Результаты поиска

TSP-1 interaction with RANK and OPG: implications for bone remodeling and osteolytic bone metastasis.

Excessive bone disruption, driven by upregulation of bone-degrading osteoclasts, occurs in several pathologies, including breast cancer osteolytic bone metastasis, a condition associated with poor prognosis and diminished quality of life for patients. The matricellular protein thrombospondin-1 (TSP-1) plays pleiotropic roles in physiological and pathological remodeling of several tissues, including bone, and in shaping the microenvironment of primary tumors and metastasis. This study aimed to explore the role of TSP-1 in bone remodeling associated with osteolytic bone metastasis. We have ident

Development and characterization of chimeric antigen receptor macrophages for amyloid clearance.

Systemic amyloidosis is a protein folding disorder characterized by the extracellular deposition of protein fibrils in tissues and vital organs, leading to dysfunction and mortality. While there are monoclonal antibody-based therapies that promote cell-mediated amyloid clearance in various stages of clinical development, there are currently no treatment options which focus on reducing the tissue amyloid burden. Therefore, the urgent need for a transformative approach to facilitate amyloid clearance and restore organ function remains paramount. We demonstrate that a short, polybasic peptide (p5

Совпадение в полном тексте источника
… Introduction The group of progressive debilitating diseases characterized by the deposition of protein fibrils in the extracellular space of tissues and organs are collectively known as systemic amyloidosis ( 1 ). …

Pro-inflammatory Cytokines, Ferroptosis, and Cancer.

Ferroptosis, iron-dependent regulated cell death, is induced by the polyunsaturated fatty acid peroxidation of membrane phospholipids and is controlled by glutathione peroxidase 4. In recent years, convincing evidence has emerged, demonstrating a close relationship between chemo-, radio-, immuno-, and targeted therapy resistance and ferroptosis resistance. In this review, we discuss the basic principles of ferroptosis in cancer. Considerable attention is paid to the formation of an immunosuppressive tumor microenvironment. The main focus is centered on the involvement of the excessive, chronic

IL-34 в неврологическом гомеостазисе и его многогранная роль в заболеваниях центральной нервной системы.

Interleukin-34 (IL-34), лиганд для рецептора макрофажных колоний (CSF1R), играет незаменимую роль в развитии и поддержании гомеостазиса центральной нервной системы (CNS). В настоящем обзоре систематически излагаются основные механизмы, с помощью которых ось сигнала IL-34/CSF1R регулирует развитие, колонизацию и функциональную дифференциацию иммунных клеток-резидентов, включая микроглию и макрофаги, связанные с границами (BAM). Она подчеркивает свою роль в критических физиологических процессах, таких, как синаптическое обрезка, созревание нервной цепи и поддержание целостности мозгового барьера

Совпадение в полном тексте источника
… Microglia as hackers of the matrix: sculpting synapses and the extracellular space. Cell Mol Immunol. (2021) 18:2472–88. doi: 10.1038/s41423-021-00751-3 12. Hu A, Schmidt MHH, Heinig N. Microglia in retinal angiogenesis and diabetic retinopathy. …

The Contribution of Tumor Derived Exosomes to Cancer Cachexia.

Cancer cachexia is defined as unintentional weight loss secondary to neoplasia and is associated with poor prognosis and outcomes. Cancer cachexia associated weight loss affects both lean tissue (i.e., skeletal muscle) and adipose tissue. Exosomes are extracellular vesicles that originate from multivesicular bodies that contain intentionally loaded biomolecular cargo. Exosome cargo includes proteins, lipids, mitochondrial components, and nucleic acids. The cargo carried in exosomes is thought to alter cell signaling when it enters into recipient cells. Virtually every cell type secretes exosom

Совпадение в полном тексте источника
… It is generally believed that exosome packaging serves to improve stability and survivability in the extracellular space and therefore prolongs the potential impact of miRs on cellular function. …

Prognostic utility of macrophage polarization (CD68/CD163 ratio) in Egyptian JAK2 positive myeloproliferative neoplasm patients: a single center study.

BackgroundMyeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders with variable clinical outcomes influenced by the bone marrow microenvironment. Tumor-associated macrophages (TAMs), particularly the M1 (CD68⁺) and M2 (CD163⁺) subtypes, play critical roles in inflammation, fibrosis, and immune modulation. This study evaluates CD68- and CD163-positive macrophage frequencies across MPN subtypes and their clinical/prognostic significance.MethodsIn this retrospective cohort study, 121 patients with histopathologically confirmed BCR::ABL1-negative, JAK2V617F-positive MPNs were assess

Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.

Bone marrow is the primary site of blood cell production in adults and serves as the source of osteoblasts and osteoclasts that maintain bone homeostasis. The medullary microenvironment is also involved in malignancy, providing a fertile soil for the growth of blood cancers or solid tumors metastasizing to bone. The cellular composition of the bone marrow is highly complex, consisting of hematopoietic stem and progenitor cells, maturing blood cells, skeletal stem cells, osteoblasts, mesenchymal stromal cells, adipocytes, endothelial cells, lymphatic endothelial cells, perivascular cells, and n

Совпадение в полном тексте источника
… Cysteine, typically present in its oxidized form cystine in the extracellular space, is regarded as the rate-limiting substrate for the synthesis of the antioxidant glutathione. … Bone marrow MSCs in contrast import cystine, convert it to cysteine and release it back into the extracellular space where it is taken up by CLL cells, allowing the cancer cells to synthesize glutathione and protecting them from chemotherapy-induced cytotoxicity. …

Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model.

It is increasingly apparent that cancer cells, in addition to remodelling their metabolism to survive and proliferate, adapt and manipulate the metabolism of other cells. This property may be a telling sign that pre-clinical tumour metabolism studies exclusively utilising in-vitro mono-culture models could prove to be limited for uncovering novel metabolic targets able to translate into clinical therapies. Although this is increasingly recognised, and work towards addressing the issue is becoming routinary much remains poorly understood. For instance, knowledge regarding the biochemical mechan

Total adenosine deaminase cases as an inflammatory biomarker of pleural effusion syndrome.

BACKGROUND: Although inflammatory diseases commonly affect the pleura and pleural space, their mechanisms of action remain unclear. The presence of several mediators emphasizes the concept of pleural inflammation. Adenosine deaminase (ADA) is an inflammatory mediator detected at increased levels in the pleural fluid. AIM: To determine the role of total pleural ADA (P-ADA) levels in the diagnosis of pleural inflammatory diseases. METHODS: 157 patients with inflammatory pleural effusion (exudates, n = 124, 79%) and non-inflammatory pleural effusion (transudates, n = 33, 21%) were included in t

Совпадение в полном тексте источника
… Once released into the extracellular space, adenosine can be deaminated to inosine by adenosine deaminase enzyme (ADA) or taken up directly by cells by specific nucleoside transporters and re-phosphorylated to ATP[ 3 - 5 ]. …

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

Совпадение в полном тексте источника
… During normal apoptosis nucleotides liberated from membrane-bound organelles are rapidly degraded by nucleases such as DNase and RNase, but during damage or un-programmed cell death, nucleic acids can also be released into the extracellular space as immune stimulators. … Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus . J. Neurosci . 17 , 7673 – 7682 . 9315889 10.1523/JNEUROSCI.17-20-07673.1997 PMC6793930 Feldman P. Due M. R. Ripsch M. S. Khanna R. White F. A. ( 2012 ). …

Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loade

Внеклеточные нуклеотиды являются посредником в вирусных инфекциях центральной нервной системы: ключи от нейроинфламмации и нейродегенерации.

Недавний рост инфекционных заболеваний, затрагивающих центральную нервную систему, вызвал обеспокоенность по поводу их роли в нейроинфламмации и нейродегенерации. Вирусные патогены или их продукты могут вторгаться в центральную нервную систему и вызывать повреждения, ведущие к менингиту, энцефалиту, менингоэнцефалиту, миелиту или постинфекционным демиелинизирующим заболеваниям. Хотя изначально нейроинфламмация имеет защитную функцию, хроническое воспаление может способствовать развитию нейродегенеративных заболеваний. Такие механизмы, как агрегация белков и клеточные расстройства, связаны с ко

Совпадение в полном тексте источника
… ATP is maintained in millimolar concentrations in the intracellular environment but can be released into the extracellular space through compromised plasma membranes or various transporters, for example, membrane channels (such as pannexins or connexins), transport in vesicles or exocytosis from secretory … In the context of amyloid-β (Aβ) accumulation in AD, one of its many detrimental effects is the induction of ATP release into the extracellular space (Ronning et al., 2023). …

Расследовать роль Интравокселя Несогласованного движения Диффузиум Взятые воображения в оценке множественных склерозных лиз.

Фон: Множественный склероз (MS) является хроническим и разнородным заболеванием, характеризующимся демиелинацией, аксонной потерей и повреждением. Для различения этих изменений в различных видах поражения MS использовались магнитные резонансные изображения (MRI). Цели: Мы поставили перед собой цель оценить диффузию и перфузионную диффузию внутривоксельного несогласованного движения (ИВИМ) в различных регионах мозга в здоровых людях и различных видах поражения MS, включая усиленные, неусиленные и черные дыры. Методы: Включено перспективное исследование 237 пациенты с синдромом MS (MS)65 мужчины

Совпадение в полном тексте источника
… For example, the mean ADC for black hole MS lesions is significantly higher than that of normal white matter, likely reflecting increased extracellular space and reduced cellular density resulting from severe tissue destruction [ 40 ]. … ADC values were markedly higher in black hole MS lesions compared to both enhanced and non-enhanced MS lesions, indicating that black hole lesions are associated with the most severe tissue destruction and increased extracellular space [ 40 , 46 ]. The IVIM- D values showed a distinct pattern. …

Role of the Bone Microenvironment in the Development of Painful Complications of Skeletal Metastases.

Cancer-induced bone pain (CIBP) is the most common and painful complication in patients with bone metastases. It causes a significant reduction in patient quality of life. Available analgesic treatments for CIBP, such as opioids that target the central nervous system, come with severe side effects as well as the risk of abuse and addiction. Therefore, alternative treatments for CIBP are desperately needed. Although the exact mechanisms of CIBP have not been fully elucidated, recent studies using preclinical models have demonstrated the role of the bone marrow microenvironment (e.g., osteoclast

Совпадение в полном тексте источника
… During the bone resorption process, osteoclasts acidify (pH 4.0–4.5) the extracellular space by releasing protons and chloride ions through membrane transport (V-type H + ATPase) [ 38 ]. … To prevent cell death mediated by this intracellular acidification, tumor cells actively pump out the protons and lactate to the extracellular space. …

Роль Neurofilament fight (NfL) и глиального фибрового кислотного белка (GFAP) в MS и AQP4-NMOSD: развитие клинического применения.

Важную роль в диагностике, мониторинге и оценке терапевтической реакции в таких условиях, как мультипликативный склероз (MS) и аквапорин-4 Нейромиелит Оптика Спектрум (AQP4-NMOSD), играют плавучие биомаркеры, такие, как глиальные фибриллярные протеины (GFAP) и Neurofilament Light (NfL). Эти биомаркеры позволяют получить ключевые сведения о патофизиологических механизмах, лежащих в основе этих заболеваний, что позволяет осуществлять эффективные последующие мероприятия и применять индивидуализированные методы лечения, которые имеют существенно важное значение для улучшения результатов лечения па

Совпадение в полном тексте источника
… Upon axonal and astrocytic damage, neurofilament and GFAP proteins are released into the extracellular space, cerebrospinal fluid (CSF), and blood. These cleavage products can be detected by highly sensitive immunoassays, making them valuable biomarkers for diagnosing neurological disorders. … Upon axonal and astrocytic damage, neurofilament and GFAP proteins are released into the extracellular space, cerebrospinal fluid (CSF), and blood. These cleavage products can be detected by highly sensitive immunoassays, making them valuable biomarkers for diagnosing neurological disorders. …

Extracellular Vesicles in Diffuse Large B Cell Lymphoma: Characterization and Diagnostic Potential.

Diffuse large B cell lymphoma (DLBCL) is an aggressive B cell lymphoma characterized by a heterogeneous behavior and in need of more accurate biological characterization monitoring and prognostic tools. Extracellular vesicles are secreted by all cell types and are currently established to some extent as representatives of the cell of origin. The present study characterized and evaluated the diagnostic and prognostic potential of plasma extracellular vesicles (EVs) proteome in DLBCL by using state-of-the-art mass spectrometry. The EV proteome is strongly affected by DLBCL status, with multiple

Совпадение в полном тексте источника
… The cellular location of deregulated proteins included the extracellular space, blood microparticles, and the nucleosome and complement complex ( Figure 6 d). 2.6. DLBCL vs. … Indeed, GO functional enrichment analysis of cellular components of identified proteins among DLBCL and HD groups are equally enriched in cellular component categories such as extracellular region, extracellular vesicular exosome, extracellular space, proteasome complex and blood microparticle ( Figure …

A 65-Year-Old Woman with an Enlarged Tongue Due to Amyloidosis.

BACKGROUND Amyloidosis is a clinical condition characterized by the extracellular deposition of insoluble, abnormal amyloid fibrils in various body tissues. It is generally categorized into 2 forms - localized and systemic - with a wide range of signs and symptoms. This case report discusses the localized amyloidosis involvement of the oral cavity and its treatment. CASE REPORT A 65-year-old woman presented to the oral medicine clinic reporting painless tongue enlargement, which has been slowly progressing over several years, leading to difficulty in tongue movement, eating, and swallowing. Ex

Перенос Митохондрии для ремонта миелина.

Обезвоживание является общей характеристикой нейро-воспалительных и дегенеративных заболеваний центральной нервной системы (КНС), таких, как множественный склероз (МС). Часто это связано с нарушениями межклеточной связи, биоэнергетики и метаболического баланса в сочетании с митохондриальной дисфункцией в таких клетках, как олигодендроциты, нейроны, астроциты и микроглиа. Несмотря на то, что нынешние методы лечения MS сосредоточены на иммуномодуляции, они не могут остановить или обратить вспять прогресс демиэлизации. Последние достижения подчеркивают межклеточный митохондриальный обмен в качест

Взаимодействие между нейтрофилами и элементами барьера крови и мозга в контексте множественного склероза и ишемического разрушения.

Барьер мозга крови (BBB) представляет собой полупроницаемую мембрану в физиологических условиях, но в патологии, такой, как множественный склероз (MS) и ишемический инсульт (IS), его проницаемость возрастает. В этом обзоре основное внимание уделяется нейтрофильам и их взаимодействию с клеточными компонентами ББД: эндотелиальными клетками (ЭК), перицитами (ПХ) и астроцитами (АК). В настоящее время нейтрофилы получают больше внимания, главным образом благодаря передовым методам исследований, которые показывают сложность их населения. Кроме того, нейтрофилы способны засекать внеклеточные везикли

Совпадение в полном тексте источника
… These cells also maintain ionic homeostasis of the extracellular space, regulate pH and neurotransmitter uptake, and mediate signals from neurons to the vasculature [ 10 ]. Changes in AC characteristics contribute to the impairment of BBB integrity [ 11 ]. … Additionally, neutrophils, as most of other cells, are able to secrete extracellular vesicles (EVs) into extracellular space [ 64 ]. The main subtypes of EVs are exosomes, microvesicles, and apoptotic bodies. Their sizes and contents are different, and they perform different functions [ 65 ]. …

Bone marrow fibrosis in newly diagnosed multiple myeloma and its correlation with clinicopathological factors.

BACKGROUND: Bone marrow fibrosis (BMF) severely impacts both the quality of life and the efficacy of diagnostic procedures. However, the correlation between BMF and clinicopathological features, cytogenetic changes, and prognosis of newly diagnosed multiple myeloma (NDMM) remains unclear. This study determined the incidence, patient characteristics, and clinical outcomes of patients with NDMM with BMF. METHODS: The clinical data, histological features, and clinical outcomes of patients with NDMM were collected. Reticular fiber staining was performed on the enrolled cases, and the degree of re