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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

Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions.

The tumor microenvironment (TME) is a complex system composed of multiple cells, such as non-cancerous fibroblasts, adipocytes, immune and vascular cells, as well as signal molecules and mediators. Tumor cells recruit and reprogram other cells to produce factors that maintain tumor growth. Communication between cancerous and surrounding cells is a two-way process and engages a diverse range of mechanisms that, in consequence, can lead to rapid proliferation, metastasis, and drug resistance, or can serve as a tumors-suppressor, e.g., through tumor-immune cell interaction. Cross-talk within the

Несапонин из Панакс Гинсенг поддерживает целостность мозгового барьера, подавляя NF-ИБ и p38 MAP cinase сигнализирующих путей для предотвращения развития экспериментального аутоиммунного энцефаломиэлита.

НЕСАпонинская (NS) фракция является важным активным компонентом Панакс Гинсенга, имеющей многофункциональную фармакологическую деятельность, включая нейрозащиту, иммунную регламентацию, противовоспалительные и антиоксидантные эффекты. Однако воздействие НС на множественный склероз (МС) - хроническое и аутоиммунное демиелионирующее расстройство - пока еще не доказано. Цель настоящего исследования состояла в том, чтобы продемонстрировать фармакологические действия НСУ по дисфункциям движения и соответствующие механизмы действий с использованием экспериментальной аутоиммунной энцефаломиелитной мо

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… ANOVA, Analysis of variance; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; ICAM-1, Intercellular adhesion molecule-1; LPS, Lipopolysaccharide; ns, non-significant; NS, Non-saponin; VCAM-1, Vascular cell adhesion molecule-1. … ANOVA, Analysis of variance; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; ICAM-1, Intercellular adhesion molecule-1; LPS, Lipopolysaccharide; ns, non-significant; NS, Non-saponin; VCAM-1, Vascular cell adhesion molecule-1. …

Endotheliopathy in CAR T-Cell Therapy: Mechanistic Insights into the VWF/ADAMTS13 Axis and the Angiopoietin-Tie2 Pathway.

Chimeric antigen receptor (CAR) T cell therapy has transformed the management of hematologic malignancies, yet its clinical success is tempered by severe immune-mediated toxicities, including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), often accompanied by CAR T cell therapy-related coagulopathy (CARAC). Converging evidence identifies therapy-related endotheliopathy as a central pathophysiological link between cytokine excess, hemostatic dysregulation, capillary leak, and organ injury. Parallel efforts aim to identify circulating biomarke

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… adhesion molecule-1 (ICAM-1), thereby limiting leukocyte recruitment and platelet adhesion, while PGI 2 restrains platelet activation and leukocyte extravasation. … Ang, angiopoietin; NF-κB, Nuclear factor-κB; ICAM-1, intercellular adhesion molecule-1; PI3K-AKT, phosphoinositide-3-kinase-protein kinase (PI3K-AKT) pathway; VCAM-1, vascular cell adhesion molecule 1; VWF, von Willebrand factor. …

Сопротивление лекарствам в Множественной миеломе: опухоль-интринтические механизмы и микроокружающая среда костного мозга.

Множественная миелома (ММ) — злокачественное расстройство плазменных клеток, и, несмотря на значительные улучшения в прогнозе, полученные благодаря химиотерапии, иммунной терапии и автологической трансплантации стволовых клеток, у большинства пациентов в конечном счете возникает рецидив или рефракторное заболевание. Сопротивление лекарствам (DR) все чаще признается как динамическо развивающаяся экосистема, формируемая из опухоли-интенсивной пластичности и непрерывной реконструкцией микроокружающей среды костного мозга (BMME), а не как одно молекулярное повреждение. В настоящем обзоре резюмирую

Tumor buster - where will the CAR-T cell therapy 'missile' go?

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME

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… EGFR: epidermal growth factor receptor; GD2: ganglioside2; MUC1: mucin 1; NKG2DL: natural killer group 2 member D ligand; HER2: human epidermal growth factor receptor 2; HNSCC: head and neck squamous cell carcinoma; TC: thyroid cancer; ICAM-1: intercellular adhesion molecule-1; LCa: lung cancer; PD-L1 … EGFR: epidermal growth factor receptor; GD2: ganglioside2; MUC1: mucin 1; NKG2DL: natural killer group 2 member D ligand; HER2: human epidermal growth factor receptor 2; HNSCC: head and neck squamous cell carcinoma; TC: thyroid cancer; ICAM-1: intercellular adhesion molecule-1; LCa: lung cancer; PD-L1 …

Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment.

Systemic sclerosis (SSc, scleroderma) is a severe disease characterized by peripheral microcirculation abnormalities manifesting with Raynaud's phenomenon, nailfold videocapillaroscopic (NVC) changes, and even ischemic digital ulcers (DUs) that are often refractory to treatments. In the wake of previously described associations between the circulating levels of soluble junctional adhesion molecules (sJAMs) and SSc clinical features, here, we measured sJAM-A and sJAM-C levels by enzyme-linked immunosorbent assay in serum samples from a large case series of 110 SSc patients and 85 healthy contro

Механистические знания о перекрестке нейроглии в нейродегенеративных заболеваниях.

Нейродегенеративные заболевания, такие, как болезнь Альцгеймера (AD), болезнь Паркинсона (PD), Множественный Склероз (MS) и болезнь Хантингтона (HD), хотя и отличаются по своим клиническим проявлениям, имеют общую отличительную черту: нарушенная нейро-воспалительная среда, вызванная дисрегулированием нейроглиальной межклеточной связи. Нейроглиальный перекресток физиологически обеспечивается внеклеточными посредниками и деятельностью коннексинов (Cxs), формирующими белки пятен соединений пятен (Gjs) и гемиханнелей (HC), которые поддерживают внутриклеточный и внеклеточный гомеостаз. Однако накоп

Pemphigus vulgaris.

Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can

Roles of Microvesicles in Tumor Progression and Clinical Applications.

Microvesicles are extracellular vesicles with diameter ranging from 100 to 1000 nm that are secreted by tumor cells or other cells in the tumor microenvironment. A growing number of studies demonstrate that tumor-derived microvesicles are involved in tumor initiation and progression, as well as drug resistance. In addition, tumor-derived microvesicles carry a variety of immunogenic molecules and inhibit tumor response to immunotherapy; therefore, they can be exploited for use in tumor vaccines. Moreover, because of their high stability, tumor-derived microvesicles extracted from body fluids ca

Current progress and mechanisms of bone metastasis in lung cancer: a narrative review.

Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and

Генетическое или терапевтическое нарушение траектории подачи сигналов Reelin/Apoer2 улучшает воспалительные результаты артрита.

Ремутатоидный артрит (RA) — хроническое аутоиммунное заболевание, характеризующееся синновальным воспалением, образованием паннуса и постепенным совместным разрушением. Вспыльчивая среда в RA приводит к активации эндотелиальных клеток и к повышению регулирования молекул сцепления, что облегчает проникновение лейкоцитов в синовый. Релин, циркулирующий гликопротеин, ранее связанный с активацией эндотели и вербовкой лейкоцитов для лечения таких заболеваний, как атеросклероз и множественный склероз, стал потенциальным регулятором этих процессов. Однако его роль в патогенезе РА остается слабой. Зде

Exosomes and organ-specific metastasis.

The transmission of information between tumor cells and other cell types in the tumor microenvironment plays an important role in tumor metastasis and is critically modulated by exosomes and other mediators. Tumor-derived exosomes can promote epithelial-mesenchymal transition, angiogenesis, immune escape, formation of the pre-metastatic microenvironment, and transmission of drug-resistant molecules, thereby promoting tumor growth, invasion, and metastasis. Integrins are important regulatory molecules on exosomes that can locate metastatic cells at the initial stage of metastasis and show good

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… The group of adhesive molecules include ICAM-1 (CD54 – intercellular adhesion molecule-1), ICAM-2 (CD102), VCAM-1 (CD106 – vascular cell adhesion molecule) and PECAM-1 (CD31 – platelet-endothelial cell adhesion molecule). …

Протеиновый профиль множественных миеломных экстраклелярных везиков для открытия биомаркеров, связанных с новелом миеломой.

Несмотря на терапевтические достижения, множественная миелома (ММ) по-прежнему характеризуется продвижением и рецидивом, что подчеркивает необходимость надежных биомаркеров для раннего обнаружения и мониторинга. Внешнеклеточные везикулы (ЭМ) представляют собой клеточные, липидные двуслойные частицы, которые способствуют межклеточному общению и циркулируют в жидкостях тела, что делает их перспективными биомаркерами. В этом исследовании проводится сопоставление протеома ЭМ, полученного с помощью ММ, с материнскими клетками и оценивается, является ли ЭМ высшим источником биомаркеров с учетом ММ.

Bench-to-bedside review: Angiopoietin signalling in critical illness - a future target?

Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and - despite many unanswered questions - therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting mu

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… Tie2 activation also inhibits the NF-κB-dependent expression of inflammatory genes, such as those encoding luminal adhesion molecules (for example, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin). … Tie2 activation also inhibits the NF-κB-dependent expression of inflammatory genes, such as those encoding luminal adhesion molecules (for example, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin). …

Нацеливаюсь на иммунологический синапс в нескольких миэломах.

Иммунологический синапс, высокоорганизованный соединитель клеток, является важной основой для эффективного убийства раковых клеток с помощью Т. Однако в миеломе терапевтическое сопротивление отражает множество взаимодействующих слоев, включая синаптическое нарушение, клональную эволюцию, метаболическую перепрограммирование и пространственные неоднородные ниши костного мозга, которые могут способствовать дисфункции Т-клеток и иммунной отток. В этом обзоре иммунологический синапс в качестве потенциально изменяемого межклеточного интерфейса: мы описываем, как ниша костного мозга влияет на синапти

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… Adhesion molecules provide the mechanical and spatial scaffolding for synapse assembly: high-affinity lymphocyte function-associated antigen-1 (LFA-1) binding to intercellular adhesion molecule-1 (ICAM-1) stabilizes close membrane apposition, supports centripetal actin flows that consolidate signaling … Abbreviations B-cell maturation antigen Bispecific T-cell engager Chimeric antigen receptor Chimeric antigen receptor T cell(s) Central supramolecular activation cluster Distal supramolecular activation cluster Dominant-negative transforming growth factor-β receptor Intercellular adhesion molecule …

Multifunctionality of Calebin A in inflammation, chronic diseases and cancer.

Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge worldwide, because of their complexity and many inflammatory pathways such as JNK, p38/MAPK, MEK/ERK, JAK/STAT3, PI3K and NF-κB among others being implicated in their pathogenesis. Together with the versatility of chronic disease classical mono-target therapies are often insufficient. Therefore, the anti-inflammatory as well as anti-cancer capacities of polyphenols are currently investigated to complement and improve the effect of

The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.

PurposeIn 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121-167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.MethodsA literature search mainly focusing on the role of the glycocalyx in the

Effects of human umbilical cord mesenchymal stem cells derived from exosomes on migration ability of endometrial glandular epithelial cells.

The present study aimed to investigate the effects of human umbilical cord mesenchymal stem cells (Huc‑MSCs)‑derived exosomes on the migratory abilities of endometrial glandular epithelial cells, and to evaluate the underlying mechanism from the perspective of epithelial‑mesenchymal transition (EMT). Huc‑MSCs were prepared from human umbilical cord, and eutopic endometrial glandular epithelial cells were isolated from patients with endometriosis. The exosomes derived from Huc‑MSCs (Huc‑MSCs‑exo) were prepared using an exosome extraction kit. The endometrial glandular epithelial cells were rand

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… MSCs can migrate from the original tissue to the site of pathophysiological changes in response to inducing factors, such as intercellular adhesion molecule-1 ( 7 ). Human umbilical cord MSCs (Huc-MSCs) are active throughout pregnancy. … Intercellular adhesion molecule-1 enhances the therapeutic effects of MSCs in a dextran sulfate sodium-induced colitis models by promoting MSCs homing to murine colons and spleens. Stem Cell Res Ther. 2019;10:267. doi: 10.1186/s13287-019-1384-9. 8. …