographics, typical education and income levels in the locale, and insurance status. A total of 30 767 eligible patients were included. The median OS values were 9, 7, 3, 9 months in married, divorced/separated, widowed, and single patients, respectively. After adjustment for other covariates, married patients had better OS and CSS than other patients had. In addition to marital status, demographic factors, disease progression factors, local educational level, and insurance status were also associated with survival in GBM. Furthermore, subgroup analyses revealed the protective effect of marriage in most of the comparisons. Notably, the protective effect of marriage becomes more and more apparent as time goes on. The advantageous effect of marriage on GBM survival is especially prominent in patients who are male, older than 60 years of age, White, or living in middle-income counties. In conclusion, marital status is an independent prognostic factor for GBM.

Marital status is associated with survival of patients with astrocytoma.

The prognostic role of marital status in patients with astrocytoma has not been fully explored. In this study we investigated the association of marital status and survival of astrocytoma. We extracted the eligible patients with astrocytoma diagnosed after 2000 from the Surveillance, Epidemiology, and End Results (SEER) database. The marital status was classified into married, divorced/separated, widowed, and single. The differences in OS and CSS were compared using the Kaplan-Meier log-rank test, and multivariate Cox regression was applied to analyze the risk factors for OS and CSS. Subgroup analyses were conducted to explore the association of marital status with patients in different sex, age, race, histologic type based on 2016 WHO grade, year of diagnosis, median household income and surgery status. A total of 43, 324 eligible patients were included. The median overall survival is 17, 11, 9, 3 months in single, married, divorced/separated patients, and widowed patients, respectively. Although single patients seemed to have the longest overall survival, after adjusted for other co-variables, married patients had the best OS and CSS compared with others, while divorced/separated or widowed patients had the worst CSS in different subgroups. Furthermore, subgroup analyses revealed some interesting results such as the CSS showed no difference between single and married for women (P = 0.122). In conclusion, marital status was an independent prognostic factor for astrocytoma patients. The healthcare system should aware of that patients with an aborted marriage need more social and physiological support.

Hypoxia increases amyloid-ß level in exosomes by enhancing the interaction between CD147 and Hook1.

Hypoxia promotes the accumulation of amyloid-ß (Aß), which is related to the pathogenesis of Alzheimer's disease (AD). CD147 is considered as an additional subunit of γ-secretase regulated by hypoxia, and has been identified in exosomes. Aß is also found in exosomes that participate in the intercellular communication and amyloids propagation. This study was to investigate the role of CD147 in hypoxia-induced accumulation of Aß in exosomes. Our results showed that hypoxia increased the levels of Aß40 and Aß42 in exosomes and enhanced the interaction between CD147 and Hook1 in SH-SY5YAPP695 cells. Moreover, hypoxia increased the interaction between amyloid precursor protein (APP) and CD147 as well as the expression of CD147 in isolated membrane. After we interfered the interaction between CD147 and Hook1 by decreasing Rab22a expression, the hypoxia induced Aß accumulation in exosomes was significantly suppressed. In addition, the increased interaction between CD147 and Hook1 was further confirmed in hypoxia exposed C57BL/6 mice. Our findings reveal that hypoxia may increase exosome Aß level by enhancing the interaction between CD147 and Hook1.

Effects of Melatonin Levels on Neurotoxicity of the Medial Prefrontal Cortex in a Rat Model of Parkinson's Disease.

BACKGROUND: Damage of the medial prefrontal cortex (mPFC) results in similar characteristics to the cognitive deficiency seen with the progress of Parkinson's disease (PD). Since the course of mPFC damage is still unclear, our study aimed to investigate the effects of melatonin (MT) on neurotoxicity in the mPFC of a rat model of PD. METHODS: One hundred and fifty-four normal, male Wistar rats were randomly divided into the following five groups: normal + normal saline (NS), normal + 6-hydroxydopamine (6-OHDA), sham pinealectomy (PX) + 6-OHDA, PX + 6-OHDA, and MT + 6-OHDA. 6-OHDA was injected into the right substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) of each group, except normal + NS, 60 days after the PX. In the MT treatment group, MT was administered immediately after the intraperitoneal injection at 4 p.m. every day, for 14 days. Neuronal apoptosis in the mPFC was examined using the TUNEL method, while the expression of tyrosine hydroxylase (TH), Bax,and Bcl-2 in this region was measured using immunohistochemistry. The concentration of malondialdehyde (MDA) in the mPFC was examined using the thiobarbituric acid method. RESULTS: Rats in the normal + 6-OHDA and sham PX + 6-OHDA groups were combined into one group (Group N + 6-OHDA) since there was no significant discrepancy between the groups for all the detected parameters. Apoptosis of cells in the NS, MT + 6-OHDA, N + 6-OHDA, and PX + 6-OHDA groups was successively significantly increased (Hc = 256.25, P < 0.001). The gray value of TH (+) fibers in the NS, MT + 6-OHDA, N + 6-OHDA, and PX + 6-OHDA groups was also successively significantly increased (F = 99.33, P < 0.001). The staining intensities of Bax and Bcl-2 were as follows: Group NS +/+, Group MT + 6-OHDA ++/+, Group N + 6-OHDA ++/+, and PX + 6-OHDA +++/+. The concentrations of MDA in the NS, MT + 6-OHDA, N + 6-OHDA, and PX + 6-OHDA groups were significantly increased in sequence (Hc = 296.309, P < 0.001). CONCLUSIONS: Neuronal damage of the VTA by 6-OHDA might induce VTA-mPFC nerve fibers to undergo anterograde nerve damage, in turn inducing transneuronal damage of the mPFC. PX significantly exacerbated the neurotoxicity in the mPFC, which was induced by the neuronal injury of the VTA. However, MT replacement therapy significantly alleviated the neurotoxicity in the mPFC.

Roles of sigma-1 receptors in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of senile dementia all over the world. Still no existing drugs can effectively reverse the cognitive impairment. However, Sigma-1 (σ-1) receptors have been long implicated in multiple neurological and psychiatric conditions over these years. In this review, we discuss the current understanding of σ-1 receptor functions. Through regulation of lipid rafts, secretases, kinases, neuroceptors and ion channels, σ-1 receptors can influence cellular signal transduction, TCA cycle, oxidative stress, neuron plasticity and neurotransmitter release etc. Based on this, we suggest the key cellular mechanisms linking σ-1 receptor to Alzheimer's disease. Besides, we detail the evidences showing that σ-1 receptors agonists, being the promising compounds for treatment of cognitive dysfunction, exhibit robust neuroprotection and anti-amnesia effect against Aß neurotoxicity in the progress of Alzheimer's disease. The evidence comes from animal models, preclinical studies in humans and full clinical trials. In addition, the questions to be solved regarding this receptor are also presented. When concerned with NMDAR, σ-1 receptor activation may result in two totally different influences on AD. Utilization of σ-1 agents early in AD remains an overlooked therapeutic opportunity. This article may pave the way for further studies about sigma-1 receptor on Alzheimer's disease.