Altered gut microbiota in temporal lobe epilepsy with anxiety disorders.

Introduction: Patients with epilepsy are particularly vulnerable to the negative effects of anxiety disorders. In particular, temporal lobe epilepsy with anxiety disorders (TLEA) has attracted more attention in epilepsy research. The link between intestinal dysbiosis and TLEA has not been established yet. To gain deeper insight into the link between gut microbiota dysbiosis and factors affecting TLEA, the composition of the gut microbiome, including bacteria and fungi, has been examined. Methods: The gut microbiota from 51 temporal lobe epilepsy patients has been subjected to sequencing targeting 16S rDNA (Illumina MiSeq) and from 45 temporal lobe epilepsy patients targeting the ITS-1 region (through pyrosequencing). A differential analysis has been conducted on the gut microbiota from the phylum to the genus level. Results: TLEA patients' gut bacteria and fungal microbiota exhibited distinct characteristics and diversity as evidenced by high-throughput sequencing (HTS). TLEA patients showed higher abundances of Escherichia-Shigella (genus), Enterobacterales (order), Enterobacteriaceae (family), Proteobacteria (phylum), Gammaproteobacteria (class), and lower abundances of Clostridia (class), Firmicutes, Lachnospiraceae (family), Lachnospirales (order), and Ruminococcus (genus). Among fungi, Saccharomycetales fam. incertae sedis (family), Saccharomycetales (order), Saccharomycetes (class), and Ascomycota (phylum) were significantly more abundant in TLEA patients than in patients with temporal lobe epilepsy but without anxiety. Adoption and perception of seizure control significantly affected TLEA bacterial community structure, while yearly hospitalization frequency affected fungal community structures in TLEA patients. Conclusion: Here, our study validated the gut microbiota dysbiosis of TLEA. Moreover, the pioneering study of bacterial and fungal microbiota profiles will help in understanding the course of TLEA and drive us toward preventing TLEA gut microbiota dysbiosis.

The Effect of Long-Term or Repeated Use of Antibiotics in Children and Adolescents on Cognitive Impairment in Middle-Aged and Older Person(s) Adults: A Cohort Study.

Objectives: We evaluated the effects of long-term/recurrent use of antibiotics in childhood on developing cognitive impairment in middle and old age from UK Biobank Database. Methods: UK Biobank recruited participants aged 37-73 years. Cognitive impairment was ascertained by fluid intelligence questionnaire. Primary outcome was the occurrence of cognitive impairment in middle and old age. Multivariate logistic regression models were used to explore the relationship between long-term/recurrent use of antibiotics and cognitive impairment. Results: Over 3.8-10.8 years' follow-up, 4,781 of the 35,921 participants developed cognitive impairment. The odds of cognitive impairment in middle and old age among long-term/recurrent use of antibiotics in childhood were increased by 18% compared with their counterparts (adjusted odd ratio 1.18, 95% confidence interval 1.08-1.29, p < 0.01). The effect of long-term/recurrent use of antibiotics in childhood on cognitive impairment was homogeneous across different categories of various subgroup variables such as sex, age, APOE4, ethnic groups, income before tax, smoking status, alcohol status, BMI, hypertension and diabetes but the effect of long-term/recurrent use of antibiotics in childhood was modified by the educational qualification (p-value for interaction <0.05). Conclusion: Long-term/recurrent use of antibiotics in childhood may increase the risk of cognitive impairment in middle and old age.

The Prevalence of Vascular Dementia in China: A Systematic Review and Meta-Analysis from 2009-2019.

BACKGROUND: Vascular dementia (VD), as the second-largest type of dementia, is a serious stage of vascular cognitive impairment. It is significant to conduct retrospective epidemiological studies to characterize further the disease for public health. This study estimated the prevalence of VD among the population aged 18 yr and older in China. METHODS: Epidemiological investigations on VD published in journals and covering the period from 1999 to 2019 were identified manually and online by using Chinese databases (such as Chinese BioMedical Literature Database, Chinese National Knowledge Infrastructure database, Chinese science-technology databases, and the Chinese Wan-fang and Chongqing VIP database) and English databases (such as PubMed, Elsevier Science Bibliographic Databases and Cochrane library). Studies were included if the diagnostic criteria for VD are clear and the quality of the included literature was evaluated using the quality evaluation criteria of epidemiological research methods. A random-effects model was employed according to the statistical test of homogeneity. RESULTS: Twenty-six studies met the inclusion criteria, including 100,923 subjects and 977 VD patients. The pooled prevalence of VD was 0.96% (95% [confidence interval, CI] 0.63%∼2.1%). The prevalence of VD increased with increasing age. There was a higher prevalence of VD in the northeast China population, in urban areas and males. CONCLUSION: We stratified the included studies based on age, location, gender, and geographical distribution for prevalence. The prevalence of VD has slowly risen since 1999. It is obviously different between the North & South and urban &rural districts. While there are many benefits of systematic reviews, the methods presented have inherent limitations.

Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis.

Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.

SCD rs41290540 single-nucleotide polymorphism modifies miR-498 binding and is associated with a decreased risk of coronary artery disease.

BACKGROUND: Atherosclerosis is the primary cause of coronary artery disease (CAD), and stearoyl-CoA desaturase (SCD) is associated with atherosclerosis. However, the associations between variants of SCD and CAD have not yet been decided. METHODS: This study analyzed SCD rs41290540 single-nucleotide polymorphism (SNP) in the 3'-untranslated region for an association with a risk of CAD among the Chinese Han population. CAD patients and controls were genotyped for SNP rs41290540 in SCD by SNaPshot. The binding affinity of miR-498 to rs41290540 was determined by a luciferase assay, and SCD expression was assessed using Western blot. RESULTS: A total of 969 CAD patients and 1,095 control subjects were involved in this study. The SCD rs41290540CC genotype is associated with a decreased risk of CAD compared with the AA genotype. Furthermore, the CC genotype is associated with lower serum total cholesterol (TC). Western blot analysis demonstrated that miR-498 suppressed the expression of SCD. A luciferase assay confirmed that rs41290540 A>C variation in the SCD 3'UTR inhibits miR-498 binding. CONCLUSION: This study demonstrates that the SCD rs41290540 may be associated with a decreased risk of CAD, lower serum TC, and decreased miR-498 binding.

The effect of nonpharmacologic therapy on global cognitive functions in patients with Alzheimer's disease: an updated meta-analysis of randomized controlled trials.

Background: The effectiveness of non-pharmacologic therapy (NPT) in treating the global cognition dysfunction associated with Alzheimer's disease (AD) has not been clearly demonstrated. Therefore, we performed a meta-analysis to address this issue.Methods: The Cochrane Central Register of Controlled Trials, PUBMED, EMBASE and other databases were searched, and outcomes measured by the Mini-Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) were analysed.Results: Seven types of NPT were included, 25 randomized controlled trials (RCTs) were selected and 3238 participants were included in the meta-analysis. There were significant differences between the NPT and control groups in the MMSE and ADAS-cog scores.Conclusions: Although more extensive trials need to be performed, NPT has been observed to be beneficial in AD patients.

Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment.

Outer membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well-known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood-brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3ß (GSK-3ß) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin-1ß, and tumour necrosis factor-α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK-3ß pathway and finally leading to cognitive impairment.

Metabolic Alterations in the Outer Membrane Vesicles of Patients with Alzheimer's Disease: An LC-MS/MS-based Metabolomics Analysis.

OBJECTIVE: To characterize the specific metabolomics profiles in the outer membrane vesicles (OMVs) of patients with Alzheimer's Disease (AD) and to explore potential metabolic biomarkers and their diagnostic roles. METHODS: Nine AD patients and age- and sex-matched healthy controls were enrolled, and feces were collected. OMVs were extracted, purified, and then analyzed using liquid chromatography-tandem mass chromatography (LC-MS/MS) method coupled with a series of multivariate statistical analyses. RESULTS: Remarkable differences were found between the OMVs from AD patients and those from healthy controls. A number of differential metabolites and several top-altered metabolic pathways were identified. The levels of aspartate, L-aspartate, imidazole-4-acetate and L-glutamate were confirmed to be highly upregulated in AD-OMVs. Other differential metabolites, such as arachidic acid, prostaglandin G2, and leukotriene B4, were also identified. Furthermore, the differential metabolites possessed higher areas under the ROC curve (AUCs). CONCLUSION: Metabolic activity is significantly altered in the OMVs from AD patients. This data might be helpful for identifying novel biomarkers and their diagnostic roles in AD. Furthermore, OMVs metabolomics analysis combined with GWAS could enrich our understanding of the genetic spectrum of AD and lead to early predictions and diagnosis and clinical applications of better AD treatments.

The Prevalence of Alzheimer's Disease in China: A Systematic Review and Meta-analysis.

BACKGROUND: Several studies have investigated the prevalence of Alzheimer's disease (AD) among the general population in several parts of China. However, the results have been inconsistent. This meta-analysis was conducted to estimate the overall prevalence of AD between 2007 and 2017 in China. METHODS: English and Chinese electronic databases were searched with a date range from Nov 2007 to Nov 2017 and the reference lists of the included studies were screened as well. Cross-sectional studies addressing the prevalence of AD among the general Chinese population were retrieved irrespective of the age, location or sex of the participants. Study quality was assessed using the recommended checklist of STROBE. RESULTS: Overall, 184058 subjects and 7445 patients with AD were included from 17 studies in this meta-analysis. The overall prevalence of AD in China was calculated to be 0.04(95% CI:0.04-0.05). The prevalence was higher in older age groups, among females, and in the rural areas of the country, with an increasing trend in recent years. CONCLUSION: AD is a common problem among those in the Chinese population older than 65 yr. Furthermore, an increasing trend of the disease over the past 10 years is indicative of a critical public health problem in China in the near future. Further evidence based on a national survey is needed to estimate the exact prevalence of the disease in the country.

[The dynamic effect of yiqi qingwen jiedu heji on the protein expressions of cytokine IFN-gamma, TNF-alpha, IL-10 and IL-6 in the lungs of mice infected by IV FM1].

OBJECTIVE: To find the function and functioning mechanism of Yiqi Qingwen Jiedu Heji in resisting influenza immune damage by studying its effect on the expressions of cytokine. METHOD: Taking IV FM1 infected mice as its model and doing ELISA (double antibody sandwichenzyme linked immunosorbent assay), we dynamically observed the change of cytokine TNF-alpha, IL-6, IFN-gamma and IL-10 after giving Yiqi Qingwen Jiedu Heji treatment. RESULT AND CONCLUSION: After the mice are infected by influenza virus, their protein expressions of the model group are higher than those of the control group, of which TNF-alpha, IL-6, IFN-gamma reach the peak in three days. The three expressions of Yiqi Qingwen Jiedu Heji treated group are decreased and the decrease becomes remarkable on the third day, compared with those of the model group. However, the expression of IL-10 of the treated group is remarkably increased. It indicates that Yiqi Qingwen Jiedu Heji can resist the expressions of TNF-alpha, IL-6 and IFN-gamma pro-inflammatory cytokine,increase the expression of IL-10, and thus, alleviate inflammatory injury. So the clinical application of such medicine can shorten the course of disease.