BACKGROUND: Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user\'s health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood.
METHODS: To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions.
RESULTS: In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation.
CONCLUSIONS: These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence.

In the present work, a neutral polysaccharide (DHP-2W) with attenuating cognitive disorder was identified from Dendrobium huoshanense and its structure was clarified. The polysaccharide was successfully purified from D. huoshanense by column chromatography and its activity was evaluated. With a molecular weight of 508.934kDa, this polysaccharide is composed of mannose and glucose at a molar ratio of 75.81: 24.19. Structural characterization revealed that DHP-2W has a backbone consisting of 4)-β-D-Manp-(1 and 4)-β-D-Glcp-(1. In vivo experiments revealed that DHP-2W improved cognitive disorder in D-galactose treated mice and relieved oxidative stress and inflammation. DHP-2W attenuates D-galactose-induced cognitive disorder by inhibiting the BCL2/BAX/CASP3 pathway and activating the AMPK/SIRT pathway, thereby inhibiting apoptosis. Furthermore, DHP-2W had a significant effect on regulating the serum levels of Flavin adenine dinucleotide, Shikimic acid, and Kynurenic acid in aged mice. These, in turn, had a positive impact on AMPK/SIRT1 and BCL2/BAX/CASP3, resulting in protective effects against cognitive disorder.

UNASSIGNED: Hyperglycemia is associated with worse stroke outcomes, but it is uncertain whether tight glycemic control during the acute stroke period is associated with a better outcome. We conducted a meta-analysis to compare the effect of tight glycemic control versus loose glycemic control in the acute phase of stroke patients.
UNASSIGNED: A literature search was performed to identify randomized controlled trials comparing the safety and efficacy of tight glycemic control with a relatively loose control of blood glucose of acute stroke (ischemic or hemorrhagic) patients within 24 h after stroke onset. We required that the blood glucose level of the patients should not be lower than 6.11 mmol/L at the time of enrollment, and for the intensive blood glucose control range, we defined the blood glucose level as lower than that of the control group. The primary efficacy outcome measure was deaths from any cause at 90 days. Secondary efficacy outcomes comprised the number of participants with modified Rankin score (mRS). We define mRS scores 0-2 as favorable scores, recurrent stroke, and the National Institute of Health Stroke Scale or the European Stroke Scale scores. We defined the number of participants with hypoglycemia as our primary safety outcome. Subgroup analysis was performed according to age, the variety of interventions, maintained glucose level, and status of hypoglycemia on National Institute of Health Stroke Scale (NIHSS) scores or European Stroke Scale (ESS) scores.
UNASSIGNED: Fifteen randomized controlled trials (RCTs) with 2957 participants meeting the including criteria were identified and included in this meta-analysis, although not all included data on every outcome measure. Data on the primary efficacy endpoint, mortality at 90 days, was available in 11 RCTs, a total of 2575 participants. There was no significant difference between the intervention and control groups (odds ratio (OR): 1.00; 95% confidence interval (CI): 0.81-1.23; P = 0.99). For secondary endpoints, there was no difference between intervention and control groups for a mRS from 0 to 2 (OR: 0.96; 95% CI: 0.80-1.15; P = 0.69; data from 9 RCTs available), or recurrent stroke (OR: 1.34; 95% CI: 0.92-1.96; P = 0.13; data from 3 RCTs available). For NIHSS scores or ESS scores, there was a small difference in favor of intensive controls (standardized mean difference: -0.29; 95% CI: -0.54 to -0.04; P = 0.02). There was a marked increase in hypoglycemia with tight control: (OR of 9.46 (95% CI: 4.59-19.50; P < 0.00001; data from 9 RCTs available).
UNASSIGNED: There was no difference between tight and loose glycemic control on mortality, independence, or recurrent stroke outcome in acute stroke, but an increase in hypoglycemia. There was a small effect improvement on neurological scales, but the relevance of this needs to be confirmed in future adequately powered studies.

Osthole, a natural coumarin found in various medicinal plants, has been previously reported to have neuroprotective effects. However, the specific mechanism by which Osthole alleviates dysmnesia associated with Alzheimer\'s disease (AD) remains unclear. This study aimed to investigate the neuroprotective properties of Osthole against cognitive impairment in rats induced by D-galactose and elucidate its pharmacological mechanism. The rat model was established by subcutaneously injecting D-galactose at a dose of 150 mg/kg/day for 56 days. The effect of Osthole on cognitive impairment was evaluated by behavior and biochemical analysis. Subsequently, a combination of in silico prediction and experimental validation was performed to verify the network-based predictions, using western blot, Nissl staining, and immunofluorescence. The results demonstrate that Osthole could improve memory dysfunction induced by D-galactose in Sprague Dawley male rats. A network proximity-based approach and integrated pathways analysis highlight two key AD-related pathological processes that may be regulated by Osthole, including neuronal apoptosis, i.e., neuroinflammation. Among them, the pro-apoptotic markers (Bax), anti-apoptotic protein (Bcl-2), the microgliosis (Iba-1), Astro-cytosis (GFAP), and inflammatory cytokines (TNF-R1) were evaluated in both hippocampus and cortex. The results indicated that Osthole significantly ameliorated neuronal apoptosis and neuroinflammation in D-galactose-induced cognitive impairment rats. In conclusion, this study sheds light on the pharmacological mechanism of Osthole in mitigating D-galactose-induced memory impairment and identifies Osthole as a potential drug candidate for AD treatment, targeting multiple signaling pathways through network proximity and integrated pathways analysis.

BACKGROUND: Noise is an important environmental stressor in the industrialized world and has received increasing attention in recent years. Although epidemiological research has extensively demonstrated the relationship between noise and cognitive impairment, the specific molecular mechanisms and targets remain to be fully explored and understood.
METHODS: To address this issue, 5-month-old C57BL/6 mice were divided into two groups, with one group exposed to white noise at 98 dB. The effects of noise on cognition in mice were investigated through molecular biology and behavioral experiments. Subsequently, transcriptomic sequencing of the hippocampus in both groups of mice was performed and enrichment analysis of differentially expressed genes (DEGs) was conducted using KEGG and GO databases. Furthermore, LASSO analysis was used to further narrow down the relevant DEGs, followed by enrichment analysis of these genes using KEGG and GO databases. The DEGs were further validated by rt-qPCR.
RESULTS: Following noise exposure, the hippocampus levels of inflammation-related factors increased, the phosphorylation of Tau protein increased, the postsynaptic density protein decreased, the number of Nissl bodies decreased, and cell shrinkage in the hippocampus increased. Moreover, the behavioral experiments manifest characteristics indicative of a decline in cognitive.A total of 472 DEGs were identified through transcriptomic analysis, and seven relevant genes were screened by the LASSO algorithm, which were further validated by PCR to confirm their consistency with the omics results.
CONCLUSIONS: In conclusion, noise exposure affects cognitive function in mice through multiple pathways, and the omics results provide new evidence for the cognitive impairment induced by noise exposure.

UNASSIGNED: To investigate the clinical variables that might predict the outcome of developmental and epileptic encephalopathy (DEE) after vagus nerve stimulation (VNS) therapy and identify the risk factors for poor long-term outcome.
UNASSIGNED: We retrospectively studied 32 consecutive children with drug-resistant DEE who had undergone VNS surgery from April 2019 to July 2021, which were not suitable for corpus callosotomy. In spite of combining valproic acid, levetiracetam, lamotrigine, topiramate, etc. (standard anti-seizure medicine available in China) it has not been possible to effectively reduce seizures in the population we investigate (Cannabidiol and brivaracetam were not available in China). A responder was defined as a frequency reduction decrease > 50%. Seizure freedom was defined as freedom from seizures for at least 6 months. Sex, electroencephalograph (EEG) group, neurodevelopment, time lag, gene mutation, magnetic resonance imaging (MRI), and epilepsy syndrome were analyzed with Fisher\'s exact test, The age at onset and age at VNS therapy were analyzed with Kruskal-Wallis test, statistical significance was defined as p < 0.05. And used the effect size to correction.
UNASSIGNED: Among the 32 patients, the median age at VNS implantation was 4.7 years (range: 1-12 years). At the most recent follow-up, five children (15.6%) were seizure-free and 22 (68.8%) were responders. Univariate analysis demonstrated that the responders were significantly associated with mild development delay/intellectual disability (p = 0.044; phi coefficient = 0.357) and a multifocal EEG pattern (p = 0.022; phi coefficient = -0.405). Kaplan-Meier survival analyses demonstrated that a multifocal EEG pattern (p = 0.049) and DEE without epileptic spasm (ES) (p = 0.012) were statistically significant (p = 0.030). Multivariate analysis demonstrated that DEE with ES had significant predictive value for poor long-term outcome (p = 0.014, hazard ratio = 5.433, confidence interval = 1.402-21.058).
UNASSIGNED: Our study suggested that VNS was a generally effective adjunct treatment for DEE. Although the predictive factors for VNS efficacy remain unclear, it should be emphasized that patients with ES are not suitable candidates for epilepsy surgery. Further investigations are needed to validate the present results.

The aim of this study was to investigate the effects of probiotics on cognitive function and the regulation of cortisol and IL-1β in adolescents with depression. All 180 participants were randomly assigned to a study group (treated with probiotics combined with sertraline hydrochloride) and a control group (treated with sertraline hydrochloride). The repetitive Neuropsychological State Test (RBANS) and Hamilton Depression Scale (HAMD) were administered to MDD patients. The levels of serum cortisol and IL-1β were detected using an ELISA kit. Except for speech function, factors including immediate memory, visual span, attention function, delayed memory, and the RBANS in the study group were significantly higher than those in the control group. The levels of cortisol and interleukin-1β in the study group were significantly downregulated compared to those in the control group. Except for speech function, the cortisol level was negatively correlated with the RBANS total score and other factors in the study group. Interleukin-1β was also negatively correlated with the RBANS total score and each factor score. Cortisol and interleukin-1β were predictors of the RBANS total score, which explained 46.80% of the variance. Cortisol had significant predictive effects on attention function and delayed memory, and interleukin-1β had significant predictive effects on visual span and speech function. It could be concluded that probiotics could improve cognitive function in adolescents with depression by regulating cortisol and IL-1β levels.

This study aimed to investigate the topological characteristics of the resting-state functional network and the underlying pathological mechanism in nondialysis patients with stage 5 chronic kidney disease (CKD5 ND). Eighty-five subjects (21 patients with CKD5 ND, 32 patients with CKD on maintenance hemodialysis (HD), and 32 healthy controls (HCs)) underwent laboratory examinations, neuropsychological tests, and brain magnetic resonance imaging. The topological characteristics of networks were compared with a graph-theoretical approach, and correlations between neuropsychological scores and network properties were analyzed. All participants exhibited networks with small-world attributes, and global topological attributes were impaired in both groups of patients with CKD 5 (ND and HD) compared with HCs (p < 0.05); these impairments were more severe in the CKD5 ND group than in the HD group (p < 0.05). Compared with the HC group, the degree centrality of the CKD5 ND group decreased mainly in the basal ganglia and increased in the bilateral orbitofrontal gyrus, bilateral precuneus, and right cuneus. Correlation analysis showed that the degree of small-worldness, normalized clustering coefficients, and Montreal Cognitive Assessment (MoCA) scores were positively correlated and that characteristic path length was negatively correlated with these variables in patients with CKD5 ND. The nodal efficiency of the bilateral putamen (r = 0.53, p < 0.001 and r = 0.47, p < 0.001), left thalamus (r = 0.37, p < 0.001), and right caudate nucleus (r = 0.28, p = 0.01) was positively correlated with MoCA scores. In conclusion, all CKD5 ND patients exhibited changes in functional network topological properties and were closely associated with mild cognitive impairment. More interestingly, the topological property changes in CKD5 ND patients were dominated by basal ganglia areas, which may be more helpful to understand and possibly reveal the underlying pathological mechanisms of cognitive impairment in CKD5 ND.

Recent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown.
This study aimed to investigate the safety and efficacy of FMT for cognitive impairment treatment.
Five patients aged 54-80 years (three women) were enrolled in this single-arm clinical trial from July 2021 to May 2022. The Montreal Cognitive Assessment-B (MoCA-B), Activities of Daily Living (ADL), and the cognitive section of the Alzheimer\'s Disease Assessment Scale (ADAS-Cog) were assessed at days 0, 30, 60, 90, and 180. Additionally, stool and serum samples were obtained twice before FMT was administered and six months after the treatment. The structure of fecal microbiota was analyzed by 16S RNA gene sequencing. Serum samples were analyzed for metabolomics and lipopolysaccharide (LPS)-binding proteins by liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Safety was assessed based on adverse events, vital signs, and laboratory parameters during FMT and the follow-up period.
The MoCA, ADL, and ADAS-Cog scores of patients with mild cognitive impairment (patients C and E) after FMT were improved or maintained compared with those before transplantation. However, patients with severe cognitive impairment (patients A, B, and D) had no worsening of cognitive scores. Fecal microbiota analysis showed that FMT changed the structure of gut microbiota. The results of serum metabolomics analysis suggested that there were significant changes in the serum metabolomics of patients after FMT, with 7 up-regulated and 28 down-regulated metabolites. 3b,12a-dihydroxy-5a-cholanoic acid, 25-acetylvulgaroside, deoxycholic acid, 2(R)-hydroxydocosanoic acid, and P-anisic acid increased, while bilirubin and other metabolites decreased. KEFF pathway analysis indicated that the main metabolic pathways were bile secretion and choline metabolism in cancer. No adverse effects were reported throughout the study.
In this pilot study, FMT could maintain and improve cognitive function in mild cognitive impairment by changing gut microbiota structure and affecting serum metabolomics. Fecal bacteria capsules were safe. However, further studies are needed to evaluate the safety and efficacy of fecal microbiota transplantation. ClinicalTrials.gov Identifier: CHiCTR2100043548.

Our present knowledge about the efficacy of tea consumption in improving age-related cognitive disorders is incomplete since previous epidemiological studies provide inconsistent evidence. This unified systematic review and meta-analysis based on updated epidemiological cohort studies and randomized controlled trials (RCTs) evidence aimed to overcome the limitations of previous reviews by examining the efficacy of distinct types of tea consumption. PubMed, Embase, and MEDLINE were searched up to May 20, 2022, and 23 cohorts and 12 cross-sectional studies were included. Random-effects meta-analyses were conducted to obtain pooled RRs or mean differences with 95% CIs. The pooled RRs of the highest versus lowest tea consumption categories were 0.81 (95% CIs: 0.75-0.88) and 0.69 (95% CIs: 0.61-0.77), respectively. The pooled mean difference of four included RCTs revealed a beneficial effect of tea on cognitive dysfunction (MMSE ES: 1.03; 95% CI, 0.14-1.92). Subgroup analyses further demonstrated that green and black tea intake was associated with a lower risk of cognitive disorders in eastern countries, especially in women. The evidence quality was generally low to moderate. The present review provides insight into whether habitual tea consumption can be an effective approach against age-related neurodegenerative cognitive disorders and summarizes potential mechanisms based on currently published literature.