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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

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

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

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

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

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,

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

Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review.

Hyaluronic acid (HA) is a linear polysaccharide and crucial component of the extracellular matrix (ECM), maintaining tissue hydration and tension. Moreover, HA contributes to embryonic development, healing, inflammation, and cancerogenesis. This review summarizes new research on the metabolism and interactions of HA with its binding proteins, known as hyaladherins (CD44, RHAMM), revealing the molecular basis for its distinct biological function in the development of cancer. The presence of HA on the surface of tumor cells is a sign of an adverse prognosis. The involvement of HA in malignancy h

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… This mechanism was demonstrated in melanoma cells resulting in increased production of matrix metalloproteinase 9 (MMP-9) and the inflammatory cytokines IL-8 and IL-1β, which may promote tumor growth ( Figure 3 A) [ 136 ]. …

The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update.

Cancer is caused by abnormal proliferation of cells and aberrant recognition of the immune system. According to recent studies, natural products are most likely to be effective at preventing cancer without causing any noticeable complications. Among the bioactive flavonoids found in fruits and vegetables, quercetin is known for its anti-inflammatory, antioxidant, and anticancer properties. This review aims to highlight the potential therapeutic effects of quercetin on some different types of cancers including blood, lung and prostate cancers.

Molecular factors associated with lung cancer in people living with HIV.

Lung cancer is the most common Non-AIDS-Defining Cancer (NADC) and a leading cause of cancer-related death in People Living With HIV (PLWH). Despite antiretroviral therapy, PLWH are at higher risk of developing cancer compared to the general population. This increased susceptibility reflects a combination of immunosuppression, chronic inflammation, smoking, and direct oncogenic effects of HIV proteins. Tat, gp120, and Nef modulate cell cycle control, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune evasion. Persistent HIV reservoirs in lung tissue (mainly effector memory

Research advances in peptide‒drug conjugates.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, link

Дисфункция мозгового барьера (BBB) в заболеваниях CNS: уделение внимания перицитам.

Дизфункция мозгового барьера (BBB) является важным патологическим механизмом в заболеваниях центральной нервной системы (CNS) и может вызвать ряд патологических реакций, таких, как нейроинфламмационная реакция, окислительный стресс, иммунная инфильтрация и т.д., что усугубляет повреждение мозга. Вместе с тем исследователи часто игнорируют перициты, и ни одно обзорное исследование пока еще не подытожило механизм, с помощью которого перициты способствуют дисфункции ББД в заболеваниях КНС.Поэтому в настоящем обзоре изучается патофизиология дисфункции ББД в связи с заболеваниями КНС и содержится п

Mediterranean Diet Food Components as Possible Adjuvant Therapies to Counteract Breast and Prostate Cancer Progression to Bone Metastasis.

Bone metastasis is a serious and often lethal complication of particularly frequent carcinomas, such as breast and prostate cancers, which not only reduces survival but also worsens the patients' quality of life. Therefore, it is important to find new and/or additional therapeutic possibilities that can counteract the colonization of bone tissue. High adherence to the Mediterranean diet (MD) is effective in the prevention of cancer and improves cancer patients' health, thus, here, we considered its impact on bone metastasis. We highlighted some molecular events relevant for the development of

Гипоксичная нейроинфламмация в патогенезе множественного склероза.

Множественный склероз (MS) — аутоиммунная болезнь, которая повреждает миелиновую оболочку вокруг аксонов центральной нервной системы, что приводит к неврологической дисфункции. Хотя первоначальное повреждение вызвано воспалением, гипоксия была зарегистрирована в нескольких районах мозга пациентов MS, однако значение этого для прогнозирования и лечения остается неясным. Нейроинфламмация может вызывать гипоксию, а гипоксия может вызывать и усугублять нейроинфламму, образуя порочный круг. Повреждения MS часто сопровождаются обезвоживанием, которое может восстановить неврологическую функцию. Однак

Impact of Periodontal Host-Modulation Therapies on Oral-Gut Microbiome Axis in Periodontitis Patients with Hematological Diseases: A Narrative Review.

Host-modulating therapies and oral microbiome-targeted approaches are emerging options in periodontal care and are especially relevant for patients undergoing immunotherapy for hematologic malignancies. Immune dysregulation induced by immune checkpoint inhibitors or CAR-T cell therapy may worsen periodontal inflammation and alter the composition and functions of the oral microbiota. Beyond these, other immunomodulatory treatments commonly employed in hematologic malignancies-including monoclonal antibodies (e.g., rituximab, daratumumab), immunomodulatory drugs (e.g., lenalidomide, thalidomide)

Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors.

The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural

The effects of coagulation factors on the risk of autoimmune diseases: A Mendelian randomization study.

The objective of this study was to investigate the potential causal relationship between coagulation factors and autoimmune diseases (ADs). We employed Mendelian randomization to investigate the associations between selected 7 coagulation factors and 10 ADs, leveraging genetic variants as instrumental variables to assess causal relationships between exposures of interest and outcomes. Within the scope of this investigation, coagulation factors were designated as the exposure source, while ADs were observed to manifest as the consequent outcome. Our analysis using the inverse-variance weighted

Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.

Compelling evidences have manifested that breast cancer cells prefer to metastasize to certain distant organs, including brain, lung, bone and liver. According to the canonical "seed and soil" theory, this prominent biological behavior, termed as metastatic organotropism, involves intricate interactions between breast cancer cells (the "seeds") and specific residents in the tumor microenvironment (the "soil"), initiating from pre-metastatic niche formation to metastatic outgrowth. Recently, multifaceted heterogeneity of tissue-specific macrophages (TSMs) and their roles played in organotropic

Annexin A1 affects tumor metastasis through epithelial-mesenchymal transition: a narrative review.

Background and objectiveAnnexin A1 (annexin I, ANXA1), the first discovered member of the annexin superfamily, plays important roles in tumor development, invasion, metastasis, apoptosis and drug resistance based on tumor type-specific patterns of expression. The acquisition of the epithelial-mesenchymal transition (EMT) characteristics is an essential mechanism of metastasis because they increase the mobility and invasiveness of cancer cells. Cancer invasion and metastasis remain major health problems worldwide. Elucidating the role and mechanism of ANXA1 in the occurrence of EMT will help ad

Minocycline ameliorates CNS autoimmunity through restraint of CD4+CD11bc+ cells.

Minocycline is a tetracycline antibiotic with profound anti-inflammatory activity directed primarily against microglial cells and macrophages. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as an important target of minocycline. This drug has been considered a promising therapeutic for multiple sclerosis, an autoimmune disorder of the central nervous system (CNS). Still, its effect on CNS autoimmunity is not entirely understood. The aim of this study was to investigate the potency of short-term minocycline administration in fully developed CNS inflammation. To t