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Association between Activity Quotient and cause-specific mortality – A prospective cohort study of 0.5 million participants in Asia
No full text[[abstract]]Background: Regular physical activity (PA) is important for reducing the risk of chronic diseases and improving overall health. Activity Quotient (AQ) is a novel metric that translates heart rate during PA into a weekly score, providing an objective measure of an individual's PA. We prospectively examined the association of AQ with cancer and cardiovascular (CVD) mortality outcomes, the two major causes of death, in a Taiwanese population. Methods: A cohort of 515,608 healthy adults (52 % women) enrolled in a standard medical screening program was followed for mortality outcomes. The weekly AQ score of each participant was estimated based on self-reported PA intensity and weekly duration, and placed into six categories (0, ≤50, 51–99,100–149, 150–199, or ≥ 200 AQ per week). We used multivariable Cox proportional hazard models adjusted for potential confounders to estimate the hazard ratios (HR) and 95 % confidence intervals (CI). Results: Higher weekly AQ scores were associated with lower risks of CVD, cancer, and all-cause mortalities. Compared with inactive individuals, HRs (CI) for the association of AQ scores of ≤50, 50–99, 100–149, 150–199, and ≥ 200 were 0.93 (0.89–0.97), 0.91 (0.85–0.96), 0.84 (0.77–0.91), 0.84 (0.74–0.96), and 0.81 (0.73–0.90) with cancer mortality; and 0.88 (0.83–0.93), 0.86 (0.80–0.93), 0.81 (0.73–0.90), 0.71 (0.60–0.85), and 0.73 (0.64–0.84) with CVD mortality, respectively. Subgroup analyses showed that meeting 50 AQ a week was associated with lower risk of disease specific mortality risk across age groups and among individuals with known risk factors. Higher weekly AQ scores were also associated with longer life expectancy, with the highest gains observed among those achieving 150–199 weekly AQ. Conclusion: Our findings show that AQ may be an objective tool for assessing and tracking PA and predicting mortality risks. Encouraging individuals to achieve ≥50 AQ a week could have substantial public health benefits, including lower mortality from major chronic diseases as well as prolonged health- and life expectancy
Benzimidazole compounds and use thereof for treating alzheimer's disease or huntington's disease
No full text[[abstract]]Benzimidazole compounds of formula (I), shown below, are disclosed. The compounds are potent human glutaminyl cyclase inhibitors. Also disclosed is a pharmaceutical composition containing one of these compounds and a pharmaceutical acceptable carrier, as well as a method of treating Alzheimer's disease or Huntington's disease by administering to a subject in need thereof an effective amount of such a compound
Benzimidazole compounds and use thereof for treating alzheimer's disease or huntington's disease
No full text[[abstract]]Benzimidazole compounds of formula (I), shown below, are disclosed. The compounds are potent human glutaminyl cyclase inhibitors. Also disclosed is a pharmaceutical composition containing one of these compounds and a pharmaceutical acceptable carrier, as well as a method of treating Alzheimer's disease or Huntington's disease by administering to a subject in need thereof an effective amount of such a compound
Thiazolidinone compounds and use thereof
No full text[[abstract]]A pharmaceutical composition containing a compound of Formula (I) for treating an opioid receptor-associated condition. Also disclosed is a method for treating an opioid receptor-associated condition using such a compound. Further disclosed are two sets of thiazolidinone compounds of formula (I): (i) compounds each having an enantiomeric excess greater than 90% and (ii) compounds each being substituted with deuterium
Opioid receptor modulators and use thereof
No full text[[abstract]]Disclosed is an in vitro screening method for identifying an antagonist-to-agonist allosteric modifier of a mu-opioid receptor and an in vivo method for confirming that a test compound is such a modifier of a mu-opioid receptor. Also disclosed is a metho
[[alternative]]Opioid receptor modulators and use thereof
No full text[[abstract]]Disclosed is an in vitro screening method for identifying an antagonist-to-agonist allosteric modifier of a mu-opioid receptor and an in vivo method for confirming that a test compound is such a modifier of a mu-opioid receptor. Also disclosed is a method for treating an opioid receptor-associated condition using a compound of Formula (I) and a pharmaceutical composition containing the same
Dual and opposing roles of androgen receptor/YAP/miRNAs axis in prostate cancer metastasis
No full text[[abstract]]AR has been reported to promote disease progression and metastasis of prostate cancer (PCa). However, other studies suggested a suppressor role of AR on metastasis. We therefore studied the role of AR and androgen (AD) in PCa metastasis. Transwell assay and zebrafish model showed AR repressed the migration and invasion of cells in the absence of AD using PC-3AR(PC-3 cells with AR gene) cells. However, AR stimulated the cancer metastasis of PCa cells when AD was present. Co-IP showed AD augmented the interaction between YAP and AR inside nucleus. Knockdown of YAP abolished the AD-induced migration and invasion of PCa cells, while overexpression of YAP showed opposite effects. The miRNA array revealed AD decreased miR-5001-5p but increased miR-203a and miR-210-3p in PC-3AR cells. Treatment with inhibitors targeting miR-203a or miR-210-3p, or overexpression of miR-5001-5p suppressed the migration and invasion of PCa cells as well as decreased the expression of N-cadherin and YAP but increased abundance of E-cadherin. The data showed AR exhibits dual roles in PCa metastasis depending on the presence or absence of AD and is via regulation of miR-203a, miR-210-3p, miR-5001-5p and YA
[[alternative]]IGFBP3 promotes radiosensitivity of OSCC via appositive feedback of NFκB/IL-6/ROS signaling
No full text[[abstract]]Insulin-like growth factor binding protein 3 promotes expression previously demonstrated to enhance lymph node metastasis of oral squamous cell carcinoma cells. However, OSCC patients with high IGFBP3 expression had a better prognostic outcome than those with low IGFBP3 expression. We found that ectopic IGFBP3 expression enhanced the ionizing radiation -induced cell-killing effect. In vivo, IGFBP3 reduced tumor growth and increased apoptotic signals in nude mice treated with IR. Combined with IR, ectopic IGFBP3 expression induced mitochondria-dependent cell apoptosis. IGFBP3-induced cell death as evidenced by mitochondria destruction and increase of reactive ROS production. IGFBP3 expression enhanced NK- κ B activation and downstream cytokine expression. IGFBP3-mediated ROS production was reduced by the NK- κ B inhibitor BMS-345541, while exogenous IL-6 rescued the NF- κ B-inhibited, IGFBP3-mediated ROS production. Collectively, our data demonstrated that IGFBP3, a penitential radiosensitive biomarker, promoted OSCC cell death under IR via positive feedback of ROS production by inducing NF- κ B activation and cytokine expression
Multicenter prospective first-line helicobacter pylori eradication for localized gastric “Pure” diffuse large B-cell lymphoma
No full textMore pronounced neuroaxonal integrity disturbances in methamphetamine-associated persistent psychosis compared to schizophrenia
No full text[[abstract]]Background: Methamphetamine (METH) can cause multiple physical and psychological harms. Psychosis is one of the most serious health consequences from using METH, with this requiring aggressive treatment and being associated neurocognitive impairment and structural brain abnormalities. While the majority of METH-associated psychosis are brief (METH-associated brief psychosis, MBP); the psychosis can become persistent for >1 month in a subset of people (METH-associated persistent psychosis, MPP), with a symptom profile substantially similar to schizophrenia. Blood levels of neurofilament light chain (NFL) have been proposed as a measure of neuroaxonal integrity in several neuropsychiatric disorders. Aims & Objectives: We aimed to delineate the neuroaxonal damage linked to METH-associated psychosis, especially its persistent form, and compare it to schizophrenia. Methods: We enrolled 135 individuals with METH use disorder (55 with no psychosis [MNP group], 54 with MBP, and 24 with MPP), 78 with schizophrenia, and 85 healthy controls. Blood NFL levels measured by single molecule array (SiMoA) immunoassay. We compared NFL levels between different groups and used regression analyses to identify clinical variables related to NFL levels. Results: Individuals with MUD had significantly higher NFL levels compared to controls but comparable to patients with schizophrenia. We found age (p<.01) and duration of METH use (p = 0.01) were positively correlated with NFL levels whereas BMI is negatively correlated with NFL levels. Subsequent group comparisons showed that the NFL levels in MPP group were higher than MBP and MNP group while the levels were comparable between the latter two groups. Interestingly, MPP group had increased NFL levels compared to schizophrenia group. Furthermore, those with a prolonged psychosis associated with METH, i.e. schizophrenia-like, had a even higher NFL levels than all the resting groups. Discussion & Conclusions: These results suggest substantial neuroaxonal alterations following METH use, with a longer duration associated with higher injury. In particular, persistent psychosis The pronounced increase of NFL levels in the people with MPP and suffering from persistent psychosis might indicate that dual disruptive effect (from METH use and psychosis) on the neuroaxonal integrity and the pathology could differentiate MPP and schizophrenia