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Identification of miR-143 as a Major Contributor for Human Stenotic Aortic Valve Disease.

Calcification of aortic valves leads to aortic stenosis mainly in elderly individuals, but the underlying molecular mechanisms are still not understood. Here, we studied microRNA (miR, miRNA) expression and function in healthy and stenotic human aortic valves. We identified miR-21, miR-24, and miR-143 to be highly upregulated in stenotic aortic valves. Using luciferase reporter systems, we found direct binding of miR-143 to the 3'UTR region of the matrix gla protein (MGP), which in turn is a key factor to sustain homeostasis in aortic valves. In subsequent experiments, we demonstrated a therap

Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic biomarker.

A case-control study was conducted to estimate the association of cartilage oligomeric matrix protein (COMP) with knee osteoarthritis (OA) and to examine the potential utility of COMP as a diagnostic and prognostic biomarker in early knee OA. The COMP levels were estimated in the blood sera of 150 subjects belonging to study group (n = 100) and control one (n = 50). Patients with confirmed clinical isolated knee OA diagnosed through American College of Rheumatology criteria were included and were without any other cause of knee pain. ELISA was used to determine the levels of COMP, interleukin-

Polymorphisms of the human matrix gla protein (MGP) gene, vascular calcification, and myocardial infarction.

The matrix Gla protein (MGP) is an important inhibitor of vessel and cartilage calcification that is strongly expressed in human calcified, atherosclerotic plaques and could modulate plaque calcification and coronary heart disease risk. Using a genetic approach, we explored this possibility by identifying polymorphisms of the MGP gene and testing their possible association with myocardial infarction (MI) and plaque calcification. Eight polymorphisms were identified in the coding and 5'-flanking sequences of the MGP gene. All polymorphisms were investigated in 607 patients with MI and 667 contr

Interstitial fibrosis in mice with overload proteinuria: deficiency of TIMP-1 is not protective.

BACKGROUND: Progressive renal interstitial fibrosis is characterized by up-regulated expression of the gene that encodes the tissue inhibitor of metalloproteinases-1 (TIMP-1), a regulator of extracellular matrix remodeling, suggesting that impaired matrix turnover contributes to the fibrogenic process. The present study was designed to develop a murine model of renal interstitial fibrosis, and to determine the functional significance of up-regulated Timp-1 expression by comparing the severity of this renal disease in wild-type mice and mice genetically deficient in Timp-1. METHODS: Initial pi

Altered protein conformation and lower stability of the dystrophic transforming growth factor beta-induced protein mutants.

PURPOSE: Transforming growth factor beta-induced protein (TGFBIp) is a widely expressed extracellular matrix protein that plays roles in cell adhesion and migration, differentiation, apoptosis, bone morphogenesis, and carcinogenesis. Mutations of TGFBIp have been linked to stromal corneal dystrophies, a group of protein conformational diseases characterized by abnormal protein aggregations in the cornea. However, the underlying pathogenic mechanism remains elusive due to a lack of insight into the molecular properties of the disease-causing mutants. In the current study, we applied spectroscop

Large-scale plasma proteomic profiling enhances prediction of heart failure among hypertensive individuals: prospective insights from the UK Biobank.

BACKGROUND: Hypertension is a major risk factor for heart failure (HF), but current clinical models have limited ability to identify high-risk individuals before overt disease. Plasma proteomics may capture early molecular changes and improve risk prediction. METHODS: We analysed 16,128 hypertensive UK Biobank Pharma Proteomics Project participants without baseline HF. Plasma levels of 2,911 proteins were measured using the Olink Explore platform. Participants were randomly split 1:1 into training and validation sets. HF-associated proteins were identified using Cox models in the training set

[Erianin inhibits proliferation and migration of breast cancer cells in vitro by inhibiting Wnt/β-catenin signaling].

OBJECTIVES: To investigate the effect of erianin on proliferation, migration, invasion, and apoptosis of breast cancer cells and the underlying mechanisms. METHODS: Breast cancer cell lines T-47D and MCF-7 treated with 0, 12.5, 25, 50, and 100 nmol/L erianin for 12, 24, 36, 48, and 72 h were examined for cell viability using CCK-8 assay. The effects of erianin on cell proliferation, migration, invasion, senescence and apoptosis were evaluated using clone formation, wound healing, Transwell invasion, and senescence assays and flow cytometry. mRNA microarray analysis and the Enrichr database we

T3 and curcumin regulates collagen-IV and collagen-VI expression: role in suppression of amyloid-β via TGFβ1-Sp1 signaling in hypothyroid mice brain.

Hypothyroidism has been associated with cognitive disorders and high risk of neurodegenerative disorders like Alzheimer's disease (AD), which is caused by amyloid-β (Aβ) accumulation in brain. The aim of the study is to examine the therapeutic ability of triiodothyronine (T3) and curcumin in regulating two key extracellular matrix proteins (ECM), collagen IV and collagen VI in brain since both drugs have neuroprotective and anti-fibrotic effects. The study further explored the possible role of signaling molecules such as transforming growth factor β1 (TGFβ1) and specificity protein 1 (Sp1) in …

Circadian rhythm disruption impairs time-dependent dentine regeneration and reprograms the late-stage dental proteome in a mouse pulp injury model.

Circadian rhythms coordinate metabolic and regenerative programs, yet their contribution to pulp healing and tertiary dentinogenesis remains unclear. Here, we investigated whether chronic circadian rhythm disruption (CRD) alters time-dependent dentine repair and proteomic remodeling after dental pulp injury (DPI) in male BALB/c mice. Animals were maintained either under a stable 12:12 h light-dark cycle or under a chronic jet-lag model with a daily 2 h phase advance. DPI was induced in the maxillary first molars, followed by immediate direct pulp capping with mineral trioxide aggregate and sea

Deep plasma and tissue proteome profiling of knockout mice reveals pathways associated with Svep1 deficiency.

Despite strong causal associations with cardiovascular and metabolic disorders including coronary artery disease, hypertension, and type 2 diabetes, as well as a range of other diseases, the exact function of the protein SVEP1 remains largely unknown. Animal models have been employed to investigate how SVEP1 contributes to disease, with a focus on murine models exploring its role in development, cardiometabolic disease and platelet biology. In this study, we aimed to comprehensively phenotype the proteome of Svep1 +/- mice compared to wild-type (WT) littermates using liquid chromatography-tand

Phosphoproteomic profiling highlights CDC42 and CDK2 as key players in the regulation of the TGF-β pathway in ALMS1 and BBS1 knockout models.

The primary cilium is a sensory organelle that extends from the plasma membrane. It plays a vital role in physiological and developmental processes by controlling different signalling pathways such as WNT, Sonic hedgehog (SHh), and transforming growth factor β (TGF-β). Ciliary dysfunction has been related to different pathologies such as Alström (ALMS) or Bardet-Biedl (BBS) syndrome. The leading cause of death in adults with these syndromes is chronic kidney disease (CKD), which is characterised by fibrotic and inflammatory processes often involving the TGF-β pathway. Using genomic editing wit

Bleomycin-induced lung fibrosis and dysfunction is exacerbated by G6PD deficiency.

Pulmonary fibrosis (PF) is a major cause of morbidity and mortality. Although increased oxidative stress and altered metabolism are implicated in PF pathobiology, our knowledge regarding the contribution of the glucose metabolism to the synthesis of extracellular matrix (ECM) is still incomplete. Therefore, our objective was to determine altered metabolic pathways that contribute to bleomycin (BLM; 5 mg/kg) sulfate-induced PF in rats. We determined the effects of nebulized BLM on PF in CRISPR-edited rats expressing glucose-6-phosphate dehydrogenase (G6PD) variant (S188F; G6PDS188F) and their w

Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study.

BACKGROUND: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone. METHODS: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and

New insights into the natural history of bronchopulmonary dysplasia from proteomics and multiplexed immunohistochemistry.

Bronchopulmonary dysplasia (BPD) is a disease of prematurity related to the arrest of normal lung development. The objective of this study was to better understand how proteome modulation and cell-type shifts are noted in BPD pathology. Pediatric human donors aged 1-3 yr were classified based on history of prematurity and histopathology consistent with "healed" BPD (hBPD, n = 3) and "established" BPD (eBPD, n = 3) compared with respective full-term born (n = 6) age-matched term controls. Proteins were quantified by tandem mass spectroscopy with selected Western blot validations. Multiplexed im

Identification of Matriglycan by Dual Exoglycosidase Digestion of α-Dystroglycan.

Matriglycan is a linear polysaccharide of alternating xylose and glucuronic acid units [-Xyl-α1,3-GlcA-β1,3]n that is uniquely synthesized on α-dystroglycan (α-DG) and is essential for neuromuscular function and brain development. It binds several extracellular matrix proteins that contain laminin-globular domains and is a receptor for Old World arenaviruses such as Lassa Fever virus. Monoclonal antibodies such as IIH6 are commonly used to detect matriglycan on α-DG. However, endogenous expression levels are not sufficient to detect and analyze matriglycan by mass spectrometry approaches. Thus…

Аденовиральная трансдукция Dickopf-1 Alleviates Silica Industed Silicos Development in Lungs of Mice.

Силикоз - это профессиональная болезнь, вызванная вдыханием силичной пыли, которая характеризуется прогрессивным фиброзом легких, связанным с плохим прогнозом. Сигнал Wnt/β-ctenin имеет отношение к развитию фиброза и является терапевтической целью для лечения фибротических заболеваний. Предыдущие клинические исследования пациентов с пневмокониозом, включая силикоз, выявили увеличение концентрации циркулирующих белков WNT3A и DK1 и подстрекательских клеток в бронхоальвеолярном туалете по сравнению со здоровыми субъектами. В настоящем исследовании дается оценка воздействия аденовирусного трансду

Совпадение в аннотации оригинала
Silicosis is an occupational disease caused by inhalation of silica dust, which is hallmarked by progressive pulmonary fibrosis associated w … ccompanied by the reduced expression of epithelia--mesenchymal transition markers and deposition of extracellular matrix proteins compared with mice treated with "null" adenoviral vector. Mechanistically, AdDkk1 is able to attenuate the lung silicosis by inhibiting a silica-induced spike in TGF-β/Smad signaling. In addition, the forced expression of Dkk1 suppressed silica-indu …

Ivabradine induces cardiac protection by preventing cardiogenic shock-induced extracellular matrix degradation.

INTRODUCTION AND OBJECTIVES: Ivabradine reduces heart rate by blocking the I(f) current and preserves blood pressure and stroke volume through unknown mechanisms. Caveolin-3 protects the heart by forming protein complexes with several proteins, including extracellular matrix (ECM)-metalloproteinase-inducer (EMMPRIN) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HN4), a target of ivabradine. We hypothesized that ivabradine might also exert cardioprotective effects through inhibition of ECM degradation. METHODS: In a porcine model of cardiogenic shock, we studied the effect

Haploinsufficiency of X-linked intellectual disability gene CASK induces post-transcriptional changes in synaptic and cellular metabolic pathways.

Heterozygous mutations in the X-linked gene CASK are associated with intellectual disability, microcephaly, pontocerebellar hypoplasia, opti … rain uncovers a very limited number of changes, with most differences arising in the transcripts of extracellular matrix proteins and the transcripts of a group of nuclear proteins. In contrast to limited changes at the transcript level, quantitative whole-brain proteomics using iTRAQ quantitative mass-spectrometry reveals major changes in synaptic, metabolic/mitochondrial, cy …

Proteomic Analysis of Vocal Fold Fibroblasts Exposed to Cigarette Smoke Extract: Exploring the Pathophysiology of Reinke's Edema.

Reinke's edema is a smoking-associated, benign, mostly bilateral lesion of the vocal folds leading to difficulties in breathing and voice problems. Pronounced histological changes such as damaged microvessels or immune cell infiltration have been described in the vocal fold connective tissue, the lamina propria Thus, vocal fold fibroblasts, the main cell type of the lamina propria, have been postulated to play a critical role in disease mediation. Yet information about the pathophysiology is still scarce and treatment is only surgical, i.e. symptomatic. To explore the pathophysiology of Reinke

Determination of minimum inhibitory concentrations of various antifungal agents in clinical isolates of Candida species.

BACKGROUND: Sialolithiasis or salivary gland stones are associated with high clinical morbidity. The advances in the treatment of sialolithiasis has been limited, however, by our understanding of their composition. More specifically, there is little information regarding the formation and composition of the protein matrix, the role of mineralogical deposition, or the contributions of cell epithelium and secretions from the salivary glands. A better understanding of these stone characteristics could pave the way for future non-invasive treatment strategies. METHODS: Twenty-nine high-quality du