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Inflammatory stromal and T cells mediate human bone marrow niche remodeling in clonal hematopoiesis and myelodysplasia.

Somatic mutations in hematopoietic stem/progenitor cells (HSPCs) can lead to clonal hematopoiesis of indeterminate potential (CHIP) and progression to myelodysplastic syndromes (MDS). Using single-cell and anatomical profiling of a large cohort of human bone marrow (BM), we show that the HSPC BM niche in CHIP and MDS is undergoing inflammatory remodeling. This includes loss of CXCL12⁺ adipogenic stromal cells and the emergence of a distinct population of inflammatory mesenchymal stromal cells (iMSCs), which arise in CHIP and become more prevalent in MDS. Functional studies in primary BM HSPC-M

Revisiting potential value of antitumor drugs in the treatment of COVID-19.

Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of d

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… Retinoic acid receptors (RARs) are ligand-dependent transcription factors that act as heterodimers with retinoid X receptors (RXRs) to participate in the regulation of organogenesis, organ homeostasis, cell proliferation and differentiation [ 38 ]. …

Synthetic Flozins in Cancer Prevention and Combination Strategies: Structural Insights and Therapeutic Potential.

The growing number of cancer cases highlights the urgent need to develop new therapies based on effective molecules. Although anticancer activity remains a key element of oncological pharmacology, the importance of agents that support physiological functions and improve the quality of life of cancer patients is also recognised. Compounds that combine these two functions could represent a significant trend in oncology. Moreover, repurposing approved drugs for conditions beyond their original indications could be a promising strategy. An interesting example of this is synthetic flozins (SGLT2 in

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… Sonic hedgehog signaling in organogenesis, tumors, and tumor microenvironments Int. J. Mol. Sci. 2020 21 758 10.3390/ijms21030758 31979397 PMC7037908 135. Okada J. Yamada E. Saito T. Yokoo H. Osaki A. Shimoda Y. Ozawa A. Nakajima Y. Pessin J.E. Okada S. …

Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.

Multiple myeloma (MM) is a hematological malignancy that leads to significant bone destruction, resulting in debilitating pain and skeletal-related events. The pathophysiology of osteolytic bone destruction in MM involves complex interactions between malignant plasma cells (PCs) and the bone marrow (BM) microenvironment. This review aims to provide a comprehensive synthesis of the cellular and molecular pathways underlying MM-associated bone disease. We discuss the role of osteoclast (OC), osteoblast (OB), osteocytes, along with the complex interactions between immune cells and the BM microenv

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… Organogenesis. 2008;4(2):68–75. doi: 10.4161/org.4.2.5851. 97. van Andel H., Kocemba K.A., Spaargaren M., Pals S.T. Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options. Leukemia. 2019;33(5):1063–1075. doi: 10.1038/s41375-019-0404-1. 98. …

Examining the potentials of stem cell therapy in reducing the burden of selected non-communicable diseases in Africa.

Stem cell therapy (SCT) is a promising solution for addressing health challenges in Africa, particularly non-communicable diseases (NCDs). With their regenerative potential, stem cells have the inherent capacity to differentiate into numerous cell types for tissue repair. Despite infrastructural, ethical, and legal challenges, SCT holds immense promise for managing chronic illnesses and deep-seated tissue injuries. The rising prevalence of NCDs in Africa highlights the need for innovative strategies and treatment options. SCT offers hope in combating conditions like burns, osteoarthritis, diab

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… Organogenesis and Development of the Liver. Dev Cell [Internet]. 2010;18(2):175–89. https://linkinghub.elsevier.com/retrieve/pii/S1534580710000559 10.1016/j.devcel.2010.01.011 20159590 75. Xue R, Meng Q, Dong J, Li J, Yao Q, Zhu Y et al. …

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigati

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… OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis Nature 1999 397 315 323 10.1038/16852 9950424 80. Bucay N. Sarosi I. Dunstan C.R. Morony S. Tarpley J. Capparelli C. Scully S. Tan H.L. Xu W. Lacey D.L. …

Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets.

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory

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… FGFs, particularly FGF2, FGF7 and FGF10, have a broad range of biological activities and participate in organogenesis, tissue homeostasis and the acquisition of androgen dependency [ 47 ]. PC cells and stromal cells in the PC microenvironment exude FGFs and convey FGF receptors (FGFRs) [ 48 ]. …

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2.

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen s

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… OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397:315–323. doi: 10.1038/16852. 55. Nakashima T., Hayashi M., Takayanagi H. New insights into osteoclastogenic signaling mechanisms. Trends Endocrinol. Metab. …

Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies.

Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients' quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the main

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… OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis Nature 1999 397 315 323 10.1038/16852 9950424 56. Giuliani N. Colla S. Sala R. Moroni M. Lazzaretti M. La Monica S. Bonomini S. Hojden M. Sammarelli G. Barille S. …

Endodontics in Systemically Compromised Patients

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… During the second trimester (14–28th week), organogenesis is completed and therefore the risk to the fetus is low. Some elective and emergent dentoalveolar procedures are more safely accomplished during the second trimester. …

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs-including spheroids, organo

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… Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases. J. Transl. Med. 2025;23:380. doi: 10.1186/s12967-025-06381-x. 104. Yin F., Zhang X., Wang L., Wang Y., Zhu Y., Li Z., Tao T., Chen W., Yu H., Qin J. …

Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges.

Gastrointestinal (GI) cancer remains the deadliest cancer in the world. The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery, and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI cancer. There is well-established evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies, which should routinely be incorporated into treatment strategies for GI cancer. Other potential therapeutic targets involve the PI3K/AKT pathwa

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… Wnt signaling mediates diverse cellular processes, including cell fate, movement, polarity, and organogenesis[ 61 ]. In recent years, the understanding of the role of Wnt secretion in tumor initiation has developed and revealed novel therapeutic targets. …

The Roadmap of RANKL/RANK Pathway in Cancer.

The receptor activator of the nuclear factor-κB ligand (RANKL)/RANK signaling pathway was identified in the late 1990s and is the key mediator of bone remodeling. Targeting RANKL with the antibody denosumab is part of the standard of care for bone loss diseases, including bone metastases (BM). Over the last decade, evidence has implicated RANKL/RANK pathway in hormone and HER2-driven breast carcinogenesis and in the acquisition of molecular and phenotypic traits associated with breast cancer (BCa) aggressiveness and poor prognosis. This marked a new era in the research of the therapeutic use o

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… OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397:315–323. doi: 10.1038/16852. 4. Nakagawa N., Kinosaki M., Yamaguchi K., Shima N., Yasuda H., Yano K., Morinaga T., Higashio K. …

Skeletal organoids.

The skeletal system, composed of bones, muscles, joints, ligaments, and tendons, serves as the foundation for maintaining human posture, mobility, and overall biomechanical functionality. However, with ageing, chronic overuse, and acute injuries, conditions such as osteoarthritis, intervertebral disc degeneration, muscle atrophy, and ligament or tendon tears have become increasingly prevalent and pose serious clinical challenges. These disorders not only result in pain, functional loss, and a marked reduction in patients' quality of life but also impose substantial social and economic burdens.

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… Organogenesis of skeletal muscle in tissue culture. Methods Mol Med. 1999;18:217–225. doi: 10.1385/0-89603-516-6:217. 52. Sinacore D. R., Gulve E. A. The role of skeletal muscle in glucose transport, glucose homeostasis, and insulin resistance: implications for physical therapy. …

Computational approaches in rheumatic diseases - Deciphering complex spatio-temporal cell interactions.

Inflammatory arthritis, including rheumatoid (RA), and psoriatic (PsA) arthritis, are clinically and immunologically heterogeneous diseases with no identified cure. Chronic inflammation of the synovial tissue ushers loss of function of the joint that severely impacts the patient's quality of life, eventually leading to disability and life-threatening comorbidities. The pathogenesis of synovial inflammation is the consequence of compounded immune and stromal cell interactions influenced by genetic and environmental factors. Deciphering the complexity of the synovial cellular landscape has accel

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… Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays. Cell. 2022;185(10):1777–1792.e21. doi: 10.1016/j.cell.2022.04.003. 71. Rae Buchberger A., DeLaney K., Johnson J., Li L. Mass spectrometry imaging: a review of emerging advancements and future insights. …

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders.

Current genetic studies of monogenic and complex bone diseases have broadened our understanding of disease pathophysiology, highlighting the need for medical interventions and treatments tailored to the characteristics of patients. As genomic research progresses, novel insights into the molecular mechanisms are starting to provide support to clinical decision-making; now offering ample opportunities for disease screening, diagnosis, prognosis and treatment. Drug targets holding mechanisms with genetic support are more likely to be successful. Therefore, implementing genetic information to the

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… OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis . Nature. ( 1999 ) 397 : 315 – 23 . 10.1038/16852 9950424 158. Angela Y Haferkamp S Weishaupt C Ugurel S Becker JC Oberndörfer F . …

Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment.

Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collecte

CXCR4: A Promising Novel Strategy for Lung Cancer Treatment.

Lung cancer remains a major public health challenge due to high incidence and mortality. The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) constitute a critical axis in tumor biology, influencing tumor cell proliferation, invasion, angiogenesis, and immune evasion. Aberrant CXCR4 expression is frequently observed in lung cancer and is closely associated with adverse prognosis, enhanced metastatic potential, and therapeutic resistance. Mechanistically, CXCR4 activates signaling pathways including PI3K/AKT, MAPK/ERK, JAK/STAT, and FAK/Src, promoting epithelial-mesenchymal transition, st

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… An essential role of the cytoplasmic tail of CXCR4 in G-protein signaling and organogenesis. PLoS ONE. 2010;5:e15397. doi: 10.1371/journal.pone.0015397. 76. …

Пространственные омики нейроинфламмации: осмысления заболеваний мозга.

Нейроинфламмация является общей патологической особенностью различных заболеваний мозга, однако подстрекательская активность редко распределяется равномерно по заболевшим тканям. Вместо этого микроглии, астроциты, проникающие в иммунные клетки и подстрекательские посредники, часто организуются вокруг конкретных патологических структур, включая амилоидные таблетки, демиелинированные поражающие ободья, ишемические границы, некротические области опухоли и белые отсеки периваскулярной материи. Хотя в рамках одноклеточных подходов, основанных на оптовых и диссоциационных подходах, было определено м

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… Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays. Cell. (2022) 185:1777–92.e21. doi: 10.1016/j.cell.2022.04.003 16. Eng CL, Lawson M, Zhu Q, Dries R, Koulena N, Takei Y, et al. Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. …

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making dia

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… Signaling mediated by hepatomegaly (Hippo) is a critical controller of organ size, organogenesis, and stem cell self-renewal ( 18 ). As a result, the Hippo signaling system was newly involved in the process of tumour growth. …