Результаты поиска

[The protective effect and mechanism of inosine on AngⅡ-induced aortic aneurysms in mice].

Objective: To investigate the protective effects of inosine on angiotensin Ⅱ (AngⅡ)-induced aortic aneurysm in mice and its underlying mechanisms. Methods: This study was conducted in three phases. In the first phase, 19 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into a control group (n=9, without any intervention) and a model group (n=10, with a mini-osmotic pump implanted subcutaneously in the back to continuously infuse Ang Ⅱ at a dose of 2 000 ng·kg⁻¹·min⁻¹ for 14 days to establish the aortic aneurysm model). At 14 days after modeling, non-targeted metabolomics technology wa

[Effect and mechanism of astaxanthin on the aging of high glucose-treated human skin fibroblasts].

Objective: To investigate the effect and mechanism of astaxanthin on the aging of high glucose-treated human skin fibroblasts (Fbs). Methods: The study was an experimental study. Human skin Fbs were collected and divided into control group with conventional culture, high glucose group treated with glucose at a final molarity of 30 mmol/L, and low astaxanthin group and high astaxanthin group pretreated with astaxanthin at final molarities of 25 and 50 μmol/L respectively and then treated as that in high glucose group. After 48 h of culture, the cell survival rate was detected by the cell counti

Matrix metalloproteinases and tissue inhibitors in multiple myeloma: promote or inhibit?

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) play a vital role in the pathogenesis of multiple myeloma (MM), especially for tumor invasion and osteolytic osteopathy. By breaking down extracellular matrix (ECM) components and releasing the proteins composing the ECM and growth factors, as well as their receptors, MMPs affect tissue integrity and promote cancer cell invasion and metastasis. A vital pathophysiological characteristic of MM is the progress of osteolytic lesions, which are brought on by interactions between myeloma cells and the bone marrow mic

Breast cancer metastasis to the bone: mechanisms of bone loss.

Breast cancer frequently metastasizes to the skeleton, interrupting the normal bone remodeling process and causing bone degradation. Osteolytic lesions are the end result of osteoclast activity; however, osteoclast differentiation and activation are mediated by osteoblast production of RANKL (receptor activator for NFκB ligand) and several osteoclastogenic cytokines. Osteoblasts themselves are negatively affected by cancer cells as evidenced by an increase in apoptosis and a decrease in proteins required for new bone formation. Thus, bone loss is due to both increased activation of osteoclasts

Targeting the CD47-TSP1 Axis in Abdominal Aortic Aneurysm: A Novel Immunotherapeutic Approach.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive dilation and weakening of the abdominal aortic wall. Despite advances in surgical repair, rupture remains associated with mortality rates exceeding 65%, and no effective pharmacological therapy exists to prevent disease progression. Increasing evidence highlights chronic inflammation, extracellular matrix degradation, and immune dysregulation as central drivers of AAA pathogenesis. Among these mechanisms, the thrombospondin-1 (TSP1)-CD47 signaling axis has emerged as a critical upstream regulat

Current Status and Perspectives of Protease Inhibitors and Their Combination with Nanosized Drug Delivery Systems for Targeted Cancer Therapy.

In cancer treatments, many natural and synthetic products have been examined; among them, protease inhibitors are promising candidates for anti-cancer agents. Since dysregulated proteolytic activities can contribute to tumor development and metastasis, antagonization of proteases with tailored inhibitors is an encouraging approach. Although adverse effects of early designs of these inhibitors disappeared after the introduction of next-generation agents, most of the proposed inhibitors did not pass the early stages of clinical trials due to their nonspecific toxicity and lack of pharmacological

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

A REVIEW OF SALIVARY BIOMARKERS OF PERIODONTAL DISEASE.

BackgroundPeriodontal disease is a complex multifactorial disease resulting from the interplay amongst microbiota, host immune response (influenced by genetic make-up) and lifestyle factors. The chronic inflammatory nature of the disease results in the destruction of the component of the periodontium. The process of the disease is associated with inflammation, collagen degradation and, bone loss which correlate with clinical features of periodontal disease. The clinical diagnosis of periodontal disease entails clinical examination involving the evaluation of probing depth, bleeding on probing,

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… Matrix metalloproteinase 8 and 9 are the major matrix metalloproteinases in saliva; in smaller amounts, saliva also contains matrix metalloproteinase 1, 2, 3, 7, 12, 13, 14, 25, and 26, as well as tissue inhibitors of matrix metalloproteinase 1 and 2. … Clinical measurements demonstrate significant positive correlations with elevated levels of salivary matrix metalloproteinase 8. The level of MMP8 reduces following therapy, suggesting it as a potential marker for monitoring periodontal disease activity 25 . …

Выбранные цитокины и матричные металопротеины в патогенезе и лечение множественных склерозов.

Множественный склероз (MS) — аутоиммунное заболевание нервной системы (NS). Аксональное дегенерация, обезвоживание и воспаление являются основными механизмами развития этого расстройства. В ходе MS паренхиловые клетки в НС активируются для производства цитокинов и цитокиновых белков, включая металопротеины матрицы (MMPs). Присутствие этих ферментов и цитокинов в центральной нервной системе (ЦНС) во время подстрекательской реакции может указывать на их участие в патогенезе или прогрессировании MS. Точное определение роли цитокинов и MMP в развитии MS может способствовать лучшему пониманию причи

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment.

Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs' augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhib

Megakaryocyte Contribution to Bone Marrow Fibrosis: many Arrows in the Quiver.

In Primary Myelofibrosis (PMF), megakaryocyte dysplasia/hyperplasia determines the release of inflammatory cytokines that, in turn, stimulate stromal cells and induce bone marrow fibrosis. The pathogenic mechanism and the cells responsible for progression to bone marrow fibrosis in PMF are not completely understood. This review article aims to provide an overview of the crucial role of megakaryocytes in myelofibrosis by discussing the role and the altered secretion of megakaryocyte-derived soluble factors, enzymes and extracellular matrices that are known to induce bone marrow fibrosis.

The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases.

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstance

Suppression of CD81 promotes bladder cancer cell invasion through increased matrix metalloproteinase expression via extracellular signal-regulated kinase phosphorylation.

PurposeCD81 is a prognostic biomarker for high-grade bladder cancer (BC). In this study, we aimed to determine the functional mechanisms underlying the role of CD81 in BC progression.Materials and methodsIn two invasive BC cell lines (T24, J82), CD81 expression was suppressed by the transfection of lentiviral vectors including CD81-specific shRNAs, and then the migration and invasion of BC cells was analyzed. Enzymatic activity of matrix metalloproteinases (MMPs) was also analyzed by collagen-zymography. The expression of MMPs was confirmed by western blotting using culture supernatants from e

Targeting mast cells tryptase in tumor microenvironment: a potential antiangiogenetic strategy.

Angiogenesis is a complex process finely regulated by the balance between angiogenesis stimulators and inhibitors. As a result of proangiogenic factors overexpression, it plays a crucial role in cancer development. Although initially mast cells (MCs) role has been defined in hypersensitivity reactions and in immunity, it has been discovered that MCs have a crucial interplay on the regulatory function between inflammatory and tumor cells through the release of classical proangiogenic factors (e.g., vascular endothelial growth factor) and nonclassical proangiogenic mediators granule-associated (

Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.

This review underscores the dynamic role of the extracellular matrix (ECM) in regulating cellular behavior and maintaining tissue homeostasis, highlighting its pivotal involvement in aging, calcification, and cancer diseases. In healthy tissues, controlled ECM remodeling provides essential biochemical and mechanical cues, but dysregulation (driven by chronic inflammation, cellular senescence, and altered intercellular communication) leads to fibrosis, calcification, and the creation of a pro-tumorigenic microenvironment. Senescent cells contribute to these changes through senescence-associated

Связанный с Ро белком GTP белок RhoE (RND3) регулирует множественные заболевания костей миэломы.

Множественное заболевание костей миеломы (ММБД) широко распространено среди многих пациентов, страдающих миеломой (ММ). Используя профиль выражения генов, мы идентифицировали Rho Family GTPase 3 (RND3) как ген, чье выражение в MM негативно связано с остротой MMBD. Используя биопсии MM пациентов, мы подтвердили, что пациенты с MMBD уменьшили экспрессию RND3 по сравнению с пациентами без MMBD. Для изучения функции RND3 в MMBD мы создали RND3 снос клеток MM (RN-KD), а также контроль (CT-KD). В человеческой модели MM xenograft мыши RN-KD MM вызвала MMBD сильнее, чем CT-KD. RN-KD MM поощряла диффер

MicroRNA-150-5p inhibits the proliferation and invasion of human larynx epidermiod cancer cells though regulating peptidyl-prolyl cis/trans isomerase.

ObjectiveThis study aimed to investigate the molecular mechanism of miR-150-5p regulating the malignant biological behavior of Human Epidermoid cancer cell (HEp-2) by targeting peptidyl-prolyl cis/trans isomerase NIMA-Interacting-1 (PIN1).MethodsFirstly, qRT-PCR and Western blot were adopted to detect the expression levels of miR-150-5p and PIN1 in cancer tissue and paracancerous tissues of patients with LSCC, and those in human bronchial epithelial cells (16 HBE) and HEp-2. Next, the targeted relationship between miR-150-5p and PIN1 was assessed by bioinformatics website and dual-luciferase r

Bone-Seeking Matrix Metalloproteinase Inhibitors for the Treatment of Skeletal Malignancy.

Matrix metalloproteinases (MMPs) are a family of enzymes involved at different stages of cancer progression and metastasis. We previously identified a novel class of bisphosphonic inhibitors, selective for MMPs crucial for bone remodeling, such as MMP-2. Due to the increasing relevance of specific MMPs at various stages of tumor malignancy, we focused on improving potency towards certain isoforms. Here, we tackled MMP-9 because of its confirmed role in tumor invasion, metastasis, angiogenesis, and immuno-response, making it an ideal target for cancer therapy. Using a computational analysis, we

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… Extra Binding Region Induced by Non-Zinc Chelating Inhibitors into the S 1 Subsite of Matrix Metalloproteinase 8 (MMP-8) J. Med. Chem. 2009;52:1040–1049. doi: 10.1021/jm801166j. 35. Fabre B., Ramos A., de Pascual-Teresa B. …

Molecular mechanisms and clinical management of cancer bone metastasis.

As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the curr

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