المؤلفون: Wang, Jiahui¹ (AUTHOR), Su, Yi¹ (AUTHOR), Liu, Hong¹ (AUTHOR), Li, Yongchun¹ (AUTHOR), Fang, Xuejie^1,2 (AUTHOR), Yu, Xinjuan^1,3 (AUTHOR), Li, Qinghai¹ (AUTHOR), Han, Wei¹ (AUTHOR)

المصدر: International Archives of Allergy & Immunology. 2024, Vol. 185 Issue 5, p480-488. 9p.

مصطلحات موضوعية: *CHRONIC obstructive pulmonary disease, *MATRIX metalloproteinase inhibitors, *PEARSON correlation (Statistics), *SMOKING

مستخلص: Introduction: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a recently discovered inhibitor of matrix metalloproteinase (MMP). There is a large number of chronic obstructive pulmonary disease (COPD) patients worldwide; however, the role of RECK on COPD has not been studied. This study explored the expression of RECK in COPD patients and its effect on neutrophil function to provide a new scientific basis for the prevention and treatment of COPD. Method: Fifty patients with acute exacerbation of COPD and fifty healthy controls were enrolled in the study. RECK was detected in lung tissue, sputum, and plasma of subjects as well as in BEAS-2B cells stimulated with cigarette smoke extract (CSE) by immunohistochemistry, ELISA, and qRT-PCR. Meanwhile, lung function (FEV1%pred) and inflammatory cytokines (IL-6 and IL-8) were examined, and correlation analysis was performed with RECK expression. The effect of RECK on proliferation, apoptosis, migration, and inflammatory cytokines and its potential mechanism was further quantified by neutrophil stimulated with recombinant human RECK protein (rhRECK) combined with CSE using CCK8, flow cytometry, Transwell assay, qRT-PCR, ELISA, and Western analysis. Results: RECK was mainly expressed on airway epithelial cells in normal lung tissue and was significantly diminished in COPD patients. The levels of RECK in sputum and plasma were also significantly decreased in COPD patients. Pearson correlation analysis showed that RECK level in plasma was positively correlated with FEV1%pred (r = 0.458, p <0.001) and negatively correlated with IL-6 and IL-8 (r = −0.386, −0.437; p = 0.006, 0.002) in COPD patients. The expression of RECK was decreased in BEAS-2B stimulated with CSE. The migration, inflammation, and MMP-9 expression of neutrophils were promoted by CSE, while inhibited by rhRECK. Conclusion: RECK is low expressed in COPD patients and negatively correlated with inflammation. It may inhibit the inflammation and migration of neutrophils by downregulating MMP-9. [ABSTRACT FROM AUTHOR]

العنوان البديل: Effects of static traction on the nucleus pulposus and annulus fibrosus of the rat intervertebral disc.

المؤلفون: 莫 骏¹, 罗宗平²

المصدر: Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu. 3/18/2024, Vol. 28 Issue 8, p1180-1185. 6p.

مصطلحات موضوعية: *NUCLEUS pulposus, *MATRIX metalloproteinase inhibitors, *MATRIX metalloproteinases, *EXTRACELLULAR matrix, *GENE expression, *INTERVERTEBRAL disk

الملخص (بالإنجليزية): BACKGROUND: Traction is clinically used for the early treatment of intervertebral disc degeneration, but its effect on the normal intervertebral disc remains unknown. Whether it directly causes intervertebral disc degeneration or has a positive effect is the key point of this study. OBJECTIVE: To design a static traction model and observe the effect of static traction on the nucleus pulposus and annulus fibrosus of the intervertebral disc METHODS: Twenty Sprague-Dawley rats, 3 months of age, were included in the study. The intervertebral disc spaces between 7/8, 8/9 and 9/10 were stretched by 1 mm, and the intervertebral disc spaces between 6/7 and 10/11 were used as control. Five rats were randomly selected at 2, 4, 6, and 8 weeks of traction to perform MRI T2-weighted scans of the caudal vertebra, tissue section staining, and RT-PCR gene assays for anabolic metabolism to observe the effects of static traction on the nucleus pulposus and annulus fibrosus of the intervertebral disc. RESULTS AND CONCLUSION: After short-term static traction of the rat caudal vertebra, the T2-weighted image signal in the nucleus pulposus region was enhanced. During the traction period, nucleus pulposus cells grew well, the intercellular matrix was abundant, and the annulus fibrosus arranged regularly. The RT-PCR results showed that after traction, the mRNA expression of proteoglycan increased, the expression of matrix metalloproteinase-3 decreased, the expression of type I and II collagen decreased, and the expression of matrix metalloproteinase-13 increased and tissue inhibitor of matrix metalloproteinase 1 increased. These gene results also indicated that traction made proteoglycan more inclined to an anabolic state, and type I and II collagen more inclined to a catabolic state. To conclude, static traction promotes proteoglycan anabolism making the nucleus pulposus moist. [ABSTRACT FROM AUTHOR]

Abstract (Chinese): 背景：牵引在临床上用于椎间盘退变早期的治疗, 但其对正常椎间盘的影响仍未可知, 是直接造成椎间盘退变还是正向作用即是此次实验 的观察要点。 目的：建立大鼠尾椎椎间盘静态拉伸模型, 观察静态拉伸对椎间盘髓核和纤维环的影响。 方法：选用20只3月龄SD大鼠, 采用外固定装置静态拉伸大鼠尾椎7/8、8/9、9/10椎间隙1 mm, 6/7、10/11椎间盘作为对照；拉伸2, 4, 6, 8周随机抽取5只大鼠进行尾椎椎间盘MRI T2加权扫描、组织切片染色、合成分解代谢RT-PCR基因检测, 观察静态拉伸对椎间盘髓核和 纤维环的影响。 结果与结论：①大鼠尾椎椎间盘经过短期静态拉伸后, 椎间盘髓核区的T2加权像信号增强；②整个拉伸期间, 髓核区域髓核细胞生长状态 良好, 细胞间基质含量丰富, 纤维环排布整齐；③RT-PCR结果显示, 拉伸之后蛋白多糖基因表达升高, 基质金属蛋白酶3表达降低, Ⅰ、 Ⅱ型胶原基因表达降低, 基质金属蛋白酶13表达升高, 基质金属蛋白酶抑制剂1表达升高, 这些基因结果也进一步表明拉伸使得蛋白多糖 更趋向合成代谢状态, Ⅰ、Ⅱ型胶原更趋向于分解代谢状态；④结果提示静态拉伸有助于促进髓核区域蛋白多糖的合成代谢, 使得水分得 以维持。 [ABSTRACT FROM AUTHOR]

المؤلفون: Santamaria, Salvatore¹ (AUTHOR) s.santamaria@surrey.ac.uk

المصدر: Pharmaceuticals (14248247). Dec2023, Vol. 16 Issue 12, p1637. 4p.

مصطلحات موضوعية: *MATRIX metalloproteinase inhibitors, *PROTEOLYTIC enzymes, *NEPRILYSIN

مستخلص: Metalloproteinases are a family of proteases involved in various biological processes and are associated with diseases such as cancer and arthritis. This Special Issue provides a comprehensive overview of different approaches to modulate metalloproteinase activity for therapeutic purposes. The articles cover topics such as the identification of inhibitors for specific metalloproteinases, the development of selective matrix metalloproteinase inhibitors, alternative mechanisms for inhibiting metalloproteinase activity, and the targeting of metalloproteinases in specific diseases such as heart failure and osteoarthritis. These studies contribute to the understanding of metalloproteinases and may lead to the development of new treatments. [Extracted from the article]

المؤلفون: Sung-Gyu Lee¹ hkang@dankook.ac.kr, Hyun Kang¹ hkang3@nate.com

المصدر: Tropical Journal of Pharmaceutical Research. Dec2023, Vol. 22 Issue 12, p2441-2447. 7p.

مصطلحات موضوعية: *CARTILAGE regeneration, *MATRIX metalloproteinase inhibitors, *ENZYME-linked immunosorbent assay, *MATRIX metalloproteinases

مستخلص: Purpose: To evaluate the anti-inflammatory properties of Drynariae rhizome (Polypodiaceae) extract (DRE) on lipopolysaccharide RAW264.7 macrophage cells and its protective effects on interleukin (IL)-1β-stimulated SW1353 chondrocyte cells. Methods: The anti-inflammatory effect of DRE (12.5, 25, 50, and 100 μg/mL) were measured by 5-lipooxygenase (LO) and cyclooxygenase (COX)-2 enzyme inhibitory activities, nitric oxide (NO) production in LPS-stimulated RAW264.7 cells using Griess reagent assay. Prostaglandins (PGE2) and leukotriene (LTB4) production were measured using enzyme-linked immunosorbent assay (ELISA). To investigate the protective effect on chondrocytes, the level of matrix metalloproteinases (MMP)-3, -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 was determined using zymography assay and ELISA kit in SW1353 cells stimulated with IL-1β. Results: Drynariae rhizome (Polypodiaceae) extract (DRE) had a significant (p < 0.05) inhibitory effect on 5-LO and COX-2 enzymes in a concentration-dependent manner compared to untreated group. In RAW264.7 cells, levels of NO, PGE2 and LTB4 of DRE group were significantly (p < 0.05) decreased in study group (treated with DRE) at 12.5 μg/mL compared to the group treated with LPS (100 ng/mL) alone. Additionally, in SW1353 human chondrocytes stimulated with IL-1β, MMP-3 and MMP-9 were significantly (p < 0.05) suppressed in DRE-treated group compared to IL-1β group alone, with no significant impact on TIMP-1 production. Conclusion: Drynariae rhizome (Polypodiaceae) extract (DRE) possesses anti-inflammatory and cartilage protection effects. It therefore has the potential to be developed as an effective natural pharmaceutical agent for inflammation or osteoarthritis. [ABSTRACT FROM AUTHOR]

المؤلفون: Rashid, Zainab Ahmed¹ (AUTHOR), Bardaweel, Sanaa K.¹ (AUTHOR) s.bardaweel@ju.edu.jo

المصدر: International Journal of Molecular Sciences. Aug2023, Vol. 24 Issue 15, p12133. 24p.

مصطلحات موضوعية: *MATRIX metalloproteinase inhibitors, *CANCER treatment, *METALLOENZYMES, *CARCINOGENESIS, *EXTRACELLULAR matrix, *CANCER invasiveness

الشركة/الكيان: UNITED States. Food & Drug Administration

مستخلص: Matrix metalloproteinases (MMPs) belong to a family of zinc-dependent proteolytic metalloenzymes. MMP-9, a member of the gelatinase B family, is characterized as one of the most intricate MMPs. The crucial involvement of MMP-9 in extracellular matrix (ECM) remodeling underscores its significant correlation with each stage of cancer pathogenesis and progression. The design and synthesis of MMP-9 inhibitors is a potentially attractive research area. Unfortunately, to date, there is no effective MMP-9 inhibitor that passes the clinical trials and is approved by the FDA. This review primarily focuses on exploring the diverse strategies employed in the design and advancement of MMP-9 inhibitors, along with their anticancer effects and selectivity. To illuminate the essential structural characteristics necessary for the future design of novel MMP-9 inhibitors, the current narrative review highlights several recently discovered MMP-9 inhibitors exhibiting notable selectivity and potency. [ABSTRACT FROM AUTHOR]

المؤلفون: Antonsen, Kristian W., Jensen, Anne G., Carstensen, Mikkel, Nejsum, Lene N., Sorensen, Boe S., Etzerodt, Anders, Moestrup, Søren K., Møller, Holger J.

المصدر: European Journal of Immunology; Jul2024, Vol. 54 Issue 7, p1-14, 14p

مصطلحات موضوعية: PHAGOCYTOSIS, CD47 antigen, MATRIX metalloproteinase inhibitors, PHAGOCYTIC function tests, BLOCKADE

مستخلص: Antibody‐based CD47 blockade aims to activate macrophage phagocytosis of tumor cells. However, macrophages possess a high degree of phenotype heterogeneity that likely influences phagocytic capacity. In murine models, proinflammatory (M1) activation increases macrophage phagocytosis of tumor cells, but in human models, results have been conflicting. Here, we investigated the effects of proinflammatory polarization on the phagocytic response of human monocyte‐derived macrophages in an in vitro model. Using both flow cytometry‐based and fluorescence live‐cell imaging‐based phagocytosis assays, we observed that mouse monoclonal anti‐CD47 antibody (B6H12) induced monocyte‐derived macrophage phagocytosis of cancer cells in vitro. Proinflammatory (M1) macrophage polarization with IFN‐γ+LPS resulted in a severe reduction in phagocytic response to CD47 blockade. This reduction coincided with increased expression of the antiphagocytic membrane proteins LILRB1 and Siglec‐10 but was not rescued by combination blockade of the corresponding ligands. However, matrix metalloproteinase inhibitors (TAPI‐0 or GM6001) partly restored response to CD47 blockade in a dose‐dependent manner. In summary, these data suggest that proinflammatory (M1) activation reduces phagocytic response to CD47 blockade in human monocyte‐derived macrophages. [ABSTRACT FROM AUTHOR]

: Copyright of European Journal of Immunology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Huang, Weijing, Zeng, Wenhui, Huang, Zheng, Fang, Daqing, Liu, Hong, Feng, Min, Mao, Liang, Ye, Deju

المصدر: Angewandte Chemie International Edition; Jun2024, Vol. 63 Issue 26, p1-13, 13p

مصطلحات موضوعية: RADIATIVE transitions, BRAIN tumors, MATRIX metalloproteinase inhibitors, ENERGY transfer, GLIOMAS

مستخلص: Ratiometric afterglow luminescent (AGL) probes are attractive for in vivo imaging due to their high sensitivity and signal self‐calibration function. However, there are currently few ratiometric AGL probes available for imaging enzymatic activity in living organisms. Here, we present an energy diversion (ED) strategy that enables the design of an enzyme‐activated ratiometric AGL probe (RAG‐RGD) for in vivo afterglow imaging. The ED process provides RAG‐RGD with a radiative transition for an 'always on' 520‐nm AGL signal (AGL520) and a cascade three‐step energy transfer (ET) process for an 'off‐on' 710‐nm AGL signal (AGL710) in response to a specific enzyme. Using matrix metalloproteinase‐2 (MMP‐2) as an example, RAG‐RGD shows a significant ~11‐fold increase in AGL710/AGL520 toward MMP‐2. This can sensitively detect U87MG brain tumors through ratiometric afterglow imaging of MMP‐2 activity, with a high signal‐to‐background ratio and deep imaging depth. Furthermore, by utilizing the self‐calibration effect of ratiometric imaging, RAG‐RGD demonstrated a strong negative correlation between the AGL710/AGL520 value and the size of orthotopic U87MG tumor, enabling accurate monitoring of orthotopic glioma growth in vivo. This ED process may be applied for the design of other enzyme‐activated ratiometric afterglow probes for sensitive afterglow imaging. [ABSTRACT FROM AUTHOR]

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المؤلفون: Perarivalan, I., Karunakaran, Janani, Anbalagan, Nathashri, Harishma, S., Prasad, Vishnu

المصدر: Journal of Conservative Dentistry & Endodontics; Jun2024, Vol. 27 Issue 6, p566-571, 6p

مصطلحات موضوعية: MATRIX metalloproteinase inhibitors, DENTAL adhesives, OPERATIVE dentistry, MATRIX metalloproteinases, BOND strengths, IMPACT strength

مستخلص: Matrix metalloproteinases (MMPs) have been identified as agents that disintegrate the collagen structures of dental hybrid layers, resulting in reduced restorative bond strength. Multiple MMP inhibitors (MMPIs) are known to counteract this degenerative mechanism, thereby preserving bond strength and promoting the longevity of resin-based restorations. Additionally, literature suggests that certain MMPI materials possess antimicrobial/anticariogenic properties, potentially reducing the risk of secondary caries development. Therefore, this review article aims to narrate on the integration of matrix metalloproteinase inhibitors into adhesive systems and their impact on bond strength. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Conservative Dentistry & Endodontics is the property of Wolters Kluwer India Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Akiko Hori, Atsuko Takahashi, Yuta Miharu, Satoru Yamaguchi, Masatoshi Sugita, Takeo Mukai, Fumitaka Nagamura, Tokiko Nagamura-Inoue

المصدر: Frontiers in Cell & Developmental Biology; 2024, p1-13, 13p

مصطلحات موضوعية: STROMAL cells, SOMATOMEDIN C, BONE marrow, PLATELET-derived growth factor, MATRIX metalloproteinase inhibitors

مستخلص: Introduction: Mesenchymal stromal cells (MSCs) are activated upon inflammation and/or tissue damage and migrate to suppress inflammation and repair tissues. Migration is the first important step for MSCs to become functional; however, the migration potency of umbilical cord-derived MSCs (UC-MSCs) remains poorly understood. Thus, we aimed to assess the migration potency of UC-MSCs in comparison with those of bone marrow-derived MSCs (BMMSCs) and adipose tissue-derived MSCs (AD-MSCs) and investigate the influence of chemotactic factors on the migration of these cells. Methods: We compared the migration potencies of UC-, BM-, and AD-MSCs toward allogeneic stimulated mononuclear cells (MNCs) in mixed lymphocyte reaction (MLR). The number of MSCs in the upper chamber that migrated toward the MLR in the lower chamber was counted using transwell migration assay. Results and discussion: UC-MSCs showed significantly faster and higher proliferation potencies and higher migration potency toward unstimulated MNCs and MLR than BM- and AD-MSCs, although the migration potencies of the three types of MSCs were comparable when cultured in the presence of fetal bovine serum. The amounts of CCL2, CCL7, and CXCL2 in the supernatants were significantly higher in UC-MSCs co-cultured with MLR than in MLR alone and in BM- and AD-MSCs co-cultured with MLR, although they did not induce the autologous migration of UC-MSCs. The amount of CCL8 was higher in BM- and AD-MSCs than in UC-MSCs, and the amount of IP-10 was higher in AD-MSCs cocultured with MLR than in UC- and BM-MSCs. The migration of UC-MSCs toward the MLR was partially attenuated by platelet-derived growth factor, insulin-like growth factor 1, and matrix metalloproteinase inhibitors in a dose-dependent manner. Conclusion: UC-MSCs showed faster proliferation and higher migration potency toward activated or non-activated lymphocytes than BM- and AD-MSCs. The functional chemotactic factors may vary among MSCs derived from different tissue sources, although the roles of specific chemokines in the different sources of MSCs remain to be resolved. [ABSTRACT FROM AUTHOR]

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المؤلفون: Pitchaikani, Sasikumar, Mukilan, Murugan, Govindan, Pothiaraj, Kathiravan, Ganesan, Shakila, Harshavardhan

المصدر: Journal of Experimental Biology & Agricultural Science; Feb2024, Vol. 12 Issue 1, p49-59, 11p

مصطلحات موضوعية: MYCOBACTERIUM tuberculosis, MYCOBACTERIAL diseases, MATRIX metalloproteinases, MATRIX metalloproteinase inhibitors, COMMUNICABLE diseases, ALVEOLAR macrophages, DRUG resistance in microorganisms

مستخلص: Tuberculosis (TB) is one of the major threats to public health; annually it kills more than 1.5 million people around the globe. Tuberculosis is caused by an intracellular pathogen named Mycobacterium tuberculosis (Mtb). This Mtb enters the lung through the respiratory passage by inhalation in healthy individuals. Infection of this disease starts from the settlement of Mtb to the lung alveoli of the host from the external bacilli air droplets. After settlement, the multiplication of Mtb results in the induction of innate immunity through the alveolar macrophages. Compared to other infectious diseases, tuberculosis infection was transmitted rapidly by the infected aerosols released from infected persons to healthy persons through the air. After infection, disease development results in the formation of drug-resistance TB (DR-TB) with four subcategories, i.e. Single-drug resistant TB (SDR-TB), multi-drug resistant TB (MDR-TB), extensive drugresistant TB (XDR-TB), and total-drug resistant TB (TDR-TB). As a result, this DR-TB may act as a major source of TB death due to spontaneous antimicrobial resistance (AMR). This AMR makes the anti-TB drugs ineffective. In the current scenario, researchers are trying to find the drug target to decrease tuberculosis progression instead of drug resistance. The present review reports that the outcome of research studies showed that matrix metalloproteinase (MMP) may act as a suitable target for treating Mtb infection with the help of specific proteinase inhibitors. Recent reports have shown the specific role of matrix metalloproteinases 1, 8, and 9 in the disease progression and its role in normal homeostasis mechanism with the help of specific animal models/In vitro models. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Experimental Biology & Agricultural Science is the property of Journal of Experimental Biology & Agricultural Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)