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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

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… Research shows that although IL-34 is dispensable during the embryonic period, in the adult brain, IL-34 derived from mural cells (such as pericytes and vascular smooth muscle cells) and fibroblasts is a core signal for maintaining BAM survival ( 21 ). … However, key questions are yet to be addressed: How exactly does IL-34 modulate BBB-associated cells (endothelial cells, pericytes, astrocytes, border-associated macrophages)? Does it act solely through CSF1R, and how do its effects compare with or differ from those of CSF-1? …

PTGS2 as a potential target for apigenin to promote spinal cord injury repair.

Spinal cord injury (SCI) is characterized by damage to the spinal cord caused by various reasons, and there is a lack of effective drug treatments. Apigenin, a well-known natural small molecule drug, may serve as a therapeutic agent for a variety of diseases. However, the potential mechanisms by which Apigenin exerts its effects in SCI remain unclear. By utilizing an integrative multiomics strategy that combines network pharmacology, Mendelian randomization, and single-cell transcriptomic profiling, we established a systems-level target identification framework. Mechanistic analysis revealed a

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… differences between PTGS2-high and PTGS2-low groups Combined with previous scRNA-seq data for the rat sham and SCI groups (Li et al. 2022a , b , c ), we identified ten distinct cell types (Fig. 4 A), including Astrocyte, Endothelial, Ependymal, Microglia, Monocytes/macrophages, Neurons, Oligodendrocytes, Pericytes …

Роль CD20+T клеток в раннем множественном склерозе.

Релапсирующий множественный склероз (RRMS) — хроническое иммунное заболевание центральной нервной системы (CNS), характеризующееся эпизодическими рецидивами неврологических симптомов. Ранняя диагностика и лечение пациентов имеют ключевое значение для предотвращения рецидивов и необратимого ущерба для ЦНС. Вместе с тем развитие методов лечения, ориентированных на ранние МЗ, сдерживается отсутствием знаний о патогенезе ранней МЗ. В RRMS повреждение нервной ткани вызывается иммунными клетками CNS, в том числе Т. Таким образом, цель этого исследования заключалась в изучении ранних случаев инфильтр

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… The BBB, also known as the neurovascular unit, consists of a tight network of cooperating cells, including endothelial cells, pericytes, and astrocytes ( 14 ). …

Innovative Approaches in Knee Osteoarthritis Treatment: A Comprehensive Review of Bone Marrow-Derived Products.

Knee osteoarthritis (OA) is a chronic articular disease characterized by the progressive degeneration of cartilage and bone tissue, leading to the appearance of subchondral cysts, osteophyte formation, and synovial inflammation. Conventional treatments consist of non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and glucocorticoids. However, the prolonged use of these drugs causes adverse effects. NSAIDs, for instance, are known to be nephrotoxic, increasing the damage to articular cartilage. New therapies capable of accelerating the process of tissue regeneration and repair are bein

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… The cells found in these tissues can be classified into two groups: (A) non-hematopoietic cells (pericytes, endothelial cells, osteoblasts, adipocytes, and Schwann cells) and (B) hematopoietic cells (neutrophils, lymphocytes, megakaryocytes, monocytes, and osteoclasts) [ 19 ]. …

Neurological updates: neurological complications of CAR-T therapy.

Chimeric antigen receptor (CAR)-expressing T cells now offer an effective treatment option for people with previously refractory B cell malignancies and are under development for a wide range of other tumours. However, neurological toxicity is a common complication of CAR-T cell therapy, seen in over 50% of recipients in some cohorts. Since 2018, the term immune effector cell-associated neurotoxicity syndrome (ICANS) has been used to describe and grade neurotoxicity seen after CAR-T cells and other similar therapies. ICANS following CAR-T therapy is usually self-limiting but can necessitate ad

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… In susceptible individuals, a more permeable BBB may expose brain vascular pericytes to high concentrations of circulating cytokines, inducing further endothelium-activation [ 11 ]. This process is somewhat analogous to eclampsia or posterior reversible encephalopathy syndrome (PRES) [ 8 ]. …

The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.

The advent of cancer immunotherapy has fundamentally restructured the oncological paradigm, moving away from agents that directly target tumor cell kinetics toward strategies that empower the host immune system to recognize and eliminate malignancy. Central to this revolution is the cytotoxic T lymphocyte (CTL), now harnessed as a potent "living drug" through engineered and naturally selected modalities. This review provides a critical, in-depth examination of the three dominant pillars of T cell-driven therapies: Chimeric Antigen Receptor T-cell (CAR-T) therapy, Tumor-Infiltrating Lymphocyte

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… Furthermore, cutting-edge single-cell transcriptomic profiling of the human brain has revealed low-level endogenous expression of CD19 on brain mural cells and pericytes. … This suggests that a degree of on-target, off-tumor recognition by circulating CD19 CAR-T cells may directly trigger pericyte death and the subsequent structural collapse of the blood-brain barrier, providing a compelling mechanistic explanation for the disproportionately high rates of neurotoxicity …

Metastatic Breast Cancer: Review of Emerging Nanotherapeutics.

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed b

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… The BBB is a highly specialized structure that consists of endothelial cells (ECs), tight junctions (TJs), astrocytes, pericytes, microglia, basement membranes, transporters, and enzymes. … Subsequently, a change in pericyte phenotype involving the altered expression of desmin and CD13 affects the permeability of the barrier, as seen in BC brain metastasis [ 79 ]. These changes allow metastatic BC cells to easily cross the BBB. …

Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.

The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated sec

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… These stimulating factors can induce adipocytes, mesenchymal stem cells, pericytes, and other cells to transform cancer-associated fibroblasts (CAFs). Similarly, miRNA-21 induces CAF formation via its inhibition of the Smad7 pathway. … Stromal population The stromal TME within tissue is made up of various components, including fibroblasts, endothelial cells, pericytes, adipocytes, the ECM, and immune cells, and plays a major role in TME homeostasis. …

Neutrophil diversity and function in health and disease.

Neutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells,

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… Neutrophils are required to pass through several barriers consisting of vascular endothelial cells, basement membranes, and pericytes to get to the site of infection or inflammation. 43 Paracellular diapedesis represents the predominant pathway for leukocyte extravasation from the vasculature. … through an ICAM-1-dependent interactions to form extensions that connect with pericyte projections, ultimately seeking out gaps leaving the vascular system. 135 Pericytes may also reduce contractility through stimulation with a macrophage migration inhibitory factor secreted by endothelial cells, enhancing …

The paracrine effects of tumor-resident mesenchymal stem/stromal cells in the microenvironment of brain metastases.

BACKGROUND: Tumor-resident mesenchymal stem/stromal cells (MSCs) were identified in several cancers, and were implicated in regulating multiple aspects of tumor progression. However, the role of tumor-resident MSCs in the pathophysiology of brain metastases (BrMs) -the most prevalent type of malignant brain tumor- is currently unknown, and was investigated in this study. METHODS: Tumor-resident MSCs were isolated from fresh human lung-BrM tissues (n=3) and were phenotypically assessed in FFPE lung-BrM tissues (n=11). The paracrine effects of BrM-MSCs on neutrophil granulocytes and endothelial

Префронтальные нейроваскулярные отклонения, связанные с когнитивными характеристиками при множественном склерозе.

КОЛИЧЕСТВО: Когнитивное расстройство является распространенной и изнуряющей характеристикой в множестве склерозов (MS), однако его патофизиология по-прежнему не до конца изучена. Дисфункция нейроваскулярного блока (NVU) и поврежденного нейроваскулярного соединения (NVC) может быть связана с когнитивными характеристиками в MS, но этот путь остается недостаточно изученным. В этом исследовании изучалось, связаны ли отклонения NVC с когнитивными характеристиками в MS. МЕТОДЫ: Ninety-seven Психиатрические заболевания и 83 Здоровый контроль (HC) получил функциональное магнитное резонансное изображен

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… This critical process depends on the coordinated function of the neurovascular unit (NVU), which comprises vascular‐associated cells, including endothelial cells, astrocytes, and pericytes, as well as neurons and other glial cells that form the neurovascular microenvironment [ 9 ]. …

Platinum-induced ototoxicity and hearing impairment in children and adolescents.

Platinum compounds play a crucial role in the treatment of solid tumours in paediatric patients, significantly improving survival rates. However, these treatments can result in hearing loss as a side-effect that can significantly impact the quality of life of young cancer survivors. Whilst the therapeutic benefits of platinum compounds in paediatric oncology are indisputable, addressing the challenge of ototoxicity remains a priority. Early and regular auditory function assessments, with tools such as audiometry, otoacoustic emissions and auditory brainstem response testing, are critical durin

A Rapid Review of Adenocarcinoma and Pulmonary Tumor Thrombotic Microangiopathy: A Deadly Duo.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare paraneoplastic syndrome associated with various adenocarcinomas, most commonly gastric adenocarcinoma. This condition can progressively worsen pulmonary arterial hypertension, leading to acute or subacute pulmonary heart failure and respiratory insufficiency. This paper examines the pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of PTTM. Given PTTM's poor prognosis, we emphasize treatment strategies. PTTM in adenocarcinoma patients can mimic other pulmonary diseases, causing diagnostic delays. Current PTTM tr

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… and idiopathic pulmonary arterial hypertension J Scleroderma Relat Disord Friedman SH Harley RA Williams J 23971983241296721 2024 39619640 10.1177/23971983241296721 PMC11603424 34 Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes …

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

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… The BBB comprises molecular and cellular components, such as extracellular matrix, endothelial cells, pericytes, and astrocytes. …

От ожирения до митохондриальной дисфункции в периферальных тканях и в центральной нервной системе.

Ожирение - это состояние хронического низкосортного воспаления, затрагивающего периферийные органы тела, а также центральную нервную систему. Дефункция жировой ткани, возникающая в условиях ожирения, является ключевым фактором возникновения и развития различных заболеваний, включая нейродегенеративные расстройства. Митохондрия, ключевые органеллы в производстве клеточной энергии, играет важную роль в этой дисфункции тканей. В многочисленных исследованиях подчеркивается тесная связь между ожирением и дисфункцией митохондриалов адипоцита, что приводит к чрезмерному производству ROS и воспалению

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… The structural integrity of the BBB is one of the most critical factors in maintaining brain homeostasis and is regulated by intricate interactions among various cell types, such as endothelial cells, pericytes, and astrocytes [ 16 ]. …

Neuroimmune crosstalk and its impact on cancer therapy and research.

Cancer is a major health problem as it is the first or second leading cause of death worldwide. The global cancer burden is expected to rise 47% relative to 2020 cancer incidence. Recently, the fields of neuroscience, neuroimmunology and oncology have elaborated the neuroimmune crosstalk role in tumor initiation, invasion, progression, and metastases. The nervous system exerts a broad impact on the tumor microenvironment by interacting with a complex network of cells such as stromal, endothelial, malignant cells and immune cells. This communication modulates cancer proliferation, invasion, met

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… through circulating epinephrine/norepinephrine. b-adrenergic secretion can directly affect carcinogenesis signaling, inhibit DNA damage repair, downregulate p53-associated apoptosis, modulate various growth and survival pathways, and activate mesenchymal cell types present in TME such as fibroblasts, pericytes …

Возможная роль метаформы и фибробластного роста Factor-21 В Multical Sclerosis Neuropathology: Birds of a Feather Flock Common.

Множественный склероз (MS) — прогрессивное демиелинизирующее заболевание CNS, характеризующееся воспалением, образованием CNS-клеров и повреждением нейронной миелинской оболочки (graphical abstract). Фактор роста фибробласта 21 (FGF21) занимается различными метаболическими расстройствами и нейродегенеративными заболеваниями. FFF21 и его корецептор β-Kloth имеют существенно важное значение для процесса ремиелиции MS. Метформин, инсулин-сенсибилизирующее лекарство, которое является первой линией лечения для типа 2 Мэлитус диабета (T2DM) может оказывать потенциальное нейрозащитное воздействие, ре

A Comprehensive Review of Interventional Clinical Trials in Patients with Bone Metastases.

Bone metastasis is one of the most important factors associated with poor prognosis for patients with prostate, breast, thyroid, and lung cancer. In the past two decades, 651 clinical trials, including 554 interventional trials, were being registered in ClinicalTrials.gov and pharma.id.informa.com to combat bone metastases from different perspectives. In this review, we comprehensively analyzed, regrouped, and discussed all the interventional trials on bone metastases. Clinical trials were re-grouped into bone-targeting agents, radiotherapy, small molecule targeted therapy, combination therapy

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… Pericytes in the premetastatic niche. Cancer Res . 2018;78(11):2779–2786. doi: 10.1158/0008-5472.CAN-17-3883 10. Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer . 2003;3(6):453–458. doi: 10.1038/nrc1098 11. Yoneda T, Hiraga T. …

Circulating sRANKL, Periostin, and Osteopontin as Biomarkers for the Assessment of Activated Osteoclastogenesis in Myeloma Related Bone Disease.

The hallmark of multiple myeloma is myeloma related bone disease. Interactions between myeloma plasma cells (MPCs), stromal cells, and the bone marrow (BM) microenvironment play a critical role in the pathogenesis of MBD. Bone remodeling is severely dysregulated with the prevalence of osteoclast activity. We aimed to assess circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in NDMM patients at diagnosis and in the course of treatment, correlations with clinical and laboratory data, and to evaluate their potential as additional biomarkers for the assessment of MBD

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… It is expressed by a wide variety of cell types such as bone cells, neurons, epithelial cells, pericytes, fibroblasts, hepatocytes, tubular cells, vascular smooth muscle cells, and immune cells [ 34 ]. …

Mesenchymal stem cell transplantation plays a role in relieving cancer pain.

Tumors can invade, compress, and damage nerves, leading to persistent pain and seriously affecting the quality of life of patients. However, their treatment is challenging. Sensitization of peripheral receptors, abnormal activity of primary sensory neurons, activation of glial cells, enhanced inflammatory responses, and sensory information transmission contribute towards cancer pain. Therefore, considerable attention has been paid to exploring prospective methods to inhibit the occurrence of these factors and relieve cancer pain. Studies on different types of pains have revealed that the trans

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… Homing MSCs differentiate into pericytes, induce tumor angiogenesis, and promote tumor regrowth ( Razmkhah et al., 2019 ). Research shows that breast cancer cells can devour MSCs, thereby enhancing their metastasis ( Augimeri et al., 2023 ). …