Exercise-Induced Reduction of IGF1R Sumoylation Attenuates Neuroinflammation in APP/PS1 Transgenic Mice.

INTRODUCTION: Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R) and its post-translational modifications, especially sumoylation, is crucial in understanding the progression of AD and exploring novel therapeutic avenues. OBJECTIVES: This study investigates the impact of exercise on the sumoylation of IGF1R and its role in ameliorating AD symptoms in APP/PS1 mice, with a specific focus on neuroinflammation and innovative therapeutic strategies. METHODS: APP/PS1 mice were subjected to a regimen of moderate-intensity exercise. The investigation encompassed assessments of cognitive functions, alterations in hippocampal protein expressions, neuroinflammatory markers, and the effects of exercise on IGF1R and SUMO1 nuclear translocation. Additionally, the study evaluated the efficacy of KPT-330, a nuclear export inhibitor, as an alternative to exercise. RESULTS: Exercise notably enhanced cognitive functions in AD mice, possibly through modulations in hippocampal proteins, including Bcl-2 and BACE1. A decrease in neuroinflammatory markers such as IL-1ß, IL-6, and TNF-α was observed, indicative of reduced neuroinflammation. Exercise modulated the nuclear translocation of SUMO1 and IGF1R in the hippocampus, thereby facilitating neuronal regeneration. Mutant IGF1R (MT IGF1R), lacking SUMO1 modification sites, showed reduced SUMOylation, leading to diminished expression of pro-inflammatory cytokines and apoptosis. KPT-330 impeded the formation of the IGF1R/RanBP2/SUMO1 complex, thereby limiting IGF1R nuclear translocation, inflammation, and neuronal apoptosis, while enhancing cognitive functions and neuron proliferation. CONCLUSION: Moderate-intensity exercise effectively mitigates AD symptoms in mice, primarily by diminishing neuroinflammation, through the reduction of IGF1R Sumoylation. KPT-330, as a potential alternative to physical exercise, enhances the neuroprotective role of IGF1R by inhibiting SUMOylation through targeting XPO1, presenting a promising therapeutic strategy for AD.

The antitumor effects of herbal medicine Triphala on oral cancer by inactivating PI3K/Akt signaling pathway: based on the network pharmacology, molecular docking, in vitro and in vivo experimental validation.

BACKGROUND: This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS: The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS: The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS: Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.

Phospholipase D regulates ferroptosis signal transduction in mouse spleen hypoxia response.

High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.

Neuropeptides as Potential Biomarkers in Vascular Dementia.

Neuropeptides are endogenous active substances within the central and peripheral nervous systems that play important roles in a wide range of brain functions, including metabolism, food intake, social behavior, reproduction, learning, sleep, and wakefulness. This article reviews recent advances in the involvement of neuropeptides in vascular dementia. Neuropeptides are present in the brain as chemical signals and last for nearly 50 years. Peptide hormones are chemical signals of the endocrine system. Thus, neuropeptides are the most diverse class of signaling molecules in the brain, involving the genomes of many mammals, encoding neuropeptide precursors and many bioactive neuropeptides. Here the aim is to describe the recent advances in classical neuropeptides, as well as putative neuropeptides from other families, in the control of or as diagnostic tools for vascular dementia. Additionally, its molecular mechanisms are described to explore new avenues of treatment and early diagnosis, as there is increasing evidence that dysregulation of vascular processes is associated with different pathological conditions.

Identification of immune-associated genes in vascular dementia by integrated bioinformatics and inflammatory infiltrates.

Objective: Dysregulation of the immune system plays a vital role in the pathological process of vascular dementia, and this study aims to spot critical biomarkers and immune infiltrations in vascular dementia employing a bioinformatics approach. Methods: We acquired gene expression profiles from the Gene Expression Database. The gene expression data were analyzed using the bioinformatics method to identify candidate immune-related central genes for the diagnosis of vascular dementia. and the diagnostic value of nomograms and Receiver Operating Characteristic (ROC) curves were evaluated. We also examined the role of the VaD hub genes. Using the database and potential therapeutic drugs, we predicted the miRNA and lncRNA controlling the Hub genes. Immune cell infiltration was initiated to examine immune cell dysregulation in vascular dementia. Results: 1321 immune genes were included in the combined immune dataset, and 2816 DEGs were examined in GSE122063. Twenty potential genes were found using differential gene analysis and co-expression network analysis. PPI network design and functional enrichment analysis were also done using the immune system as the main subject. To create the nomogram for evaluating the diagnostic value, four potential core genes were chosen by machine learning. All four putative center genes and nomograms have a solid diagnostic value (AUC ranged from 0.81 to 0.92). Their high confidence level became unquestionable by validating each of the four biomarkers using a different dataset. According to GeneMANIA and GSEA enrichment investigations, the pathophysiology of VaD is strongly related to inflammatory responses, drug reactions, and central nervous system degeneration. The data and Hub genes were used to construct a ceRNA network that includes three miRNAs, 90 lncRNA, and potential VaD therapeutics. Immune cells with varying dysregulation were also found. Conclusion: Using bioinformatic techniques, our research identified four immune-related candidate core genes (HMOX1, EBI3, CYBB, and CCR5). Our study confirms the role of these Hub genes in the onset and progression of VaD at the level of immune infiltration. It predicts potential RNA regulatory pathways control VaD progression, which may provide ideas for treating clinical disease.

[Mechanism of IL-17 Signaling Pathway in Spleen Inflammatory Response Induced by Altitude Hypoxia in Mice]. / IL-17ä¿¡å·é€šè·¯åœ¨é«˜åŽŸä½Žæ°§è¯±å¯¼å°é¼ è„¾è„ç‚Žç—‡ååº”çš„ä½œç”¨æœºåˆ¶.

Objective: To explore the mechanism of spleen tissue inflammatory response induced by altitude hypoxia in mice. Methods: C57BL/6 mice were randomly assigned to a plain, i.e., low-altitude, normoxia group and an altitude hypoxia group, with 5 mice in each group. In the plain normoxia group, the mice were kept in a normoxic environment at the altitude of 400 m above sea level (with an oxygen concentration of 19.88%). The mice in the altitude hypoxia group were kept in an environment at the altitude of 4200 m above sea level (with an oxygen concentration of 14.23%) to establish the animal model of altitude hypoxia. On day 30, spleen tissues were collected to determine the splenic index. HE staining was performed to observe the histopathological changes in the spleen tissues of the mice. Real time fluorogenic quantitative PCR (RT-qPCR) and Western blot were conducted to determine the mRNA and protein expressions of interleukin (IL)-6, IL-12, and IL-1ß in the spleen tissue of the mice. High-throughput transcriptome sequencing was performed with RNA sequencing (RNA-seq). KEGG enrichment analysis was performed for the differentially expressed genes (DEGs). The DEGs in the key pathways were verified by RT-qPCR. Results: Compared with the plain normoxia group, the mice exposed to high-altitude hypoxic environment had decreased spleen index (P<0.05) and exhibited such pathological changes as decreased white pulp, enlarged germinal center, blurred edge, and venous congestion. The mRNA and protein expression levels of IL-6, IL-12, and IL-1ß in the spleen tissue of mice in the altitude hypoxia group were up-regulated (P<0.05). According to the results of transcriptome sequencing and KEGG pathway enrichment analysis, 4218 DEGs were enriched in 178 enrichment pathways (P<0.05). DEGs were significantly enriched in multiple pathways associated with immunity and inflammation, such as T cell receptor signaling pathway, TNF signaling pathway, and IL-17 signaling pathway (P<0.05) in the spleen of mice exposed to high-altitude hypoxic environment. Among them, IL-17 signaling pathway and the downstream inflammatory factors were highly up-regulated (P<0.05). Compared with the plain normoxia group, the mRNA expression levels of key genes in the IL-17 signaling pathway, including IL-17, IL-17R, and mitogen-activated protein kinase genes (MAPKs), and the downstream inflammatory factors, including matrix metallopeptidase 9 (MMP9), S100 calcium binding protein A8 gene (S100A8), S100 calcium binding protein A9 gene (S100A9), and tumor necrosis factor α (TNF-α), were up-regulated or down-regulated (P<0.05) in the altitude hypoxia group. According to the validation of RT-qPCR results, the mRNA expression levels of DEGs were consistent with the RNA-seq results. Conclusion: Altitude hypoxia can induce inflammatory response in the mouse spleen tissue by activating IL-17 signaling pathway and promoting the release of downstream inflammatory factors.

Phospholipase D regulates ferroptosis signal transduction in mouse spleen hypoxia response

High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.

Akkermansia muciniphila might improve anti-PD-1 therapy against HCC by changing host bile acid metabolism.

PD-1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD-1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD-1mAb against HCC in a tumor-bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+ T proportion in the tumor microenvironment. Additionally, AKK downregulates PD-L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD-1mAb against HCC through its impact on bile acid metabolism.

Mechanisms of multi-omics and network pharmacology to explain traditional chinese medicine for vascular cognitive impairment: A narrative review.

BACKGROUND: The term "vascular cognitive impairment" (VCI) describes various cognitive conditions that include vascular elements. It increases the risk of morbidity and mortality in the elderly population and is the most common cognitive impairment associated with cerebrovascular disease. Understanding the etiology of VCI may aid in identifying approaches to target its possible therapy for the condition. Treatment of VCI has focused on vascular risk factors. There are no authorized conventional therapies available right now. The medications used to treat VCI are solely approved for symptomatic relief and are not intended to prevent or slow the development of VCI. PURPOSE: The function of Chinese medicine in treating VCI has not yet been thoroughly examined. This review evaluates the preclinical and limited clinical evidence to comprehend the "multi-component, multi-target, multi-pathway" mechanism of Traditional Chinese medicine (TCM). It investigates the various multi-omics approaches in the search for the pathological mechanisms of VCI, as well as the new research strategies, in the hopes of supplying supportive evidence for the clinical treatment of VCI. METHODS: This review used the Preferred Reporting Items for Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. Using integrated bioinformatics and network pharmacology approaches, a thorough evaluation and analysis of 25 preclinical studies published up to July 1, 2023, were conducted to shed light on the mechanisms of TCM for vascular cognitive impairment. The studies for the systematic review were located using the following databases: PubMed, Web of Science, Scopus, Cochrane, and ScienceDirect. RESULTS: We discovered that the multi-omics analysis approach would hasten the discovery of the role of TCM in the treatment of VCI. It will explore components, compounds, targets, and pathways, slowing the progression of VCI from the perspective of inhibiting oxidative stress, stifling neuroinflammation, increasing cerebral blood flow, and inhibiting iron deposition by a variety of molecular mechanisms, which have significant implications for the treatment of VCI. CONCLUSION: TCM is a valuable tool for developing dementia therapies, and further research is needed to determine how TCM components may affect the operation of the neurovascular unit. There are still some limitations, although several research have offered invaluable resources for searching for possible anti-dementia medicines and treatments. To gain new insights into the molecular mechanisms that precisely modulate the key molecules at different levels during pharmacological interventions-a prerequisite for comprehending the mechanism of action and determining the potential therapeutic value of the drugs-further research should employ more standardized experimental methods as well as more sophisticated science and technology. Given the results of this review, we advocate integrating chemical and biological component analysis approaches in future research on VCI to provide a more full and objective assessment of the standard of TCM. With the help of bioinformatics, a multi-omics analysis approach will hasten the discovery of the role of TCM in the treatment of VCI, which has significant implications for the treatment of VCI.

Transcriptomics and metabolomics study in mouse kidney of the molecular mechanism underlying energy metabolism response to hypoxic stress in highland areas.

Exposure to hypoxia disrupts energy metabolism and induces inflammation. However, the pathways and mechanisms underlying energy metabolism disorders caused by hypoxic conditions remain unclear. In the present study, a hypoxic animal model was created and transcriptomic and non-targeted metabolomics techniques were applied to further investigate the pathways and mechanisms of hypoxia exposure that disrupt energy metabolism. Transcriptome results showed that 3,007 genes were significantly differentially expressed under hypoxic exposure, and Gene Ontology annotation analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis showed that the differentially expressed genes (DEGs) were mainly involved in energy metabolism and were significantly enriched in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) pathway. The DEGs IDH3A, SUCLA2, and MDH2 in the TCA cycle and the DEGs NDUFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1 in the OXPHOS pathway were validated using mRNA and protein expression, and the results showed downregulation. The results of non-targeted metabolomics showed that 365 significant differential metabolites were identified under plateau hypoxia stress. KEGG enrichment analysis showed that the differential metabolites were mainly enriched in metabolic processes, such as energy, nucleotide and amino acid metabolism. Hypoxia exposure disrupted the TCA cycle and reduced the synthesis of amino acids and nucleotides by decreasing the concentration of cis-aconitate, α-ketoglutarate, NADH, NADPH and that of most amino acids, purines, and pyrimidines. Bioinformatics analysis was used to identify inflammatory genes related to hypoxia exposure and some of them were selected for verification. It was shown that the mRNA and protein expression levels of IL1B, IL12B, S100A8 and S100A9 in kidney tissues were upregulated under hypoxic exposure. The results suggest that hypoxia exposure inhibits the TCA cycle and the OXPHOS signalling pathway by inhibiting IDH3A, SUCLA2, MDH2, NDUFFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1, thereby suppressing energy metabolism, inducing amino acid and nucleotide deficiency and promoting inflammation, ultimately leading to kidney damage.

Effectiveness of creative story therapy for dementia: a systematic review and meta-analysis.

OBJECTIVE: To conduct a meta-analysis of the effectiveness of creative story therapy versus routine nursing alone for the treatment of dementia. METHODS: We manually searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China VIP Database (VIP), China Biomedical Literature Database (CBM), and Wanfang Data up to May 2023. Randomized controlled trials (RCTs) of creative story therapy combined with routine nursing versus routine nursing for the treatment of dementia were included. RESULTS: A total of 597 participants were enrolled in the 9 RCTs. Among them, 296 were in the creative story therapy group, and 301 were in the routine nursing group. We found statistically significant effects of creative story therapy combined with routine nursing on cognitive function [standardized mean difference (SMD) = 0.99, 95% CI 0.57, 1.41, P < 0.00001], CSDD score [mean difference (MD) = - 1.71, 95% CI - 3.27, - 0.14, P < 0.00001], quality of life [SMD = 0.97, 95% CI 0.04, 1.90, P = 0.04], and social communication [MD = 0.46, 95% CI 0.17, 0.74, P < 0.00001] between the creative story therapy group and routine nursing groups; no significant difference in change in basic needs communication [MD = 0.09, 95% CI - 0.58, 0.76, P < 0.00001]. CONCLUSION: This meta-analysis shows that creative story therapy combined with routine nursing has significant effectiveness in improving cognitive function and depression in people with dementia. More high-quality RCTs are required to validate these results.

Functional roles of magnetic nanoparticles for the identification of metastatic lymph nodes in cancer patients.

Staging lymph nodes (LN) is crucial in diagnosing and treating cancer metastasis. Biotechnologies for the specific localization of metastatic lymph nodes (MLNs) have attracted significant attention to efficiently define tumor metastases. Bioimaging modalities, particularly magnetic nanoparticles (MNPs) such as iron oxide nanoparticles, have emerged as promising tools in cancer bioimaging, with great potential for use in the preoperative and intraoperative tracking of MLNs. As radiation-free magnetic resonance imaging (MRI) probes, MNPs can serve as alternative MRI contrast agents, offering improved accuracy and biological safety for nodal staging in cancer patients. Although MNPs' application is still in its initial stages, exploring their underlying mechanisms can enhance the sensitivity and multifunctionality of lymph node mapping. This review focuses on the feasibility and current application status of MNPs for imaging metastatic nodules in preclinical and clinical development. Furthermore, exploring novel and promising MNP-based strategies with controllable characteristics could lead to a more precise treatment of metastatic cancer patients.

Emodin attenuates diabetic kidney disease by inhibiting ferroptosis via upregulating Nrf2 expression.

Diabetic kidney disease (DKD) poses a threat to people's health. The current treatments only provide partial relief of symptoms. Therefore, seeking a promising therapeutic medication for the prevention and control on DKD will benefit patients. Recently, a novel iron-dependent and non-apoptotic regulated mode of cell death, termed as ferroptosis, is expected to offer us a novel insight into the mechanism of DKD. We conducted experiments to investigate the role of ferroptosis in the development of DKD. Iron accumulation, weakened antioxidant capacity and ROS overproduction were observed in the renal tissues of STZ-induced diabetic rats. A persistent high glucose condition contributed to down regulated levels of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11) which marked the occurrence of ferroptosis. Treatment of Emodin in DKD models could significantly attenuated these changes and reduced renal injury. Besides, NFE2-related factor 2 (Nrf2), an important antioxidant regulator, was inhibited in both in vivo and in vitro assay, which contributes to Reactive Oxygen Species (ROS) generation that further promoted the expression of ferroptosis related protein. These unwanted effects were offset by the intervention of Emodin. The specific Nrf2 knock out enhanced cell's sensitivity to ferroptosis by being exposed to high glucose culture, which was improved by treatment of Emodin via restoring activity of Nrf2. In conclusion, our research demonstrated that Emodin exerted renal protection against DKD via inhibiting ferroptosis and restoring Nrf2 mediated antioxidant capacity, which could be employed as a novel therapeutic medication against DKD.

Tea intake or consumption and the risk of dementia: a meta-analysis of prospective cohort studies.

Purpose: Dementia affects as many as 130 million people, which presents a significant and growing medical burden globally. This meta-analysis aims to assess whether tea intake, tea consumption can reduce the risk of dementia, Alzheimer's disease (AD) and Vascular dementia (VD). Patients and methods: Cochrane Library, PubMed and Embase were searched for cohort studies from inception to November 1, 2022. The Newcastle Ottawa Quality Assessment Scale (NOS) was applied to evaluate the risk of bias of the included studies. We extracted the data as the relative risks (RRs) for the outcome of the interest, and conducted the meta-analysis utilizing the random effect model due to the certain heterogeneity. Sensitivity analysis were performed by moving one study at a time, Subgroup-analysis was carried out according to different ages and dementia types. And the funnel plots based on Egger's and Begger's regression tests were used to evaluate publication bias. All statistical analyses were performed using Stata statistical software version 14.0 and R studio version 4.2.0. Results: Seven prospective cohort studies covering 410,951 individuals, which were published from 2009 and 2022 were included in this meta-analysis. The methodological quality of these studies was relatively with five out of seven being of high quality and the remaining being of moderate. The pooling analysis shows that the relationship between tea intake or consumption is associated with a reduced risk of all-cause dementia (RR = 0.71, 95% CI [0.57-0.88], I2 = 79.0%, p < 0.01). Further, the subgroup-analysis revealed that tea intake or consumption is associated with a reduced risk of AD (RR = 0.88, 95% CI [0.79-0.99], I2 = 52.6%, p = 0.024) and VD (RR = 0.75, 95% CI [0.66-0.85], I = 0.00%, p < 0.001). Lastly, tea intake or consumption could reduce the risk of all-cause dementia to a greater degree among populations with less physical activity, older age, APOE carriers, and smokers. Conclusion: Our meta-analysis demonstrated that tea (green tea or black tea) intake or consumption is associated with a significant reduction in the risk of dementia, AD or VD. These findings provide evidence that tea intake or consumption should be recognized as an independent protective factor against the onset of dementia, AD or VD.

Comparison of various exercise interventions on cognitive function in Alzheimer's patients: A network meta-analysis.

OBJECTIVE: Exercise helps enhance cognitive function in Alzheimer's patients, although the most effective forms of exercise remain unknown. METHODS: This network meta-analysis was registered in INPLASY (INPLASY202330066). According to predetermined criteria, this investigation comprised randomized controlled studies involving exercise therapies in people with Alzheimer's disease. The exercise intervention was ranked using surface under the cumulative ranking curve (SUCRA) and mean ranking, with the critical goal outcomes being overall cognition, executive function, and memory function. RESULTS: Resistance exercise is the most likely strategy to be beneficial for slowing down overall cognitive function loss in Alzheimer's patients (72.4%). Additionally, multi-component exercise was the most effective way to improve executive function (30.4%). The only type of exercise that significantly affects memory function is resistance exercise. Memory is the cognitive function that is least responsive to exercise. CONCLUSION: Resistance exercise may be an efficient intervention for overall cognitive function decline in patients with Alzheimer's and conjointly for their memory function. Multi-component exercise is more effective in improving executive function in patients with Alzheimer's disease.

Plant-derived extracellular vesicles (PDEVs) in nanomedicine for human disease and therapeutic modalities.

BACKGROUND: The past few years have witnessed a significant increase in research related to plant-derived extracellular vesicles (PDEVs) in biological and medical applications. Using biochemical technologies, multiple independent groups have demonstrated the important roles of PDEVs as potential mediators involved in cell-cell communication and the exchange of bio-information between species. Recently, several contents have been well identified in PDEVs, including nucleic acids, proteins, lipids, and other active substances. These cargoes carried by PDEVs could be transferred into recipient cells and remarkably influence their biological behaviors associated with human diseases, such as cancers and inflammatory diseases. This review summarizes the latest updates regarding PDEVs and focuses on its important role in nanomedicine applications, as well as the potential of PDEVs as drug delivery strategies to develop diagnostic and therapeutic agents for the clinical management of diseases, especially like cancers. CONCLUSION: Considering its unique advantages, especially high stability, intrinsic bioactivity and easy absorption, further elaboration on molecular mechanisms and biological factors driving the function of PDEVs will provide new horizons for the treatment of human disease.

Mycobacterium tuberculosis Infection among 1,659 Silicosis Patients in Zhejiang Province, China.

Silicosis is a well-established risk factor for Mycobacterium tuberculosis infection. This study aimed to estimate the burden and risk factors of M. tuberculosis infection. Silicosis patients from Zhejiang Province were screened for M. tuberculosis by sputum culture, chest radiographs, whole-blood gamma interferon (IFN-γ) release assay (QuantiFERON-TB Gold In-Tube [QFT-GIT]), and tuberculin skin test (TST). Potential risk factors for M. tuberculosis were identified. Data for 1,659 patients were obtained from 1,684 participants. Of these, 1,656 (99.8%) were men, and the average age was 58 (54 to 63) years. The prevalence of active tuberculosis (ATB) was 6,340/100,000 (6.34%) people; the proportion of patients with latent tuberculosis infection (LTBI) was 50.6%. Age (odds ratio [OR] = 1.059, 95% confidence interval [CI] = 1.020 to 1.099, P = 0.003), being underweight (OR = 2.320, 95% CI = 1.057 to 5.089, P = 0.036), and having a history of exposure to TB patients (OR = 4.329, 95% CI = 1.992 to 9.434, P < 0.001) were associated with ATB; BCG vaccination could reduce ATB risk in silicosis patients (OR = 0.541, 95% CI = 0.307 to 0.954, P = 0.034). Among patients without ATB, the QFT-GIT positivity rate was 40.5%, which was affected by silicosis severity, while that of TST was 57.2%. BCG vaccination was an independent factor for LTBI risk reduction (OR = 0.612, 95% CI = 0.468 to 0.801, P < 0.001). The quantitative results of QFT-GIT decreased with silicosis stage (H = 6.037; P = 0.048). In conclusion, M. tuberculosis prevalence was high in silicosis patients. BCG vaccination reduced the risk of both ATB and LTBI in silicosis patients. IMPORTANCE This study evaluated the prevalence of Mycobacterium tuberculosis infection in silicosis patients in mainland China and identified the potential risk factors for both active tuberculosis (ATB) and latent tuberculosis infection (LTBI). We believe that our study makes a significant contribution to the literature because we demonstrated that M. tuberculosis prevalence was high among silicosis patients. BCG vaccination was an independent factor that reduced the risk of M. tuberculosis infection in patients with silicosis. Furthermore, we show that the prevalence of LTBI in patients with silicosis may have been underestimated by immunological detection methods. This study can help to identify targeted subgroups prioritized for M. tuberculosis control and to reduce the risk of disease development.