Lack of TRIC‐B dysregulates cytoskeleton assembly, trapping β‐catenin at osteoblast adhesion sites

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

The trimeric intracellular cation channel B (TRIC‐B), encoded by TMEM38B , is a potassium (K + ) present in the endoplasmic reticulum membrane, where it counterbalances calcium (Ca 2+ exit. Lack of TRIC‐B activity causes recessive form skeletal disease osteogenesis imperfecta (OI), namely OI type XIV, characterized impaired Ca flux and defects osteoblast (OB) differentiation activity. Taking advantage OB‐specific Tmem38b knockout mouse ( Runx2Cre;Tmem38b fl / ; cKO), we investigated how ion imbalance affects osteogenetic process. We found an abnormal cytoskeleton cKO OBs, with actin accumulation at OB adhesion sites. reduced amount active ‐dependent actin‐binding proteins myristoylated alanine‐rich C‐kinase substrate (MARCKS) fascin, which modulate cytoskeletal dynamics, explains altered assembly. clusters sites trap β‐catenin, key structural protein cell–cell junction sites, that abnormally accumulates despite significant reduction both N‐ E‐cadherins. Besides its fuction cell borders, β‐catenin also has pivotal role as transcription factor for proper osteoblastogenesis. Immunofluorescence nuclei revealed nuclear translocation, further validated human fetal knocked out was not rescued specifically stimulating canonical Wnt pathway. Thus, demonstrated vitro alterations homeostasis, consequence lack TRIC‐B, cause disorganization resulting contributing to

Язык: Английский

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Radiologic Anatomy of the Thorax of the Southern Giant Pouched Rat (Cricetomys ansorgei)

Anatomia Histologia Embryologia, Год журнала: 2025, Номер 54(2)

Опубликована: Фев. 12, 2025

ABSTRACT The southern giant pouched rat ( Cricetomys ansorgei ) is a large rodent native to the savannahs of and East Africa, commonly kept as pet used for medical purposes, including detection pulmonary tuberculosis, Brucella infection, land mines. Despite its biomedical significance, limited information exists on thoracic radiological anatomy. This study aimed describe normal radiographic anatomy support anatomical clinical research. Radiographs 34 adult rats were taken under general anaesthesia, right lateral (RL) dorsoventral (DV) views thorax. Most exhibited 13 vertebrae pairs ribs, with last two floating pairs. All displayed six sternebrae, trachea was visible without mineralised cartilaginous rings. cranial mediastinum appeared wider than spine in all individuals. border cardiac silhouette poorly visualised RL view but more clearly defined oblong‐shaped DV view. mean vertebral heart size (VHS) measured (10.59) significantly larger that (9.49). Additionally, gravel sand grains observed abdomen. While shares some characteristics other rodents, rabbits, domestic cats, several distinctive features identified. These findings provide valuable reference studies, applications, routine assessments.

Язык: Английский

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Modeling reproductive and pregnancy-associated tissues using organ-on-chip platforms: challenges, limitations, and the high throughput data frontier

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 13

Опубликована: Апрель 1, 2025

Over the past decade, organ-on-chip technology (microphysiological systems or tissue chips) has reshaped in-vitro physiological and pathological modeling pharmaceutical drug assessment. FDA Modernization Act 2.0 allows for alternatives to animal testing use of appropriate non-animal models/new approach methods (NAMs), such as Organ-on-chips (OC) platforms in silico simulation models, generate pre-clinical trial data regulatory purposes primes microfluidic field have exponential growth coming years. The changes approaches agencies could significantly impact development therapeutics during pregnancy. However, limitations devices molecular biochemical assay shortfalls hinder progress OOC field. This review describes available reproductive pregnancy-related platforms, current methodologies utilized endpoint datasets (e.g., microscopic imaging, immunocytochemistry, real-time polymerase chain reaction, cytokine multiplex analysis). Microfluidic platform limitations, fewer number cells low supernatant volumes restrictions regarding fabrication materials, are described. Novel spatial transcriptomics, imaging cytometry by time flight, exosomes analysis using Exoview) overcome these challenges primed provide biologically relevant clinically translational that can revolutionize modeling, discovery, toxicologic risk engineering adaptations increase throughput (i.e., device arrays) biological advancements improve both needed reach their full potential.

Язык: Английский

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Study of tree shrew biology and models: A booming and prosperous field for biomedical research

动物学研究, Год журнала: 2024, Номер 45(4), С. 877 - 909

Опубликована: Янв. 1, 2024

The tree shrew (Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due its close evolutionary relationship with primates. In recent years, significant advances have facilitated studies, including the determination of genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, mapping brain atlas. However, limited availability shrews globally remains substantial challenge field. Additionally, determining key questions best answered constitutes another difficulty. Tree models historically used study hepatitis B virus (HBV) C (HCV) infection, myopia, psychosocial stress-induced depression, more studies focusing on developing animal for infectious neurodegenerative diseases. Despite these efforts, impact not yet matched that rodent or NHP research. This review summarizes prominent advancements reflects biological addressed this model. We emphasize intensive dedication robust international collaboration are essential achieving breakthroughs studies. use unique resource is expected gain considerable attention application advanced techniques development viable models, meeting increasing demands life science

Язык: Английский

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Genetic models of fibrillinopathies

Genetics, Год журнала: 2023, Номер 226(1)

Опубликована: Ноя. 16, 2023

The fibrillinopathies represent a group of diseases in which the 10-12 nm extracellular microfibrils are disrupted by genetic variants one genes encoding fibrillin molecules, large glycoproteins matrix. best-known fibrillinopathy is Marfan syndrome, an autosomal dominant condition affecting cardiovascular, ocular, skeletal, and other systems, with prevalence around 1 3,000 across all ethnic groups. It caused FBN1 gene, fibrillin-1, interacts elastin to provide strength elasticity connective tissues. A number mouse models have been created attempt replicate human phenotype, although limitations. There also natural bovine engineered pig rabbit. Variants FBN2 fibrillin-2 cause congenital contractural arachnodactyly for this produced. In most animals, including birds, reptiles, amphibians, there third fibrillin, fibrillin-3 (FBN3 gene) creation has difficult as gene degenerate nonfunctional mice rats. Other eukaryotes such nematode C. elegans zebrafish D. rerio some homology fibrillins used discover more about function family proteins. This review looks at inheritance, relevance various animal different fibrillinopathies.

Язык: Английский

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Neutrophil extracellular traps boost laser‐induced mouse choroidal neovascularization through the activation of the choroidal endothelial cell TLR4/HIF‐1α pathway

FEBS Journal, Год журнала: 2023, Номер 290(22), С. 5395 - 5410

Опубликована: Авг. 8, 2023

Choroidal neovascularization (CNV) is characterized by the infiltration of immune cells, particularly neutrophils. Neutrophil extracellular trap (NET) facilitates angiogenesis pulmonary endothelial cells via activating Toll-like receptor 4 (TLR4). TLR4 promotes expression transcription factor hypoxia inducible factor-1α (HIF-1α), which inflammation and up-regulation metalloproteinase-9 (MMP-9) interleukin-1β (IL-1β). In present study, we aimed to identify formation NET its role in CNV. Our results showed that levels were increased a mouse laser-induced CNV model oxidative stress, whereas inhibition alleviated vitro, activated TLR4/HIF-1α pathway human choroidal (HCECs). Additionally, MMP-9 IL-1β HCECs pathway. Meanwhile, promoted inflammatory response accompanied proliferation, migration tube MMP-9- IL-1β-dependent manner. conclusion, was up-regulated cells. data uncovered novel promoting The underlying mechanism could be targeted delay process

Язык: Английский

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The Species Effect: Differential Sphingosine-1-Phosphate Responses in the Bone in Human Versus Mouse

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(10), С. 5118 - 5118

Опубликована: Май 8, 2024

The deterioration of osteoblast-led bone formation and the upregulation osteoclast-regulated resorption are primary causes diseases, including osteoporosis. Numerous circulating factors play a role in homeostasis by regulating osteoblast osteoclast activity, sphingolipid-sphingosine-1-phosphate (S1P). However, to date no comprehensive studies have investigated impact S1P activity on human murine osteoblasts osteoclasts. We observed species-specific responses both osteoclasts, where stimulated mineralisation reduced pre-osteoclast differentiation mineral resorption, thereby favouring formation. opposite was true for resulting more less deposition. Species-specific differences were potentially explained differential expression receptor 1. By contrast, osteoclasts expressed comparable levels receptors but showed patterns two sphingosine kinase enzymes responsible production. Ultimately, we reveal that models may not accurately represent how cells will respond S1P, thus suitable model exploring physiology or potential therapeutic agents.

Язык: Английский

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Proteomic reference map for sarcopenia research: mass spectrometric identification of key muscle proteins located in the sarcomere, cytoskeleton and the extracellular matrix

European Journal of Translational Myology, Год журнала: 2024, Номер unknown

Опубликована: Май 24, 2024

Sarcopenia of old age is characterized by the progressive loss skeletal muscle mass and concomitant decrease in contractile strength. Age-related dysfunctions play a key pathophysiological role frailty syndrome can result drastically diminished quality life elderly. Here we have used spectrometric analysis mouse hindlimb musculature to establish protein constellation at advanced widely sarcopenic animal model. Proteomic results were further analyzed systems bioinformatics voluntary muscles. In this report, proteomic survey aged muscles has focused on expression patterns proteins involved contraction-relaxation cycle, membrane cytoskeletal maintenance formation extracellular matrix. This includes markers fast versus slow phenotypes myosin-containing thick filaments actin-containing thin filaments, as well that are associated with non-sarcomeric cytoskeleton various matrisomal layers. The bioanalytical usefulness newly established reference map was demonstrated comparative screening normal dystrophic age, findings verified immunoblot analysis.

Язык: Английский

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Body Weight-Based Animal Laboratory Classification Utilizing Load Cell and IoT

Опубликована: Авг. 7, 2024

Язык: Английский

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In vivo electrical properties of the healthy liver and the hepatic tumor in a mouse model between 1 Hz and 1 MHz during a thermal treatment

International Journal of Hyperthermia, Год журнала: 2024, Номер 41(1)

Опубликована: Сен. 1, 2024

Objective: Understansding the changing patterns of in vivo electrical properties for target tissue is crucial accurate temperature monitoring and treatment efficacy thermal therapy. Our research aims to investigate reversibility both healthy livers liver tumors a mouse model over frequency range 1 Hz MHz at temperatures between 30 °C 90 °C.

Язык: Английский

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