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Disruption of the microenvironmental ecosystem in subchondral bone marrow lesions: Roles in osteoarthritis pathophysiology, pain and progression.

This narrative review explores the role of subchondral bone in the pathophysiology of osteoarthritis (OA), emphasizing the biomechanical and biochemical contributions that it makes to disease progression. A fresh perspective is presented by the authors in the form of a novel hypothesis that implicates mechano-inflammatory disruption of the bone marrow (BM) microenvironmental ecosystem (BM niche), unresolved inflammation, and fibrosis as key drivers of OA pathogenesis and pain. BMLs, detectable via magnetic resonance imaging (MRI), serve as dynamic imaging biomarkers that correlate with pain se

Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor-bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies pu

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 also noticed that PGRN could increase capacity in terms of the invasiveness and metastasis of breast and ovarian cancer via the upregulation of MMP-9 and the activation of matrix metalloproteinase 2 (MMP-2) [ 36 , 89 ]. …

Human Amniotic Membrane Dressing as a Non-Surgical Alternative for Extensive Chronic Ulcers: A Comparative Case Study.

Chronic wound management remains a significant clinical challenge, requiring adaptive therapeutic approaches to achieve wound closure that nonetheless frequently prove fruitless. Balancing the initial pro-inflammatory response with debris removal and tissue rebuilding remains elusive in most cases, leading to pain, drastic quality-of-life deterioration, and, eventually, amputation. Meanwhile, patient adherence is an overarching theme. Furthermore, non-surgical alternatives that effectively promote tissue rebuilding are essential for patients seeking to avoid further invasive procedures. We rep

Преодоление сопротивления CD44-overexpressing миэлома через комбинированную терапию с клетками ATRA, борцезомиба и NK.

CD44 — гликпротеин, часто переоцениваемый раком и связанный с плохим прогнозом. Мы проанализировали прогнозируемую значимость CD44 в перевыражении в миеломе (MM) и изучили терапевтическую эффективность сочетания естественной клеточной терапии убийцы (NK) с транс-ретиновой кислотой (ATRA) и борцезомибом (Bor) против CD44-overexpressing Мм. Для оценки результатов выживаемости по отношению к выражению CD44 были проанализированы клинические данные из базы данных CoMMpass. Ячейки NK были расширены за счет здоровых доноров с использованием K562-OX40L-mbIL-18/21 кормовые клетки, дополненные интерлейк

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

Methamphetamine induces transcriptional changes in cultured HIV-infected mature monocytes that may contribute to HIV neuropathogenesis.

HIV-associated neurocognitive impairment (HIV-NCI) persists in 15-40% of people with HIV (PWH) despite effective antiretroviral therapy. HIV-NCI significantly impacts quality of life, and there is currently no effective treatment for it. The development of HIV-NCI is complex and is mediated, in part, by the entry of HIV-infected mature monocytes into the central nervous system (CNS). Once in the CNS, these cells release inflammatory mediators that lead to neuroinflammation, and subsequent neuronal damage. Infected monocytes may infect other CNS cells as well as differentiate into macrophages,

Melphalan flufenamide inhibits osteoclastogenesis by suppressing proliferation of monocytes.

Myeloma bone disease is a major complication in multiple myeloma affecting quality of life and survival. It is characterized by increased activity of osteoclasts, bone resorbing cells. Myeloma microenvironment promotes excessive osteoclastogenesis, a process of production of osteoclasts from their precursors, monocytes. The effects of two anti-myeloma drugs, melphalan flufenamide (melflufen) and melphalan, on the activity and proliferation of osteoclasts and their progenitors, monocytes, were assessed in this study. In line with previous research, differentiation of monocytes was associated wi

A Triazaspirane Derivative Inhibits Migration and Invasion in PC3 Prostate Cancer Cells.

Cancer is a serious health problem due to the complexity of establishing an effective treatment. The purpose of this work was to evaluate the activity of a triazaspirane as a migration and invasion inhibitor in PC3 prostatic tumor cells through a possible negative regulation of the FAK/Src signal transduction pathway and decreased secretion of metalloproteinases 2 and 9. Molecular docking analysis was performed using Moe 2008.10 software. Migration (wound-healing assay) and invasion (Boyden chamber assay) assays were performed. In addition, the Western blot technique was used to quantify prote

Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.

Chemokines, a category of cytokines exhibiting chemotactic properties, have been thoroughly investigated as targets in cancer treatment in recent decades. In oral squamous cell carcinoma (OSCC), a prevalent and high-risk malignancy of the head and neck, chemokines interact with their specific receptors to initiate downstream signaling pathways. This signaling influences not only tumor cell proliferation, migration, invasion, and metastasis of oral cancer cells but also angiogenesis and vascular maturation. Furthermore, they modulate the tumor microenvironment (TME), which consists of diverse c

Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update.

Serum biomarkers of osteoarticular diseases have been in the limelight of current clinical research trends. Laboratory validation of defined and candidate biomarkers for both osteoarthritis and osteoporosis is of key importance for future decisional algorithms in the diagnosis, monitoring, and prognosis of these diseases. The current guidelines recommend the use of collagen degradation remnants, eg, CTX-I and CTX-II, in the complementary diagnosis of both osteoporosis and osteoarthritis. Besides the collagen degradation markers, enzymes that regulate bone and articular metabolism are useful in

Chondroprotection and Molecular Mechanism of Action of Phytonutraceuticals on Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease and an important cause of incapacitation. There is a lack of drugs and effective treatments that stop or slow the OA progression. Modern pharmacological treatments, such as analgesics, have analgesic effects but do not affect the course of OA. Long-term use of these drugs can lead to serious side effects. Given the OA nature, it is likely that lifelong treatment will be required to stop or slow its progression. Therefore, there is an urgent need for disease-modifying OA treatments that are also safe for clinical use over long periods. Phytonu

Tumor metastasis to bone.

Establishment of skeletal metastasis involves bidirectional interactions between the tumor cell and the cellular elements in the bone microenvironment. A better understanding of the pathophysiology of bone metastasis will be critical in developing the means to prevent bone metastasis or inhibit its progression. The receptor activator of nuclear factor-kappaB (RANK)/RANK ligand pathway has emerged as the key pathway regulating osteolysis in skeletal metastasis. A number of candidate factors, including the Wnt (wingless int) proteins, endothelin-1, and bone morphogenetic proteins, have been impl

Beta-blockers and glioma: a systematic review of preclinical studies and clinical results.

Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and prolifer

FGA Controls VEGFA Secretion to Promote Angiogenesis by Activating the VEGFR2-FAK Signalling Pathway.

BackgroundOur previous work revealed the high expression of fibrinogen alpha chain (FGA) in patients with endometriosis (EM) and that it could promote the migration and invasion of endometrial stromal cells. Angiogenesis is the key condition for the development of EM. This study was aimed to elucidate the role of FGA in endometrial stromal cells involved in angiogenesis in EM.MethodsImmunohistochemistry was used to detect the microvessel density (MVD) and VEGF expression in the eutopic endometrium samples from EM and non-EM. The conditioned medium (CM) of human primary eutopic endometrial stro

Knockdown of LINC00963 targets miR-1252-5p to reduce inflammatory levels and ECM degradation in nucleus pulposus cells of IDD.

BACKGROUND: In middle-aged and older adults, intervertebral disc degeneration (IDD) is a major cause of chronic low back pain and disability. This pathological process is closely linked to the activation of inflammatory factors resulting from an imbalance in extracellular matrix (ECM) metabolism and abnormalities in Nucleus pulposus cells (NPCs). This study aims to clarify the functional importance of LINC00963 in IDD and its potential molecular mechanisms. METHODS: 102 IDD patients and 88 scoliosis controls were enrolled. IL-1β-stimulated NPCs modeled IDD in vitro. RT-qPCR detected LINC00963,

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

Osteoarthritis of the knee - biochemical aspect of applied therapies: a review.

The most prevalent form of arthritis is osteoarthritis (OA) of the knee, which is characterized by a degeneration of articular cartilage resulting in the development of osteophytes, or bone spurs. Main goals of OA treatment are to reduce pain, slow the disease progression, and improve joint function and the quality of life. The purpose of this study was to verify all the therapies recommended by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) from the biochemical point of view. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesi

Understanding Mesangial Pathobiology in AL-Amyloidosis and Monoclonal Ig Light Chain Deposition Disease.

Patients with plasma cell dyscrasias produce free abnormal monoclonal Ig light chains that circulate in the blood stream. Some of them, termed glomerulopathic light chains, interact with the mesangial cells and trigger, in a manner dependent of their structural and physicochemical properties, a sequence of pathological events that results in either light chain-derived (AL) amyloidosis (AL-Am) or light chain deposition disease (LCDD). The mesangial cells play a key role in the pathogenesis of both diseases. The interaction with the pathogenic light chain elicits specific cellular processes, whi

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