RESUMO
Vanadium is a well-known essential trace element, which usually exists in oxidation states in the form of a vanadate cation intracellularly. The pharmacological study of vanadium began with the discovery of its unexpected inhibitory effect on ATPase. Thereafter, its protective effects on ß cells and its ability in glucose metabolism regulation were observed from the vanadium compound, leading to the application of vanadium compounds in clinical trials for curing diabetes. Alzheimer's disease (AD) is the most common dementia disease in elderly people. However, there are still no efficient agents for treating AD safely to date. This is mainly because of the complexity of the pathology, which is characterized by senile plaques composed of the amyloid-beta (Aß) protein in the parenchyma of the brain and the neurofibrillary tangles (NFTs), which are derived from the hyperphosphorylated tau protein in the neurocyte, along with mitochondrial damage, and eventually the central nervous system (CNS) atrophy. AD was also illustrated as type-3 diabetes because of the observations of insulin deficiency and the high level of glucose in cerebrospinal fluid (CSF), as well as the impaired insulin signaling in the brain. In this review, we summarize the advances in applicating the vanadium compound to AD treatment in experimental research and point out the limitations of the current study using vanadium compounds in AD treatment. We hope this will help future studies in this field.
RESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by senile plaques formed by amyloid-beta (Aß) extracellularly and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein intracellularly. Apart from these two features, insulin deficiency and insulin resistance have also been observed in AD brains. Thus, AD has also been referred to as type 3 diabetes by some of the scientists in this field. Insulin plays a pivotal role in learning and memory and is involved in regulating tau phosphorylation though the PI3KAkt-GSK3b signaling pathway. Interestingly, recent studies revealed that in AD brains the microglia transformed into a disease-associated microglia (DAM) status in a TREM2-dependent manner to restrain the toxicity of Aß and propagation of tau. This also correlated with PI3K-Akt signaling through the adaptor of TREM2. Whether insulin has any effect on microglia activation in AD pathology is unclear so far. However, many studies demonstrated that diabetes increased the risk of AD. In this review, we summarize the main strategies for curing AD, including lowering the level of Aß, suppressing the phosphorylation of tau, the ablation and/or repopulation of microglia, and especially the supply of insulin. We also propose that attention should be given to the influences of insulin on microglia in AD.
RESUMO
AIM: To verify the association between retinopathy, nephropathy, and periodontitis in type 2 diabetic (T2D) patients. METHODS: Several electronic databases were available for our comprehensive search including China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang, Web of Science, ScienceDirect and PubMed and were queried for relevant citations (updated to Mar. 2019). RevMan was utilized to perform Meta analysis and publication bias detection. After evaluation of the methodological quality of included studies, a fixed or random effect model was utilized to analyze data from included studies. RESULTS: A total of eight articles were finally included in this Meta analysis. In all 3987 subjects, there were 1207 T2D patients accompanying with microvascular complications and 1734 patients with periodontitis as well. The Meta forest plot presented little heterogeneity of the eight studies (P<0.00001, I 2=89%). The total effect demonstrated periodontitis was associated with overall microvascular complications (OR: 1.96, 95%CI: 1.67-2.30, Z=8.25, P<0.00001). Subgroup investigations among the studies in Asian (OR: 2.33, 95%CI: 1.91-2.85) and North American (OR: 1.42, 95%CI: 1.08-1.86) populations confirmed the existed association between retinopathy, nephropathy, and periodontitis. While the strength of such associations between periodontitis and diabetic microvascular complications were more obvious in the Asians than North Americans. All the results indicated that periodontitis was associated with diabetic retinopathy (OR: 3.77, 95%CI: 2.71-5.24), diabetic nephropathy (OR: 1.55, 95%CI: 1.24-1.94) in T2D patients. CONCLUSION: The periodontitis is associated with diabetic retinopathy, diabetic nephropathy among T2D patients and further large sample size clinical trials are in need to confirm the findings.
RESUMO
Mycobacterium tuberculosis (M. tuberculosis) invading and activating microglia causes the most serious subtypes of tuberculosis called tubercular meningitis. However, the developmental process of tubercular meningitis, especially the early phase, is poorly understood due to lacking well-established and well-accepted visible models in vitro and in vivo. Here, consistent with one recent report, we found Mycobacterium marinum (M. marinum) invade the zebrafish brain and subsequently cause granuloma-like structures. We further showed that M. marinum, which shares similar characteristics with M. tuberculosis, can invade microglia and replicate in microglia, which subsequently promote the secretion of pro-inflammatory cytokines such as IL-1ß, IL-6, and TNF-α. M. marinum infection in microglia can also promote autophagy, which conversely limits the replication of M. marinum. Thus, pharmacological activation of autophagy by rapamycin could prevent M. marinum replication. Our study provides in vivo and in vitro models to study underlying pathogenic mechanisms of tubercular meningitis by using M. marinum. Our results also showed that activation of autophagy could be a meaningful way to prevent tubercular meningitis.