Research progress on lncRNAs in Alzheimer's disease.

Alzheimer's disease (AD) is the common neurodegenerative disease in the center never system and the typical dementia in old people. The major pathological changes of AD are the accumulation of amyloid-ß (Aß) plaques, neurofibrillary tangles, loss of cholinergic neurons, inflammation and metabolism dysfunction. However, the molecular mechanism leading to AD pathogenesis is not clear. More and more studies reported that long non-coding RNAs (lncRNAs) play important roles in AD. In this review, we briefly introduce the recent research progress on lncRNAs in AD, including their regulation of clearance of the Aß plaques, synaptic function, inflammation reaction and mitochondrial function, and thus providing the references for that lncRNAs can serve as a potential diagnostic biomarker and therapeutic target in AD.

Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke.

Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome. Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0-2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome. Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17+ γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05). Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.

Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients.

Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 µmol/L in the CKD patients, which was significantly higher than the 2.08 µmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions. CKD patients had higher percentages of opportunistic pathogens from gamma-Proteobacteria and reduced percentages of beneficial microbes, such as Roseburia, Coprococcus, and Ruminococcaceae. The PICRUSt analysis demonstrated that eight genes involved in choline, betaine, L-carnitine and trimethylamine (TMA) metabolism were changed in the CKD patients. Moreover, we transferred faecal samples from CKD patients and healthy controls into antibiotic-treated C57BL/6 mice and found that the mice that received gut microbes from the CKD patients had significantly higher plasma TMAO levels and different composition of gut microbiota than did the comparative mouse group. Our present study demonstrated that CKD patients had increased plasma TMAO levels due to contributions from both impaired renal functions and dysbiosis of the gut microbiota.

[Iron metabolism and neonatal hypoxic ischemic brain damage].

Iron is an essential element for nervous system development, and maintaining a normal iron level in nervous system is controlled by multiple factors. Recent studies reported that iron dysregulation and the following iron metabolic pathways played an important role in hypoxic ischemic brain damage (HIBD) in neonates. Circulatory iron level is altered after hypoxia-ischemia exposure, which may cause abnormal iron deposition in the nervous system followed by neuronal injury. Finding the causing factors for abnormal iron metabolism after hypoxia-ischemia exposure, as well as understanding the mechanisms how iron metabolism contributes to HIBD, will shed lights on HIBD prevention and treatment. In this mini-review, we summarized changes in iron metabolism after neonatal hypoxia-ischemia exposure, its possible regulatory factors and how iron abnormalities contribute to HIBD.

[Expression of TROP2 mRNA in left-sided and right-sided colon cancer and its clinical significance].

OBJECTIVE: To investigate the expression of TROP2 in the left-sided and right-sided colon cancer and its clinical significance. METHODS: A total of eighty patients, who received radical resection of colon cancer between June 2001 and April 2005 and were staged as II( and III(, were identified, including forty with left-sided colon cancer(LSCC) and forty with right-sided colon cancer (RSCC). The expression of TROP2 was detected by real-time quantitative RT-PCR in paired cancer and normal tissue. Subsequently, the relationship between TROP2 expression and clinicopathological variables as well as the effect on the patients' prognosis were analyzed. RESULTS: The expression of TROP2 mRNA in the cancer tissue was significantly higher than that in normal tissue(P<0.01, paired Wilcoxon test). However, its expression in LSCC was markedly higher than that in RSCC with significant difference (P=0.009, Mann-Whitney U test). The patients with TROP2 high expression were found more frequently in LSCC than in RSCC(67.5% vs 32.5%, P=0.002, chi(2) test). Cancer-related mortality of the patients with TROP2 high expression was four times as high as low expression(40% vs 10%, P=0.002, chi(2) test). From the stratified survival analysis through Kaplan-Meier curve, the TROP2 high expression group had a significantly poorer median survival time than the low expression group for the patients with LSCC(45.9:63.1 months, P=0.032, log-rank test). By contrast, for the patients with RSCC, TROP2 expression had no marked effect on the survival time(P=0.235, log-rank test). In multivariable analysis, for the cohort of the present study, serosal invasion and lymphatic/vascular invasion were the independent prognostic factors of RSCC. Serosal invasion, lymph node metastasis and lymphatic/vascular invasion were the independent prognostic factors of LSCC. TROP2 high expression showed marginal significance(RR:6.244, 95% CI:0.755-51.636, P=0.089). CONCLUSION: (1)TROP2 is a differentially expressed gene between RSCC and LSCC. (2)TROP2 high expression is closely related to the factors indicating poor prognosis. (3)TROP2 has distinct clinical significance to the patients with different tumor sites. TROP2 high expression is potentially an independent prognostic factor of LSCC. (4)LSCC and RSCC seem to be two distinct diseases with significant molecular heterogeneity.