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A Comprehensive Biological and Clinical Perspective Can Drive a Patient-Tailored Approach to Multiple Myeloma: Bridging the Gaps between the Plasma Cell and the Neoplastic Niche.

There is a broad spectrum of diseases labeled as multiple myeloma (MM). This is due not only to the composite prognostic risk factors leading to different clinical outcomes and responses to treatments but also to the composite tumor microenvironment that is involved in a vicious cycle with the MM plasma cells. New therapeutic strategies have improved MM patients' chances of survival. Nevertheless, certain patients' subgroups have a particularly unfavorable prognosis. Biological stratification can be subdivided into patient, disease, or therapy-related factors. Alternatively, the biological sig

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… Their expression was enhanced by VEGF, FGF-2, HGF, and MM-PC-conditioned medium and their silencing RNA knockdown affected MMEC angiogenesis-related functions, including spreading, migration, and tubular morphogenesis [ 69 ]. …

Curcumin as a promising therapeutic agent for diabetic neuropathy: from molecular mechanisms to functional recovery.

Diabetes mellitus is an endocrine disorder characterized by prolonged hyperglycemia. It results from either insulin deficiency (type 1 diabetes mellitus, T1DM) or insulin resistance (type 2 diabetes mellitus, T2DM). This condition has emerged as a significant health concern in recent years. Hyperglycemia induces the overproduction of reactive oxygen species (ROS), which can modulate multiple pathways, including AGEs-RAGE, PKC stimulation, NF-κB and PI3K/AKT. These pathways contribute to diabetes-related complications such as inflammation, oxidative stress, insulin resistance, and reduced gluco

Physiological functions and pharmacological targeting of transient receptor potential channels.

Transient receptor potential (TRP) channels represent an extensive and diverse protein family fulfilling salient roles as versatile cellular sensors and effectors. The pivotal role of TRP and related ion channels in sensory processes has been well documented. Over the last few years, a new concept has emerged that TRP proteins control an exceptionally broad spectrum of homeostatic physiological functions such as maintenance of body temperature, blood pressure, transmitter release from neurons, mineral and energy homeostasis, and reproduction. This notion is further supported by more than 20 he

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

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… It was suggested that prolonged PGRN/EPHA2 interaction is responsible for downstream signalling by MAPK and AKT, resulting in the stimulation of capillary morphogenesis [ 66 ]. This phenomenon could be potentially associated with PGRN overexpression across a broad spectrum of cancers. …

Organoids as Innovative Models for Bone and Joint Diseases.

Bone is one of the key components of the musculoskeletal system. Bone and joint disease are the fourth most widespread disease, in addition to cardiovascular disease, cancer, and diabetes, which seriously affect people's quality of life. Bone organoids seem to be a great model by which to promote the research method, which further could improve the treatment of bone and joint disease in the future. Here, we introduce the various bone and joint diseases and their biology, and the conditions of organoid culture, comparing the in vitro models among 2D, 3D, and organoids. We summarize the differin

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… Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature. 2011;472:51–56. doi: 10.1038/nature09941. 46. Eiraku M., Watanabe K., Matsuo-Takasaki M., Kawada M., Yonemura S., Matsumura M., Wataya T., Nishiyama A., Muguruma K., Sasai Y. …

Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments.

The importance of defining new molecules to fight cancer is of significant interest to the scientific community. In particular, it has been shown that cancer stem cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity; on the other side, circulating tumor cells (CTCs) seem to split away from the primary tumor and appear in the circulatory system as singular units or clusters. It is becoming more and more important to discover new biomarkers related to these populations of cells in combination to define the network am

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… The Order of Cancer: A Theory of Malignant Progression by Inverse Morphogenesis Front. Oncol. 2019 9 416 10.3389/fonc.2019.00416 31192124 PMC6548852 25. Kim W.-T. Ryu A.C.J. …

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances.

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug

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… The Hedgehog pathway is involved in cell growth, migration, morphogenesis, and tissue maintenance and repair. TGF-β is an important prognostic marker for various types of cancer and plays a role in the initial phase of CSC development and self-renewal [ 1 , 3 , 10 ]. 2.7. …

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies.

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowl

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… BSP is produced by many different cell types during bone morphogenesis such us osteoblasts, osteoclasts, osteocytes and hypertrophic chondrocytes [ 55 , 56 ]. …

Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a

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… Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am. J. Pathol. 2000;156:899–909. doi: 10.1016/S0002-9440(10)64959-0. 100. Nangia-makker P., Hogan V., Honjo Y., Baccarini S., Tait L., Bresalier R., Raz A. …

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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… Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature. 2011;472:51–56. doi: 10.1038/nature09941. 7. Lancaster M. A., Renner M., Martin C. A., Wenzel D., Bicknell L. S., Hurles M. E., Homfray T., Penninger J. M., Jackson A. P., Knoblich J. A. …

Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures.

Chemotherapy and targeted therapy have opened new avenues in clinical oncology. However, there is a lack of response in a substantial percentage of cancer patients and diseases frequently relapse in those who even initially respond. Resistance is, at present, the major barrier to conquering cancer, the most lethal age-related pathology. Identification of mechanisms underlying resistance and development of effective strategies to circumvent treatment pitfalls thereby improving clinical outcomes remain overarching tasks for scientists and clinicians. Growing bodies of data indicate that stromal

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… Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol. 2009;10(3):165–177. doi: 10.1038/nrm2639. 104. Brunckhorst MK, Xu Y, Lu R, Yu Q. Angiopoietins promote ovarian cancer progression by establishing a procancer microenvironment. …

Cellular and molecular mechanisms of muscle atrophy.

Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of co

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… DHPR alpha1S subunit controls skeletal muscle mass and morphogenesis . EMBO J. 29 , 643 – 654 20033060 10.1038/emboj.2009.366 PMC2830706 Puigserver P. Rhee J. Donovan J. Walkey C. J. Yoon J. C. Oriente F. Kitamura Y. Altomonte J. Dong H. Accili D. ( 2003 ). …

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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… They demonstrate autonomous beating, chamber-like morphogenesis, and vascular network formation, reflecting key aspects of human cardiac development and physiology ( Figure 3 , Table 1 ). …

Nanomaterial-Driven Precision Immunomodulation: A New Paradigm in Therapeutic Interventions.

Immunotherapy is a rapidly advancing field of research in the treatment of conditions such as cancer and autoimmunity. Nanomaterials can be designed for immune system manipulation, with precise targeted delivery and improved immunomodulatory efficacy. Here, we elaborate on various strategies using nanomaterials, including liposomes, polymers, and inorganic NPs, and discuss their detailed design intricacies, mechanisms, and applications, including the current regulatory issues. This type of nanomaterial design for targeting specific immune cells or tissues and controlling release kinetics could

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… Emerging strategies for spatiotemporal control of stem cell fate and morphogenesis Trends Biotechnol. 2013 31 78 84 10.1016/j.tibtech.2012.11.001 23219200 PMC3557560 132. Chagri S. Ng D.Y.W. Weil T. Designing bioresponsive nanomaterials for intracellular self-assembly Nat. Rev. …

HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.

The hypoxic microenvironment is an essential characteristic of most malignant tumors. Notably, hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulatory factor of cellular adaptation to hypoxia, and many critical pathways are correlated with the biological activity of organisms via HIF-1α. In the intra-tumoral hypoxic environment, HIF-1α is highly expressed and contributes to the malignant progression of tumors, which in turn results in a poor prognosis in patients. Recently, it has been indicated that HIF-1α involves in various critical processes of life events and tumor development via r

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… There are three isoforms, α, β/δ, and γ, which are closely associated with lipid storage and mobilization, glucose metabolism, morphogenesis, and inflammatory responses. 60 Among them, the expression of PPAR-γ was known to be modulated by HIF-1α. 61 Simvastatin, a cholesterol-lowering drug, can suppress …

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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… In another study, RANKL ablation in mammary epithelium blocked progesterone-induced morphogenesis, and systemic RANKL administration was able to trigger the proliferation of mammary cells in absence of PR signaling [ 102 ]. …

Role of Exosomal Non-Coding RNAs in Bone-Related Diseases.

Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and "package" non-coding RNAs and "deliver" them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are invol

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… MicroRNAs Regulate Brain Morphogenesis in Zebrafish . Science 308 ( 5723 ), 833 – 838 . 10.1126/science.1109020 15774722 Glyn-Jones S. Palmer A. J. R. Agricola R. Price A. J. Vincent T. L. Weinans H. ( 2015 ). Osteoarthritis . …

Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism.

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic strategy for the treatment of malignant (leukemia and lymphoma) and non-malignant (thalassemia, anemia, and immunodeficiency) hematopoietic diseases. Thanks to the improvement in patient care and the development of more tolerable conditioning treatments, which has extended the applicability of therapy to the elderly, a growing number of patients have successfully benefited from HSCT therapy and, more importantly, HSCT transplant-related mortality has consistently reduced in recent years. However, concomitantly to long

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… Several studies have reported that one early side effect of HSCT is the failure of bone morphogenesis, due to a severe reduction of osteoblast progenitor cells in bone marrow, causing post-transplant BMD loss ( 106 , 108 , 170 – 172 ). …

Molecular interactions of miR-338 during tumor progression and metastasis.

BackgroundCancer, as one of the main causes of human deaths, is currently a significant global health challenge. Since the majority of cancer-related deaths are associated with late diagnosis, it is necessary to develop minimally invasive early detection markers to manage and reduce mortality rates. MicroRNAs (miRNAs), as highly conserved non-coding RNAs, target the specific mRNAs which are involved in regulation of various fundamental cellular processes such as cell proliferation, death, and signaling pathways. MiRNAs can also be regulated by long non-coding RNAs (lncRNAs) and circular RNAs (

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… Homeobox proteins are developmental transcription factors with pivotal roles during morphogenesis and differentiation. LINC00689 upregulation was observed in GC tissues and cell lines. …

Histone deacetylase 6: A new player in oxidative stress‑associated disorders and cancers (Review).

Histone deacetylase 6 (HDAC6), a distinctive member of the histone deacetylase family, plays a crucial role in regulating the cellular response to oxidative stress. Unlike other HDACs, HDAC6 primarily deacetylates non‑histone proteins, influencing various cellular functions critical to the pathogenesis of numerous oxidative stress‑related diseases. This review summarizes the latest research on how HDAC6 affects oxidative stress pathways and its impact on diseases such as neurodegeneration, cancer and cardiovascular disorders. Additionally, the therapeutic potential of targeting HDAC6, as evide

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… Cortactin deacetylation by HDAC6 and SIRT2 regulates neuronal migration and dendrite morphogenesis during cerebral cortex development. Mol Brain. 2020;13:105. doi: 10.1186/s13041-020-00644-y. 9. Wu TY, Chen M, Chen IC, Chen YJ, Chen CY, Wang CH, Cheng JJ, Nepali K, Chuang KH, Liou JP. …