Postmortem analyses of myocardial microRNA expression in sepsis.

Background: Sepsis can lead to myocardial depression, playing a significant role in sepsis pathophysiology, clinical care, and outcome. To gain more insight into the pathophysiology of the myocardial response in sepsis, we investigated the expression of microRNA in myocardial autopsy specimens in critically ill deceased with sepsis and non-septic controls.

Materials And Methods: In this retrospective observational study, we obtained myocardial tissue samples collected during autopsy from adult patients deceased with sepsis (n = 15) for routine histological examination.

Genetic variants associated with cardiac hypertrophy-related sudden cardiac death and cardiovascular outcomes in a Finnish population.

Background: Hypertrophic cardiomyopathy is a common cause of non-ischaemic sudden cardiac death (SCD). Left ventricular hypertrophy (LVH) without cardiomyopathy-related myocardial disarray is a common autopsy finding and is often associated with prior hypertension in SCD subjects. Our aim was to investigate novel rare gene variants among SCD subjects with presumably hypertension-related LVH and myocardial fibrosis at autopsy.

Novel Genetic Variants Associated with Primary Myocardial Fibrosis in Sudden Cardiac Death Victims.

Myocardial fibrosis is a common finding in victims of sudden cardiac death (SCD). Whole exome sequencing was performed in 127 victims of SCD with primary myocardial fibrosis as the only pathological finding. These cases are derived from the Fingesture study which has collected data from autopsy-verified SCD victims in Northern Finland.

Apelin regulates skeletal muscle adaptation to exercise in a high-intensity interval training model.

Plasma apelin levels are reduced in aging and muscle wasting conditions. We aimed to investigate the significance of apelin signaling in cardiac and skeletal muscle responses to physiological stress. Apelin knockout (KO) and wild-type (WT) mice were subjected to high-intensity interval training (HIIT) by treadmill running.

α-Melanocyte-stimulating hormone alleviates pathological cardiac remodeling via melanocortin 5 receptor.

α-Melanocyte-stimulating hormone (α-MSH) regulates diverse physiological functions by activating melanocortin receptors (MC-R). However, the role of α-MSH and its possible target receptors in the heart remain completely unknown. Here we investigate whether α-MSH could be involved in pathological cardiac remodeling.

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis.

New Genetic Variants in and Support the Role of Oxidative Stress in Familial Ménière's Disease.

The objective was to study the genetic etiology of Ménière's disease (MD) using next-generation sequencing in three families with three cases of MD. Whole exome sequencing was used to identify rare genetic variants co-segregating with MD in Finnish families. In silico estimations and population databases were used to estimate the frequency and pathogenicity of the variants.

NRF3 Decreases during Melanoma Carcinogenesis and Is an Independent Prognostic Marker in Melanoma.

The prognostic significance of the major redox regulator, nuclear factor erythroid-2-related factor 2 (NRF2), is recognized in many cancers, but the role of NRF3 is not studied. Analysis from the Gene Expression Omnibus datasets showed that NRF3 mRNA levels increased from benign to dysplastic naevi ( = 0.04).

Genetic Variants Associated With Sudden Cardiac Death in Victims With Single Vessel Coronary Artery Disease and Left Ventricular Hypertrophy With or Without Fibrosis.

Cardiac hypertrophy with varying degrees of myocardial fibrosis is commonly associated with coronary artery disease (CAD) related sudden cardiac death (SCD), especially in young victims among whom patterns of coronary artery lesions do not entirely appear to explain the cause of SCD. Our aim was to study the genetic background of hypertrophy, with or without fibrosis, among ischemic SCD victims with single vessel CAD. The study population was derived from the Fingesture study, consisting of all autopsy-verified SCDs in Northern Finland between the years 1998 and 2017 ( = 5,869).

MiR-185-5p regulates the development of myocardial fibrosis.

Background: Cardiac fibrosis stiffens the ventricular wall, predisposes to cardiac arrhythmias and contributes to the development of heart failure. In the present study, our aim was to identify novel miRNAs that regulate the development of cardiac fibrosis and could serve as potential therapeutic targets for myocardial fibrosis.

Methods And Results: Analysis for cardiac samples from sudden cardiac death victims with extensive myocardial fibrosis as the primary cause of death identified dysregulation of miR-185-5p.

Extracellular matrix proteins produced by stromal cells in idiopathic pulmonary fibrosis and lung adenocarcinoma.

Idiopathic pulmonary fibrosis (IPF) and lung cancer share common risk factors, epigenetic and genetic alterations, the activation of similar signaling pathways and poor survival. The aim of this study was to examine the gene expression profiles of stromal cells from patients with IPF and lung adenocarcinoma (ADC) as well as from normal lung. The gene expression levels of cultured stromal cells derived from non-smoking patients with ADC from the tumor (n = 4) and the corresponding normal lung (n = 4) as well as from patients with IPF (n = 4) were investigated with Affymetrix microarrays.

A single genetic locus associated with pediatric fractures: A genome-wide association study on 3,230 patients.

The understanding of the biological and environmental risk factors of fractures in pediatrics is limited. Previous studies have reported that fractures involve heritable traits, but the genetic factors contributing to the risk of fractures remain elusive. Furthermore, genetic influences specific to immature bone have not been thoroughly studied.

Exome Sequencing Reveals a Phenotype Modifying Variant in ZNF528 in Primary Osteoporosis With a COL1A2 Deletion.

We studied a family with severe primary osteoporosis carrying a heterozygous p.Arg8Phefs*14 deletion in COL1A2, leading to haploinsufficiency. Three affected individuals carried the mutation and presented nearly identical spinal fractures but lacked other typical features of either osteogenesis imperfecta or Ehlers-Danlos syndrome.

Prognostic significance of Twist, ZEB1 and Slug in peripheral T-cell lymphomas.

To investigate the protein expression of the epithelial-mesenchymal transition-inducing transcription factors (TFs) Twist, ZEB1 and Slug in peripheral T-cell lymphomas (PTCL) and their correlation with clinical parameters. The expression of these TFs was studied in 53 diagnostic biopsy specimens of several different PTCL subtypes with immunohistochemistry. Patient data were retrospectively collected from patient records and a statistical analysis was performed.

NRF1 and NRF2 mRNA and Protein Expression Decrease Early during Melanoma Carcinogenesis: An Insight into Survival and MicroRNAs.

The prognostic significance of the major redox regulator nuclear factor erythroid-2-related factor (NRF2) is recognized in many cancers, but the role of NRF1 is not generally well understood in cancer. Our aim was to investigate these redox transcription factors in conjunction with redox-related microRNAs in naevi and melanoma. We characterized the immunohistochemical expression of NRF1 and NRF2 in 99 naevi, 88 primary skin melanomas, and 67 lymph node metastases.

Whole-exome sequencing suggests multiallelic inheritance for childhood-onset Ménière's disease.

The genetic background of Ménière's disease (MD) was studied in one patient with childhood-onset MD and his grandfather affected with middle age-onset MD. Whole-exome sequencing was performed and the data were compared to 76 exomes from unrelated subjects without MD. Thirteen rare inner ear expressed variants with pathogenic estimations were observed in the case of childhood-onset MD.

Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes.

Background: Low back pain (LBP) is a common disabling condition. Lumbar disc degeneration (LDD) may be a contributing factor for LBP. Modic change (MC), a distinct phenotype of LDD, is presented as a pathological bone marrow signal change adjacent to vertebral endplate on MRI.

Whole exome sequencing in Finnish families identifies new candidate genes for osteoarthritis.

Introduction: Osteoarthritis (OA) is the most common degenerative joint disease and one of the major causes of disability worldwide. It is a multifactorial disorder with a significant genetic component. The heritability of OA has been estimated to be 60% for hip OA and 39% for knee OA.

Rare Copy Number Variants in Array-Based Comparative Genomic Hybridization in Early-Onset Skeletal Fragility.

Early-onset osteoporosis is characterized by low bone mineral density (BMD) and fractures since childhood or young adulthood. Several monogenic forms have been identified but the contributing genes remain inadequately characterized. In search for novel variants and novel candidate loci, we screened a cohort of 70 young subjects with mild to severe skeletal fragility for rare copy-number variants (CNVs).

The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma.

Background: Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC).

Methods: MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression.

Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

Objective: To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls.

Study Design: Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups.

TUFT1, a novel candidate gene for metatarsophalangeal osteoarthritis, plays a role in chondrogenesis on a calcium-related pathway.

Osteoarthritis (OA) is the most common degenerative joint disorder and genetic factors have been shown to have a significant role in its etiology. The first metatarsophalangeal joint (MTP I) is highly susceptible to development of OA due to repetitive mechanical stress during walking. We used whole exome sequencing to study genetic defect(s) predisposing to familial early-onset bilateral MTP I OA inherited in an autosomal dominant manner.

A Whole Exome Study Identifies Novel Candidate Genes for Vertebral Bone Marrow Signal Changes (Modic Changes).

Study Design: A family-based study.

Objective: The aim of this study was to identify rare genetic factors predisposing to Modic changes (MCs).

Summary Of Background Data: Lumbar disc degeneration (LDD) is one of the contributing factors behind low back pain (LBP).