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High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer.

Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC‑BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC‑BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility gr

Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Rec

Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.

The development of brain metastasis is a major cause of significantly reduced survival in breast cancer patients. The initiation and progression of breast cancer brain metastasis (BCBM) involve multiple distinct molecular pathways and reprogramming of the tumor microenvironment (TME). This review systematically summarizes key mechanisms underlying BCBM, including epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and the spatiotemporal dynamics of metabolic reprogramming regulated by critical signaling pathways during brain colonization. In particular, we highlight

Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat.

BACKGROUND: Traumatic brain injury (TBI) is a global health concern that typically causes emotional disturbances and cognitive dysfunction. Secondary pathologies following TBI may be associated with chronic neurodegenerative disorders and an enhanced likelihood of developing dementia-like disease in later life. There are currently no approved drugs for mitigating the acute or chronic effects of TBI. METHODS: The effects of the drug pomalidomide (Pom), an FDA-approved immunomodulatory agent, were evaluated in a rat model of moderate to severe TBI induced by controlled cortical impact. Post-TBI

Biologics for bone regeneration: advances in cell, protein, gene, and mRNA therapies.

Bone fractures represent a significant global healthcare burden. Although fractures typically heal on their own, some fail to regenerate properly, leading to nonunion, a condition that causes prolonged disability, morbidity, and mortality. The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing. Traditional treatment approaches, including autografts, allografts, xenografts, and synthetic biomaterials, face limitations such as donor site pain, immune rejection, and insufficient mechanical

Ferroptosis in Haematological Malignancies and Associated Therapeutic Nanotechnologies.

Haematological malignancies are heterogeneous groups of cancers of the bone marrow, blood or lymph nodes, and while therapeutic advances have greatly improved the lifespan and quality of life of those afflicted, many of these cancers remain incurable. The iron-dependent, lipid oxidation-mediated form of cell death, ferroptosis, has emerged as a promising pathway to induce cancer cell death, particularly in those malignancies that are resistant to traditional apoptosis-inducing therapies. Although promising findings have been published in several solid and haematological malignancies, the major

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… Recently, nanoparticles loaded with a drug that targets N 6 -methyl-adenosine (m 6 a) RNA methylation were shown to be effective against AML cells both in vitro and in vivo [ 174 ]. …

Историческое развитие иммуноэндокринных концепций психических расстройств и их терапии.

Отношения между центральной нервной, иммунной и эндокринной системами являются предметом психиатрических исследований, особенно в области депрессии и шизофрения. У поля длинные предтечи. Наблюдаемые явления, связанные с этими отношениями, восходят к неолитической эпохе. Теории иммуноэндокринной системы в самом широком смысле записаны в древности. В 19th Крепелин и Вагнер-Джаурег сообщили о первых клинических наблюдениях у пациентов психиатрических учреждений. Von Bestow, Эддисон и Кушинг описали психические симптомы у пациентов, страдающих эндокринными заболеваниями. :: 20th откровение века с

Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features.

The indiscriminate consumption of antimalarials against coronavirus disease-2019 emphasizes the longstanding clinical weapons of medicines. In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines th

Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.

Disease overviewChronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.DiagnosisThe diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers.Prognosis and stagingTwo clinical staging systems, Rai

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Marizomib in the therapy of brain tumors-how far did we go and where do we stand?

Out of several types of tumors of the central nervous system (CNS), glioblastoma (GBM) represents one of the most frequent and malignant forms of brain neoplasms. To date, GBM holds very limited therapeutic options leaving patients with poor prognosis of survival. As such, novel treatment approaches are constantly quested. One of these strategies is based on the utilization of proteasome inhibitors (PIs). However, although several PIs have been approved as therapy for patients with hematological malignancies, these treatment benefits cannot not be easily extrapolated to brain tumors. This is m

Engineered mesenchymal stem cell-derived exosomes: A revolutionary approach to unlocking liver disease treatment.

Exosomes, a specific type of extracellular vesicle with diameters ranging from 30 to 150 nm, play a vital role in coordinating various physiological and pathological processes through direct cell-to-cell communication. These vesicles transport a diverse range of molecules, including proteins, mRNAs, miRNAs, and lipids, that originate from parent cells. Exosomes are released by nearly all cell types, including mesenchymal stem cells (MSCs), and possess significant potential due to their regenerative and immunomodulatory properties. In the context of liver disease treatment, these capabilities o

Cytogenetic Abnormalities in Myelodysplastic Syndromes: An Overview.

Karyotype is one of the main constituents of the International Prognostic Scoring System (IPSS) and revised-IPSS that are the cornerstones for the prognostication of patients with myelodysplastic syndromes (MDS). Del(5q), -7/del(7q), +8 and -Y are among the most extensively studied cytogenetic abnormalities in MDS. The same applies for normal karyotype. There are hundreds of other rare cytogenetic abnormalities that have been reported in MDS, included but not limited to -X, 3q abnormalities, +13/del(13q), i(17q), +21/-21. However, due to a very low number of patients, their impact on the progn

Mechanisms of chemotherapy-induced behavioral toxicities.

While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of lif

Machine Learning for Multi-Omics Characterization of Blood Cancers: A Systematic Review.

Artificial Intelligence and machine learning are increasingly used to interrogate complex biological data. This systematic review evaluates their application to multi-omics for the molecular characterization of hematological malignancies, an area with unmet clinical need. We searched PubMed, Embase, Institute of Electrical and Electronics Engineers Xplore, and Web of Science from January 2015 to December 2024. Two reviewers screened records, extracted data, and used a modified appraisal emphasizing explainability, performance, reproducibility, and ethics. From 2847 records, 89 studies met incl

Chemoprevention in Skin Cancer: What Advice?

The incidence of melanoma and non-melanoma skin cancers (NMSCs) is increasing worldwide. While NMSCs are more common, melanoma remains the most challenging because of its higher aggressiveness. Although the use of sunscreens is key in high-risk populations, it provides limited protection, which highlights the need for alternative solutions. In this review, we discuss current evidence on chemopreventive therapies, as well as their efficacy and adverse events, including immunocompetent and immunosuppressed patients. Acitretin, nicotinamide, 5-fluorouracil, and photodynamic therapy have shown ove

The prevention of disease relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia.

Disease relapse represents by far the most frequent cause of hematopoietic cell transplantation (HCT) failure. Patients with acute leukemia suffering relapse after HCT have limited conventional treatment options with little possibility of cure and represent, de facto, suitable candidates for the evaluation of novel cellular and biological-based therapies. Donor lymphocyte infusions (DLI) has been one of the first cellular therapies adopted to treat post HCT relapse of acute leukemia patients and still now, it is widely adopted in preemptive and prophylactic settings, with renewed interest for

Decoding Immunodeficiencies with Artificial Intelligence: A New Era of Precision Medicine.

Primary and secondary immunodeficiencies comprise a wide array of illnesses marked by immune system abnormalities, resulting in heightened vulnerability to infections, autoimmunity, and cancers. Notwithstanding progress in diagnostic instruments and an enhanced comprehension of the underlying pathophysiology, delayed diagnosis and underreporting persist as considerable obstacles. The implementation of artificial intelligence into clinical practice has surfaced as a viable method to enhance early detection, risk assessment, and management of immunodeficiencies. Recent advancements illustrate ho

Искусственный интеллект в педиатрической нейрорадиологии: текущий ландшафт, проблемы и будущие направления.

В настоящем обзоре содержится информация о нынешнем ландшафте искусственного интеллекта (АИ) в области педиатрической и эмбриональной нейрорадиологии, критическая оценка текущей практики, барьеров на пути к клиническому усыновлению и будущего потенциала. Мы искали рецензированные исследования за последнее десятилетие, сфокусировавшись на сегментации изображений, обнаружении повреждений, классификации, прогнозировании и поддержке клинического решения при педиатрической съемке мозга. Особое внимание было уделено уникальным педиатрическим факторам, таким, как развитие мозга и нехватка данных. Мет

Prospects and Challenges of Lung Cancer Vaccines.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this contex