BMP signalling

BACKGROUND: Recent reports have unveiled the potential utility of l-carnitine to alleviate metabolic dysfunction-associated steatohepatitis (MASH) by enhancing mitochondrial metabolic function. However, its efficacy at preventing the development of HCC has not been assessed fully. METHODS: l-carnitine (2 g/d) was administered to 11 patients with MASH for 10 weeks, and blood liver function tests were performed. Five patients received a serial liver biopsy, and liver histology and hepatic gene expression were evaluated using this tissue...

The aim of this study was to analyze signaling pathways associated with differentially expressed messenger RNAs in people with restless legs syndrome (RLS). Seventeen RLS patients and 18 controls were enrolled. Coding RNA expression profiling of 12,857 gene transcripts by next-generation sequencing was performed. Enrichment analysis by pathfindR tool was carried-out, with p-adjusted ≤0.001 and fold-change ≥2.5. Nine main different network groups were significantly dysregulated in RLS: infections, inflammation, immunology, neurodegeneration, cancer, neurotransmission and biological, blood and metabolic mechanisms...

PFAAs (Perfluoroalkyl acids) are a class of bioaccumulative, persistent and ubiquitous environmental contaminants which primarily occupy the hydrosphere and its sediments. Currently, a paucity of toxicological information exists for short chain PFAAs and complex mixtures. In order to address these knowledge gaps, we performed a 3-week, aqueous exposure of rainbow trout to 3 different concentrations of a PFAA mixture (50, 100 and 500 ng/L) modeled after the composition determined in Lake Ontario. We conducted an additional set of exposures to individual PFAAs (25 nM each of PFOS (12,500 ng/L), PFOA (10,300 ng/L), PFBS (7500 ng/L) or PFBA (5300 ng/L) to evaluate differences in biological response across PFAA congeners...

The use of mesenchymal stem cells (MSCs) in cartilage regeneration has gained significant attention in regenerative medicine. This paper reviews the molecular mechanisms underlying MSC-based cartilage regeneration and explores various therapeutic strategies to enhance the efficacy of MSCs in this context. MSCs exhibit multipotent capabilities and can differentiate into various cell lineages under specific microenvironmental cues. Chondrogenic differentiation, a complex process involving signaling pathways, transcription factors, and growth factors, plays a pivotal role in the successful regeneration of cartilage tissue...

BACKGROUND: Bone deficiency-related diseases caused by various factors have disrupted the normal function of the skeleton and imposed a heavy burden globally, urgently requiring potential new treatments. The multi-faceted role of compounds like ginsenosides and their interaction with the bone microenvironment, particularly osteoblasts can promote bone formation and exhibit anti-inflammatory, vascular remodeling, and antibacterial properties, holding potential value in the treatment of bone deficiency-related diseases and bone tissue engineering...

(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated the therapeutic effects of the active ingredient Eleutheroside B (EB) from the traditional Chinese medicine Eleutheroside on diabetes mellitus in a zebrafish model. Concomitant hepatic injury was also analysed, along with the study of possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies...

Mesenchymal stromal cells (MSCs) that are promising for cartilage tissue engineering secrete high amounts of prostaglandin E2 (PGE2), an immunoactive mediator involved in endochondral bone development. This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-β1 and insulin to overcome the PGE2 inhibition by dexamethasone...

OBJECTIVE: Heterotopic ossification (HO), also known as ossifying myositis, is a condition that produces abnormal bone and cartilage tissue in the soft tissues. Hypoxia inducible factor lα (HIF-lα) regulates the expression of various genes, which is closely related to the promotion of bone formation, and Drosophila mothers against decapentaplegic protein (SMAD) mediates the signal transduction in the Bone morphogenetic protein (BMP) signaling pathway, which affects the function of osteoblasts and osteoclasts, and thus plays a key role in the regulation of bone remodeling...

Functional tissue-engineered artificial skeletal muscle tissue has great potential for pharmacological and academic applications. This study demonstrates an in vitro tissue engineering system to construct functional artificial skeletal muscle tissues using self-organization and signal inhibitors. To induce efficient self-organization, we optimized the substrate stiffness and extracellular matrix (ECM) coatings. We modified the tissue morphology to be ring-shaped under optimized self-organization conditions...

Traditional fibrous membranes employed in guided tissue regeneration (GTR) in the treatment of periodontitis have limitations of bioactive and immunomodulatory properties. We fabricated a novel nTPG/PLGA/PCL fibrous membrane by electrospinning which exhibit excellent hydrophilicity, mechanical properties and biocompatibility. In addition, we investigated its regulatory effect on polarization of macrophages and facilitating the regeneration of periodontal tissue both in vivo and in vitro. These findings showed the 0...

Induced pluripotent stem cells (iPSCs) are obtained by introducing exogenous genes or adding chemicals to the culture medium to induce somatic cell differentiation. iPSCs have the ability to differentiate into all three embryonic cell lines, similar to embryonic stem cells. iPSCs can differentiate into cardiac muscle cells through two-dimensional differentiation methods such as monolayer cell culture and co-culture, or through embryoid body and scaffold-based three-dimensional differentiation methods. In addition, the process of iPSCs differentiation into cardiac muscle cells also requires activation or inhibition of specific signaling pathways,such as Wnt, BMP, Notch signaling pathways to mimic the development of the heart in vivo ...

The gastroesophageal squamocolumnar junction (GE-SCJ) is a critical tissue interface between the esophagus and stomach, with significant relevance in the pathophysiology of gastrointestinal diseases. Despite this, the molecular mechanisms underlying GE-SCJ development remain unclear. Using single-cell transcriptomics, organoids, and spatial analysis, we examine the cellular heterogeneity and spatiotemporal dynamics of GE-SCJ development from embryonic to adult mice. We identify distinct transcriptional states and signaling pathways in the epithelial and mesenchymal compartments of the esophagus and stomach during development...

During the morphological changes occurring in osteoblast differentiation, Sonic hedgehog (Shh) plays a crucial role. While some progress has been made in understanding this process, the epigenetic mechanisms governing the expression of Hh signaling members in response to bone morphogenetic protein 7 (BMP7) signaling in osteoblasts remain poorly understood. To delve deeper into this issue, we treated pre-osteoblasts (pObs) with 100 ng/mL of BMP7 for up to 21 days. Initially, we validated the osteogenic phenotype by confirming elevated expression of well-defined gene biomarkers, including Runx2, Osterix, Alkaline Phosphatase (Alp), and bone sialoprotein (Bsp)...

Hemojuvelin (HJV) is a GPI-anchored protein of the repulsive guidance molecule (RGM) family acting as a bone morphogenetic protein (BMP) co-receptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV) mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3...

BACKGROUND: In vitro chondrogenesis of mesenchymal stromal cells (MSCs) driven by the essential chondro-inducer transforming growth factor (TGF)-β is instable and yields undesired hypertrophic cartilage predisposed to bone formation in vivo. TGF-β can non-canonically activate bone morphogenetic protein-associated ALK1/2/3 receptors. These have been accused of driving hypertrophic MSC misdifferentiation, but data remained conflicting. We here tested the antihypertrophic capacity of two highly specific ALK1/2/3 inhibitors - compound A (CompA) and LDN-212854 (LDN21) - in order to reveal potential prohypertrophic contributions of these BMP/non-canonical TGF-β receptors during MSC in vitro chondrogenesis...

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial infarction has likely contributed to the increased prevalence of heart failure(HF).As a result of ventricular remodeling and reduced cardiac function, colonic blood flow decreases, causing mucosal ischemia and hypoxia of the villous structure of the intestinal wall.This damage in gut barrier function increases bowel wall permeability, leading to fluid metabolism disorder,gut microbial dysbiosis, increased gut bacteria translocation into the circulatory system and increased circulating endotoxins, thus promoting a typical inflammatory state...

Maternal heat stress during late pregnancy can lead to intrauterine hyperthermia and affect fetal hypothalamic-pituitary-adrenal axis development and function. Herein, we investigated the effects of chronic environmental heat stress exposure of Holstein cows in the last 2 mo of gestation on their offspring's adrenal gland histomorphology and transcriptome. Cows in their last 54 ± 5 d of gestation were either heat-stressed (i.e., housed under the shade of a free stall barn) or provided heat-stress abatement via active cooling (i...

Gametogenesis drives the maturation of germ cell precursors into functional gametes, facilitated by interactions with the niche environment. However, the molecular mechanisms, especially in invertebrates, remain incompletely understood. In this study, the gonadal microenvironment and gametogenic processes in the Pacific oyster, a model for diffuse gonadal organization and periodic gametogenesis, are investigated. We combine single-nucleus RNA-seq and bulk RNA-seq to analyze gonadal microenvironments in oysters...

The Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. Here, we use high-quality scRNA-seq, validated by anatomical identification, to create a comprehensive census of larval VNC cell types. We show that the neural lineages that comprise the adult VNC are already defined, but quiescent, at the larval stage. Using fluorescence-activated cell sorting (FACS)-enriched populations, we separate all motor neuron bundles and link individual neuron clusters to morphologically characterized known subtypes...

Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut-metabolism-mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum...