Mckinneybrock2002
These findings indicate that advanced paternal age is an independent protective factor against various cancers in offspring.
Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a key role in atherosclerosis. Long noncoding RNA ANRIL (lncRNA-ANRIL) is critical in vascular homeostasis. Metformin produces multiple beneficial effects in atherosclerosis. However, the underlying mechanisms need to be elucidated.
Metformin increased lncRNA-ANRIL expression and AMPK activity in cultured VSMCs, and inhibited the phenotypic switching of VSMCs to the synthetic phenotype induced by platelet-derived growth factor (PDGF). Overexpression of lncRNA-ANRIL inhibited phenotypic switching and reversed the reduction of AMPK activity in PDGF-treated VSMCs. While, gene knockdown of lncRNA-ANRIL by adenovirus or silence of AMPKγ through siRNA abolished AMPK activation induced by metformin in VSMCs. RNA-immunoprecipitation analysis indicated that the affinity of lncRNA-ANRIL to AMPKγ subunit was increased by metformin.
, administration of metformin increased the levels of lncRNA-ANRIL, suppressed VSMC phenotypic switching, and prevented the development of atherosclerotic plaque in
mice fed with western diet. These protective effects of metformin were abolished by infecting
mice with adenovirus expressing lncRNA-ANRIL shRNA. The levels of AMPK phosphorylation, AMPK activity, and lncRNA-ANRIL expression were decreased in human atherosclerotic lesions.
Metformin activates AMPK to suppress the formation of atherosclerotic plaque through upregulation of lncRNA-ANRIL.
Metformin activates AMPK to suppress the formation of atherosclerotic plaque through upregulation of lncRNA-ANRIL.Bone marrow mesenchymal stem cells (BMMSCs)-based therapy has emerged as a promising novel therapy for Traumatic Brain Injury (TBI). NSC 163062 However, the therapeutic quantity of viable implanted BMMSCs necessary to initiate efficacy is still undetermined. Increased oxidative stress following TBI, which leads to the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling pathway, has been implicated in accounting for the diminished graft survival and therapeutic effect. To prove this assertion, we silenced the expression of NADPH subunits (p22-phox, p47-phox, and p67-phox) and small GTPase Rac1 in BMMSCs using shRNA. Our results showed that silencing these proteins significantly reduced oxidative stress and cell death/apoptosis, and promoted implanted BMMSCs proliferation after TBI. The most significant result was however seen with Rac1 silencing, which demonstrated decreased expression of apoptotic proteins, enhanced in vitro survival ratio, reduction in TBI lesional volume and significant improvement in neurological function post shRac1-BMMSCs transplantation. Additionally, two RNA-seq hub genes (VEGFA and MMP-2) were identified to play critical roles in shRac1-mediated cell survival. In summary, we propose that knockdown of Rac1 gene could significantly boost cell survival and promote the recovery of neurological functions after BMMSCs transplantation in TBI mice.Systemic sclerosis (SSc) is a prototypic fibrotic disease characterized by localized or diffuse skin thickening and fibrosis. Tissue fibrosis is driven by myofibroblasts, and factors affecting myofibroblast activation may also be involved in the development of SSc. In this study, we examined molecular mechanisms underlying SSc by focusing on myofibroblast activation processes. Bioinformatics analysis conducted to identify differentially expressed miRNAs (DEMs) and genes (DEGs) revealed that microRNA-16-5p (miR-16-5p) was downregulated and NOTCH2 was upregulated in SSc patients. In vitro experiments confirmed that miR-16-5p was able to bind directly to NOTCH2 and inhibit myofibroblast activation. Moreover, miR-16-5p-dependent inhibition of NOTCH2 decreased collagen and α-SMA expression. MiR-16-5p downregulation and NOTCH2 upregulation was also confirmed in vivo in SSc patients, and NOTCH2 activation promoted fibrosis progression in vitro. These results indicate that miR-16-5p suppresses myofibroblast activation by suppressing NOTCH signaling.
The Affordable Care Act (ACA) gives states the option of expanding Medicaid coverage to low-income individuals; however, not all states have chosen to expand Medicaid. The ACA Medicaid expansions are particularly important for Americans with mental health conditions because they are substantially more likely than other Americans to have low incomes.
We examine the impact of Medicaid expansion on adults who were newly eligible for Medicaid using the 2008-2017 Medical Expenditure Panel Survey (MEPS).
We use the AHRQ PUBSIM model to identify low-income adults aged 19-64 who were either newly Medicaid eligible if they lived in an expansion state or would have been eligible had their state opted to expand its Medicaid program. We estimate linear probability models within a difference-in-difference framework. An additional interaction term allows us to test for differences among those with serious psychological distress (SPD) or probable depression (PD). Outcomes of interest are insurance coverage by type, beatus but the overall effect on insurance coverage was stronger among those with SPD/PD. The lack of an effect on treatment use suggests that providing insurance coverage alone may be insufficient to guarantee that people with mental illness will receive the treatment they need. Limitations include that our difference-in-difference estimator may not account for time-varying factors that change contemporaneously with the expansions. Our estimates may also be affected by other provisions of the ACA that went into effect at the same time as the Medicaid expansions. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE AND IMPLICATIONS FOR HEALTH POLICIES Although the ACA has resulted in increased coverage for low-income individuals, more outreach efforts may be needed to encourage individuals with mental illness to get the treatment they need.
Illegal drug use causes a variety of negative consequences for the society -- referred to as the social costs of illegal drug use -- and therefore they are estimated in many countries. The main purpose of social cost estimation is prevention or, at least, attenuation of the negative effects of illegal drug use.
The main aim of the study was the estimation of the basic social costs of illegal drug use in Poland in the year 2015 with the use of standardized methodology and the standardized presentation of results, which can ensure better comparison of the costs between countries. The other aim of the study was to present a method to fill the gaps in statistical data concerning the criminal justice system costs attributable to illegal drugs use.
Cost-of-illness (COI), human capital, and prevalence-based approaches were applied to costs estimation. The author proposed a method combining survey results with official statistical data, which allows for rough estimation of some of the criminal justice costs. Furthermore, the method for and the results of the estimation of mortality rates for drug users and non-users and their life expectation were presented.
