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Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus.

Angiogenesis is the biological process by which new blood vessels are formed from pre-existing vessels. It is considered one of the classic hallmarks of cancer, as pathological angiogenesis provides oxygen and essential nutrients to growing tumors. Two of the seven known human oncoviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), belong to the Gammaherpesvirinae subfamily. Both viruses are associated with several malignancies including lymphomas, nasopharyngeal carcinomas, and Kaposi's sarcoma. The viral genomes code for a plethora of viral factors, includin

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… Following the formation of the new blood vessel, pericytes are recruited and attached to newly matured endothelial cells ( Weis and Cheresh, 2011 ). … Matrix metalloproteinase enzymes (MMPs) are a group of zinc-containing endopeptidases capable of degrading ECM components and mediating pericyte detachment from vessels undergoing angiogenesis ( Rundhaug, 2005 ). …

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brai

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… The impact of pericytes on the blood-brain barrier integrity depends critically on the pericyte differentiation stage . Int J Biochem Cell Biol ( 2011 ) 43 ( 9 ): 1284–93 . doi: 10.1016/j.biocel.2011.05.002 21601005 32 Klein A Schwartz H Sagi-Assif O Meshel T Izraely S Ben Menachem S . …

Endothelial TFEB signaling-mediated autophagic disturbance initiates microglial activation and cognitive dysfunction.

Cognitive impairment caused by systemic chemotherapy is a critical question that perplexes the effective implementation of clinical treatment, but related molecular events are poorly understood. Herein, we show that bortezomib exposure leads to microglia activation and cognitive impairment, this occurs along with decreased nuclear translocation of TFEB (transcription factor EB), which is linked to macroautophagy/autophagy disorder, STAT3 (signal transducer and activator of transcription 3) phosphorylation and IL23A (interleukin 23 subunit alpha) expression. Pharmacological enhancement of TFEB

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… The BBB forms a tightly regulated neurovascular unit that is constructed of endothelial cells, pericytes, astrocytes and neurons and protects against circulating toxins or drugs entering the brain and maintains homeostasis [ 5 ]. … Nitration of TRPM2 as a molecular switch induces autophagy during brain pericyte injury . Antioxid Redox Signal . 2017 ; 27 ( 16 ): 1297 – 1316 . 28292196 10.1089/ars.2016.6873 [48] Liu Y , Xue X , Zhang H , et al . …

Chronic Kidney Disease: Strategies to Retard Progression.

Chronic kidney disease (CKD), defined as the presence of irreversible structural or functional kidney damages, increases the risk of poor outcomes due to its association with multiple complications, including altered mineral metabolism, anemia, metabolic acidosis, and increased cardiovascular events. The mainstay of treatments for CKD lies in the prevention of the development and progression of CKD as well as its complications. Due to the heterogeneous origins and the uncertainty in the pathogenesis of CKD, efficacious therapies for CKD remain challenging. In this review, we focus on the follo

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… The origin of myofibroblasts in the kidney remains uncertain, but several candidates have been suggested, including resident fibroblasts, bone marrow-derived fibroblasts, or transition from pericytes or endothelial cells [ 15 ]. … Gli1 + Pericyte Loss Induces Capillary Rare-faction and Proximal Tubular Injury. J. Am. Soc. Nephrol. 2017;28:776–784. doi: 10.1681/ASN.2016030297. 42. Sato Y., Yanagita M. Immune cells and inflammation in AKI to CKD progression. Am. J. Physiol. …

Zebrafish Avatars towards Personalized Medicine-A Comparative Review between Avatar Models.

Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored according to average response rates. "Omics" approaches are used for patient stratification and choice of therapeutic options towards a more precise medicine. These methods, however, do not consider all genetic and non-genetic dynamic interactions that occur upon drug treatment. Therefore, the need to dir

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… Moreover, tumor cells are not alone: the tumor ecosystem is comprised by a complex network of fibroblasts, adipocytes, endothelial cells, pericytes, and a variety of immune cells embedded in the ECM [ 1 ]. … These include endothelial cells to reconstruct blood and lymphatic systems, pericytes that cover endothelial cells, tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs) and other immune cells that constitute the complex TME [ 1 , 53 , 54 ]. …

The Mediterranean Diet, a Rich Source of Angiopreventive Compounds in Cancer.

Diet-based chemoprevention of cancer has emerged as an interesting approach to evade the disease or even target its early phases, reducing its incidence or slowing down tumor progression. In its basis in the essential role of angiogenesis for tumor growth and metastasis, angioprevention proposes the use of inhibitors of angiogenesis in cancer prevention. The anti-angiogenic potential exhibited by many natural compounds contained in many Mediterranean diet constituents makes this dietary pattern especially interesting as a source of chemopreventive agents, defined within the angioprevention str

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… Thereafter, the degradation of the capillary wall by extracellular proteinases occurs, followed by migration of endothelial cells, formation of new capillaries, and finally, the interconnection of the new vessels (anastomosis) and their stabilization by recruitment of pericytes [ 2 ]. … The newly-formed vasculature is aberrant, with altered interactions between endothelial cells and pericytes, abnormal blood flow, and increased permeability—all due to a chaotic and poorly-regulated expression of pro- and antiangiogenic factors. …

Cabozantinib Cutaneous Toxicity-Comprehensive Review.

BackgroundIn the context of modern cancer therapy, the management of adverse effects of systemic therapies can lead to the avoidance of underdosing and withdrawal and increases in the quality of the therapeutic act and the quality of life. This review offers an overview of the skin-related toxicities associated with Cabozantinib, a multikinase inhibitor (MKI) that is approved for treating advanced kidney cancer, hepatocellular carcinoma, and medullary thyroid cancer. It covers the most common dermatological side effects, such as palmar-plantar erythrodysesthesia, stomatitis, hair alterations,

Therapeutic potential of single-nucleotide polymorphism-mediated IL6R inhibitors in ankylosing spondylitis treatment.

OBJECTIVE: Interleukin-6 (IL-6) is a multiple-effect cell factor implicated in the etiopathogenesis of several rheumatologic disorders. The blockade of the IL-6 pathway via IL6R inhibitors effectively treats these disorders. However, the clinical significance of the IL6R blockade for ankylosing spondylitis (AS) therapy remains controversial. With advances in genomics, increasing evidence has revealed the role of heritability in the etiology of disease, and Mendelian randomization (MR) analyses are being used more broadly to infer causation. Therefore, this MR study aims to evaluate the potenti

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… Moreover, Wang et al. found that Th1/Th2 ratios were increased significantly in the mild and severe AS groups when compared with normal controls by obtaining pericytes from lesions and sera of 55 patients with AS and that imbalance of these T-cell subpopulations may lead to enhanced IFN-γ and thus promote …

Получил от "Puff of Domoke"-A Case-Review on the Challenging Discrimination of CNS Demielining Beace and Moyamoya Angiopatia.

Moyamoya aнгиопатия (MMA) — цереброваскулярное заболевание, определяющее хроническое прогрессивное включение надклиноидных внутренних артерий сонной артерии и их основных веток. Патогенез ММА по-прежнему в значительной степени неизвестен. Множественный склероз (MS) является хроническим, подстрекательским и демиелинизирующим заболеванием центральной нервной системы, характеризующимся постепенным накоплением фокусных демиелионирующих повреждений, патофизиология которых была теоретической, но до сих пор не до конца понята. Помимо неправильной диагностики из-за имитирующих эти два расстройства осо

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… In MS, many histopathological reports have highlighted the presence of damaged blood vessels due to loss of endothelial cell tight junctions and pericytes, detachment and consequent activation of astrocytes, and vessel disruption that is operated by oligodendrocytes progenitor cells (OPCs). …

Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

ObjectiveTo evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL).MethodologyForty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of bloo

Editorial: The Role of Complement in Health and Disease.

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… Castellano et al. showed a mechanism by which ischemia-reperfusion induces trans-differentiation from pericytes to myofibroblasts by regulating the peritubular capillary lumen through pERK signaling. …

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

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… ultra-high-risk NB subgroup with a survival rate below 15%. 73 Cells in the NB-TME can be divided into immune, including tumor-associated macrophages (TAMs), dendritic cells, natural killer (NK), natural killer T (NKT) cells, B and T lymphocytes, and non-immune cells comprising endothelial cells, pericytes … This figure represents the complex interplay of the heterogenous cellular and molecular components within the NB tumor microenvironment: tumor cells, stromal cells (pericytes, tumor-associated fibroblasts, endothelial and mesenchymal stromal cells), immune cells (tumor-associated macrophages, dendritic …

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies.

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival

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… Identification of O-GlcNAc modification targets in mouse retinal pericytes: Implication of p53 in pathogenesis of diabetic retinopathy PLoS ONE 2014 9 e95561 10.1371/journal.pone.0095561 24788674 PMC4006792 52. Zeng J. Zhao H. Chen B. … DJ-1/PARK7 inhibits high glucose-induced oxidative stress to prevent retinal pericyte apoptosis via the PI3K/AKT/mTOR signaling pathway Exp. Eye Res. 2019 189 107830 10.1016/j.exer.2019.107830 31593688 53. Li R. Li H. Zhang Q. …

Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑

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… RT can induce pericyte senescence and promote the secretion of senescence-associated secretory phenotype factors, including IL-6, TNF-α, IL-1β and CCL2, which can disrupt blood-brain barrier (BBB) integrity and impair endothelial tight junctions in vitro ( 168 ). … Dasatinib plus quercetin and all-trans retinoic acid can selectively eliminate senescent pericytes and reduce senescence-associated secretory phenotype secretion, thereby improving BBB integrity and cognitive function ( 176 - 178 ). …

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies.

Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T cell therapies are complex and can be challenging to diagnose and treat. In this review, we summarize the major adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR T-cell associated HLH (carHLH), and discuss their pathophysiology, symptoms, grading, and diagnosis systems, as well as management. In a future outlook, we also provide an overview of

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… Other cells involved in ICANS include brain pericytes, which produce IL-6 and VEGF in response to TNF-α and IFN-γ and further amplify endothelial activation and BBB permeability [ 89 , 93 ]. … Jansson D Rustenhoven J Feng S A role for human brain pericytes in neuroinflammation J Neuroinflammation 2014 11 104 10.1186/1742-2094-11-104 24920309 PMC4105169 94. …

Time to evolve: predicting engineered T cell-associated toxicity with next-generation models.

Despite promising clinical results in a small subset of malignancies, therapies based on engineered chimeric antigen receptor and T-cell receptor T cells are associated with serious adverse events, including cytokine release syndrome and neurotoxicity. These toxicities are sometimes so severe that they significantly hinder the implementation of this therapeutic strategy. For a long time, existing preclinical models failed to predict severe toxicities seen in human clinical trials after engineered T-cell infusion. However, in recent years, there has been a concerted effort to develop models, in

Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures.

Chemotherapy and targeted therapy have opened new avenues in clinical oncology. However, there is a lack of response in a substantial percentage of cancer patients and diseases frequently relapse in those who even initially respond. Resistance is, at present, the major barrier to conquering cancer, the most lethal age-related pathology. Identification of mechanisms underlying resistance and development of effective strategies to circumvent treatment pitfalls thereby improving clinical outcomes remain overarching tasks for scientists and clinicians. Growing bodies of data indicate that stromal

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… however, transformed tumor cells initiate significant changes that can convert the adjacent microenvironment into a TME that supports pathological progression. 21 In solid tumors, the TME is composed of ECM, carcinoma-associated fibroblasts (CAFs), immune and inflammatory cells, neuroendocrine cells, pericytes … inflammation, and enhance angiogenesis, thereby providing a favorable niche for the development of treatment-resistant tumors. 34 It is not surprising that increased CAF secretion of multiple soluble factors in primary tumors closely correlates with poor prognosis in clinical oncology. 35 Endothelial cells, pericytes …

Ускоренная клеточная сенсация в прогрессивном многоразовом склерозе: гистопатологическое исследование.

ЦЕЛЬ: Неверодегенеративные процессы, приводящие к росту инвалидности при прогрессивном множественном склерозе (P-MS), не были в полной мере разъяснены. Последние данные увязывают клеточную сенсацию (CS) с нейродегенерацией. Мы расследовали доказательства CS в P-MS и пытались определить их структуру. Мы использовали 53BP1, p16 и липофускин в качестве маркеров CS при повреждениях белого материала (WML), обычном виде белого вещества (NAWM), обычном виде кортикального серого вещества (NAGM), контроле белого вещества (CWM) и контроле серого вещества (CGM) при вскрытии материала пациента с P-MS и зд

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… changes in gene expression, and other phenotypic changes that accompany cellular senescence constitute serious restrictions in the functionality of neurons and glia. 13 Cellular senescence has been shown to affect neurons, microglia, astrocytes, oligodendrocytes, oligodendrocyte progenitor cells, pericytes …

CXCL13 Повреждает позвоночник крови, поощряя RNF6/Sqstm1-Ubictiination.

Повреждение позвоночника крови (BSCB) приводит к нарушению иммунной микроокружающей среды в центральной нервной системе во время развития множественного склероза (MS) и экспериментального аллергического энцефаломиэлита (EAE). Тем не менее основные механизмы, связанные с повреждением барьера, по-прежнему недостаточно изучены. Здесь, анализируя белковые профили в периферической сыворотке крови, хемокин (C-X-C motif) Ligand 13 (CXCL13) был определен как возрастающий по мере развития MS и EAE. Отсутствие CXCL13 привело к снижению симптомов EAE, о чем свидетельствует сокращение числа клинических оц

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… of disease progression such as demyelination, axonal injury, and neuronal degeneration. [ 5 ] These selective barriers between the blood system and the central nervous system are composed of continuous microvascular endothelial cells and tight junctions between cells, intact basal membrane, pericytes …

Сфингосин 1-phosphate рецептор 1 Модераторы оказывают нейрозащитное воздействие на нарушения центральной нервной системы.

Фингозин 1-phosphate (S1P) Пути подачи сигналов имеют важные и разнообразные функции. Рецепторы S1P (S1PR) участвуют в регулировании торговли лимфоцитами, сердечно-церебральной функции, сосудистой проницаемости и бронхиолярного тона и были признаны в качестве терапевтических целей для различных заболеваний. Ряд лекарственных средств, связанных с траекторией подачи сигналов S1P, был утвержден для клинического использования при лечении множественных склерозов, и многие аналогичные препараты в настоящее время также проходят испытания в ходе клинических испытаний на различных этапах. Как представл

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… The blood-brain barrier (BBB), which consists of endothelial cells, pericytes, astrocytes, and microglia, protects the CNS from harmful circulating substances ( Benz and Liebner, 2022 ). …