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Advances in the mechanism and therapies of achondroplasia.

Achondroplasia (ACH), is the prevailing type of genetic dwarfism in humans, caused by mutations in fibroblast growth factor receptor 3 (FGFR3) that are inherited in an autosomal dominant manner. FGFR3 is mainly expressed in condensed mesenchyme, chondrocytes, and mature osteoblasts and osteoclasts, in which it regulates the formation, development, growth, and remodeling of the skeletal system. Mutations in FGFR3 causing ACH result in enhanced FGFR3 signaling through combined mechanisms including enhancing FGF dimerization and tyrosine kinase activity and stabilizing FGF receptors. In ACH, supp

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and inva

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… The mechanisms mediating the immunosuppressive role of TANs are not fully elucidated and include the local production of neutrophil extracellular traps (NETs) after IL-8 stimulation [ 241 – 243 ] and release of immunosuppressive signals such as TGF-β, Arginase-1 and ROS [ 244 – 247 ]. …

Hydrogels-Assisted Cell Engraftment for Repairing the Stroke-Damaged Brain: Chimera or Reality.

The use of advanced biomaterials as a structural and functional support for stem cells-based therapeutic implants has boosted the development of tissue engineering applications in multiple clinical fields. In relation to neurological disorders, we are still far from the clinical reality of restoring normal brain function in neurodegenerative diseases and cerebrovascular disorders. Hydrogel polymers show unique mechanical stiffness properties in the range of living soft tissues such as nervous tissue. Furthermore, the use of these polymers drastically enhances the engraftment of stem cells as w

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

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… Neutrophils employ ROS for pathogen clearance and NETosis: NOX‐dependent pathways involve phorbol myristate acetate (PMA)‐activated protein kinase C (PKC)/NADPH oxidase (NOX)/myeloperoxidase (MPO)‐generated ROS activating ERK/p38/c‐Jun N‐terminal kinase (JNK) to release neutrophil extracellular traps … Moreover, the formation of neutrophil extracellular traps (NETs) is similarly impacted by ROS levels. Additionally, in dendritic cells (DCs), ROS plays a pivotal role in the regulation of cross‐presentation capacity [ 27 , 28 , 29 ]. …

Role of Long Non-Coding RNA X-Inactive-Specific Transcript (XIST) in Neuroinflammation and Myelination: Insights from Cerebral Organoids and Implications for Multiple Sclerosis.

Background/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunoflu

Pathogenesis and kidney prognosis of renal amyloidosis.

Light chain (AL), serum amyloid A (AA), transthyretin (ATTR), leukocyte cell derived chemotaxin 2 (ALECT2), and fibrinogen Aa (AFib) amyloidosis are some of the most common types of protein-deposition disorders involving the kidney. Each amyloidogenic protein differs in its origin and little is known about the exact mechanisms that govern renal tropism and tissue injury for each amyloid subtype. While amyloidogenic precursor protein is different in each subtype of amyloidosis, its aggregation into fibrils depositing in target organs and leading to disruption of tissue architecture and progress

The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis.

Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates tha

Chronic stress and myeloid immunosuppression in cancer: A neuroimmune link to behavioral dysfunction.

Cancer progression is profoundly influenced by the complex interplay between the tumor microenvironment (TME), the immune system, and the patient's psychological state. This review delineates a critical pathway linking chronic stress to worsened cancer outcomes through inflammatory factors, anti-tumor immune suppression, and the induction of behavioral comorbidities. We postulate that sustained stress hormone signaling via the sympathetic nervous system and hypothalamic-pituitary-adrenal axis activation orchestrates a systemic immunosuppressive cascade. A central mechanism is the stress-induce

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… A key mechanism proposed from preclinical work involves glucocorticoid signaling, which is understood to dysregulate neutrophil function and induce the formation of neutrophil extracellular traps (NETs). … In addition to myeloid suppression and impaired antigen presentation, recent studies indicate that chronic stress can drive neutrophil dysfunction and the formation of neutrophil extracellular traps (NETs), mechanisms strongly associated with the creation of metastatic niches, tumor relapse, and cancer …

A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.

The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy. Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies. Human epidermal growth factor receptor, hormone receptors, and angiogenesis factors are among the established therapies in tumor reduction and managing side effects. Novel targeted therapies like KRAS G12C, Claudin-18 isoform 2 (CLDN18.2), Trophoblast cell-surface antigen 2 (TROP2), and epigenetic r

Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.

Persistent stimulation from cancer antigens leads to T lymphocytes (T cells) exhaustion, with up-regulated expression of co-inhibitory receptors, including programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain 3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). These receptors collectively impair T cell function via distinct molecular pathways, contributing to immune evasion and cancer progression. This review highlights the therapeutic promise of immune checkpoint inhibito

Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and Clinical Translation.

BackgroundT-cell-engaging bispecific antibodies (TCEs) have transformed haematological malignancy treatment (blinatumomab > 40% complete remission), yet solid tumour efficacy remains limited (MethodsReview of 55 phase I-III trials of CD3-based TCEs in solid tumours, including tarlatamab (DLL3-targeted, small-cell lung cancer) and xaluritamig (STEAP1-targeted, prostate cancer). Analysis of next-generation engineering strategies and resistance mechanisms via genomic and immunohistochemical data.ResultResponse rates now approach ~40% in selected settings, marking an inflection point. In extensive

Ferroptosis: Frenemy of Radiotherapy.

Recently, it was established that ferroptosis, a type of iron-dependent regulated cell death, plays a prominent role in radiotherapy-triggered cell death. Accordingly, ferroptosis inducers attracted a lot of interest as potential radio-synergizing drugs, ultimately enhancing radioresponses and patient outcomes. Nevertheless, the tumor microenvironment seems to have a major impact on ferroptosis induction. The influence of hypoxic conditions is an area of interest, as it remains the principal hurdle in the field of radiotherapy. In this review, we focus on the implications of hypoxic conditions

Drug-Induced Pulmonary Toxicity in the Era of Immunotherapy and Biologics: A Narrative Review of Mechanism, Diagnosis, and Management.

Drug-induced interstitial lung disease (DI-ILD) has emerged as a clinically significant complication associated with a broadening spectrum of therapeutic agents. DI-ILD can result in significant morbidity and mortality if not promptly diagnosed and treated. In this review, we synthesize current evidence concerning the epidemiology, risk factors, pathophysiological mechanisms, clinical manifestations, diagnostic approaches, and management strategies of DI-ILD, with focused emphasis on three major therapeutic groups: immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR-T) t

Pathogenesis and Treatment of Myeloma-Related Bone Disease.

Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/β-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins

Ferroptosis, lipid metabolism, and genetic regulation in postoperative rehabilitation of elderly hip fractures: from molecular mechanisms to clinical translation.

BACKGROUND: Elderly hip fracture represents a major global public health challenge, with postoperative rehabilitation involving complex molecular mechanisms and metabolic networks. Beyond osteoporotic fractures, pathological hip fractures caused by tumor bone metastasis constitute a non-negligible proportion in elderly patients, with molecular pathological mechanisms significantly different from osteoporotic fractures. Recent research has confirmed that ferroptosis (iron-dependent regulated cell death) and lipid metabolism dysregulation are key links in fracture healing and functional recovery

Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.

Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota-drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantati

Каннабидиол как иммунный модулятор: всеобъемлющий обзор.

Каннабидиол (КБР), непсихоактивный фитоканнабиноид, полученный из сативы Каннабиса, стал многообещающим терапевтическим агентом в силу его разнообразных фармакологических свойств, включая сильные антивоспалительные, нейрозащитные и иммунодуляторные эффекты. КБР модифицирует иммунную реакцию, включая регулирование активности клеток Т, введение апоптоза макрофага, подавление провоспалительных цитокинов и модуляцию сигнальных путей воспаления и иммунной гомеостазии. Был проведен всеобъемлющий поиск литературы с использованием баз данных PubMed, Scopus и Web of Science в целях выявления соответств

Personal Medicine and Bone Metastases: Biomarkers, Micro-RNAs and Bone Metastases.

Bone metastasis is a major cause of morbidity within solid tumours of the breast, prostate, lung and kidney. Metastasis to the skeleton is associated with a wide range of complications including bone fractures, spinal cord compression, hypercalcaemia and increased bone pain. Improved treatments for bone metastasis, such as the use of anti-bone resorptive bisphosphonate agents, within post-menopausal women have improved disease-free survival; however, these treatments are not without side effects. There is thus a need for biomarkers, which will predict the risk of developing the spread to bone

Emerging Trends in Diagnostic Radiology: Integrating Advanced Imaging Modalities for Early Detection, Clinical Monitoring, and Prognostic Evaluation of Multisystem Internal Medicine Disorders.

Diagnostic radiology has progressed from basic X-ray imaging to a highly advanced, multimodality discipline that integrates high-resolution structural techniques, functional and molecular imaging, and computational analytics. This review synthesizes emerging trends in diagnostic radiology with a particular focus on their relevance to multisystem internal medicine disorders. The historical evolution of imaging is outlined, from early radiographs to computed tomography (CT), magnetic resonance imaging (MRI), and hybrid platforms such as positron emission tomography-computed tomography (PET-CT) a

Spatiotemperal Dynamics of Osteoarthritis: Преобразование значений от стенда до Бедсайда.

Остеоартрит (OA) представляет собой многогранное дегенеративное совместное расстройство, вызванное различными факторами риска, такими, как возраст, механический стресс, воспаление и метаболическое воздействие. Эти элементы способствуют его разнообразным фенотипам и эндотипам, что подчеркивает имманентную сложность болезни. Участие нескольких тканей и их взаимодействие еще больше осложняет расследование ОА. Нынешние ограничения в области технологий пространственного фенотификации в сочетании со сложной сетью многофакторных взаимодействий препятствуют обнаружению надежных ранних диагностических