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Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization.

BackgroundBrain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential stra

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… Pericyte coverage was used to evaluate neovascular maturation and vascular barrier function, with higher pericyte coverage indicating better vascular barrier function. CD34 labeled microvascular endothelial cells and α-SMA labeled pericytes. … The whole-brain irradiation combined with MIF-silenced group had the lowest micro-vessel density and the highest pericyte coverage (Fig. 5 A). …

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy.

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy reg

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… More recently, it was shown that PDGF-BB’s role in CRC is connected to the proliferation of pericytes within tumors. … Endothelial cell survival is promoted, vascular function is regulated (for example, by modulating vessel width and permeability), and mechanical support and stability are maintained thanks to pericytes. …

The Role of TAM Receptors in Bone.

The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis

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… Inhibition of GAS6-AXL signaling enhanced mineralization of pericyte nodules in vitro, but the number of mineralized nodules was decreased [ 72 ]. … Receptor tyrosine kinase Axl modulates the osteogenic differentiation of pericytes. Circ. Res. 2003;92:1123–1129. doi: 10.1161/01.RES.0000074881.56564.46. 73. Attwell D., Mishra A., Hall C.N., O’Farrell F.M., Dalkara T. What is a pericyte? J. Cereb. …

Direct Intercellular Communications and Cancer: A Snapshot of the Biological Roles of Connexins in Prostate Cancer.

Tissue homeostasis is the result of a complex intercellular network controlling the behavior of every cell for the survival of the whole organism. In mammalian tissues, cells do communicate via diverse long- and short-range communication mechanisms. While long-range communication involves hormones through blood circulation and neural transmission, short-range communication mechanisms include either paracrine diffusible factors or direct interactions (e.g., gap junctions, intercellular bridges and tunneling nanotubes) or a mixture of both (e.g., exosomes). Tumor growth represents an alteration

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… TNTs could also be involved in tumor angiogenesis originating from pericytes that are looking to actively explore the microenvironment and connecting with targeted vessels through other pericytes or endothelial cells [ 48 ]. … TME includes multiple different types of non-malignant cells, such as activated fibroblasts, infiltrating macrophages and other immune cells, as well as the tumor microvasculature composed of endothelial cells and pericytes [ 103 ]. …

Revisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer.

A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier (BBB) and overexpression of ATP-binding cassette (ABC) transporters, which decrease drug penetration into the central nervous system and ultimately into tumors. It is noteworthy that the ABC transporters, ABCB1 [known as P-glycoprotein (P-gp)] and ABCG2 [known as breast cancer resistance protein (BCRP)], are overexpressed in brain tumors, including common gliomas. The co-presence of these transporters may negate the inhibition of either transporter, pa

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… The endothelium of the BBB is formed by close contact with astrocytes and/or pericytes and is mediated in part by differences in cell adhesion molecules between central and peripheral cells 49 . Astrocytes and pericytes support membrane integrity, stability, and homeostasis 45 . … The BTB has a loss of endothelial tight junctions, microvascular proliferation forming new leaky blood vessels, altered astrocytic end feet connections, and altered pericyte function. …

Endothelial dysfunction and hemostatic imbalance in CAR T-cell-associated toxicities: pathophysiological insights and the role of circulating biomarkers.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory hematologic malignancies. While its clinical efficacy is well established, CAR T-cell therapy is frequently associated with severe immune-mediated toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), coagulopathy, and hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Increasing evidence suggests that endothelial dysfunction, hemostatic imbalance, and complement activation are key contributors to the pathogenesis of

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… Moreover, Parker et al. identified CD19 and its chaperone CD81 in human brain pericytes, with sustained CD19 expression from development though adulthood. … This variable expression may lead to off-target interactions between anti-CD19 CAR T-cells and pericytes, contributing to an enhanced BBB breakdown. …

Эгоистические нейрофармацевтики: открытие кровеносного барьера для лечения следующего поколения.

Блокирование мозга крови (ББД) представляет собой огромную проблему в нейрофармакологии, ограничивая доставку терапевтических агентов в мозг. Экзосомы, нанокарьеры природы, стали многообещающим решением из-за их биосовместимости, низкой иммуногенности и врожденной способности пересекать ББД. Тщательное изучение анатомии и физиологии ББД свидетельствует о сложности доставки неврологических наркотиков и подчеркивает ограниченность традиционных методов. В настоящем обзоре изучается потенциал нейрофармацевтики с экзосомной силой, при этом особое внимание уделяется их структурным и функциональным с

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… Pericytes communicate with endothelial cells through gap junctions and signaling molecules, such as transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF) [ 32 ]. … In pathological conditions, such as stroke and neurodegenerative diseases, the loss of pericytes disrupts BBB integrity, leading to increased vascular permeability and inflammation [ 33 ]. …

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

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… Specifically, CXCR4 on the surface of endothelial cells and pericytes can bind to the chemokine CXCL12, and this interaction will promote the expression of PDGF-BB; subsequently, PDGFRβ on the surface of pericytes specifically binds to PDGF-BB, driving pericytes to migrate to endothelial cells and bind … CXCL12 can not only specifically bind to CXCR4 and directly recruit endothelial progenitor cells to the site of angiogenesis, stimulate the proliferation and migration of pericytes, but also stimulate the binding of PDGF-BB and PDGF-Rβ to indirectly promote the arrangement of pericytes and vascular smooth …

Galectins in the Pathogenesis of Common Retinal Disease.

Diseases of the retina are major causes of visual impairment and blindness in developed countries and, due to an ageing population, their prevalence is continually rising. The lack of effective therapies and the limitations of those currently in use highlight the importance of continued research into the pathogenesis of these diseases. Vascular endothelial growth factor (VEGF) plays a major role in driving vascular dysfunction in retinal disease and has therefore become a key therapeutic target. Recent evidence also points to a potentially similarly important role of galectins, a family of β-g

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… Notably, the inner BRB endothelial cells should always be considered in the context of their surrounding abutting and regulating cells, in particular pericytes, astrocytes and Müller cells, which are collectively referred to as a neurovascular unit ( Figure 3C ). … In the retinal vasculature AGEs induce pericyte apoptosis and increased production of endothelial growth factors and inflammatory cytokines ( Antonetti, et al., 2021 ). …

Integrative meta-analysis identifies microRNA-regulated networks in infantile hemangioma.

BackgroundHemangioma is a common benign tumor in the childhood; however our knowledge about the molecular mechanisms of hemangioma development and progression are still limited. Currently, microRNAs (miRNAs) have been shown as gene expression regulators with an important role in disease pathogenesis. Our goals were to identify miRNA-mRNA expression networks associated with infantile hemangioma.MethodsWe performed a meta-analysis of previously published gene expression datasets including 98 hemangioma samples. Deregulated genes were further used to identify microRNAs as potential regulators of

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… In infantile hemangioma, neural crest markers (NG2 and nestin), pericytes markers (δ-like kinase, smooth muscle actin, calponin and CD90) and stem cell markers (OCT4, NANOG and SOX2) are frequently over-expressed both at mRNA and protein levels. … In addition, pericytes (perivascular cells surrounding microvessels and that are related to the development and regulation of angiogenesis) and the derm of the face are derived from neural crest, suggesting that the neural crest may be involved in disease pathogenesis [ 10 ]. …

Mesenchymal stem cells in cancer therapy; the art of harnessing a foe to a friend.

For a long time, mesenchymal stem cells (MSCs) were discussed only as stem cells which could give rise to different types of cells. However, when it became clear that their presence in the tumor microenvironment (TME) was like a green light for tumorigenesis, they emerged from the ashes. This review was arranged to provide a comprehensive and precise description of MSCs' role in regulating tumorigenesis and to discuss the dark and the bright sides of cancer treatment strategies using MSCs. To gather the details about MSCs, we made an intensive literature review using keywords, including MSCs,

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… For example, in osteosarcoma, MSCs-tumor cells interplay stimulates TGF-β/Smad2/3 axis in MSCs and generates IL-6, which then autocrinally facilitates the differentiation of MSCs into fibroblasts or pericytes. … Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1. Mol Cancer. 2010;9:1–12. doi: 10.1186/1476-4598-9-209. 78. Brindle NP, Saharinen P, Alitalo K. …

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and inva

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… MSCs support cancer growth by differentiating into other pro-tumorigenic stromal components, enhancing the EMT, augmenting cancer cell survival, promotion cancer metastasis, endorsing angiogenesis, and suppressing the immune response 46–47 Pericytes Pericytes are mural cells located between the endothelial … MSCs support cancer growth by differentiating into other pro-tumorigenic stromal components, enhancing the EMT, augmenting cancer cell survival, promotion cancer metastasis, endorsing angiogenesis, and suppressing the immune response | 46–47 Pericytes | Pericytes are mural cells located between the endothelial …

Острая ТРЕМ2 ингибиция истощает MAFB-высокую микроглию и препятствует воссоединению.

Мы изучили роль в регенерации миелоидных клеток 2 (TREM2) в мозгу. TREM2 является рецептором, который активирует микроглию, которая имеет решающее значение для удаления миелинового мусора и поощрения ремиэлизации. Предыдущие исследования в мышечной модели демиелинции, вызванной медным агентом Cuprizone (CPZ), показали, что стимуляция TREM2 с моноколональным антителом уменьшает демиелинацию, в то время как удаление гена Trem2 в мышах ухудшает ремиелионацию. Здесь мы резко заблокировали функцию TREM2 с антителом как на стадии обезвоживания, так и на стадии ремиэлирования модели CPZ и проанализир

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… These included endothelial cells (Endothelial 1 and Endothelial 2), pericytes, smooth muscle cells (SMCs), and fibroblasts (fibroblasts 1-3) ( SI Appendix , Fig. S6 A and B ). … An analysis of subcluster frequencies revealed that anti-TREM2 led to a decrease in pericytes, while the Endothelial 2 subcluster expanded during remyelination ( SI Appendix , Fig. S6 E and F ). …

Mesenchymal stem cells in the treatment of osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multi-potentia

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… Some adipose tissue-derived MSCs (ASCs) expresses CD34 38 and these CD34+ASCs pericytes-like interact with endothelial cells 39 . … A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. …

Методологии изучения мозговых органоидов для изучения механизмов заболевания в прогрессивном множественном склерозе.

Множественный склероз (MS) — изнуряющее аутоиммунное расстройство, направленное против центральной нервной системы (CNS), отмечен непрерывным обезвоживанием и воспалением. В клинической форме она представляет в трех различных формах: повторные выбросы MS (RRMS), первичные прогрессивные MS (PPMS) и вторичные прогрессивные MS (SPMS). Несмотря на то, что лечение с целью изменения болезней (ДМР) оказывает определенное содействие людям, страдающим СВЗ, варианты лечения прогрессивных СЗМ (ПМС) по-прежнему являются крайне неадекватными. Этот пробел свидетельствует о настоятельной необходимости примен

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… In vivo , vascular system development relies on key transcription factors and signaling cues that facilitate the self-organization and vessel formation of ECs and perivascular cells such as pericytes ( Risau, 1997 ). … Subsequent treatment with Wnt7a has been shown to enhance the formation of pericyte-like cells around the vascular tubes, better mimicking the in vivo BBB structure. …

Targeting vascular endothelial growth receptor-2 (VEGFR-2): structural biology, functional insights, and therapeutic resistance.

Angiogenesis, the process of new blood vessel formation, is a fundamental physiological process implicated in several pathological disorders. The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are crucial for angiogenesis and vasculogenesis. Among them, the tyrosine kinase receptor VEGFR-2 is primarily expressed in endothelial cells (ECs). These cells regulate various physiological responses, including differentiation, cell proliferation, migration, and survival, by binding to VEGF mitogens. Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) is a key regulator of

Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.

Vascular endothelial growth factor (VEGF) signaling is a critical regulator of vasculogenesis, angiogenesis, and lymphangiogenesis, processes that are vital for the development of vascular and lymphatic systems, tissue repair, and the maintenance of homeostasis. VEGF ligands and their receptors orchestrate endothelial cell proliferation, migration, and survival, playing a pivotal role in dynamic vascular remodeling. Dysregulated VEGF signaling drives diverse pathological conditions, including tumor angiogenesis, cardiovascular diseases, and ocular disorders. Excessive VEGF activity promotes tu

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… VEGFR2-platelet-derived growth factor receptor β (PDGFRβ) heterodimers (Fig. 5b ) link angiogenesis to vessel maturation via pericyte recruitment, stabilizing tumor vasculature. 142 VEGFR2-epidermal growth factor receptor (EGFR) heterodimers, formed in the presence of both EGF and VEGF, offer a ligand-dependent … Fig. 8 VEGF/VEGFR signaling controls angiogenesis and vascular permeability. a Role of VEGF/VEGFR signaling pathway in angiogenesis. (1) The vascular stability of quiescent microvessels covered by pericytes and basement membrane (BM) is maintained by non-VEGF/VEGFR signaling pathways such as Ang/TIE …

Emerging Nanotherapeutic Approaches to Overcome Drug Resistance in Cancers with Update on Clinical Trials.

A key issue with modern cancer treatments is the emergence of resistance to conventional chemotherapy and molecularly targeted medicines. Cancer nanotherapeutics were created in order to overcome the inherent limitations of traditional chemotherapeutics. Over the last few decades, cancer nanotherapeutics provided unparalleled opportunities to understand and overcome drug resistance through clinical assessment of rationally designed nanoparticulate delivery systems. In this context, various design strategies such as passive targeting, active targeting, nano-drug, and multimodal nano-drug combin

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… The TME barriers’ contributions toward nanoparticles extravasation include high interstitial fluid pressure (HIFP), pericytes coverage, basement membrane, and composition of ECM. … Pericytes coverage presents another barrier for nanoparticles-mediated drug delivery. An earlier report indicated that pericytes dysfunction leads to loss of vascular coverage and plays an important role in disease progression [ 171 ]. …

Retinal Vein Occlusion-Background Knowledge and Foreground Knowledge Prospects-A Review.

Thrombosis of retinal veins is one of the most common retinal vascular diseases that may lead to vascular blindness. The latest epidemiological data leave no illusions that the burden on the healthcare system, as impacted by patients with this diagnosis, will increase worldwide. This obliges scientists to search for new therapeutic and diagnostic options. In the 21st century, there has been tremendous progress in retinal imaging techniques, which has facilitated a better understanding of the mechanisms related to the development of retinal vein occlusion (RVO) and its complications, and conseq

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… The internal blood–retinal barrier consists of endothelial cells and their intercellular junctions, pericytes, and retinal glial cells. The latter include microglia and Müller glial cells (RMG) and astrocytes. … By the end of the 20th century, the loss of pericytes (PC) was demonstrated in an experimental BRVO model in monkeys, suggesting that similar phenomena may occur in human eyes [ 49 ]. …

Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Nanotechnology-based medicinal

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… During neuroinflammation of the CNS, the brain uses microglia and pericytes as antigen-presenting cells (APCs), which often triggers neurological disorders [ 40 ]. … The BBB, acting as a barrier, forms from a tight restriction of cerebral capillary endothelium, astrocytes, pericytes, basal membranes with infrequent transcytosis, and endocytosis [ 52 ]. …