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Neurodegenerative diseases such as Alzheimer's disease and polyglutamine diseases are characterized by abnormal accumulation of misfolded proteins, leading to neuronal dysfunction and subsequent neuron death. However, there is a lack of studies that integratemolecular, morphological, and functional analyses in neurodegenerative models to fully characterize these time-dependent processes. In this study, we used C. elegans models expressing Ab1-42 and polyglutamine to investigate early neuronal pathogenic features in olfactory neurons. Both models demonstrated significant reductions in odor sensitivity in AWB and AWC chemosensory neurons as early as day 1 of adulthood, while AWA chemosensory neurons showed no such decline, suggesting cell-type-specific early neuronal dysfunction. At the molecular level, Ab1-42 or Q40 expression caused age-dependent protein aggregation and morphological changes in neurons. By day 6, both models displayed prominent protein aggregates in neuronal cell bodies and neurites. Notably, AWB neurons in both models showed significantly shortened cilia and increased instances of enlarged cilia as early as day 1 of adulthood. Furthermore, AWC neurons expressing Ab1-42 displayed calcium signaling defects, with significantly reduced responses to odor stimuli on day 1, further supporting early behavioral dysfunction. In contrast, AWA neuron did not exhibit reduced calciumresponses, consistent with the absence of detectable decreases in olfactory sensitivity in these neurons. These findings suggest that decreased calcium signaling and dysfunction in specific sensory neuron subtypes are early indicators of neurodegeneration in C. elegans, occurring prior to the formation of visible protein aggregates. We found that the ER unfolded protein response (UPR) is significantly activated in worms expressing Ab1-42. Activation of the AMPK pathway alleviates olfactory defects and reduces fibrillar Ab in these worms. This study underscores the use of C. elegans olfactory neurons as a model to elucidate mechanisms of proteostasis in neurodegenerative diseases and highlights the importance of integrated approaches. [ABSTRACT FROM AUTHOR]

Background: Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism. Methods: Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR. Results: Salidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2'-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration. Conclusions: Salidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Objective To investigate the changes of retinal nerve fiber layer (RNFL) thickness and superficial vascular density in patients with Parkinson's disease (PD), and analyze the correlation between the changes and disease severity. Methods Total 43 patients (76 eyes) with PD admitted to the Affiliated Hospital of North Sichuan Medical College from June 2021 to March 2022, and 45 patients (90 eyes) with normal neurological and visual functions from their family members were recruited as the control group. Optical coherence tomography angiography (OCTA) was used to measure RNFL thickness, retinal blood vessel length density and perfusion density, and the area and circumference of foveal avascular zone (FAZ). Disease severity was evaluated by modified Hoehn - Yahr staging, and motor function was evaluated by Unified Parkinson's Disease Rating Scale III (UPDRS III) in PD group. Pearson and partial correlation analyses were used to investigate the correlation between retinal parameters and PD severity. Results Comparison of OCTA related parameters between the 2 groups: RNFL thickness (t = - 6.424, P = 0.000), central length density (t = - 3.629, P = 0.000), inner ring length density (Z = - 2.846, P = 0.004) and central perfusion density (Z = - 2.703, P = 0.007) in the PD group were lower than those in the control group. Correlation analysis showed that RNFL thickness was negatively correlated with UPDRS-III score (r = - 0.625, P = 0.000). Conclusions RNFL thickness may be a potential indicator for early diagnosis and evaluation of the severity of PD. [ABSTRACT FROM AUTHOR]

Introduction. Transient global ischaemia in rodents causes selective loss of hippocampal CA1neurons, but the potential involvement of endocytic pathways has not been fully explored. The aim of this study was to investigate the changes in early endosomes in the CA1 subfield after ischaemia and reperfusion. Material and methods. A four-vessel occlusion (4-VO) model was established in Wistar rats to induce 13 minutes of global cerebral ischaemia. Neuronal death was detected by Fluoro-Jade B (FJ-B) staining at various intervals after reperfusion, and intracellular membrane changes in ischaemic neurons were revealed using DiOC6(3), a lipophilic fluorescent probe. Ras-related protein Rab5 (Rab5) immunostaining was performed to detect changes in early endosomes in ischaemic neurons. Western blot analysis was used to confirm the morphological observations on Rab5 in the CA1 hippocampal subfield. Results. FJ-B staining confirmed progressive neuronal death in the CA1 subfield in ischaemic rats after reperfusion. DiOC6(3) staining revealed abnormally increased membranous components in ischaemic CA1 neurons. Specifically, early endosomes, as labelled by Rab5 immunostaining, significantly increased in number and size in CA1 neurons at 1.5 and 2 days post-reperfusion, followed by rupture at day 3 and a decrease in staining intensity at day 7 post-reperfusion. Western blot analysis confirmed a significant upregulation of Rab5 protein levels at day 2, which returned to near control levels by day 7. Conclusions. Our study revealed significant changes in the dynamics of early endosomes in CA1 neurons after ischaemia-reperfusion injury. The initial increase in the area fraction of early endosomes in CA1 neurons may reflect an upregulation of endocytic activity, whereas the fragmentation and reduction of early endosomes at the later stage may indicate a failure of adaptive mechanisms of ischaemic neurons against ischaemia-induced death. Understanding the temporal dynamics of early endosomes provides critical insights into the cellular mechanisms that govern fate of CA1 hippocampal neuronsl after ischaemia/reperfusion. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics of anti-neuronal antibody positive paraneoplastic neurological syndrome related to immune checkpoint inhibitors (ICI-PNS). Methods and Results A total of 5 patients with anti-neuronal antibody positive ICI-PNS in Peking Union Medical College Hospital from January 2012 to March 2024 were included. Tumor types included small cell lung cancer (2 cases), malignant melanoma (one case), Hodgkin lymphoma (one case) and cervical cancer (one case). Immune checkpoint inhibitors (ICIs) included programmed death 1 (PD-1) inhibitors (3 cases), programmed cell death ligand 1 (PD-L1) inhibitors (one case) and bispecific PD-1/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors (one case). All 5 patients presented with high-risk neurologic phenotypes of paraneoplastic neurological syndrome (PNS), of which 4 presented with limbic encephalitis and one presented with rapidly progressive cerebellar syndrome. Anti-neuronal antibodies detected in serum and/or cerebrospinal fluid of patients included anti-Hu, γ-aminobutyric acid receptor type B (GABABR), sex-determining region of Y chromosome-related high mobility group box 1 (SOX1), metabotropic glutamate receptor 5 (mGluR5) and Yo antibodies. Neurological syndromes occurred within 2 weeks after receiving ICIs in 4 patients. The modified Rankin Score (mRS) of 4 patients was 3 at peak of illness, and one patient was 5 at peak of illness. The Common Terminology Criteria for Adverse Events (CTCAE) was grade 3 in all 5 patients. After withdrawal of ICIs and treatment with glucocorticoids and intravenous immunoglobulin (IVIg), the neurological symptoms of the patients were improved. Conclusions High/intermediate-risk anti-neuronal antibodies are diagnostic markers of ICI-PNS. Evaluation of ICI-PNS clinical phenotypes and CTCAE grading are important for immunotherapy. Discontinuation of ICIs, administration of glucocorticoids and IVIg can improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between retinal nerve fiber layer (RNFL) thickness and cognitive dysfunction in patients with mild ischemic stroke. Methods Total 146 patients with mild ischemic stroke that diagnosed and treated in Chengde Central Hospital in Hebei from January 2020 to December 2021 were included. Optical coherence tomography (OCT) was used to measure the RNFL thickness in each quadrant of both eyes, and Mini -Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Results In patients with mild ischemic stroke, the RNFL thickness at the superior side of left eye was greater than right eye (t = - 4.589, P = 0.000), and the RNFL thickness at the temporal side of right eye was greater than left eye (t = 3.639, P = 0.000). Correlation analysis showed that the correlation between the RNFL thickness at the superior side of the left eye and the MMSE score (r = 0.385, P = 0.000), the RNFL thickness at the temporal side of the left eye and the National Institutes of Health Stroke Scale (NIHSS) score at admission (r = 0.170, P = 0.020) were positively correlated. The correlation between the RNFL thickness at the inferior side of the left eye and the history of drinking (r = - 0.216, P = 0.011), the RNFL thickness at the temporal side of the right eye and the history of hypertension (r = - 0.194, P = 0.023) were negativley correlated. Conclusions The thinning of RNFL in patients with mild ischemic stroke may have a certain degree of association with cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: The ventral tegmental area (VTA) is less affected compared to substantia nigra pars compacta (SNc) in Parkinson's disease (PD). This study aimed to quantitatively evaluate iron content in the VTA across different stages of PD in order to help explain the selective loss of dopamine neurons in PD. Methods: Quantitative susceptibility mapping (QSM) data were obtained from 101 PD patients, 35 idiopathic rapid eye movement sleep behavior disorder (RBD) patients, and 62 healthy controls (HCs). The mean QSM values in the VTA and SNc were calculated and compared among the groups. Results: Both RBD and PD patients had increased iron values in the bilateral SNc compared with HCs. RBD and PD patients in the Hoehn-Yahr (H & Y) stage 1 did not show elevated iron values in the VTA, while PD patients with more than 1.5 H & Y staging had increased iron values in bilateral VTA compared to HCs. Discussion: This study shows that there is no increased iron accumulation in the VTA during the prodromal and early clinical stages of PD, but iron deposition increases significantly as the disease becomes more severe. [ABSTRACT FROM AUTHOR]

Background and objectives: Depression is a common comorbidity of dementia and may be a risk factor for dementia. Accumulating evidence has suggested that the cholinergic system plays a central role in dementia and depression, and the loss of cholinergic neurons is associated with memory decline in aging and Alzheimer's patients. A specific loss of cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) is correlated with depression and dysfunction of cognition in mice. In this study, we examined the potential regenerative mechanisms of knockdown the RNA-binding protein polypyrimidine tract binding protein (PTB) in reversing depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons. Methods: We lesioned cholinergic neurons in mice induced by injection of 192 IgG-saporin into HDB; then, we injected either antisense oligonucleotides or adenoassociated virus-shRNA (GFAP promoter) into the injured area of HDB to deplete PTB followed by a broad range of methodologies including behavioral examinations, Western blot, RT-qPCR and immunofluorescence. Results: We found that the conversion of astrocytes to newborn neurons by using antisense oligonucleotides on PTB in vitro, and depletion of PTB using either antisense oligonucleotides or adeno-associated virus-shRNA into the injured area of HDB could specifically transform astrocytes into cholinergic neurons. Meanwhile, knockdown of PTB by both approaches could relieve the depression-like behaviors shown by sucrose preference, forced swimming or tail-suspension tests, and alleviate cognitive impairment such as fear conditioning and novel object recognition in mice with lesioned cholinergic neurons. Conclusion: These findings suggest that supplementing cholinergic neurons after PTB knockdown may be a promising therapeutic strategy to revert depressionlike behaviors and cognitive impairment. [ABSTRACT FROM AUTHOR]

As one of the important by-products of T axus chinensis (Pilg.) Rehder, its fruit (TCF) has a sweet taste, which is commonly used in folklore to make health care wine reputed for enhancing immune function and promoting anti-aging effects, especially popular in the longevity villages of China for a long history. Evidences had showed that Taxus chinensis fruit contained polysaccharides, flavonoids, amino acids and terpenoids, which all were free of toxic compounds, but its medicinal value has not been fully recognized. Our previous studies have found that TCF extract may reverse many biological events, including oxidative stress, inflammatory response, neuronal apoptosis, etc. by in silico methods, suggesting potential avenues for future pharmaceutical exploration in aging and age-related diseases. Yet, the anti-aging properties of TCF have not been specifically studied, this study aims to fill this gap by investigating the effects of TCF extract (TCFE) in an aging mouse model, particularly focusing on its role in inhibiting microglial activation and elucidating its underlying anti-aging mechanisms. An aging mouse model was induced using D-galactose, with interventions involving high, medium, and low doses of TCFE compared to a positive control (2 mg/kg rapamycin combined with 100 mg/kg metformin). The methodology involved evaluating behavioral changes, serum oxidative and antioxidative markers, hypothalamic β-galactosidase activity, expression of the aging-related protein P63, serum inflammatory factors, and the TLR4/NF-κB/NLRP3 inflammatory pathway in hypothalamic tissues. Additionally, to strengthen our in vivo findings, we conducted in vitro experiments on LPS-stimulated BV2 microglial cells. Finally, UPLC-MS/MS for precise component analysis using compound standards, coupled with molecular docking analyses, were employed to discern and elucidate the anti-inflammatory mechanisms of TCF. In vivo results revealed TCFE significantly ameliorated behavioral deficits, reduced oxidative stress markers (MDA) and pro-inflammatory cytokines (IL1-β, IL-6, IFNg, TNFα, IL-17), and increased in antioxidants (SOD, T-AOC) and anti-inflammatory factors (IL-10). TCFE also reduced hypothalamic senescence, improved cellular integrity, lowered p63, and inhibited microglia activation and inflammatory pathways (TLR4, NFKB, NLRP3). The overall effect of TCFE was better than that of the positive drug group (rapamycin combined with metformin). In vitro results further revealed that TCFE markedly decreased IL1-β, NFKB, and TLR4 levels in BV2 microglial cells, showing comparable efficacy to a TLR4 classic positive inhibitor C34, supporting its anti-inflammatory role. Through UPLC-MS/MS analysis coupled with compound standards, we identified ten bioactive compounds, including gallocatechin, epigallocatechin, catechin, procyanidin B2, kaempferol, quercetin, rutin, naringin, apigenin, ginkgetin. All these compounds showed strong binding affinity to TLR4, notably procyanidin B2 and rutin, potentially through hydrogen bonds, aromatic cation-π interactions, and hydrophobic interactions, suggesting a molecular basis for their anti-inflammatory action. TCFE showed strong anti-aging effects by inhibiting microglia activation and lessening oxidative stress and modulating inflammatory pathways. This research supports TCF's use in anti-aging and sets a base for future drug development in the realms of neuroinflammation and aging. [Display omitted] • TCFE attenuated aging behaviors and neuroinflammation. • TCFE reduced oxidative stress, inhibited microglia activation and inflammation response. • TCFE suppresses hypothalamic aging markers and enhances cellular integrity. • TCFE inhibited inflammatory pathways (TLR4,NFKB, NLRP3) in microglia. • Procyanidin B2 and rutin strongly bind to TLR4, contributing to anti-inflammatory effects of TCFE. [ABSTRACT FROM AUTHOR]

Regulation of endoplasmic reticulum stress (ER) stress-induced apoptosis and nerve regeneration is a hopeful way for acute spinal cord injury (SCI). Sitagliptin (Sita) is one of dipeptidyl peptidase-4 (DPP-4) inhibitor, which is beneficial neurons damaged diseases. However, its protective mechanisms of avoiding nerve injury remain unclear. In this study, we further investigated the mechanism of the anti-apoptotic and neuroprotective effects of Sita in promoting locomotor recovery from SCI. In vivo results showed that Sita treatment reduced neural apoptosis caused by SCI. Moreover, Sita effectively attenuated the ER tress and associated apoptosis in rats with SCI. A striking feature was the occurrence of nerve fiber regeneration at the lesion site, which eventually led to significant locomotion recovery. In vitro results showed that the PC12 cell injury model induced by Thapsigargin (TG) also showed similar neuroprotective effects. Overall, sitagliptin showed potent neuroprotective effects by targeting the ER stress-induced apoptosis both in vivo and vitro, thus facilitating the regeneration of the injured spinal cord. [ABSTRACT FROM AUTHOR]

Objective: ECG recordings often suffer from a set of artifacts with varying types, severities, and durations, and this makes an accurate diagnosis by machines or medical doctors difficult and unreliable. Numerous studies have proposed ECG denoising; however, they naturally fail to restore the actual ECG signal corrupted with such artifacts due to their simple and naive noise model. In this pilot study, we propose a novel approach for blind ECG restoration using cycle-consistent generative adversarial networks (Cycle-GANs) where the quality of the signal can be improved to a clinical level ECG regardless of the type and severity of the artifacts corrupting the signal. Methods: To further boost the restoration performance, we propose 1D operational Cycle-GANs with the generative neuron model. Results: The proposed approach has been evaluated extensively using one of the largest benchmark ECG datasets from the China Physiological Signal Challenge (CPSC-2020) with more than one million beats. Besides the quantitative and qualitative evaluations, a group of cardiologists performed medical evaluations to validate the quality and usability of the restored ECG, especially for an accurate arrhythmia diagnosis. Significance: As a pioneer study in ECG restoration, the corrupted ECG signals can be restored to clinical level quality. Conclusion: By means of the proposed ECG restoration, the ECG diagnosis accuracy and performance can significantly improve. [ABSTRACT FROM AUTHOR]

Honokiol, the main bioactive extract of Magnolia officinalis, exhibits extensive therapeutic actions. Its treatment for advanced non-small cell lung cancer is undergoing clinical trials in China. However, the published safety evaluation studies have focused on extract mixtures of Magnolia officinalis in which the honokiol content was well below the reported clinical dose of the honokiol monomer. Therefore, safety assessment of the honokiol monomer is urgently needed. Our previous studies have already demonstrated that a high dose of the honokiol microemulsion (0.6 μg/mL) induces developmental toxicity in rats and zebrafish by inducing oxidative stress. By exploring the relationship between time and toxicity, we found that developmental toxic responses were stage-dependent. They mainly occurred within the first 24 h post fertilization (hpf) especially the first 12 hpf. In zebrafish, low doses of honokiol microemulsion (0.15, 0.21 μg/mL) significantly decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the mRNA expression of bcl-2. In contrast, high dose (0.6 μg/mL) increased the levels of ROS and MDA, decreased activities and mRNA expression of superoxide dismutase (SOD) and catalase (CAT), and increased mRNA expression of bax, c-jnk, p53 and bim. By acridine orange staining, we found that a high dose of honokiol microemulsion induced apoptosis mainly in zebrafish brain. In rat pheochromocytoma cells (PC12 cells), low doses of the honokiol microemulsion (1, 5, 10 µM) exerted a protective effect against H2O2-induced oxidative damage while high doses (≥20 µM) induced oxidative stress, which further confirms the dual effects of honokiol microemulsion on nerve cells. These dual roles of the honokiol microemulsion in oxidation–reduction reactions and apoptosis may be regulated by the forkhead box class O (FoxO) signaling pathway. Due to the potential of developmental toxicity, we recommend that the administration of high dose honokiol microemulsion in pregnant women should be considered with caution. [ABSTRACT FROM AUTHOR]

Objective To investigate the role and mechanism of erythroid precursor cells (EPC) and its subtypes in Alzheimer's disease (AD). Methods The patients with AD (AD group) firstly diagnosed and treated in Qinghai Provincial People's Hospital from October 2018 to October 2019 were included, and olanzapine combined with donepezil were used for treatment; while 30 healthy volunteers were selected as the control group. The proportion of EPC, CD45+EPC and CD45-EPC in peripheral blood in control group and AD group before and after treatment was detected and sorted by flow cytometry. Primary cortical neurons were used to construct AD cells model, flow cytometry was used to detect the apoptosis of neurons in control group, AD model group, CD45+EPC group, CD45-EPC group and Artemin block group. Results There was no significant difference in the proportion of EPC in peripheral blood between AD group and control group, or between AD group before and after treatment (P > 0.05, for all). However, the proportion of CD45+EPC subtype (t = 7.277, P = 0.000) and ROS content (t =10.817, P = 0.000) in AD group before treatment were higher than those in control group. The proportion of CD45 EPC subtype (t = 7.277, P = 0.000) and Artemin content (t = 6.547, P = 0.000) were lower than those in control group, but there were no significant differences in proportion of CD45+EPC and CD45-EPC subtypes, ROS and Artemin contents before and after treatment in AD group (P > 0.05, for all). Neuronal apoptosis experiment showed the proportion of neuronal apoptosis in different treatment groups was significantly different (F = 25.662, P = 0.000). The proportion of neuronal apoptosis in AD model group (t = 9.330, P = 0.000), CD45+EPC group (t = 14.362, P = 0.000), CD45-EPC group (t = 2.423, P = 0.036) and Artemin block group (t = 9.970, P = 0.000) were higher than those in control group. AD model group (t = 4.548, P = 0.001), CD45+EPC group (t = 8.759, P = 0.000), Artemin block group (t = 5.387, P = 0.000) were higher than those in CD45-EPC group. CD45+EPC group was also higher than that in AD model group (t = 5.091, P = 0.000) and Artemin block group (t = 3.175, P = 0.004). Conclusions The proportion of CD45+EPC subtype in peripheral blood of AD patients was significantly increased and the proportion of CD45-EPC subtype was decreased. CD45-EPC subtype can reduce the neuronal apoptosis induced by AD by secreting Artemin. [ABSTRACT FROM AUTHOR]

Objective: Acoustic neuroma (AN) is a common benign tumor. Little is known of neuropsychological studies in patients with acoustic neuroma, especially cognitive neuropsychology, and the neuropsychological abnormalities of patients affect their life quality. The purpose of this study was to explore the changes in the cognitive function of patients with acoustic neuroma, and the possible mechanism of these changes by structural magnetic resonance imaging. Materials and methods: We used a neuropsychological assessment battery to assess cognitive function in 69 patients with acoustic neuroma and 70 healthy controls. Then, we used diffusion tensor imaging data to construct the structural brain network and calculate topological properties based on graph theory, and we studied the relation between the structural brain network and cognitive function. Moreover, three different subnetworks (shortrange subnetwork, middle-range subnetwork, and long-range subnetwork) were constructed by the length of nerve fibers obtained from deterministic tracking. We studied the global and local efficiency of various subnetworks and analyzed the correlation between network metrics and cognitive function. Furthermore, connectome edge analysis directly assessed whether there were differences in the number of fibers in the different brain regions. We analyzed the relation between the differences and cognitive function. Results: Compared with the healthy controls, the general cognitive function, memory, executive function, attention, visual space executive ability, visual perception ability, movement speed, and information processing speed decreased significantly in patients with acoustic neuroma. A unilateral hearing loss due to a left acoustic neuroma had a greater impact on cognitive function. The results showed that changes in the global and local metrics, the efficiency of subnetworks, and cognitively-related fiber connections were associated with cognitive impairments in patients with acoustic neuroma. Conclusion: Patients exhibit cognitive impairments caused by the decline of the structure and function in some brain regions, and they also develop partial compensation after cognitive decline. Cognitive problems are frequent in patients with acoustic neuroma. Including neuropsychological aspects in the routine clinical evaluation and appropriate treatments may enhance the clinical management and improve their life quality. [ABSTRACT FROM AUTHOR]

Introduction: Alterations in the visual pathway involving the retina have been reported in amyotrophic lateral sclerosis (ALS) but they lack consistency and subgroup analysis. We aimed to assess the retinal nerve fiber layer (RNFL) and retinal ganglion cells (RGCs) alterations in different stages of ALS patients and their association with ALS progression parameters. Methods: The study population consisted of 70 clinically diagnosed ALS patients and 55 age, sex matched controls. All of them underwent ophthalmic assessments and optical coherence tomography imaging. Four quadrants of the peripapillary RNFL and ganglion cell/inner plexiform complex (GCIP) were observed and automatically measured. Early-stage distal motor neuron axon dysfunction in ALS was detected by compound muscle action potential (CMAP) of the distal limbs within 12 months. The ALS disease parameters included the ALSFRS-R score and the disease progression rate (ΔFS). Results: Generally compared with controls, the nasal (p = 0.016) quadrant of the RNFL was thicker in ALS patients. When controlling for age and ΔFS, the RNFL(r = 0.37, p = 0.034) and GCIP(r = 0.40, p = 0.021) were significantly thickened as disease progressed within 12 months, while the RNFL declined with time after one year (r = −0.41, p = 0.037). ALS patients was subclassified into thickened RNFL (T-RNFL, >95th percentile of normal), impaired RNFL (I-RNFL, <5th percentile of normal) and normal RNFL. There were significant differences in the GCIP among the three groups (p < 0.001). In the T-RNFL group (n = 18), the RNFL was negatively correlated with the abductor pollicis brevis-CMAP amplitude within 12 months (r = −0.56, p = 0.01). Patients within 12 months in this group progressed faster than others (p = 0.039). In the normal RNFL group (n = 22), 13 patients were diagnosed beyond 12 months, whose ΔFS was remarkably lower (p = 0.007). In I-RNFL group (n = 30), the early stage patients (<12 months) had significant higher ΔFS (p = 0.006). One patient was with SOD1 pathogenic variant (p.A5V). Conclusion: Alterations of retinal nerve were not consistent in ALS patients with diverse phenotypes and progression rates. Generally speaking, the RNFL thickened during the first year and then gradually declined, which is related to but preceding the thickness change of the RGCs. Patients with a significant RNFL thinning in the early stage may have a faster progression rate. The inverse U-shaped curve transformation might be in accordance with early-stage motor neuron axonopathy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acute cerebral infarction indicates hypoxic-ischemic necrosis in brain tissue, which has become the first cause of death in China. Hypoxiainducible factor-1α plays a dual role on the occurrence and development of cerebral infarction. Therefore, it is particularly important to use its inhibitor at immediate time in clinical therapy. OBJECTIVE: To investigate the effects of hypoxia-inducible factor-1α on the regulation of brain injury/protection in rats with acute cerebral infarction. METHODS: Male Sprague-Dawley rats were randomized into three groups: sham operation group (sham), MACO-24 h group, and MACO-72 h group. A middle cerebral artery occlusion (MCAO) model was prepared by thread embolization in the latter two groups. TTC, Nissl staining, immunohistochemical staining and western blot were used to detect infarct volume and microglia morphology in rat brain tissue, the expression levels of hypoxia-inducible factor 1α, caspase 3, interleukin-1β and p-NF-κBp65 were detected, and the secretion levels of interleukin-6 and tumor necrosis factor-α in rat peripheral blood. The study protocol was approved by the Animal Ethics Committee of the First Affiliated Hospital of Jiamusi University (approval No. JMSU-210). RESULTS AND CONCLUSION: Compared with the sham group, the cerebral infarction area in the MCAO groups was significantly increased, and the brain nerve cells were seriously damaged, arranged disorderly and reduced significantly in number. However, there was no significant difference between the MCAO-24 h group and the MCAO-72 h group. Compared with the sham group, the expression levels of hypoxia-inducible factor 1α, caspase3, p-NF-κBp65, and interleukin- 1β in the brain tissue of the MCAO groups were significantly increased (P < 0.05, P < 0.01). The secretion levels of interleukin-6 and tumor necrosis factor-α was significantly increased (P < 0.01) in the peripheral blood. However, compared with the MCAO-24 h group, the expression of caspase 3 in the MCAO-72 h group was significantly decreased, while the secretion of interleukin-6 and tumor necrosis factor-α increased. To conclude, hypoxia-inducible factor 1α participates in the brain injury/protection process after acute cerebral infarction, and the time target is determined as 24-72 hours after MCAO. The determination of the time target can provide a sufficient theoretical basis and therapeutic strategy for determining the optimal use time of clinical hypoxia-inducible factor-1α inhibitors. [ABSTRACT FROM AUTHOR]

Background: Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer's disease (AD) involving imbalanced beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). MicroRNAs (miRNAs) are associated with AD.Objective: This study aimed to investigated whether plasma miRNAs can predict prodromal AD or are associated with AD pathology.Methods: Participants in the discovery set (n = 10), analysis set (n = 30), and validation set (n = 80) were screened from the China Longitudinal Aging Study. RNA was extracted from the participants' plasma. Microarray sequencing provided miRNA profiles and differentially expressed miRNAs (DEmiRNAs) in the discovery set included patients with 18F-Flutemetamol positron emission tomography scan-confirmed aMCI. Potential biomarkers were screened in the analysis set. The predict capability of candidate miRNAs was assessed in the validation set. Candidate miRNAs modulation of BACE1 expression was explored in rat and human hippocampal neurons in vitro.Results: We verified 46 significant DEmiRNAs between the aMCI and NC groups (p < 0.05), among which 33 were downregulated. In the analysis set, miR-1185-2-3p, miR-1909-3p, miR-22-5p, and miR-134-3p levels decreased significantly in the aMCI group. These miRNAs and previously identified miR-107 were selected as potential biomarkers. A prediction model comprising these five miRNAs showed outstanding accuracy (81.25%) to discriminate aMCI at cut-off value of 0.174. Except for miR-134-3p, the other four miRNAs significantly suppressed Bace1 expression in rat hippocampal neurons in vitro. BACE1 modulation of miR-1185-2-3p, miR-1909-3p, and miR-134-3p was confirmed in human hippocampal neurons in vitro.Conclusion: A predictive model consisting of five BACE1-related plasma miRNAs could be a novel biomarker for aMCI. [ABSTRACT FROM AUTHOR]

Recent advances in functional genomics have facilitated the identification of multiple genes and isoforms associated with the genetic risk of schizophrenia, yet the causal variations remain largely unclear. A previous study reported that the schizophrenia risk single-nucleotide polymorphism (SNP) rs7085104 at 10q24.32 was in high linkage disequilibrium (LD) with a human-specific variable number of tandem repeat (VNTR), and both were significantly associated with the brain mRNA expression of a human-unique AS3MT d2d3 isoform in Europeans and African Americans. In this study, we have shown the direct regulation of the AS3MT d2d3 mRNA expression by this VNTR through an in vitro minigene splicing assay, suggesting that it is likely a causative functional variation. Intriguingly, we have further confirmed that the VNTR and rs7085104 are significantly associated with AS3MT d2d3 mRNA expression in brains of Han Chinese donors, and rs7085104 is also associated with risk of schizophrenia in East Asians. Finally, the overexpression of AS3MT d2d3 in cultured primary hippocampal neurons results in significantly reduced densities of mushroom dendritic spines, implicating its potential functional impact. Considering the crucial roles of dendritic spines in neuroplasticity, these results reveal the potential regulatory impact of the schizophrenia risk VNTR on AS3MT d2d3 and provide insights into the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

BACKGROUND: The porous scaffold fabricated with collagen and heparin sulfate can effectively immobilize neurotrophic factor and greatly improve neurological and locomotor function recovery. OBJECTIVE: To investigate the effect of collagen/heparan sulfate scaffold loaded with brain-derived neurotrophic factor in the treatment of traumatic brain injury(TBI). METHODS: Collagen scaffolds, collagen/heparan sulfate scaffolds and collagen/heparan sulfate scaffolds loaded with brain-derived neurotrophic factor were prepared. The porosity, water absorption, compression modulus and compression stress of collagen scaffolds and collagen/heparan sulfate scaffolds were measured. The in vitro sustained-release performance of collagen/heparan sulfate scaffolds loaded with brain-derived neurotrophic factor was measured. The cytotoxicity and cytocompatibility of collagen/heparin sulfate scaffolds and collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor were detected. Forty-eight Sprague-Dawley rats were randomly assigned to undergo corresponding interventions: opening bone window followed by suture(control group), induction of craniocerebral trauma(model group), induction of craniocerebral trauma + implantation of collagen/heparin sulfate scaffolds(scaffold group), and induction of craniocerebral trauma + implantation of collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor(brain-derived neurotrophic factor group). After surgery, modified neurological severity scoring and Morris water maze test were performed to evaluate the recovery of neurological and locomotor function. Rat cerebral morphology was performed. This study was approved by the Animal Ethics Committee of Characteristic Medical Center of Chinese People’s Armed Police Force, China. RESULTS AND CONCLUSION: (1) The porosity, compression modulus and compression stress of the collagen/heparin sulfate scaffold were significantly higher than those of the collagen scaffold(P < 0.05), and the water absorption rate of the collagen/heparin sulfate scaffold was lower than that of the collagen scaffold(P < 0.05). (2) Collagen/heparin sulfate scaffolds had no cytotoxicity, and collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor were more conducive to the proliferation of cerebral microvascular endothelial cells; cerebral microvascular endothelial cells grew well and distributed evenly in the micropores of the collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor. (3) There were a large number of newly formed nerve cells and nerve fibers in the lesions in the scaffold and brain-derived neurotrophic factor groups. The number of nerve cells and the density of nerve fibers in the scaffold group were higher compared with the brain-derived neurotrophic factor group. (4) In the brain-derived neurotrophic factor group, escape latency was shorter(P < 0.01, P < 0.05), quadrant stay time and the number of crossing the platform were higher(P < 0.01, P < 0.05) compared with the scaffold and model groups. (5) The modified neurological severity score in the brain-derived neurotrophic factor group was significantly lower than that in the scaffold and model groups, respectively at postoperative 3-7 weeks(P < 0.05, P < 0.01). (6) These results suggest that collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor can promote neurological and locomotor function recovery in rats after traumatic brain injury. [ABSTRACT FROM AUTHOR]

Lipopolysaccharides (LPS) are proinflammation mediators that can induce the inflammatory model of the hippocampal neuron, and neuroinflammation participates in the pathophysiology of depression. Xiaoyao Pill is a classical Chinese medicine formula that has been used for the treatment of mental disorders such as depression in China since the Song dynasty. We established a hippocampal neuronal cell inflammation model by LPS and investigate the intervention effect and mechanism of Xiaoyao Pills. The expression levels of IL-6, TNF-α, IDO, 5-HT, brain-derived neurotrophic factor, and β-nerve growth factor were detected by enzyme-linked immunosorbent assay. mRNA levels of IL-6, TNF-α, 5-HT1A, IDO-1, brain-derived neurotrophic factor, nerve growth factor, tropomyosin receptor kinase B, tropomyosin receptor kinase A, and cAMP response element-binding protein were detected by reverse transcription-polymerase chain reaction. To further validate, protein expression was determined by western blot and immunofluorescence. Lipopolysaccharide-induced neuroinflammatory state resulted in the release of IL-6, TNF-α, and IDO and a decrease of BDNF, NGF, TrkB, TrkA, CREB, p-CREB, p-CREB/CREB, and SYP and inhibited hippocampal neurogenesis in the hippocampal neuron. Xiaoyao Pills significantly decreased the levels of IL-6, TNF-α, and IDO in cell supernatant and increased the expression of BDNF, NGF, TrkB, TrkA, CREB, p-CREB, p-CREB/CREB, and SYP as well as the average optical density of BrdU/NeuN double-labelled positive cells. Our study shows that lipopolysaccharides induce inflammation and nerve damage in hippocampal neurons, which are closely related to the pathological mechanism of depression. Xiaoyao Pills (XYW) play an important neuroprotective effect, which is related to its inhibition of neuronal inflammation and promoting the recovery of nerve injury. These results provide a pharmacologic basis for the treatment of depression of XYW in clinical application. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. More than 25 ALS-related genes have been identified, accounting for approximately 10% of sporadic ALS (SALS) and two-thirds of familial ALS (FALS) cases. Several recent studies showed that genetic factors might have a larger contribution to young-onset ALS than to ALS cases overall. However, the genetic profile of young-onset ALS patients is not yet fully understood. Here, we investigated a cohort of 27 young-onset ALS patients (onset age < 45 years) through whole-exome sequencing (WES). Genetic analysis identified pathogenic variants of FUS (25.9%), SOD1 (22.2%), TARDBP (3.7%), and VCP (3.7%) in 27 young-onset ALS patients. Of 12 identified types of mutations, c.1528A > C in FUS and c.266G > A in VCP were novel. All of the cases in this study reflect a monogenic origin with an autosomal dominant mode of inheritance. Notably, a novel de novo missense mutation, c.1528A > C (p.K510Q), in FUS was identified in a 29-year-old ALS patient. Expression of the K510Q mutant FUS resulted in cytoplasmic mislocalization of FUS in cultured cells and induced neural toxicity in a fly model. This study provides further evidence of the genetic profile of young-onset ALS patients from China and expands the mutational spectrum of the FUS gene, with one new K510Q mutation identified. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spinal cord injuries triggers the release of high mobility group box 1 (HMGB1) from nerve cells to activate the nuclear factor-kappa B (NF-κB) by binding to cell membrane surface receptor, thereby inducing a series of pathological reactions, such as spinal cord edema or inflammation. However, little is reported on whether inhibition of HMGB1/NF-κB pathway could attenuate spinal cord astrocytes apoptosis after oxygen-glucose deprivation/reoxygenation (OGD/R). OBJECTIVE: To investigate the effect of HMGB1/NF-κB pathway on spinal cord astrocytes apoptosis after OGD/R. METHODS: Spinal cord astrocytes of newborn Sprague-Dawley rats (provided by the Laboratory Animal Center of Shanxi Medical University, China) were cultured in vitro and an OGD/R model was established. Spinal cord astrocytes were subjected to reoxygenation 6, 12, and 24 hours. Release of HMGB1 in the culture medium was detected by ELISA. The expression of HMGB1, Bcl-2 and Bax were detected by western blot and the cell survival rate was determined by MTT. The optimal reoxygenation time was then selected for the following experiments. Spinal cord astrocytes at passage 4 were divided into normal group, OGD6h/R24h group, OGD6h/R24h+ethyl pyruvate group, OGD6h/R24h+Bay 11-7082 group. After 24 hours of reoxygenation, the release of HMGB1 was detected by ELISA, the expression of HMGB1, NF-κB, Bcl-2 and BAX was analyzed by western blot, the survival rate of astrocytes was determined by MTT, and the apoptosis of astrocytes was measured by flow cytometry. RESULTS AND CONCLUSION: (1) The results showed that the best reoxygenation time was 24 hours, which was used for subsequent experiments. (2) Compared with the normal group, the release and expression of HMGB1 and NF-κB as well as the apoptotic rate of astrocytes were obviously increased in the OGD6h/R24h group (P < 0.05), while the survival rate of astrocytes and the ratio of Bcl-2/Bax were obviously declined in the OGD6h/R24h group (P < 0.05). Compared with the OGD6h/R24h group, the astrocyte survival rate and the ratio of Bcl-2/Bax were significantly raised (P < 0.05), while the expression of NF-κB and the apoptosis rate of astrocytes were remarkably decreased (P < 0.05) in the OGD6h/R24h+ethyl pyruvate and OGD6h/R24h+Bay 11-7082 groups. To conclude, the HMGB1/NF-κB signal pathway is involved in the regulation of apoptosis in spinal cord astrocytes after OGD/R. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive impairments. Vitegnoside is a flavonoid present in the medicinal plant Vitex negundo, widely used as a folk medicine in several Asian countries including China. It possesses several biological activities, including axon outgrowth, but no evidence is available on its effect on AD. Since no effective treatment is available to cure AD, the effect of vitegnoside on this disease was investigated. The human neuroblastoma SH-SY5Y cell line carrying the Swedish mutation that induces AβPP overexpression was used as an in vitro AD cell model. AβPP overexpression does not induce toxicity per se unless triggered by copper. Vitegnoside promoted neuroprotection through the improvement of cell viability, maintenance of cytomembrane integrity and nuclear homogeneity in these cells, but these effects were not observed in the copper-treated SH-SY5Y cells without AβPP overexpression used as the wild-type control, indicating that vitegnoside exerted neuroprotection under copper-triggered Aβ toxic conditions. Vitegnoside failed to decrease AβPP expression, Aβ40/42 levels, and oxidative stress due to copper-induced Aβ toxicity. However, its administration protected the mitochondrial function and restored the imbalance between pro-apoptotic and anti-apoptotic proteins. Additionally, vitegnoside inactivated p38 MAPK/MK2, JNK/c-Jun, and downstream NF-κB inflammatory transductions. Furthermore, the inactivation of p38 MAPK/JNK signaling contributed to vitegnoside-mediated neuroprotection resulting from pharmacological inhibition of p38 MAPK/JNK and in silico interaction prediction. Our study revealed the neuroprotective effect of vitegnoside and its potential mechanisms against copper-induced Aβ neurotoxicity. These findings highlighted the potential therapeutic effect of vitegnoside against AD progression. [ABSTRACT FROM AUTHOR]

Background: The article proposes a network public opinion risk assessment model for earthquake disasters, which can provide an effective support for emergency departments of China. Method: It uses the accelerated genetic algorithm (AGA) to improve BP neural network. The main contents: This article selects 10 indexes by using the methods of the principal component analysis (PCA) and cumulative contribution (CC) to assess the risk of the earthquake network public opinion. The article designs a BP algorithm to measure the risk degree of the earthquake network public opinion and uses AGA to improve the BP model for parameter optimization. Results: The experiment results of the improved BP model shows that its global error is 7.12×10, and the error is reduced to 22.35%, which showed the improving BP model has advantages in convergence speed and evaluation accuracy. Conclusion: The risk assessment method of network public opinion can be used in the practice of earthquake disaster decision. [ABSTRACT FROM AUTHOR]

Neural stem cells are multipotent stem cells that generate functional newborn neurons through a process called neurogenesis. Neurogenesis in the adult brain is tightly regulated and plays a pivotal role in the maintenance of brain function. Disruption of adult neurogenesis impairs cognitive function and is correlated with numerous neurologic disorders. Deciphering the mechanisms underlying adult neurogenesis not only advances our understanding of how the brain functions, but also offers new insight into neurologic diseases and potentially contributes to the development of effective treatments. The field of adult neurogenesis is experiencing significant growth in China. Chinese researchers have demonstrated a multitude of factors governing adult neurogenesis and revealed the underlying mechanisms of and correlations between adult neurogenesis and neurologic disorders. Here, we provide an overview of recent advancements in the field of adult neurogenesis due to Chinese scientists., (© 2023 Japanese Society of Developmental Biologists.)

Background: AIDS is a worrying public health issue in China and lacks timely and effective surveillance. With the diffusion and adoption of the Internet, the ‘big data’ aggregated from Internet search engines, which contain users’ information on the concern or reality of their health status, provide a new opportunity for AIDS surveillance. This paper uses search engine data to monitor and forecast AIDS in China. Methods: A machine learning method, artificial neural networks (ANNs), is used to forecast AIDS incidences and deaths. Search trend data related to AIDS from the largest Chinese search engine, Baidu.com, are collected and selected as the input variables of ANNs, and officially reported actual AIDS incidences and deaths are used as the output variable. Three criteria, the mean absolute percentage error, the root mean squared percentage error, and the index of agreement, are used to test the forecasting performance of the ANN method. Results: Based on the monthly time series data from January 2011 to June 2017, this article finds that, under the three criteria, the ANN method can lead to satisfactory forecasting of AIDS incidences and deaths, regardless of the change in the number of search queries. Conclusions: Despite the inability to self-detect HIV/AIDS through online searching, Internet-based data should be adopted as a timely, cost-effective complement to a traditional AIDS surveillance system. [ABSTRACT FROM AUTHOR]

Wampee (Clausena lansium) is a common fruit in South Asia. The pulp is a tasty food, and the seed is a typical traditional herb in China. However, we identified a primary toxic compound, Lansamide I, by NMR and X-ray diffraction of single-crystal. The compound occurred at 4.17 ± 0.16 mg/kg of dried seed and 0.08 ± 0.01 g/kg of fresh fruit. In our phenotype-based toxicity investigation, the compound caused decreased hatchability of zebrafish eggs, increased malformations such as enlarged yolk sacs and pericardial edema, and delayed body length development. Moreover, the compound also caused nerve cell damage and decreased locomotor activity. The compound caused an increase in peroxidation levels in vivo , with increases in both malondialdehyde and superoxide dismutase levels, but did not interfere with acetylcholinesterase levels. Metabolomic studies found that the compound caused significant up-regulation of 16 metabolites, mainly amino acids and peptides, which were involved in the nucleotide metabolism pathway and the betaine biosynthesis module. The qRT-PCR revealed that the substance interfered with the mRNA expression of tat and dctpp. These discoveries offer fresh perspectives on the toxicity mechanisms and metabolic response to the primary harmful molecules in wampee, which could inform the rational usage of wampee resources. [ABSTRACT FROM AUTHOR]

Purpose. To determine the correlations between peripapillary vessel density, retinal nerve fibre layer (RNFL) thickness, and myopic indices at retina quadrants with optical coherence tomography angiography (OCTA) in Chinese. Methods. Fifty-six subjects with a mean spherical equivalent (MSE) of −3.63 ± 0.29 D were included. Peripapillary RNFL thickness and retinal vessel density in four sectors (superior, nasal, inferior, and temporal quadrants) were determined by OCTA, and correlations of the main outcomes were analyzed. Results. Negative correlations were found between the peripapillary RNFL thickness and axial length (AL) at superior (r=−0.335, P=0.001) and inferior (r=−0.551, P<0.001) quadrants. There was a significant positive correlation with spherical equivalent (SE) at the corresponding quadrants as well as at the nasal quadrant (r=0.339, P=0.001; r=0.379, P<0.001; and r=0.209, P=0.039, resp.). Peripapillary retinal vessel density was also negatively correlated with AL at the nasal quadrant (r=−0.392, P<0.001), and only at the nasal quadrant, there was a positive correlation between the peripapillary vessel density and SE (r=0.319, P=0.001). Conclusions. The degree of myopia and elongation of AL were negatively correlated with peripapillary RNFL thickness at superior and inferior quadrants and with peripapillary retinal vessel density at the nasal quadrant. [ABSTRACT FROM AUTHOR]

Background: Recent research findings suggest that BDNF and BDNF signaling pathways participate in the development of major depressive disorder. Mitogen-activated extracellular signal-regulated kinase (MEK) is the most important kinase in the extracellular signal-regulated kinase pathway, and the extracellular signal-regulated kinase pathway is the key signaling pathway of BDNF, so it may play a role in development of depressive disorder. The aim of this study is to investigate the association between polymorphisms of the MAP2K1 (also known as MEK) gene and depressive disorder.Results: Three single nucleotide polymorphisms (SNPs), were significantly associated with depressive disorder: rs1549854 (p = 0.006), rs1432441 (p = 0.025), and rs7182853 (p = 0.039). When subdividing the sample by gender, two of the SNPs remained statistically associated with depressive disorder in females: rs1549854 (p = 0.013) and rs1432441 (p = 0.04).Conclusion: The rs1549854 and rs1432441 polymorphisms of the MAP2K1 gene may be associated with major depressive disorder, especially in females. This study is the first to report that the MAP2K1 gene may be a genetic marker for depressive disorder. [ABSTRACT FROM AUTHOR]

We previously reported a novel danshensu derivative ()-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM), which conferred cardioprotective and anti-thrombotic effects in vitro and in vivo. Here, we examined the neuroprotective actions of ADTM on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells 1 in vitro and zebrafish in vivo. Pretreatment with ADTM significantly inhibited 6-OHDA-induced cytotoxicity and production of reactive oxygen species (ROS) in PC12 cells through Akt signaling. Moreover, treatment with ADTM also inhibited expression of inducible nitric oxide synthase (iNOS) and production of intracellular nitric oxide (NO), which are associated with inflammation. In addition, ADTM exhibited significant protection against 6-OHDA-induced loss of tyrosine hydroxylase-positive dopaminergic neurons in a zebrafish model. Taken together, our findings suggest that ADTM is also a potential effective therapeutic agent for neurodegenerative conditions such as Parkinson's disease (PD) through anti-oxidant cytoprotective and anti-inflammatory actions. [ABSTRACT FROM AUTHOR]

Background: Antioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats. Methods: The expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot. Immunofluorescence was used to demonstrate the cell-specific localization of Nrf2 in TNC. Sulforaphane, a Nrf2 activator, was administered to NTG-induced rats. Then, the number of c-Fos- and nNOS-immunoreactive neurons in TNC was evaluated using immunofluorescence, and c-Fos and nNOS protein levels were quantified using western blot. Von Frey hair testing was used to evaluate the tactile thresholds of rats at different time points in different groups. Results: Total cellular and nuclear levels of the proteins Nrf2, HO1, and NQO1 were elevated in TNC after NTG injection, and Nrf2 was found to be located in the nucleus and cytoplasm of the neurons. Sulforaphane pretreatment significantly increased the nuclear Nrf2, HO1, and NQO1 levels in TNC. In addition, sulforaphane exposure effectively inhibited the expression of nNOS and c-Fos, reduced the number of nNOS and c-Fos immunoreactive neurons in TNC, and attenuated the tactile thresholds induced by NTG injection. Conclusion: Oxidative stress was involved in nitroglycerin-induced hyperalgesia. Activation of the Nrf2/ARE pathway inhibited the activation of TGVS and prevented the induction of hyperalgesia. Sulforaphane might therefore be an effective agent for hyperalgesia. Further studies are needed to discover the underlying mechanisms of the process. [ABSTRACT FROM AUTHOR]

Background: Non-arteritic anterior ischemic optic neuropathy (NA-AION) is one of the most common types of ischemic optic neuropathy. Several recent studies suggested that abnormalities of choroidal thickness might be associated with NA-AION. The main objective of this case-control study was to evaluate whether choroidal thickness is an ocular risk factor for the development of NA-AION by evaluating the peripapillary and subfoveal choroidal thicknesses in affected Chinese patients.Methods: Forty-four Chinese patients with unilateral NA-AION were recruited and compared with 60 eyes of 60 normal age and refractive-error matched control subjects. Peripapillary and subfoveal choroidal thicknesses were measured by enhanced depth imaging optical coherence tomography. Choroidal thicknesses of eyes with NA-AION and unaffected fellow eyes were compared with normal controls. Choroidal thicknesses of NA-AION eyes with or without optic disc edema were also compared. The correlation between choroidal thickness and retinal nerve fiber layer (RNFL) thickness, logMAR best-corrected visual acuity (BCVA), and the mean deviation (MD) of Humphrey static perimetry in NA-AION eyes were analyzed.Results: The peripapillary choroidal thicknesses at the nasal, nasal inferior and temporal inferior segments in NA-AION eyes with optic disc edema were significantly thicker compared with that of normal subjects (P < 0.05). There was no significant difference in the choroidal thicknesses between the unaffected fellow eyes of NA-AION patients and normal eyes of healthy controls; or between the NA-AION eyes with resolved optic disc edema and normal eyes (all P > 0.05). No significant correlation between choroidal thickness and RNFL thickness, logMAR BCVA and perimetry MD was found in eyes affected by NA-AION (all P > 0.05).Conclusions: Increase in peripapillary choroid thickness in some segments was found in NA-ION eyes with optic disc edema. However, our findings do not support the hypothesis that choroidal thickness is abnormal in Chinese patients with NA-AION compared with normal subjects with similar age and refractive error status. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is accompanied by cognitive impairment and is associated with an increased risk of dementia. Damage to brain structures such as white matter network disruption may underlie this cognitive disturbance. In the present study, 886 non-diabetic and 163 type 2 diabetic participants completed a battery of neuropsychological tests. Among them, 38 diabetic patients and 34 non-diabetic participants that matched the patients for age/sex/education received a magnetic resonance imaging-based diffusion tensor imaging. Then we calculated the topological properties of the white matter network using a graph theoretical method to investigate network efficiency differences between groups. We found that type 2 diabetic patients had inferior performances compared to the non-diabetic controls, in several cognitive domains involving executive function, spatial processing, memory, and attention. We also found that diabetic patients exhibited a disrupted topological organization of the white matter network (including the global network properties, i.e., network strength, global efficiency, local efficiency and shortest path length, and the nodal efficiency of the right rolandic operculum) in the brain. Moreover, those global network properties and the nodal efficiency of the right rolandic operculum both had positive correlations with executive function in the patient group. The results suggest that type 2 diabetes mellitus leads to an alteration in the topological organization of the cortical white matter network and this alteration may account for the observed cognitive decline. [ABSTRACT FROM AUTHOR]

Objective: This report investigated the involvement of the PTEN pathway in the regulation of Tau phosphorylation using an oxygen and glucose deprivation (OGD) model with rat cortical neurons. Methods: Primary cortical neurons were used to establish the oxygen and glucose deprivation (OGD) modelin vitro. These were randomly divided into control, OGD, bpV+OGD, As+OGD, Se+OGD and Mock treatment groups. The neuron viability was assessed by MTT, the cell apoptosis was detected using TUNEL staining. The expression of Phospho-PTEN/PTEN, Phospho-Tau/Tau, Phospho-Akt/Akt and Phospho-GSK-3β/GSK-3βwere detected by Western blotting. Results: OGD induced Tau phosphorylation through PTEN and glycogen synthase kinase-3β(GSK-3β) activation, together with a decrease in AKT activity. Pre-treatment with bpv, a potent PTEN inhibitor, and PTEN antisense nucleotides decreased PTEN and GSK-3βactivity and caused alterations in Tau phosphorylation. Neuronal apoptosis was also reduced. Conclusions: The PTEN/Akt/GSK-3β/Tau pathway is involved in the regulation of neuronal injury, providing a novel route for protecting neurons following neonatal HI. [ABSTRACT FROM PUBLISHER]

Purpose: To investigate the activity of the aqueous root extract of Salvia miltiorrhiza (S. miltiorrhiza) (Lamiaceae), collected from Anhui Province, China, for the treatment of spinal cord injury (SCI) in Sprague-Dawley (SD) rats. Methods: In total, 30 adult rats were selected and divided into three groups; normal control, untreated and treated. Aqueous root extract of S. miltiorrhiza was introduced intraperitoneally to the treated group. Basso, Beattie and Bresnahan rating scale (BBB) was used to evaluate improvement in locomotor activity after SCI. Total RNA was extracted from tissue sections using Sepasol (NacalaiTesque) and RNA samples were reverse-transcribed using M-MLV reverse transcriptase. BioSense SC-810 Gel Documentation System and Gel-Pro 3.1 software were employed for the analysis of band intensity. Results: A significant reduction in SCI cavity area was observed in the S. miltiorrhiza extract-treated group, relative to the untreated group, after 11 days (0.10 ± 0.05 mm2 treated vs. 0.30 ± 0.01 mm2 untreated). Treatment with root extract also improved the BBB scores; the treated group scored 15, compared to a score of 8 for the untreated group. In addition, the degradation of neurons at the site of injury in the spinal cord was reduced in the treated group compared to the untreated group. Treatment with S. miltiorrhiza aqueous root extract also significantly increased the expression of platelet-derived growth factor-B (PDGF-B) mRNA (p < 0.01). Conclusion: These data suggest that, in addition to other pharmacological activities, S. miltiorrhiza extract has therapeutic potential for the treatment of neuronal degeneration following SCI. [ABSTRACT FROM AUTHOR]

Background: Buyang Huanwu Decoction (BYHWD) is a Traditional Chinese Medicine (TCM) formula for treating stroke-induced disability. Xiaoshuan enteric-coated capsule (XSECC), derived from the formula BYHWD, is a drug approved by the China Food and Drug Administration (CFDA) for stroke management. To further investigate the potential protective effects of XSECC on neurovascular functions, we endeavour to monitor the neurovascular functions using multimodal magnetic resonance imaging (MRI) and evaluated histopathological changes of neurovascular unit (NVU) after stroke. Methods: Ischemic stroke was induced by permanent middle cerebral artery occlusion (pMCAO). XSECC (420 mg/kg) was orally administered 2 h after stroke and daily thereafter. T2-weighted imaging (T2WI), T2 relaxometry mapping and diffusion tensor imaging (DTI) were used to measure cerebral infarct volume, edema and white matter fiber integrity, respectively. Neurochemical metabolite levels were monitored by ¹H-magnetic resonance spectroscopy (¹H-MRS). Arterial spin labeling (ASL) - cerebral blood flow (CBF) measurements and structural magnetic resonance angiography (MRA) images provided real-time and dynamic information about vascular hemodynamic dysfunction on the 3rd, 7th and 14th days after pMCAO. At the last imaging time point, immunohistochemistry, immunofluorescence as well as transmission electron microscopy (TEM) were used to test the microscopic and ultrastructural changes of NVU. Results: T2WI, T2 relaxometry mapping and Fractional anisotropy (FA) in DTI showed that XSECC significantly reduced cerebral infarct volume, relieved edema and alleviated nerve fiber injuries, respectively. ¹H-MRS provided information about improvement of neuronal/glial metabolism after XSECC treatment. Moreover, ASL - CBF measurements combined with MRA showed that XSECC significantly increased CBF and vascular signal strength and alleviated ischemia-induced morphological changes of arteries in ischemic hemisphere within 14 days after stroke. In addition, neuron specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), CD34 staining and TEM detection indicated that XSECC not only ameliorated neuronal injury, but also reduced endothelial damage and inhibited astrocyte proliferation. Conclusions: Our results suggested that XSECC has multi-target neurovascular protective effects on ischemic stroke, which may be closely correlated with the improvement of cerebral blood supply and neuronal/glial metabolism. [ABSTRACT FROM AUTHOR]