Live and pasteurized Akkermansia muciniphila ameliorates diabetic cognitive impairment by modulating gut microbiota and metabolites in db/db mice.

The established role of disturbances in the microbiota-gut-brain axis in the development of diabetic cognitive impairment (DCI) has long been recognized. It has shown the potential of Akkermansia muciniphila (A. muciniphila) in improving metabolic disorders and exerting anti-inflammatory effects. However, there remains a lack of comprehensive understanding regarding the specific effects and mechanisms underlying the treatment of DCI with A. muciniphila. This study aimed to evaluate the potential of A. muciniphila in alleviating DCI in db/db mice. Eleven-week-old db/db mice were administered either live or pasteurized A. muciniphila (5 × 109 CFU/200 µL) for a duration of eight weeks. Administering live A. muciniphila significantly ameliorated cognitive impairments, improved the synaptic ultrastructure, and inhibited hippocampal neuron loss in the CA1 and CA3 subregions in db/db mice. Both live and pasteurized A. muciniphila effectively mitigated neuroinflammation. Moreover, live A. muciniphila increased the relative abundance of Lactococcus and Staphylococcus, whereas pasteurized A. muciniphila increased the relative abundance of Lactobacillus, Prevotellaceae_UCG_001, and Alistipes. Supplementation of A. muciniphila also induced alterations in serum and brain metabolites, with a particular enrichment observed in tryptophan metabolism, glyoxylate and dicarboxylate metabolism, nitrogen metabolism, and pentose and glucuronate interconversions. Correlation analysis further demonstrated a direct and substantial correlation between the altered gut microbiota and the metabolites in the serum and brain tissue. In conclusion, the results indicate that live A. muciniphila demonstrated greater efficacy compared to pasteurized A. muciniphila. The observed protective effects of A. muciniphila against DCI are likely mediated through the neuroinflammation and microbiota-metabolites-brain axis.

Effects of short-chain fatty acids on blood glucose and lipid levels in mouse models of diabetes mellitus: A systematic review and network meta-analysis.

Short-chain fatty acids (SCFAs), the main metabolites of gut microbiota, have been associated with lower blood glucose and lipid levels in diabetic mice. However, a comprehensive summary and comparison of the effects of different SCFA interventions on blood glucose and lipid levels in diabetic mice is currently unavailable. This study aims to compare and rank the effects of different types of SCFAs on blood glucose and lipid levels by collecting relevant animal research. A systematic search through PubMed, Embase, Cochrane Library, and Web of Science database was conducted to identify relevant studies from inception to March 17, 2023. Both pairwise meta-analysis and Bayesian network meta-analysis were used for statistical analyses. In total, 18 relevant studies involving 5 interventions were included after screening 3793 citations and 53 full-text articles. Notably, butyrate therapy (mean difference [MD] = -4.52, 95% confidence interval [-6.29, -2.75]), acetate therapy (MD = -3.12, 95% confidence interval [-5.79, -0.46]), and propionate therapy (MD = -2.96, 95% confidence interval [-5.66, -0.26]) significantly reduced the fasting blood glucose levels compared to the control group; butyrate therapy was probably the most effective intervention, with a surface under the cumulative ranking curve (SUCRA) value of 85.5%. Additionally, acetate plus propionate therapy was probably the most effective intervention for reducing total cholesterol (SUCRA = 85.8%) or triglyceride levels (SUCRA = 88.1%). These findings underscore the potential therapeutic implications of SCFAs for addressing metabolic disorders, particularly in type 2 diabetes mellitus.

Correlation between inflammatory biomarkers, cognitive function and glycemic and lipid profiles in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

This study aimed to quantitatively estimate the correlation between systemic inflammation with cognitive function, as well as glycemic and lipid profiles in patients with type 2 diabetes mellitus (T2DM). The PubMed, Web of Science, EMBASE, SCOPUS, CNKI, Wanfang, VIP, and CBM databases were searched from its inception until June 2023 (PROSPERO registration: CRD42022356889). We analyzed data extracted from observational studies to quantify the correlations (r) as the pooled effect size and further performed subgroup analyses and sensitivity analyses. A total of 32 studies involving 7,483 patients with T2DM were included. The findings revealed a significant moderate negative correlation between interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) levels with Montreal Cognitive Assessment scores. TNF-α levels also had moderate negative correlation with Mini-Mental State Examination scores. For glycemic and lipid profiles, there was a significant moderate positive correlation between CRP and TNF-α levels and glycated hemoglobin (HbA1c), and TNF-α levels were also found to be lowly positively correlated with fasting blood glucose (FBG). CRP levels were found to have a low positive correlation with total cholesterol (TC), and IL-6 levels were found to be lowly positively correlated with triglycerides. The results indicate that elevated levels of IL-6, CRP, and TNF-α are significantly associated with cognitive impairment in patients with T2DM and may serve as inflammatory markers for T2DM with mild cognitive impairment. The CRP and TNF-α levels were more strongly correlated with HbA1c than with FBG and TC. Further research is needed to determine the clinical value of these inflammatory biomarkers and to investigate potential causal mechanisms underlying this association.

Status and influencing factors of elder neglect by geriatric nursing assistants in Chinese nursing homes: a cross-sectional survey.

Background: In nursing homes, elder neglect has come to the forefront. Currently, few studies have examined the impact of personal and organizational factors of geriatric nursing assistants on elder neglect. From the perspective of geriatric nursing assistants, this study aims to explore the current situation and influencing factors of elder neglect in Chinese nursing homes. Methods: A convenience sampling method was used to recruit 412 geriatric nursing assistants from 50 nursing homes in China. Participants were surveyed using a demographic questionnaire, the Elder Neglect Scale for Geriatric Nursing Assistants, the General Self-Efficacy Scale (GSES), and the Proactive Personality Scale (PPS). Spearman correlation analysis and multiple linear regression were used to analyze the factors influencing elder neglect. Results: Geriatric nursing assistants scored a median of 74 out of 85 on the Elder Neglect Scale. Multiple linear regression analyses showed that the main personal factors influencing geriatric nursing assistants' elder neglect were general self-efficacy (ß = 0.312), proactive personality (ß = 0.180), and advanced qualification (ß = 0.084), while the main organizational factors included monthly salary ≤ 1,900 RMB (ß = -0.256), no regular training after induction (ß = -0.253), and the number of days off per month (3-4 days off ß = 0.192, ≥ 5 days off ß = 0.101). Conclusion: Although geriatric nursing assistants are at low levels of elder neglect, it remains a cause for concern. Among the personal factors, geriatric nursing assistants who possessed proactive personalities, high self-efficacy and advanced qualifications, exhibited low levels of elder neglect. Among the organizational factors, those who possessed a high number of days off per month portrayed low levels of elder neglect. Conversely, those who received low monthly salaries and no regular training after induction portrayed high levels of elder neglect. To reduce the risk of elder neglect, nursing homes should give due consideration to candidates' self-efficacy and proactive personality traits when recruiting, and focus on fostering these personality traits in their employees during their work. In addition, strengthening regular training for geriatric nursing assistants, optimizing the salary structure, and arranging rest days in a reasonable manner are also necessary measures.

Higher Adherence to the AMED, DASH, and CHFP Dietary Patterns Is Associated with Better Cognition among Chinese Middle-Aged and Elderly Adults.

The available evidence regarding the association between adherence to the Alternate Mediterranean Diet (AMED) and Dietary Approaches to Stop Hypertension (DASH) dietary patterns and cognitive performance exhibits inconsistency, and its applicability within the Asian population remains uncertain. The association between adherence to the Chinese Food Pagoda (CHFP) and cognitive function is also unknown. In this study, we aimed to assess the association between adherence to the AMED, DASH, and CHFP different dietary patterns and cognitive function. The study included 3353 Chinese adults aged 55 years and over from the China Health and Nutrition Survey (CHNS) in 2006. A 24 h dietary recall over three consecutive days was used to collect dietary information. Dietary patterns included AMED, DASH, and CHFP. A subset of items from the Telephone Interview for Cognitive Status-Modified was used for cognitive screening. Poor cognitive performance was defined as a global cognitive function score < 7. Binary logistic regression was used to estimate the association between adherence to the three different dietary patterns and cognitive function. Binary logistic regression analysis showed that there is a negative association between higher adherence to the AMED, DASH, and CHFP and poorer cognitive performance (AMED: OR = 0.594, 95% CI = 0.458-0.771, p < 0.001; DASH: OR = 0.652, 95% CI = 0.504-0.843, p = 0.001; CHFP: OR = 0.599, 95% CI = 0.417-0.861, p = 0.006). There was a significant interaction between each of the three dietary patterns and residential regions (AMED: p for interaction = 0.045; DASH: p for interaction = 0.003; CHFP: p for interaction < 0.001). Higher adherence to the AMED, DASH, and CHFP dietary patterns was inversely associated with poor cognition in Chinese middle-aged and elderly adults, particularly among urban residents.

Health-related quality of life and associated factors in elderly individuals with dyslipidemia in rural Northern China.

PURPOSE: The purpose of the study was to investigate health-related quality of life (HRQOL) and its associated factors among elderly individuals with dyslipidemia in rural Northern China. METHODS: A cross-sectional study was conducted on 457 elderly individuals. The EQ-5D-5L questionnaire was used to assess HRQOL. Sociodemographic, anthropometric, lifestyle and health information was collected using a structured and standardized questionnaire. The Tobit regression model and multiple linear regression analysis were used to assess factors associated with HRQOL parameters including utility index and visual analogue score (EQ-VAS). RESULTS: The mean age of the participating individuals was 68.04 ± 5.98 years. The median utility index and EQ-VAS scores were 0.942 (P25-P75: 0.876-1.000) and 80 (P25-P75: 70-90), respectively. Pain/discomfort was the most frequently reported complaint among the five health dimensions (50.5%). Illiterate and primary education levels, unemployed, widowed, smoking, secondhand smoke exposure, with hypertension or DM, chronic disease core knowledge scores < 8, and daily sedentary time ≥ 6 h were associated with lower HRQOL. CONCLUSION: Pain/discomfort dimension was the most affected problems. Education, occupation, marital status, smoking, secondhand smoke exposure, chronic disease core knowledge, comorbidities, and daily sedentary time were significantly associated with HRQOL in the present study.

A systematic review and meta-analysis of cognitive and behavioral tests in rodents treated with different doses of D-ribose.

Background: D-ribose is an aldehyde sugar and a necessary component of all living cells. Numerous reports have focused on D-ribose intervention in animal models to assess the negative effects of D-ribose on cognition. However, the results across these studies are inconsistent and the doses and actual effects of D-ribose on cognition remain unclear. This systematic review aimed to evaluate the effect of D-ribose on cognition in rodents. Methods: The articles from PubMed, Embase, Sciverse Scopus, Web of Science, the Chinese National Knowledge Infrastructure, SinoMed, Wanfang, and Cqvip databases were screened. The results from the abstract on cognitive-related behavioral tests and biochemical markers from the included articles were extracted and the reporting quality was assessed. Results: A total of eight trials involving 289 rodents met the eligibility criteria, and both low- and high-dose groups were included. Meta-analyses of these studies showed that D-ribose could cause a significant decrease in the number of platform crossings (standardized mean difference [SMD]: -0.80; 95% CI: -1.14, -0.46; p < 0.00001), percentage of distance traversed in the target quadrant (SMD: -1.20; 95% CI: -1.47, -0.92; p < 0.00001), percentage of time spent in the target quadrant (SMD: -0.93; 95% CI: -1.18, -0.68; p < 0.00001), and prolonged escape latency (SMD: 0.41; 95% CI: 0.16, 0.65; p = 0.001) in the Morris water maze test. Moreover, D-ribose intervention increased the levels of advanced glycation end products (AGEs) in the brain (SMD: 0.49; 95% CI: 0.34, 0.63; p < 0.00001) and blood (SMD: 0.50; 95% CI: 0.08, 0.92; p = 0.02). Subsequently, subgroup analysis for the dose of D-ribose intervention revealed that high doses injured cognitive function more significantly than low D-ribose doses. Conclusion: D-ribose treatment caused cognitive impairment, and cognition deteriorated with increasing dose. Furthermore, the increase in AGEs in the blood and brain confirmed that D-ribose may be involved in cognitive impairment through non-enzymatic glycosylation resulting in the generation of AGEs. These findings provide a new research idea for unveiling basic mechanisms and prospective therapeutic targets for the prevention and treatment of patients with cognitive impairment.

Association of gut microbiota with sort-chain fatty acids and inflammatory cytokines in diabetic patients with cognitive impairment: A cross-sectional, non-controlled study.

Emerging evidence suggests that gut microbiota, short-chain fatty acids (SCFAs), and inflammatory cytokines play important roles in the pathogenesis of diabetic cognitive impairment (DCI). However, little is known about alterations of gut microbiota and SCFA levels as well as the relationships between inflammatory cytokines and cognitive function in Chinese DCI patients. Herein, the differences in the gut microbiota, plasma SCFAs, and inflammatory cytokines in DCI patients and type 2 diabetes mellitus (T2DM) patients were explored. A cross-sectional study of 30 DCI patients and 30 T2DM patients without mild cognitive impairment (MCI) was conducted in Tianjin city, China. The gut microbiota, plasma SCFAs, and inflammatory cytokines were determined using 16S ribosomal RNA (rRNA) gene sequencing, gas chromatography-mass spectrometry (GC-MS), and Luminex immunofluorescence assays, respectively. In addition, the correlation between gut microbiota and DCI clinical characteristics, SCFAs, and inflammatory cytokines was investigated. According to the results, at the genus level, DCI patients presented a greater abundance of Gemmiger, Bacteroides, Roseburia, Prevotella, and Bifidobacterium and a poorer abundance of Escherichia and Akkermansia than T2DM patients. The plasma concentrations of acetic acid, propionic acid, isobutyric acid, and butyric acid plummeted in DCI patients compared to those in T2DM patients. TNF-α and IL-8 concentrations in plasma were significantly higher in DCI patients than in T2DM patients. Moreover, the concentrations of acetic acid, propionic acid, butyric acid, and isovaleric acid in plasma were negatively correlated with TNF-α, while those of acetic acid and butyric acid were negatively correlated with IL-8. Furthermore, the abundance of the genus Alloprevotella was negatively correlated with butyric acid, while that of Holdemanella was negatively correlated with propanoic acid and isobutyric acid. Fusobacterium abundance was negatively correlated with propanoic acid. Clostridium XlVb abundance was negatively correlated with TNF-α, while Shuttleworthia abundance was positively correlated with TNF-α. It was demonstrated that the gut microbiota alterations were accompanied by a change in SCFAs and inflammatory cytokines in DCI in Chinese patients, potentially causing DCI development. These findings might help to identify more effective microbiota-based therapies for DCI in the future.

The prevalence of elder abuse and neglect in rural areas: a systematic review and meta-analysis.

PURPOSE: Many epidemiological studies have reported that elder abuse and neglect were prevalent in rural areas. However, none of them has synthesized the literature in this field. Therefore, we aimed to estimate the overall prevalence of elder abuse and neglect in rural areas through a systematic review and meta-analysis. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched to identify eligible articles, with no language restrictions. Statistical analyses were conducted using Review Manager software (version 5.3). Meta-analyses and sensitivity analysis were performed using a random-effects model. All results were reported as the pooled prevalence of elder and neglect with their 95% confidence intervals (CIs). The quality of the included studies was evaluated by strengthening the reporting of observational studies in epidemiology (STROBE) checklist. Potential publication bias was assessed by the funnel plot. RESULTS: 13 cross-sectional studies involving 10,313 participants were eligible. The prevalence of elder abuse and neglect ranged from 4.5 to 61.7% across the rural areas, and pooled prevalence estimate was 33% (95% CI 23-43). The prevalence of physical abuse was estimated at 7% (95% CI 5-9), financial abuse at 5% (95% CI 4-7), psychological/emotional abuse at 17% (95% CI 11-23), and neglect at 26% (95% CI 17-35). There was significant heterogeneity among the included studies. Stratified analyses revealed that sampling design was part of the heterogeneity source. WHO regions, gender, countries' income classification, and study quality could not explain the potential reasons for heterogeneity. CONCLUSIONS: The pooled prevalence of elder abuse and neglect was relatively high in rural areas. Early and targeted screening and prevention are needed. There is an urgent need for high quality studies using agreed definition of elder abuse and neglect to protect the potential high risk populations.

[Mechanism of Hematopoietic Reconstruction in Mice Treated with Danggui Buxue Decoction combined with Muscle-Derived Stem Cell Transplantation].

OBJECTIVE: To investigate the mechanism of hematopoietic reconstruction in mice treated with Danggui Buxue Decoction (DBD) combined with the muscle-derived stem cell transplantation (MDSCT). METHODS: Female Kunming mice were randomly divided into the 6 groups: irradiation model, the bone marrow transplantation, the MDSC transplantation, the DBD 1 (4.5 g/kg), 2 (13.5 g/kg), and 3 (22.5 g/kg) + MDSC transplantation. After a week of oral administration of normal saline or different doses of DBD, The mice were exposied to 8 Gy 137Cs γ ray and were followed by bone marrow or MDSC transplantation. The expression levels of Notch1, Jagged1 and Hes1 in bone marrow, thymus and spleen were measured at 3 and 8 weeks after irradiation and transplantation. RESULTS: In the bone marrow, 3 weeks after above-mentioned treatment, the expression of Notch1 mRNA increased obviously and the expression of Jagged1, Hes1 mRNA decreased obviously in each intervention group, compared with the irradiation model group. 8th week after treatment, the expression of Notch1 mRNA decreased obviously in each intervention group, the Jagged1 mRNA expression decreased obviously except the bone marrow group, and Hes1 mRNA expression increased (P＜0.05) in each intervention group. 3 weeks after treatment, compared with the irradiation model group, the expression of Notch1 mRNA in the thymocytes increased only in DBD1+MDSC group, Jagged1, Hes1 mRNA was increased in the MDSC transplantation group and the DBD1、2+MDSC group. 8th week after treatment, the expression of Notch1, Jagged1 mRNA expression decreased in each intervention group, the expression of Hes1 mRNA increased obviously in the MDSC transplantation group and the DBD1、2+MDSC group (P＜0.05). In the spleen, 3 weeks after treatment, the expression of Notch1, Jagged1 mRNA in the spleen of each intervention group decreased obviously, compared with the irradiation model group. The expression of Jagged1, Hes1 mRNA in each intervention group were increased obviously 8th week after treatment (P＜0.05). CONCLUSION: MDSC transplantation after pretreatment of DBD can improve the hematopoietic reconstitution in mice with lethal dose radiation damage. Notch1、Jagged1 and Hes1 play different roles in this process, but the concrete mechanism needs to be further studied.

Vitamin D Supplement for Prevention of Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Prevention of Alzheimer's disease (AD) with Vitamin D (VD) supplementation has been studied widely, but the results in the literature are very conflicting. THE STUDY QUESTION: Can VD supplementation really prevent AD? STUDY DESIGN: The literature was searched from PubMed, Cochrane library, Web of Science, and EMBASE to identify relevant randomized clinical trials (RCTs). The titles and abstracts were evaluated independently by 2 of the authors. RESULTS: Nine RCTs with 2345 participants were included. In the meta-analysis, we found no significant difference in the Mini-Mental State Examination, verbal fluency, verbal memory, visual ability, and attention scores between the VD intervention group and comparison group [standardized mean difference (SMD) = -0.05, 95% confidence interval (CI) = -0.51 to 0.41; SMD = -0.01, 95% CI = -0.13 to 0.11; SMD = 0.12, 95% CI = -0.45 to 0.69; SMD = 0.42, 95% CI = -0.15 to 1.00; and SMD = 0.01, 95% CI = -0.24 to 0.27, respectively]. In subgroup analysis, we found that the intervention with only VD or plus calcium, follow-up duration, and baseline 25(OH)D levels did not explain the cause for high heterogeneity. CONCLUSIONS: Overall, the current evidence did not support the beneficial effect of VD supplement to prevent AD. High quality RCTs and further studies are needed to clarify the effects of VD supplementation on preventing AD.