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Капиллероскопия с капиллароскопией в диабетической ретинопатии: микровирусные озарения, клиническая ценность и проблемы с переводом - обзор повествования.

Диабетическая ретинопатия (DR) является одним из основных микроваскуловых осложнений сахарного диабета и одной из основных причин предотвратимой потери зрения. В настоящее время DR рассматривается как проявление системной диабетической микроангиопатии, а не изолированного окулярного расстройства. Оценка на основе сетчатки может не в полной мере отражать системное микроваскулярное бремя, особенно в тех случаях, когда доступ к специализированной сетчатке сетчатки ограничен. Капиллероскопия с капиллярным влагом (НКЦ) позволяет напрямую и неинвазивно визуализировать периферическую капиллярную морф

VP3.15, двойной ингибитор GSK-3β/PDE7, уменьшает рост опухоли глиобластомы, изменяя микроопухоль в контексте PTEN дикой природы.

Глиобластома (ГБ) — неизлечимый рак мозга, и необходимо срочно определить эффективные методы лечения. Это может быть достигнуто либо путем идентификации новых молекул, либо путем переочистки наркотиков. Для определения терапевтического потенциала известных ингибиторов GSK-3β и/или PDE7 в GB был проведен анализ наркотиков с использованием модели глиомы Дрософила меланогастера. VP3.15, двойной ингибитор с противовоспалительными и нейрозащитными функциями при множественном склерозе, был выбран для дальнейшего изучения. VP3.15 продемонстрировал высокую антиопухоль против панели клеток человека и м

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… The analysis revealed the presence of distinct immune (macrophages, microglia and T cells), astrocytic and vascular (endothelial cells and pericytes) cell groups ( Fig. 1 a-left). … In GB, PDE7B transcription is predominantly observed in astrocytic cells (including neoplastic cells) and pericytes, whereas GSK-3β is expressed in a ubiquitous manner ( Fig. 1 a-right). …

Advanced Diagnostic Techniques

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… A, Perivascular wall tumor from the skin of a dog demonstrating a capillary vessel lumen (l) that is lined by endothelial cells (e), a pericyte (arrow), and collagen fibers (c). Neoplastic pericytes (asterisks in white) form multiple layers around the vessel. … A, Perivascular wall tumor from the skin of a dog demonstrating a capillary vessel lumen (l) that is lined by endothelial cells (e), a pericyte (arrow), and collagen fibers (c). Neoplastic pericytes (asterisks in white) form multiple layers around the vessel. …

Вирус Эпштейн-Барр и иммунная микроокружающая среда в множестве склерозов: Отличения от высокомерной съемки тканей мозга.

Вирус Эпштейн-Барр (ЭБВ) во многом связан с патогенезом множественного склероза (МС), однако его точная роль в прогрессии заболеваний остается неясной. С использованием высокомерной системы обнаружения СО путем индексации, технологии пространственной съемки, в настоящем исследовании изучается клеточная микроокружающая среда поражения MS в вторичных прогрессивных MS и первичных прогрессивных MS. Мы проанализировали взаимодействие иммунной, глиальной, нейрональной и эндотелиальной клеток в MS-повреждениях и обычно встречающейся белой материи в двух независимых группах. Наши результаты свидетельс

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… µm.) ( B ) Frequency analysis of CD31+ endothelial cells in MS lesions compared to NAWM from the same samples, with significant differences observed (mean difference = −0.9, P = 0.036). ( C – E ) Log2 odds ratio analysis showing reduced associations of Claudin-5+ endothelial cells with Vimentin+ pericytes … These included diminished interactions with Vimentin+ pericytes (log odds = −0.48, P = 0.006), Synaptophysin+ synaptic neurons (log odds = −0.49, P = 0.007), CD68+ activated macrophages (log odds = −0.39, P = 0.014) ( Fig. 6 C – E ). …

Роль ИЛ-17А в предотвращении воспламенительных реакций и прогрессии нейродегенеративных заболеваний.

IL-17A был замешан в качестве критического провоспалительного цитокина в патогенезе аутоиммунных и нейродегенеративных расстройств. Появляющиеся данные свидетельствуют о его способности активировать микроглиальные клетки и астроциты, что впоследствии приводит к созданию подстрекательских посредников, усугубляющих нейронные травмы и функциональные нарушения. Клинические наблюдения выявили продемонстрированную связь между концентрациями ИЛ-17А и дисфункцией мозгового барьера (ББД), создав патологический цикл обратной связи, усиливающий нейровоспалительные реакции. Последние достижения свидетельс

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… It should be noted that a number of cells are involved in maintaining the homeostasis of the CNS, including microglia, astrocytes, oligodendrocytes, endothelial cells, and pericytes [ 30 ]. … The BBB, composed of endothelial cells (ECs), pericytes, and astrocytes, interacts with Th17 cells and their products. While astrocytes respond to IL-17A, their role in BBB function remains unclear [ 87 ]. ECs exhibit low baseline IL-17RA expression, which increases in active MS lesions [ 88 ]. …

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

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… Alongside endothelial cells, pericytes, and astrocytic endfeet, they constitute a vital component of the neurovascular unit. … It is constituted by brain microvascular endothelial cells, pericytes, astrocytic endfeet, and the surrounding basement membrane. …

Bispecific and multispecific immune engagers for redirecting innate and adaptive immunity against hematologic cancers.

Bispecific antibodies (BsAbs) and multispecific antibodies (MsAbs) represent a transformative class of immunotherapeutics in oncology. These engineered molecules possess the unique ability to simultaneously target two or more distinct antigens, thereby facilitating precise immune cell engagement and disrupting multiple signaling pathways. This comprehensive review focuses on their pivotal role in redirecting both innate (natural killer cells, phagocytes) and adaptive (T cells) immunity, with a particular emphasis on their application against hematologic cancers. Significant clinical successes,

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… The higher incidence of ICANS with CD19xCD3 bispecific antibodies is potentially linked to on-target off-tumor toxicity from CD19 expression on pericytes and vascular smooth muscles lining the blood-brain barrier [ 9 , 74 ]. … A notable example is the neurotoxicity observed with CD19xCD3 bispecific antibodies, which is thought to be partly due to CD19 expression on pericytes and vascular smooth muscles lining the blood-brain barrier [ 9 , 94 ]. …

Abnormalities in alternative splicing of angiogenesis-related genes and their role in HIV-related cancers.

Alternative splicing of mRNA leads to an increase in proteome biodiversity by allowing the generation of multiple mRNAs, coding for multiple protein isoforms of various structural and functional properties from a single primary pre-mRNA transcript. The protein isoforms produced are tightly regulated in normal development but are mostly deregulated in various cancers. In HIV-infected individuals with AIDS, there is an increase in aberrant alternative splicing, resulting in an increase in HIV/AIDS-related cancers, such as Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer. This aberra

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… Stage 6: Endothelial cells of the new capillaries produce alternatively spliced isoforms of platelet-derived growth factor (PDGF) and recruit pericytes which in turn stabilize the new blood vessels. 145 Abbreviation: VEGF, vascular endothelial growth factor. … This leads to the maturation of mesenchymal cells into pericytes, Ang-1 then binds to Tie-2 and promotes the attachment of these pericytes to form mature, “nonleaky” blood vessels. 57 Ang-2 acts as a pro-angiogenic factor by blocking the vessel stabilizing action of angiopoietin-1 promoting endothelial …

Novel therapeutic approaches for pulmonary fibrosis.

Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of functional alveolar units and in many cases, respiratory failure. While a small number of interstitial lung diseases have known aetiologies, most are idiopathic in nature, and of these, idiopathic pulmonary fibrosis is the most common and carries with it an appalling prognosis - med

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… Finally, myofibroblasts can also be derived from pericytes. In the liver, pericytes, or hepatic stellate cells, are the principal collagen-producing cell in hepatic fibrosis [reviewed in ( Gressner and Weiskirchen, 2006 )]. … In animal studies of skin and kidney fibrosis ( Humphreys et al ., 2010 ; Liu et al ., 2010b ), pericytes have also been shown to represent a source of myofibroblasts. …

Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies.

Nowadays, chimeric antigen receptor (CAR) -T cell therapy has shown significant efficacy in treating hematological tumors, with an obvious increase in patient survival rates. However, with the widespread application of CAR-T, the incidence of CAR-T related adverse events has gradually increased, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and hemophagocytic lymphohistiocytosis (HLH). These complications may be life-threatening, so early diagnosis and intervention treatment are crucial for the prognosis of patients. In this review,

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… Other components of BBB, especially astrocytes and pericytes exacerbate inflammation and further damage the integrity of BBB when they expose to harmful cytokines [ 85 ]. … CD19 is also expressed on the pericytes of the brain, indicating that targeting CD19 by CAR-T cells may also be a contributing factor in the pathophysiology of ICANS [ 28 ]. …

Anticancer Role of PPARgamma Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes.

The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-gamma agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARgamma agonists in the treatment and prevention of

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… Host ECs, pericytes, macrophages, dendritic cells, lymphocytes, adipocytes, and fibroblasts/myofibroblasts present in the tumor microenvironment participate in the metastatic process ( Figure 2 ). … PPAR γ agonists, troglitazone, rosiglitazone, Pioglitazone, RWJ241947, and 15d-PGJ 2 , inhibit proliferation of human REC and pericytes in vitro through a PPAR γ -independent pathway [ 316 ]. …

Derivation and Characterization of Endothelial Cells from Porcine Induced Pluripotent Stem Cells.

Although the study on the regulatory mechanism of endothelial differentiation from the perspective of development provides references for endothelial cell (EC) derivation from pluripotent stem cells, incomplete reprogramming and donor-specific epigenetic memory are still thought to be the obstacles of iPSCs for clinical application. Thus, it is necessary to establish a stable iPSC-EC induction system and investigate the regulatory mechanism of endothelial differentiation. Based on a single-layer culture system, we successfully obtained ECs from porcine iPSCs (piPSCs). In vitro, the derived piP

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… Generation, expansion and functional analysis of endothelial cells and pericytes derived from human pluripotent stem cells Nat. Protoc. 2014 9 1514 1531 10.1038/nprot.2014.102 24874816 18. Lu T.-Y. Lin B. Kim J. Sullivan M. Tobita K. Salama G. Yang L. … Pericytes: Developmental, physiological, and pathological perspectives, problems, and promises Dev. Cell 2011 21 193 215 10.1016/j.devcel.2011.07.001 21839917 35. Watabe T. Nishihara A. Mishima K. Yamashita J. Shimizu K. Miyazawa K. Nishikawa S. Miyazono K. …

Proceedings of International Conference on Cell Death in Cancer and Toxicology. February 20-22, 2018. Guest Editors: Kausar M. Ansari, CSIR-IITR, India and Dhyan Chandra, Roswell Park, USA.

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Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment.

The concept of cancer as a systemic disease, and the therapeutic implications of this, has gained special relevance. This concept encompasses the interactions between tumor and stromal cells and their microenvironment in the complex setting of primary tumors and metastases. These factors determine cellular co-evolution in time and space, contribute to tumor progression, and could counteract therapeutic effects. Additionally, cancer therapies can induce cellular and molecular responses in the tumor and host that allow them to escape therapy and promote tumor progression. In this study, we descr

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… CSCs may contribute to blood vessel formation by transdifferentiation into endothelial cells or pericytes [ 60 ]. … The emerging roles of pericytes in modulating tumor microenvironment Front. Cell Dev. Biol. 2021 9 676342 10.3389/fcell.2021.676342 34179005 PMC8232225 72. Aderetti D.A. Hira V.V.V. Molenaar R.J. van Noorden C.J.F. …

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

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… astrocytes release healthy mitochondria encapsulated by EVs via CD38-mediated mechanism to deliver them to hypoxic neurons and support neuronal mitochondrial metabolism and survival. 34 , 35 A recent study reveals that astrocyte-derived EVs transfer mitochondria to brain microvascular endothelial cells and pericytes … The most prominent labeling was observed in endothelial cells and pericytes, with additional localization in brain macrophages, astrocytes, and oligodendrocytes, both at the transplantation site and in distal regions. 84 However, no evidence of colocalization was detected within neurons. 84 …

The Endosteal Niche in Breast Cancer Bone Metastasis.

The establishment of bone metastasis remains one of the most frequent complications of patients suffering from advanced breast cancer. Patients with bone metastases experience high morbidity and mortality caused by excessive, tumor-induced and osteoclast-mediated bone resorption. Anti-resorptive treatments, such as bisphosphonates, are available to ease skeletal related events including pain, increased fracture risk, and hypercalcemia. However, the disease remains incurable and 5-year survival rates for these patients are below 25%. Within the bone, disseminated breast cancer cells localize in

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… The vascular niche consists of endothelial cells, closely located pericytes and smooth muscle cells. The vascular niche is important for stem and progenitor cell function. Through secretion of angiocrine growth factors, the vascular niche recruits endothelial progenitors, MSCs and HSCs ( 16 , 17 ). … Within bone, the metastatic niche is thought to be comprised of a hematopoietic stem cell niche (HSCs), endosteal (osteoclasts (OC), osteoblasts (OB), osteocytes (OCY), fibroblasts), and vascular niche (endothelial cells, pericytes). …

CAR-Engineered Cell Therapies Beyond Cancer: Reprogramming Fibrosis and Immune-Mediated Inflammation.

Chimeric antigen receptor (CAR)-engineered cell therapies are being extended from hematological malignancies to autoimmune, inflammatory, and fibrotic diseases, although the maturity of evidence differs markedly among platforms and indications. Early clinical evidence from case reports, small case series, and early-phase trials suggests that CD19- or BCMA-directed CAR-T cells can induce deep B-cell or plasma-cell depletion and sustained remission in selected patients with refractory autoimmune diseases; however, their comparative efficacy, durability, and long-term safety remain incompletely d

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… , myofibroblasts, and related populations | CAR‐T | Renal fibrosis / CKD | Preclinical | Pericyte‐ and vasculature‐related safety requires careful evaluation TNC | Pathological ECM component / fibrotic matrix | CAR‐M | Liver fibrosis and related conditions | Preclinical | Represents an ECM‐targeting … The broader stromal distribution of PDGFRβ may enhance therapeutic coverage, but it also increases the need to assess potential on‐target effects on normal mesangial cells, pericytes, and other perivascular stromal populations. …

Advanced Diagnostic Techniques

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… A, Perivascular wall tumor from the skin of a dog demonstrating a capillary vessel lumen ( l ) that is lined by endothelial cells, a pericyte ( arrow ), and collagen fibers ( c ). Neoplastic pericytes ( asterisks ) form multiple layers around the vessel. … Also present are red blood cells ( r ), extracellular matrix ( m ), and pericytes ( arrows ). • For certain lesions (e.g., glomerular disease), it is still the gold standard method ( Fig. 17-9 ). Figure 17-9 A–D, Ultrastructure of normal kidney and glomerular disease. …

Устранение неврологических расстройств путем борьбы с нейродегенеративными ассоциированными ферментами: естественные и синтетические молекулы.

Неврологические расстройства, включая нейродегенеративные и нейро-воспалительные заболевания, создают значительные проблемы в области здравоохранения и клинических проблем. Недавние исследования показали, что различные ферменты играют ключевую роль в наступлении и развитии этих расстройств. В этом обзоре изучается терапевтический потенциал адресации этих ферментов естественными и синтетическими молекулами. К таким заболеваниям, как болезнь Альцгеймера, болезнь Паркинсона и множественный склероз, причастны основные ферменты, включая ацетилхолинестеразу, оксидазу моноамина, бета-секретазу, тау к

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… Many components comprise the blood–brain barrier (BBB), such as close interactions between extracellular matrix proteins, endothelial cells, pericytes, astrocyte endfeet, microglia, interneurons, and basement membranes. … Several extracellular matrix (ECM) proteins (e.g., heparan sulfate proteoglycans, laminin, and type IV collagen) are located in the basement membrane, which is the membrane that surrounds endothelial cells and pericytes [ 317 , 318 ]. 4. …

The neurotoxic legacy of CAR-T cells: where do we stand?

Chimeric antigen receptor T (CAR-T) cell therapy has transformed outcomes for relapsed/refractory B-cell malignancies and is increasingly reshaping the therapeutic landscape of autoimmune disorders and solid tumors, offering curative potential where options were previously limited. Its broader deployment is, however, constrained by immune-mediated toxicities, chiefly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS spans a heterogeneous spectrum from mild aphasia and tremor to seizures, cerebral edema, coma, and death, and remains diffic

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… roles. 25 Astrocytes and microglia, once activated, may sustain neuroinflammation through glutamate release and excitotoxicity, as evidenced by increased CSF glutamate and quinolinic acid early during ICANS. 14 A landmark study identified CD19 molecules expressed in human brain mural cells, including pericytes … CD19 expression on mural cells (pericytes and vascular smooth muscle cells) provides a potential on-target substrate for CAR-T cell-mediated injury, further contributing to BBB disruption. Trafficking of CAR-T cells into CSF can occur, but is not required for neurotoxicity. …