Zobrazení zdroje stránky Andrewsbauer3367

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are serious neurodegenerative diseases. Although their pathogenesis is unclear, the abnormal accumulation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological feature that exists in almost all patients. Thus far, there is no drug that can cure ALS/FTLD. Tetramethylpyrazine nitrone (TBN) is a derivative of tetramethylapyrazine, derived from the traditional Chinese medicine Ligusticum chuanxiong, which has been widely proven to have therapeutic effects on models of various neurodegenerative diseases. TBN is currently under clinical investigation for several indications including a Phase II trial of ALS. Here, we explored the therapeutic effect of TBN in an ALS/FTLD mouse model. We injected the TDP-43M337V virus into the striatum of mice unilaterally and bilaterally, and then administered 30 mg/kg TBN intragastrically to observe changes in behavior and survival rate of mice. The results showed that in mice with unilateral injection of TDP-43M337V into the striatum, TBN improved motor deficits and cognitive impairment in the early stages of disease progression. In mice with bilateral injection of TDP-43M337V into the striatum, TBN not only improved motor function, but also prolonged survival rate. Moreover, we show that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3β and AMPK/PGC-1α/Nrf2 signaling pathways. In summary, TBN is a promising agent for the treatment of ALS/FTLD.Haematopoiesis is the process by which multipotent haematopoietic stem cells are transformed into each and every type of terminally differentiated blood cell. Epigenetic silencing is critical for this process by regulating the transcription of cell-cycle genes critical for self-renewal and differentiation, as well as restricting alternative fate genes to allow lineage commitment and appropriate differentiation. There are two distinct forms of transcriptionally repressed chromatin H3K9me3-marked heterochromatin and H3K27me3/H2AK119ub1-marked Polycomb (often referred to as facultative heterochromatin). This review will discuss the role of these distinct epigenetic silencing mechanisms in regulating normal haematopoiesis, how these contribute to age-related haematopoietic dysfunction, and the rationale for therapeutic targeting of these pathways in the treatment of haematological malignancies.<br /><br /> Gene-exercise interaction on cross-sectional BMI has been extensively studied and is well established. However, gene-exercise interaction on changes in body weight/BMI remains controversial.<br /><br /> To examine the interaction between the FTO obesity variant and regular exercise on changes in body weight/BMI.<br /><br /> Taiwan Biobank participants aged 30 to 70 years (N = 20,906) were examined at both baseline and follow-up visit (mean follow-up duration 3.7 years).<br /><br /> The interaction between the FTO obesity variant rs1421085 and regular exercise habit (no exercise, ≤20METs/week exercise, &gt;20METs/week exercise) on changes in body weight/BMI.<br /><br /> Individuals with the risk allele of rs1421085 gained more weight and increased BMI than those without the risk allele if they do not exercise. In contrast, individuals with the risk allele gained less weight and BMI if they exercise regularly, indicating an interaction between rs1421085 and regular exercise habit (P = 0.030 for Δbody weight and P = 0.034 for ΔBMI). The effect of exercise on maintaining body weight was larger in those with the risk allele of rs1421085. When we focused on individuals without regular exercise at baseline, individuals with the risk allele again tended to lose more weight compared to those with a non-risk allele if they had acquired an exercise habit by the follow-up visit.<br /><br /> The beneficial effect of exercise is greater in individuals genetically prone to obesity due to the interaction between the FTO obesity variant rs1421085 and regular exercise on changes in body weight and BMI.<br /><br />The beneficial effect of exercise is greater in individuals genetically prone to obesity due to the interaction between the FTO obesity variant rs1421085 and regular exercise on changes in body weight and BMI.<br /><br /> The Affordable Care Act (ACA) Medicaid expansion improved access to health insurance and healthcare services. This study assessed whether the rate of patients with undiagnosed hypertension and the rate of patients with hypertension without anti-hypertensive medication decreased post-ACA in community health center (CHC).<br /><br /> We analyzed electronic health record data from 2012-2017 for 126,699 CHC patients aged 19-64 years with ≥1 visit pre-ACA and ≥1 post-ACA in 14 Medicaid expansion states. We estimated the prevalence of patients with undiagnosed hypertension (high blood pressure reading without a diagnosis for ≥1 day) and the prevalence of patients with hypertension without anti-hypertensive medication by year and health insurance type (continuously uninsured, continuously insured, gained insurance, and discontinuously insured). We compared the time to diagnosis or to anti-hypertensive medication pre- vs post-ACA.<br /><br /> Overall, 37.3% of patients had undiagnosed hypertension and 27.0% of patients with diagnosed hypertension were without a prescribed anti-hypertensive medication for ≥1 day during the study period. The rate of undiagnosed hypertension decreased from 2012 through 2017. [https://www.selleckchem.com/products/pf-05221304.html selleck chemicals llc] Those who gained insurance had the lowest rates of undiagnosed hypertension (2012 14.8%; 2017 6.1%). Patients with hypertension were also more likely to receive anti-hypertension medication during this period, especially uninsured patients who experienced the largest decline (from 47.0% to 8.1%). Post-ACA, among patients with undiagnosed hypertension, time to diagnosis was shorter for those who gained insurance than other insurance types.<br /><br /> Those who gained health insurance were appropriately diagnosed with hypertension faster and more frequently post-ACA than those with other insurance types.<br /><br />Those who gained health insurance were appropriately diagnosed with hypertension faster and more frequently post-ACA than those with other insurance types.