Cell and Tissue Research最新文献

Pannexin (Panx)-1-mediated ATP release has been associated with a broad range of pathological conditions. Conversely, the use of Panx1-inhibitors has shown promising results in the medication of diseases, such as neuroinflammation, melanoma and epilepsy. In addition, Panx1-inhibitors are an indispensable tool for the elucidation of both structure and physiology of Panx1. Over the past years, numerous applications of Panx1-inhibitors have led to new insights into Panx1 influences in health and disease. The major drawback of conventional Panx1-inhibitors, however, is the lack of selectivity resulting in undesired side effects. Nevertheless, these inhibitors are useful resources for drug discovery and lead optimisation approaches have therefore found their way into Panx1 research. Newly developed inhibitors show both high efficacy and selectivity. The combination of drug development and molecular dynamics simulations is a powerful tool to further elucidate both structure and gating mechanisms of Panx1.

Mammalian thyroid peroxidase (TPO), a thyroid-specific peroxidase involved in thyroid hormone synthesis, has a characteristic hydrophobic region in the C-terminus (HRC) that anchors peroxidase to the apical membrane of epithelial follicle cells. Protochordates (lancelets and ascidians) have TPO-like (TPOL) peroxidases with or without HRC, and their expression has been reported in the endostyle. We herein investigated the molecular structures of TPOL in protochordates and TPO relatives in vertebrates, including eosinophil peroxidase, myeloperoxidase, and lactoperoxidase, with a focus on the existence of HRC. Our molecular phylogenetic analysis implied that ancestral chordates evolved HRC-containing peroxidases, and mammalian TPO maintained HRC despite many TPO relatives losing it. Gene expression profiles revealed by in situ hybridization and an RNA-seq analysis showed that transcripts of TPOL genes in protochordates were distributed to pharyngeal epithelia in addition to the endostyle. Furthermore, disturbances in TPO activity by a thiourea treatment and gene knockdown experiments resulted in a deficiency of pharyngeal mucus-sheets. Collectively, these results suggest that HRC-containing TPOL was originally involved in pharyngeal mucus-sheet formation for suspension feeding in ancestral chordates, and HRC may have evolved to maintain peroxidase anchoring to the apical surface of pharyngeal epithelia.

The oviduct is an important reproductive organ that fosters fertilization and early embryo development in mammals. With growing utilization of assisted reproductive technologies (ARTs) in animal agriculture, recent advancements in cell culture modeling have the potential to optimize in vitro fertilization methods. Organoids are a three-dimensional (3D) cell culture model poised to serve a key role in our understanding of endogenous oviductal physiology in cattle. However, limited information is currently available for the use of bovine oviductal organoids. Thus, the objective of our study was to conduct a comprehensive characterization of bovine oviductal organoids including polarity, cryopreservation, responsiveness to hormonal cues, and extracellular vesicle assessment. We observed that bovine oviductal organoids have the capacity for culture longevity for at least 86 days with or without cryopreservation. Furthermore, the organoid polarity can be manipulated by presence or absence of an extracellular matrix, and they respond to stimulation with hormones associated with estrus and diestrus through gene expression changes and extracellular vesicle secretion. In conclusion, bovine organoids display similar characteristics to in vivo oviductal cells and constitute a cell culture model in which to study oviductal physiology to improve ARTs in beef and dairy agriculture.

Glioblastoma (GBM) is the most aggressive primary brain tumour in adults, characterized by extensive heterogeneity and diffuse invasion. Increasing evidence highlights the role of channel-forming proteins in glioma biology. Connexins (Cxs) and Pannexins (Panxs) are two structurally related yet functionally distinct protein families that mediate cellular communication. While both regulate overlapping processes such as ion homeostasis and ATP release, only Cxs are capable of readily forming intercellular gap junctions. Cx43 is the most extensively studied connexin in GBM and seems to display paradoxical roles, acting as a tumour suppressor by reducing proliferation while promoting invasion. In contrast, Panx1 predominantly supports tumour progression, while Panx2 exerts tumour-suppressive effects. This review synthesizes how Cxs and Panxs exert context-dependent and sometimes opposing effects across stages of GBM, including proliferation and invasion, and examines how divergent experimental models may contribute to apparent contradictions. Discrepancies among studies often arise from differences in model systems, which may not recapitulate the complexity of human GBM. Given the profound heterogeneity of this tumour, future research should prioritize patient-derived and three-dimensional models that more accurately represent the human disease context. Such approaches will be essential to clarify the context-dependent functions of Cxs and Panxs and their potential as therapeutic targets in GBM.

Aldosterone, a stress-related hormone, may contribute to pancreatic dysfunction. Its role in pancreatic physiology, inflammation, and fibrosis remains poorly understood. This study aimed to evaluate the effects of aldosterone on pancreatic histomorphology and islet cellularity under chronic stress conditions, and to determine whether eplerenone, a selective aldosterone receptor antagonist, can counteract them. Twenty-four young male Wistar rats were randomly divided into four groups (n = 6): control, chronic unpredictable mild stress (CUMS), control + vehicle (control + Veh), and CUMS + eplerenone (EP). Eplerenone was administered on postnatal day 51 via gastric tube 2 h before daily stress exposure for 4 weeks. Histological, immunohistochemical, and biochemical analyses were performed, including quantification of aldosterone, visceral adipose tissue, and pancreatic triacylglycerol. In CUMS group, the aldosterone level increased. In the exocrine pancreas, the aldosterone increased intralobular fat and triacylglycerol accumulation. Tumor necrosis factor alpha (TNFα)-positive necrotic acinar cells with pyknotic nuclei and perivascular fibrosis were evident. The endocrine pancreas exhibited increased inflammation and an altered distribution of islet sizes. Eplerenone reduced fat accumulation, inflammation, and exocrine structural damage but did not prevent TNF-α expression in islets. In conclusion, aldosterone induced by chronic stress contributes to pancreatic steatosis, and islet toxicity in young male rats, supporting aldosterone's pathogenic role.

Every year, more than two hundred billion individuals of the black soldier fly Hermetia illucens are reared on an industrial scale to convert a wide range of organic by-products into high-value materials for agricultural and industrial applications. The present ultrastructural investigation, using scanning (SEM) and transmission (TEM) electron microscopy, describes the fine morphology of antennal sensilla in males and females: three types of olfactory sensilla (two multiporous and one coeloconic), one type of uniporous grooved sensillum chaeticum with gustatory and mechanosensory functions, and one type of small peg sensillum with a probable hygroreceptive function. In addition, pseudo-lamellate sensory neurons, not connected to the cuticle, are described in the last two flagellar segments, which otherwise lack sensilla. These findings provide essential groundwork for future electrophysiological and behavioral investigations to deepen the knowledge on H. illucens sensory biology, which may contribute to optimizing global mass-rearing systems. Moreover, the results, together with hypotheses on the function of the paddle-like last flagellomere, may be relevant for exploring the evolutionary differentiation of the ancestral Dipteran flagellum into the complex sensory system characteristic of the Brachycera.

Glycogen metabolism is an important pathway in energy metabolism, and when cells require energy, glycogen is broken down into glucose-1-phosphate through glycogenolysis, which serves as an intracellular energy source. Recently, the concept of "glycogen shunt" has been proposed to regulate the synthesis, accumulation, and breakdown of glycogen to provide glucose at the appropriate time, particularly in organogenesis. This study demonstrated the timing of the localization of glycogen and molecules related to glycogen metabolism during submandibular gland development using embryonic and postnatal mice. In addition, a glycogenolysis inhibition experiment was conducted in organ culture systems of submandibular gland tissues. From embryonic day 13.5 (E13.5), glycogen synthesis started in the salivary epithelial cells, and glycogen accumulation and degradation occurred at E15.5. Conversely, in the submandibular gland tissue around birth, the number of glycogen-retained cells increased, and active glycogen synthesis and degradation occurred in acinar cells and terminal tubules. In an in vitro organ culture experiment, early branching morphogenesis was disturbed by a glycogen phosphorylase inhibitor, which significantly inhibited differentiation into acinar and myoepithelial cells. These results suggest the important role of the glycogen shunt in early growth and cell differentiation during submandibular gland development.

Kidney organoids derived from human pluripotent stem cells (hPSCs) have emerged as powerful platforms for translational nephrology, enabling complex renal pathophysiology modeling in physiologically relevant three-dimensional contexts. This review synthesizes recent advances in kidney organoid applications for disease modeling and drug discovery, highlighting their translational potential beyond developmental biology. These organoids recapitulate key human kidney architectural features, including nephron-like structures with glomeruli and tubules, while exhibiting greater cellular heterogeneity than traditional two-dimensional cultures. They effectively model monogenic renal disorders including autosomal dominant polycystic kidney disease (ADPKD), congenital nephrotic syndrome, and Alport syndrome, as well as acquired conditions like acute kidney injury and drug-induced nephrotoxicity. Kidney organoids serve as predictive nephrotoxicity screening platforms, demonstrating dose- and time-dependent responses to cisplatin, tenofovir, and aristolochic acid. However, significant challenges persist, including insufficient vascularization, developmental immaturity, segmental bias, absent urinary drainage systems, and reproducibility variability. Emerging bioengineering strategies-including endothelial co-culture, microfluidic integration, and 3D bioprinting-aim to address these limitations. Integrating stem cell biology with engineering innovations and multi-omics technologies will be crucial for refining kidney organoids into scalable, reproducible models that faithfully recapitulate human kidney physiology and disease, ultimately enabling their translation into precision medicine applications.

Collagen II scaffolds and decellularized cartilage are used for tissue engineering; however, there are no studies that compare their properties. To this aim, this study produced and characterized collagen II and decellularized cartilage scaffolds made from bovine trachea and evaluated the influence of the culture medium on the tissue type synthesized by human bone marrow mesenchymal stem cells (hBMSC) and human adipose mesenchymal stem cells (hASC) cultured on the scaffolds. Three angiogenic factors secreted by these cell cultures were also quantified. Decellularized hyaline cartilage had lower concentrations of collagen II and higher concentrations of GAG than collagen II scaffolds. The porosity, pore size, and fluid sorption capacity of the collagen scaffolds were greater than those of decellularized hyaline cartilage. Both scaffolds were hydrophilic, and their surfaces were negatively charged. The enzymatic degradation and Young's and compression moduli of decellularized cartilage were higher than those of collagen II scaffolds. hBMSC and hASC cultured on collagen II and decellularized cartilage scaffolds with chondrogenic differentiation medium synthesized different percentages of the tissue types that made up the extracellular matrix. hBMSC on decellularized hyaline cartilage produced mainly hyaline cartilage-like tissue, whereas hASC had more immature transitional tissue. When cells were seeded onto collagen II scaffolds, transitional and fibrous tissue prevailed over hyaline tissue. Our data demonstrated that stem cell chondrogenesis in vitro was more favored by decellularized hyaline cartilage than by collagen II scaffolds, and that the concentration of angiopoietin-1, VEGF and bFGF decreased with increasing hyaline tissue formation.

Integrated with artificial intelligence (AI), induced pluripotent stem cell (iPSC) technology could enhance disease modeling, cellular biology, regenerative medicine, and pharmaceutical development. AI has enhanced iPSC differentiation, cultural conditions, and speed of disease-specific model development. Furthermore, AI-based massive omics database analysis exposes hidden biological tendencies, enhancing customized treatment. Investigating new AI algorithms will enable one to solve problems, including interpretability and data quality, resulting from AI's interaction with iPSC technology. These advances fundamentally alter stem cell research and therapeutic applications, therefore facilitating the emergence of regenerative medicine and precision healthcare. AI has evolved in biomedical research into a transformational technology unique in great data analysis, predictive modeling, and automation capacity. AI integration increases the development of patient-specific cell types for disease modeling, pharmacological research, and regenerative medicine by substantially improving IPSC-based technologies. Emphasizing changes in disease models, alternative methodologies, and cellular reprogramming, this work examines current advancements in the use of AI in iPSC technology. The argument on significant obstacles and possibilities reveals how AI could alter the objectives of iPSC research and implementation.