Hanssonbengtson0813

We intended to investigate the underlying mechanism of action of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in colorectal cancer (CRC) progression, especially in tumor cell stemness. For that purpose, different assays were performed such as real-time PCR and western blotting to determine the expression of target genes. Cell stemness was determined by sphere formation assay, flow cytometry assay, and the analysis of stemness-related markers. The interplay among target genes was evaluated using bioinformatics analyses, luciferase reporter and biotin-labeled RNA pull down assays. We found that HOTAIR was highly expressed and predicted poor prognosis survival in CRC. Downregulation of HOTAIR repressed tumor malignant behaviors and cancer stemness. Mechanistically, HOTAIR facilitated the expression of the microRNA (miR)-211-5p target gene fms-like tyrosine kinase-1 (FLT-1), thereby modulating cancer stem cell (CSC) properties in CRC. We conclude that HOTAIR/miR-211-5p/FLT-1 axis contributes to CRC cancer stemness.A progressive decline in the macroautophagic/autophagic flux is a hallmark of pancreatic β-cell failure in type 2 diabetes (T2D) but the responsible intrinsic factors and underlying molecular mechanisms are incompletely understood. A stress-sensitive multicomponent cellular loop of the Hippo pathway kinase LATS2 (large tumor suppressor 2), MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) and autophagy regulates β-cell survival and metabolic adaptation. Chronic metabolic stress leads to LATS2 hyperactivation which then induces MTORC1, subsequently impairing the cellular autophagic flux and consequently triggering β-cell death. Reciprocally, under physiological conditions, autophagy controls β-cell survival by lysosomal degradation of LATS2. These signaling cross-talks and the interaction between autophagy and LATS2 are important for the regulation of β-cell turnover and functional compensation under metabolic stress.Objective To study transitions from and to chronic widespread pain (CWP) over 7 years in patients with rheumatoid arthritis (RA).Method Two postal questionnaires were sent to patients included in the BARFOT (Better Anti-Rheumatic Pharmacotherapy) study, the first in 2010 and the second in 2017. The questionnaires assessed pain, number of tender and swollen joints, functional disability, health-related quality of life (HRQoL), pharmacological treatment, lifestyle factors, and patient-reported body mass index (BMI). The responders to both questionnaires were divided into three groups according to the reported pain duration and distribution patients having no chronic pain (NCP), chronic regional pain (CRP), and CWP.Results In all, 953 patients answered the questionnaires at both time-points. One-third (324) of the patients reported CWP in 2010, and 140 (43%) of the patients had transition to NCP or CRP in 2017. In multivariate logistic regression models, adjusting for age, gender, and disease duration, transition from CWP was associated with normal BMI, fewer tender joints, less pain, less fatigue, fewer pain regions, less disability, better HRQoL, and biologic treatment. In 2010, 628 patients reported NCP or CRP, whereas 114 of them reported CWP in 2017. Transition to CWP was associated with female gender, obesity, more tender and swollen joints, higher pain-related variables, worse disability, and worse HRQoL.Conclusion There are modifiable factors associated with transitions from and to CWP that could be identified. Paying attention to these factors could improve pain treatment in the management of RA.The purpose of this study was to evaluate the function and possible mechanism of miR-212-3p in fetal growth restriction (FGR) and to demonstrate the relationship between miR-212-3p and placental growth factor (PGF). First, we used qRT-PCR to detect the expression of miR-212-3p and PGF in placental tissues of normal delivery (HC group) and FGR, as well as in human trophoblast cell HTR-8/Svneo. The results revealed that miR-212-3p expression was significantly upregulated and PGF was significantly downregulated in placental tissue in the FGR group compared with the HC group. In addition, interference with miR-212-3p expression increased the proliferation, invasion, and migration of HTR-8/SVneo cells and decreased apoptosis of cells. Meanwhile, Western blot results showed that miR-212-3p expression downregulation promoted the phosphorylated protein expression of Phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), which in turn activated the PI3K/AKT signaling pathway. And the results of dual luciferase reporter further showed that miR-212-3p could target PGF, and the expression of both was negatively correlated in FGR group tissues. In addition, downregulation of miR-212-3p expression reversed the inhibitory effect of PGF downregulation on HTR-8/SVneo cells. In conclusion, miR-212-3p can target and inhibit the PGF expression and regulate the PI3K/AKT signaling pathway to regulate trophoblast cell invasion, migration, proliferation and cell apoptosis. This provides a potential biomarker for the development of FGR.Antiphospholipid syndrome (APS) is an autoimmune disease characterized by clinical manifestations such as thrombosis and obstetric complications with documented persistence of antiphospholipid antibodies (aPLs). Recent studies have revealed that the cause of aPL-related obstetric complications is dysfunction of placental trophoblasts and inflammation of the maternal-fetal interface induced by aPLs, not thrombosis. Although aPLs are associated with recurrence of serious complications during pregnancy, appropriate combination therapy with heparin and low-dose aspirin can improve the course of 70-80% of subsequent pregnancies. Preconception counseling and patient-tailored treatment are fundamental to improving maternal and fetal outcomes. Non-anticoagulant treatments such as hydroxychloroquine and statins are being developed for cases refractory to conventional treatment. Risk factors for thrombosis after pregnancy complications were identified based on the analysis of large databases of obstetric APS.1.The conversion of the cyclophosphamide intermediate metabolite 4-hydroxycyclophosphamide (4-OHCP) to the final cytotoxic metabolite phosphoramide mustard (PAM) is classically assumed to occur via chemical hydrolysis of the phospho-ester bond. Whilst it has been suggested previously that this reaction could be enzyme-catalysed, there was only indirect evidence for this (i.e. formation of the by-product acrolein).2. Using an assay to detect formation of DNA-alkylating adducts which block PCR amplification (QPCR-block assay), we have demonstrated that 4-OHCP can be activated by peripheral blood mononuclear cells (PBMC). The DNA-alkylating potency of 4-OHCP in PBMC increased >18-fold compared to the intrinsic reactivity of 4-OHCP for purified gDNA.3. We also found that immortalised T-cells (Jurkat) had a similar ability to activate 4-OHCP into a DNA alkylating agent, whereas there was no appreciable activation in epithelial derived (Caco-2) cells. This suggests the possibility of tissue-specific enzyme expression.4. Of the candidate enzymes tested only recombinant human cAMP-phosphodiesterase-PDE4B and snake-venom phosphodiesterase (PDE-I) could catalyse this activation into a DNA-alkylating agent.5. This enzymatic catalysis of the phospho-ester bond (P-O-C) is a hitherto unrecognised feature of this important immunomodulatory drug and should be investigated further.Objective Creation of normative data with regression corrections for demographic covariates reduces risk of small cell sizes compared with traditional normative approaches. We explored whether methods of correcting for demographic covariates (e.g., full regression models versus hybrid models with stratification and regression) and choice of covariates (i.e., correcting for age with or without sex and/or education correction) impacted reliability and validity of normative data. Method Measurement invariance for sex and education was explored in a brief telephone-administered cognitive battery from the Canadian Longitudinal Study on Aging (CLSA; after excluding persons with neurological conditions N = 12,350 responded in English and N = 1,760 in French). Results Measurement invariance was supported in hybrid normative models where different age-based regression models were created for groups based on sex and education level. Measurement invariance was not supported in full regression models where age, sex, and education were simultaneous predictors. Evidence for reliability was demonstrated by precision defined as the 95% inter-percentile range of the 5th percentile. Precision was higher for full regression models than for hybrid models but with negligible differences in precision for the larger English sample. Conclusions We present normative data for a remotely administered brief neuropsychological battery that best mitigates measurement bias and are precise. In the smaller French speaking sample, only one model reduced measurement bias, but its estimates were less precise, underscoring the need for large sample sizes when creating normative data. The resulting normative data are appended in a syntax file.

Several cardiovascular, structural, and functional abnormalities have been considered as potential causes of cardioembolic ischemic strokes. Selleckchem CDK inhibitor Beyond atrial fibrillation, other sources of embolism clearly exist and may warrant urgent action, but they are only a minor part of the many stroke mechanisms and strokes that seem to be of embolic origin remain without a determined source. The associations between stroke and findings like atrial fibrillation, valve calcification, or heart failure are confounded by co-existing risk factors for atherosclerosis and vascular disease. In addition, a patent foramen ovale which is a common abnormality in the general population is mostly an innocent bystander in patients with ischemic stroke. For these reasons, experts from the national Danish societies of cardiology, neurology, stroke, and neuroradiology sought to develop a consensus document to provide national recommendations on how to manage patients with a suspected cardioembolic stroke.

Comprehensive literature searvise on how neurologist can identify cases that need referral, and what is expected by the cardiologist. Conclusions A primary neurological and neuroradiological assessment is mandatory and neurovascular specialists should manage the initiation of secondary prophylactic treatment. If a cardioembolic stroke is suspected, a dedicated cardiologist experienced in the management of cardioembolism should provide a tailored clinical and echocardiographic assessment.Mutations in the PQBP1 gene are associated with Renpenning syndrome (RENS1, MIM# 309500). Most cases are characterized by intellectual disability, but a detailed neuropsychological profile has not yet been established. The present case study of a 8.5 years-old male child with a missense novel mutation in the PQBP1 gene expands existing understanding of this syndrome by presenting a milder clinical and neuropsychological phenotype. Whole exome trio analysis sequencing revealed a maternally inherited PQBP1 missense mutation in chromosome X [NM_001032383.1, c.727C > T (p.Arg243Trp)]. Variant functional studies demonstrated a significant reduction in the interaction between PQBP1 and the component of the nuclear pre-mRNA splicing machinery, U5-15KD. A comprehensive neuropsychological assessment revealed marked deficits in processing speed, attention and executive functioning (including planning, inhibitory control and working memory) without intellectual disability. Several components of language processing were also impaired.