Subject(s)
Depression , Stroke , Aged , Humans , Cohort Studies , Depression/epidemiology , Morbidity , Stroke/epidemiologyABSTRACT
The AD7c-NTP is a promising biomarker for AD diagnosis. However, the exact urinary AD7c-NTP concentration to differentiate AD from the mild cognitive impairment (MCI) remains inconclusive. We enrolled 98 and 90 clinical defined AD and MCI patients, respectively, and access their cognition impairment with Neuropsychiatric Inventory (NPI) and Mental State Examination (MMSE) along with their urinary AD7c-NTP. We demonstrated that urinary AD7c-NTP level in sequence from high to low was AD, MCI, and healthy groups (P < .01), and the AD7c-NTP was positively and negatively correlated with the NPI and MMSE scores, respectively. Additionally, AD7c-NTP well-matched NPI subscale scores, including agitation, depression, and apathy (P < .05). Importantly, the optimal cut-off AD7c-NTP level to distinguish the AD and MCI was .94 ng/mL (sensitivity 85.71% & specificity 73.91%). Conclusively, urinary AD7c-NTP could be used for cognition impairment evaluation and differentiated diagnosis of AD and MCI.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Nerve Tissue Proteins , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Alzheimer Disease/urine , Cognition , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/urine , Humans , Nerve Tissue Proteins/urine , Neuropsychological TestsABSTRACT
BACKGROUND/AIM: Emerging evidence suggests that microRNA (miRNA) mediated gene regulation influences the maintenance of metabolic homeostasis, particularly the states of obesity and insulin resistance, thereby providing a potential link between miRNAs and nonalcoholic fatty liver disease (NAFLD). METHODS: Sprague-Dawley rats fed a high-fat diet (HFD) were used to establish a rat model of NAFLD. The miRNA expression profile of liver tissues was evaluated using Illumina HiSeq deep sequencing. Selected miRNAs were then validated by real-time PCR at both 4- and 12-week time points. Furthermore, the expression levels of these miRNAs were assessed in HepG2 cells and human hepatocytes treated with free fatty acids (FFAs) and proinflammatory factors (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). RESULTS: Our results showed that consumption of a HFD for 4 weeks caused simple steatosis, which progressed to steatohepatitis at 12 weeks. miRNA deep sequencing analysis identified 44 known up-regulated miRNAs (fold change >1.5) and 12 down-regulated miRNAs (fold change <0.5). Among the abnormally expressed miRNAs, miR-200a, miR-200b, miR-200c, miR-146a, miR-146b and miR-152 were up-regulated both in vitro and vivo. Interestingly, the expression levels of these six miRNAs were increased in HepG2 cells and human hepatocytes after treatment with FFAs and proinflammatory factors. CONCLUSION: These findings suggest a critical role for miRNAs in the pathogenesis of NAFLD.
Subject(s)
Gene Expression Regulation , MicroRNAs/biosynthesis , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Diet, High-Fat , Fatty Acids, Nonesterified/administration & dosage , Hep G2 Cells , Hepatocytes/drug effects , High-Throughput Nucleotide Sequencing , Humans , Insulin Resistance/genetics , MicroRNAs/genetics , Non-alcoholic Fatty Liver Disease/pathology , RatsABSTRACT
OBJECTIVE: X-linked adrenal hypoplasia congenital (AHC) is a rare disorder caused by mutations in DAX1 gene. We report a case of X-linked AHC in a large family to analyze the pathogenesis of this rare disease and to add to our clinical knowledge of it. METHODS: We describe 3-year-old boy's clinical features and laboratory test results, as well as the patient's nuclear family members' clinical symptoms, especially those with features of adrenal insufficiency. Genomic deoxyribonucleic acid (DNA) was extracted from the patient's and the family members' peripheral blood leukocytes, and the coding region and promoter region of DAX1 were directly sequenced. RESULTS: A 3-year-old boy who was diagnosed with X-linked AHC presented with atypical symptoms, and his laboratory test results revealed elevated serum adrenocorticotropic hormone levels (ACTH) and decreased serum cortisol levels. Three novel mutations were detected in the DAX1 coding sequence in this family: a missense mutation (c.376G>A, p.Val126Met), a synonymous mutation (c.498G>A, p.Arg166Arg), and a nonsense mutation (c.1225C>T, p. Gln409X). CONCLUSIONS: This report describes the familial transmission of AHC over several generations and further expands the number of DAX1 mutations reported in the literature. Early diagnosis and prompt treatment of X-linked AHC are important and may provide a good prognosis.
