-
Cellular & Molecular Biology Letters Jul 2024
PubMed: 38956459
DOI: 10.1186/s11658-024-00620-7 -
Nature Communications Jul 2024The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent... (Review)
Review
The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework. LAG-R aims to document animals' genetic makeup in scientific publications, providing essential details for replication and appropriate model use. While verifying complete genetic compositions may be impractical, better reporting and validation efforts enhance reliability of research. LAG-R standardization will bolster reproducibility, peer review, and overall scientific rigor.
Topics: Animals; Animals, Laboratory; Guidelines as Topic; Reproducibility of Results; Research Design; Animal Experimentation; Biomedical Research
PubMed: 38956430
DOI: 10.1038/s41467-024-49439-y -
Cell Discovery Jul 2024The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This differentiation process plays a crucial role in... (Review)
Review
The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This differentiation process plays a crucial role in bone formation and homeostasis and is regulated by two intricate processes: cell signal transduction and transcriptional gene expression. Various essential cell signaling pathways, including Wnt, BMP, TGF-β, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, and Piezo1/2, play a critical role in facilitating osteoblast differentiation, bone formation, and bone homeostasis. Key transcriptional factors in this differentiation process include Runx2, Cbfβ, Runx1, Osterix, ATF4, SATB2, and TAZ/YAP. Furthermore, a diverse array of epigenetic factors also plays critical roles in osteoblast differentiation, bone formation, and homeostasis at the transcriptional level. This review provides an overview of the latest developments and current comprehension concerning the pathways of cell signaling, regulation of hormones, and transcriptional regulation of genes involved in the commitment and differentiation of osteoblast lineage, as well as in bone formation and maintenance of homeostasis. The paper also reviews epigenetic regulation of osteoblast differentiation via mechanisms, such as histone and DNA modifications. Additionally, we summarize the latest developments in osteoblast biology spurred by recent advancements in various modern technologies and bioinformatics. By synthesizing these insights into a comprehensive understanding of osteoblast differentiation, this review provides further clarification of the mechanisms underlying osteoblast lineage commitment, differentiation, and bone formation, and highlights potential new therapeutic applications for the treatment of bone diseases.
PubMed: 38956429
DOI: 10.1038/s41421-024-00689-6 -
Cell Death & Disease Jul 2024
PubMed: 38956428
DOI: 10.1038/s41419-024-06747-x -
Scientific Reports Jul 2024Caspase-9, a cysteine-aspartate protease traditionally associated with intrinsic apoptosis, has recently emerged as having non-apoptotic roles, including influencing...
Caspase-9, a cysteine-aspartate protease traditionally associated with intrinsic apoptosis, has recently emerged as having non-apoptotic roles, including influencing cell migration-an aspect that has received limited attention in existing studies. In our investigation, we aimed to explore the impact of caspase-9 on the migration and invasion behaviors of MDA-MB-231, a triple-negative breast cancer (TNBC) cell line known for its metastatic properties. We established a stable cell line expressing an inducible caspase-9 (iC9) in MDA-MB-231 and assessed their metastatic behavior using both monolayer and the 3D organotypic model in co-culture with human Foreskin fibroblasts (HFF). Our findings revealed that caspase-9 had an inhibitory effect on migration and invasion in both models. In monolayer culture, caspase-9 effectively suppressed the migration and invasion of MDA-MB-231 cells, comparable to the anti-metastatic agent panitumumab (Pan). Notably, the combination of caspase-9 and Pan exhibited a significant additional effect in reducing metastatic behavior. Interestingly, caspase-9 demonstrated superior efficacy compared to Pan in the organotypic model. Molecular analysis showed down regulation of epithelial-mesenchymal transition and migratory markers, in caspase-9 activated cells. Additionally, flow cytometry analysis indicated a cell cycle arrest. Moreover, pre-treatment with activated caspase-9 sensitized cells to the chemotherapy of doxorubicin, thereby enhancing its effectiveness. In conclusion, the anti-metastatic potential of caspase-9 presents avenues for the development of novel therapeutic approaches for TNBC/metastatic breast cancer. Although more studies need to figure out the exact involving mechanisms behind this behavior.
Topics: Humans; Cell Line, Tumor; Caspase 9; Cell Movement; Organoids; Triple Negative Breast Neoplasms; Neoplasm Metastasis; Epithelial-Mesenchymal Transition; Female; Neoplasm Invasiveness; Coculture Techniques; Fibroblasts; MDA-MB-231 Cells
PubMed: 38956424
DOI: 10.1038/s41598-024-65711-z -
Scientific Reports Jul 2024Morgana is a ubiquitous HSP90 co-chaperone protein coded by the CHORDC1 gene. Morgana heterozygous mice develop with age a myeloid malignancy resembling human atypical...
Morgana is a ubiquitous HSP90 co-chaperone protein coded by the CHORDC1 gene. Morgana heterozygous mice develop with age a myeloid malignancy resembling human atypical myeloid leukemia (aCML), now renamed MDS/MPN with neutrophilia. Patients affected by this pathology exhibit low Morgana levels in the bone marrow (BM), suggesting that Morgana downregulation plays a causative role in the human malignancy. A decrease in Morgana expression levels is also evident in the BM of a subgroup of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients showing resistance or an incomplete response to imatinib. Despite the relevance of these data, the mechanism through which Morgana expression is downregulated in patients' bone marrow remains unclear. In this study, we investigated the possibility that Morgana expression is regulated by miRNAs and we demonstrated that Morgana is under the control of four miRNAs (miR-15a/b and miR-26a/b) and that miR-15a may account for Morgana downregulation in CML patients.
Topics: MicroRNAs; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Humans; HSP90 Heat-Shock Proteins; Animals; Mice; Gene Expression Regulation, Leukemic; Down-Regulation; Bone Marrow; Molecular Chaperones
PubMed: 38956394
DOI: 10.1038/s41598-024-65404-7 -
Nature Immunology Jul 2024Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a...
Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. Furthermore, we analyzed the distribution of NK cell subsets in the lung, tonsils and intraepithelial lymphocytes isolated from healthy individuals and in 22 tumor types. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.
PubMed: 38956378
DOI: 10.1038/s41590-024-01883-0 -
Molecular Psychiatry Jul 2024The concept of cognitive reserve was born to account for the disjunction between the objective extent of brain damage in pathology and its clinical and intellectual... (Review)
Review
The concept of cognitive reserve was born to account for the disjunction between the objective extent of brain damage in pathology and its clinical and intellectual outcome. The cognitive reserve comprises structural (brain reserve) and functional (brain maintenance, resilience, compensation) aspects of the nervous tissue reflecting exposome-driven life-long plasticity, which defines the ability of the brain to withstand aging and pathology. The mechanistic background of this concept was primarily focused on adaptive changes in neurones and neuronal networks. We present arguments favoring the more inclusive view, positing that neuroglia are fundamental for defining the cognitive reserve through homeostatic, neuroprotective, and neurodegenerative mechanisms. Neuroglia are critical for the life-long shaping of synaptically connected neuronal circuits as well as the brain connectome thus defining cognitive reserve. Neuroglial homeostatic and protective physiological responses define brain maintenance and resilience, while neuroglia regenerative capabilities are critical for brain compensation in pathology. Targeting neuroglia may represent an untrodden path for prolonging cognitive longevity.
PubMed: 38956370
DOI: 10.1038/s41380-024-02644-z -
Nature Materials Jul 2024
PubMed: 38956351
DOI: 10.1038/s41563-024-01936-7 -
Nature Materials Jul 2024
PubMed: 38956348
DOI: 10.1038/s41563-024-01934-9