Alloprevotella Can be Considered as a Potential Oral Biomarker in Intestinal Metaphase of Gastric Patients.

Gastric cancer is a malignant tumor with high incidence and death rate. Every year, Approximately 950,000 new cases of gastric cancer occur globally with nearly 700000 deaths,so gastric precancerous lesions(GPL) was crucial and important.At present, the effective diagnostic methods for gastric precancerous lesions are generally gastroscope and pathological changes of gastric mucosal, but those methods were invasive and would bring some pains to patients and not suitable for frequent and large-scale screening of gastric cancer or GPL.This study aimed to look for a sensitive,effective and non-invasive diagnostic method to improve the early diagnosis rate of GLP, and thereby reduce the incidence and death rate of gastric cancer.Tongue diagnosis is one of the classic diagnostic methods in traditional Chinese medicine(TCM).The tongue was closely related to the spleen and stomach.In the study, we collected 133 patients with chronic gastritis, including 53 cases in inflammatory group, 31 cases in atrophic group, and 49 cases in intestinal metaplasia group. and we analyzed the correlation between tongue,microbiota of tongue coating and clinical symptoms of GLP.The results showed that greasy coating was closely related to the intestinal metaphase of patients, indicating that greasy coating was closed link with intestinal metaphase phase of patients.Abundance of 209 genus were significant differences between greasy and non-greasy coating in intestinal metaphase phase of patients, Top10 were Streptococcus,norank_p__Saccharibacteria,Alloprevotella, Atopobium, Megasphaera, Gemella, Moraxella,unclassified_f__Prevotellaceae, Solobacterium and Stomatobaculum. Alloprevotella and Streptococcus were important genus markers and Alloprevotella was selected as a potential oral biomarker to diagnose intestinal metaphase phase of patients, the AUC value is 0.74.

Thiamine deficiency increases ß-secretase activity and accumulation of ß-amyloid peptides.

Thiamine pyrophosphate (TPP) and the activities of thiamine-dependent enzymes are reduced in Alzheimer's disease (AD) patients. In this study, we analyzed the relationship between thiamine deficiency (TD) and amyloid precursor protein (APP) processing in both cellular and animal models of TD. In SH-SY5Y neuroblastoma cells overexpressing APP, TD promoted maturation of ß-site APP cleaving enzyme 1 (BACE1) and increased ß-secretase activity which resulted in elevated levels of ß-amyloid (Aß) as well as ß-secretase cleaved C-terminal fragment (ß-CTF). An inhibitor of ß-secretase efficiently reduced TD-induced up-regulation of Aß and ß-CTF. Importantly, thiamine supplementation reversed the TD-induced alterations. Furthermore, TD treatment caused a significant accumulation of reactive oxygen species (ROS); antioxidants suppressed ROS production and maturation of BACE1, as well as TD-induced Aß accumulation. On the other hand, exogenous Aß(1-40) enhanced TD-induced production of ROS. A study on mice indicated that TD also caused Aß accumulation in the brain, which was reversed by thiamine supplementation. Taken together, our study suggests that TD could enhance Aß generation by promoting ß-secretase activity, and the accumulation of Aß subsequently exacerbated TD-induced oxidative stress.

Senescence accelerated mouse strain is sensitive to neurodegeneration induced by mild impairment of oxidative metabolism.

Neuronal loss and impairment of oxidative metabolism are frequently observed in aging associated neurodegenerative diseases. Thiamine deficiency (TD) induces the region selective neuronal loss in the brain, which has been used to model neurodegeneration, accompanied by mild impairment of oxidative metabolism. C57BL/6 mice were commonly used animals for TD experiments; however, the individual variations among C57BL/6 mice in response to TD limited the consistence of brain pathology. The senescence accelerated prone 8 (SAMP8) mouse strain exhibits age-related morphological changes in the brain and deficits in learning and memory. In this study, we compared the effects of TD on SAMP8 mice, senescence accelerated resistant 1 (SAMR1) mice and C57BL/6 mice. TD-induced body weight loss in SAMP8 mice was much greater than in SAMR1 and C57BL/6 mice. In addition, earlier and more severe loss of neurons in the submedial thalamic nucleus (SmTN) of the thalamus was detected in the SAMP8 mice. After 8 days of TD (TD8), the loss of NeuN-positive neurons in the SmTN of SAMP8, SAMR1 and C57BL/6 mice was 65%, 50%, and 36%, respectively. TD also caused accumulation of amyloid precursor protein (APP) in the thalamus. After TD10, APP immunoreactivity in the thalamus of SAMP8 was much more intense than that of SAMR1 and C57BL/6 mice. These results suggest that SAMP8 mice are sensitive to TD and therefore offer a useful model for studying aging related neurodegeneration caused by the impairment of oxidative metabolism.