Leptin regulation of hippocampal synaptic purpose within wellness disease.

BACKGROUND Hypertension, a common chronic disease, is associated with cognitive impairment. Cognitive impairment, especially Alzheimer's disease (AD), seriously affects older adults' quality of life and aggravates the burden of disease on society and families. Elevated Alzheimer-associated neuronal thread protein (AD7c-NTP) has been observed in the urine of patients with AD and mild cognitive impairment; however, it is not clear whether this protein can be used as a biomarker for cognitive impairment in older hypertensive patients. OBJECTIVE To explore the value of urinary AD7c-NTP, and the association of urinary AD7c-NTP with cognitive function in older hypertensive patients. METHODS This was a cross-sectional study. In total, 134 hypertensive patients aged ≥60 years were divided into two groups Lower Cognitive Function group (LCF group, n = 89) and a Normal Control group (NC group, n = 45) based on the Montreal Cognitive Assessment (MoCA). Urinary AD7c-NTP, blood glucose, serum insulin, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured. RESULTS Urinary AD7c-NTP level was significantly higher in the LCF group than in the NC group [0.48 (0.21-1.00) versus 0.25 (0.04-0.44) ng/ml, p  less then  0.001]. SOD level [(43.07±23.74) versus (53.12±25.80) U/ml, p = 0.026] and higher homeostasis model assessment of insulin resistance (HOMA-IR) [7.17 (3.74-13.94) versus 6.01 (3.78-7.43), p = 0.033] was lower in the older hypertensive patients than in the NC group. Urinary AD7c-NTP level was associated with MoCA score and HOMA-IR but not with SOD, MDA, blood glucose, and insulin. CONCLUSION The level of urinary AD7c-NTP is elevated in older hypertensive patients with lower cognitive function, and insulin resistance may be involved in the process.As the elderly population grows, chronic metabolic dysfunction including obesity and diabetes are becoming increasingly common comorbidities. Hypothalamic inflammation through CNS resident microglia serves as a common pathway between developing obesity and developing systemic aging pathologies. Despite understanding aging as a life-long process involving interactions between individuals and their environment, limited studies address the dynamics of environment interactions with aging or aging therapeutics. We previously demonstrated environmental enrichment (EE) is an effective model for studying improved metabolic health and overall healthspan in mice, which acts through a brain-fat axis. Here we investigated the CSF1R inhibitor PLX5622 (PLX), which depletes microglia, and its effects on metabolic decline in aging in interaction with EE. PLX in combination with EE substantially improved metabolic outcomes in middle-aged female mice over PLX or EE alone. Chronic PLX treatment depleted 75% of microglia from the hypothalamus and reduced markers of inflammation without affecting brain-derived neurotrophic factor levels induced by EE. Adipose tissue remodeling and adipose tissue macrophage modulation were observed in response to CSF1R inhibition, which may contribute to the combined benefits seen in EE with PLX. Our study suggests benefits exist from combined drug and lifestyle interventions in aged animals.The AKT/mTOR pathway is critical for bladder cancer (BC) pathogenesis and is hyper-activated during BC progression. In the present study, we identified a novel positive feedback loop involving oncogenic factors histone methyltransferase SMYD3, insulin-like growth factor-1 receptor (IGF-1R), AKT, and E2F-1. Selleck AT13387 SMYD3 expression was significantly up-regulated in BC tumors and positively associated with histological grade, lymph node metastasis, and shorter patient survival. Depletion of SMYD3 inhibited BC cell proliferation, colony formation, migration, invasion, and xenograft tumor growth. Mechanistically, SMYD3 inhibition led to the diminished AKT/mTOR signaling activity, thereby triggering deleterious effects on BC cells. Furthermore, SMYD3 directly activates the expression of IGF-1R, a critical activator of AKT in BC, by inducing hyper-methylation of histone H3-K4 and subsequent chromatin remodeling in the IGF-1R promoter region. On the other hand, E2F-1, a downstream factor of the AKT pathway, binds to the E2F-1 binding motifs at the SMYD3 promoter and consequently induces SMYD3 transcription and expression. Thus, SMYD3/IGF-1R/AKT/E2F-1 forms a positive feedback loop leading to the hyper-activated AKT signaling. Our findings provide not only profound insights into SMYD3-mediated oncogenic activity but also present a unique avenue for treating BC by directly disrupting this signaling circuit.Objectives To test the hypothesis that scores on a Grit scale are positively associated with personality measures that are conducive to relationship building (Empathy, Self-Esteem, Activity, and Sociability), but inversely associated with personality measures that are detrimental to interpersonal relationships (Neuroticism-Anxiety, Aggression-Hostility, Impulsive Sensation Seeking, and Loneliness). Methods Convenient sampling was used that included 241 medical students at Sidney Kimmel Medical College at Thomas Jefferson University who participated in this ex post facto research. Validated instruments were used to measure Grit, Empathy, Self-Esteem, Activity, Sociability, Neuroticism-Anxiety, Aggression-Hostility, Impulsive Sensation Seeking, and Loneliness. Bivariate correlations and multivariate regression were used to examine relationships between scores on the Grit scale and personality measures. Results Results of bivariate correlational analyses showed that scores on the Grit scale were positively and significantly (p less then 0.01) correlated with measures of Self-Esteem (r=0.35), Empathy (r=0.26), and Activity (r=0.17); but negatively and significantly (p less then 0.01) correlated with measures of Loneliness (r=-0.28), Aggression-Hostility (r=-0.23), Neuroticism-Anxiety (r=-0.22), and Impulsive Sensation Seeking (r=-0.18). Regression analysis indicated that in a multivariate model, higher scores on Self-Esteem and Empathy and lower scores on Aggression-Hostility were uniquely and significantly associated with Grit scores (R=0.43, p less then 0.01). Conclusions Research hypothesis was partially confirmed, suggesting that medical students with higher Grit scores were likely to have higher empathic orientation in patient care and greater Self-Esteem. Conversely, those with higher degrees of Grit displayed lower levels of Aggression-Hostility and Impulsive Sensation Seeking. The Implications of these findings for medical education are discussed.Selleck AT13387