Various behaviors of cancer cells are strongly influenced by their interaction with extracellular matrices(ECM).We investigate how this interaction may be influenced if the cancer cells’ability of secreting matrix me...Various behaviors of cancer cells are strongly influenced by their interaction with extracellular matrices(ECM).We investigate how this interaction may be influenced if the cancer cells’ability of secreting matrix metalloproteinases(MMPs)to degrade ECM is inhibited by adding the MMP inhibitor.We useMDA-MB-231-GFP cells as model cells and use matrigel to mimic ECM.It is found that the added MMP inhibitor significantly reduces the migration speed of cancer cells covered by matrigel but has little influence on the migration persistence and shape factor of the cells and that with the MMP inhibitor added the presence of matrigel on the top has no influence on the migration speed of the cells but increases the cells’shape factor and migration persistence.展开更多
The interaction between extracellular matrices and cancer cells plays an important role in regulating cancer cell behaviors. In this article, we use matrigel to mimic extracellular matrices and investigate experimenta...The interaction between extracellular matrices and cancer cells plays an important role in regulating cancer cell behaviors. In this article, we use matrigel to mimic extracellular matrices and investigate experimentally how matrigel influences the shape and dynamics of breast cancer cells(MDA-MB-231-GFP cells). We find that matrigel facilitates cancer cells' migration and shape deformation. The influences of the matrigel concentration are also reported.展开更多
Background: Left ventricular noncompaction with multiple left ventricular thrombi can be revealed by echocardiography, and early diagnosis seems to be imperative to prevent significant embolic events. Case Report: A 5...Background: Left ventricular noncompaction with multiple left ventricular thrombi can be revealed by echocardiography, and early diagnosis seems to be imperative to prevent significant embolic events. Case Report: A 57-year-old woman presented with symptoms of heart failure. Two-dimensional transthoracic echocardiogram demonstrated a dilated and diffusely hypokinetic left ventricle with severe impaired left ventricular systolic function. Moreover, a markedly thickened endocardium at the left ventricular apex and middle segment with numerous, excessively prominent trabeculations and deep intertrabecular recesses were present. During systole, the ratio of the noncompacted to compacted myocardial layers at the site of the maximal wall thickness was above two, a characteristic finding in left ventricular non-compaction. Multiple mobile, homogeneous, echodense thrombi were identified in the left ventricle, with the largest one in the apical noncompacted segment (dimensions, 32 × 14 mm). Cardiac magnetic resonance imaging confirmed the diagnosis of noncompacted myocardium with the presence of multiple thrombi. After anticoagulant therapy, her symptoms improved and thrombi dissolved. Unexpectedly, she re-admitted to the cardiovascular unit with progressive dyspnea. Transthoracic echocardiogram showed new large right atrial thrombi, with the largest one was 43 × 38 mm compared to the echocardiogram done 11 months ago. The patient was anticoagulated with continuous heparin infusion for several days followed by oral Apixaban. After 4 weeks, the floating thrombi completely disappeared. After a 26-month follow-up, the patient’s condition was stable without embolic complications. Conclusion: Echocardiography was the cornerstone of diagnostic methods for early detecting left ventricular thrombi to eventually prevent embolic events.展开更多
Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance.The therapeutic effect of stem cell derived-small extracellular vesicles(sEVs)for tendinopathy has been validated...Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance.The therapeutic effect of stem cell derived-small extracellular vesicles(sEVs)for tendinopathy has been validated in recent years.However,whether large extracellular vesicles(lEVs),another subset of extracellular vesicles,possesses the ability for the improvement of tendinopathy remains unknown.Here,we showed that lEVs secreted from iPSC-derived MSCs(iMSC-lEVs)significantly mitigated pain derived from tendinopathy in rats.Immuno-histochemical analysis showed that iMSC-lEVs regulated the heterogeneity of infiltrated macrophages and several inflammatory cytokines in rat tendon tissue.Meanwhile,in vitro experiments revealed that the M1 pro-inflammatory macrophages were repolarized towards M2 anti-inflammatory macrophages by iMSC-lEVs,and this effect was mediated by regulating p38 MAPK pathway.Moreover,liquid chromatography-tandem mass spectrometry analysis identified 2208 proteins encapsulated in iMSC-lEVs,including 134 new-found proteins beyond current Vesiclepedia database.By bioinformatics and Western blot analyses,we showed that DUSP2 and DUSP3,the negative regulator of p38 phosphorylation,were enriched in iMSC-lEVs and could be transported to macrophages.Further,the immunomodulatory effect of iMSC-lEVs on macrophages was validated in explant tendon tissue from tendinopathy patients.Taken together,our results demonstrate that iMSC-lEVs could reduce inflammation in tendinopathy by regulating macrophage heterogeneity,which is mediated via the p38 MAPK pathway by delivery of DUSP2 and DUSP3,and might be a promising candidate for tendinopathy therapy.展开更多
基金National Natural Science Foundation of China(Grant No.11774394)the Key Research Program of Frontier Sciences of Chinese Academy of Sciences(Grant No.QYZDB-SSW-SYS003)the K.C.Wong Education Foundation.
文摘Various behaviors of cancer cells are strongly influenced by their interaction with extracellular matrices(ECM).We investigate how this interaction may be influenced if the cancer cells’ability of secreting matrix metalloproteinases(MMPs)to degrade ECM is inhibited by adding the MMP inhibitor.We useMDA-MB-231-GFP cells as model cells and use matrigel to mimic ECM.It is found that the added MMP inhibitor significantly reduces the migration speed of cancer cells covered by matrigel but has little influence on the migration persistence and shape factor of the cells and that with the MMP inhibitor added the presence of matrigel on the top has no influence on the migration speed of the cells but increases the cells’shape factor and migration persistence.
基金support of the CAS Key Lab of Soft Matter Physics
文摘The interaction between extracellular matrices and cancer cells plays an important role in regulating cancer cell behaviors. In this article, we use matrigel to mimic extracellular matrices and investigate experimentally how matrigel influences the shape and dynamics of breast cancer cells(MDA-MB-231-GFP cells). We find that matrigel facilitates cancer cells' migration and shape deformation. The influences of the matrigel concentration are also reported.
文摘Background: Left ventricular noncompaction with multiple left ventricular thrombi can be revealed by echocardiography, and early diagnosis seems to be imperative to prevent significant embolic events. Case Report: A 57-year-old woman presented with symptoms of heart failure. Two-dimensional transthoracic echocardiogram demonstrated a dilated and diffusely hypokinetic left ventricle with severe impaired left ventricular systolic function. Moreover, a markedly thickened endocardium at the left ventricular apex and middle segment with numerous, excessively prominent trabeculations and deep intertrabecular recesses were present. During systole, the ratio of the noncompacted to compacted myocardial layers at the site of the maximal wall thickness was above two, a characteristic finding in left ventricular non-compaction. Multiple mobile, homogeneous, echodense thrombi were identified in the left ventricle, with the largest one in the apical noncompacted segment (dimensions, 32 × 14 mm). Cardiac magnetic resonance imaging confirmed the diagnosis of noncompacted myocardium with the presence of multiple thrombi. After anticoagulant therapy, her symptoms improved and thrombi dissolved. Unexpectedly, she re-admitted to the cardiovascular unit with progressive dyspnea. Transthoracic echocardiogram showed new large right atrial thrombi, with the largest one was 43 × 38 mm compared to the echocardiogram done 11 months ago. The patient was anticoagulated with continuous heparin infusion for several days followed by oral Apixaban. After 4 weeks, the floating thrombi completely disappeared. After a 26-month follow-up, the patient’s condition was stable without embolic complications. Conclusion: Echocardiography was the cornerstone of diagnostic methods for early detecting left ventricular thrombi to eventually prevent embolic events.
基金National Natural Science Foundation of China(Grant No.81870972,82072550)Science and Technology Commission of Shanghai Municipality(Grant No.21DZ2201300).
文摘Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance.The therapeutic effect of stem cell derived-small extracellular vesicles(sEVs)for tendinopathy has been validated in recent years.However,whether large extracellular vesicles(lEVs),another subset of extracellular vesicles,possesses the ability for the improvement of tendinopathy remains unknown.Here,we showed that lEVs secreted from iPSC-derived MSCs(iMSC-lEVs)significantly mitigated pain derived from tendinopathy in rats.Immuno-histochemical analysis showed that iMSC-lEVs regulated the heterogeneity of infiltrated macrophages and several inflammatory cytokines in rat tendon tissue.Meanwhile,in vitro experiments revealed that the M1 pro-inflammatory macrophages were repolarized towards M2 anti-inflammatory macrophages by iMSC-lEVs,and this effect was mediated by regulating p38 MAPK pathway.Moreover,liquid chromatography-tandem mass spectrometry analysis identified 2208 proteins encapsulated in iMSC-lEVs,including 134 new-found proteins beyond current Vesiclepedia database.By bioinformatics and Western blot analyses,we showed that DUSP2 and DUSP3,the negative regulator of p38 phosphorylation,were enriched in iMSC-lEVs and could be transported to macrophages.Further,the immunomodulatory effect of iMSC-lEVs on macrophages was validated in explant tendon tissue from tendinopathy patients.Taken together,our results demonstrate that iMSC-lEVs could reduce inflammation in tendinopathy by regulating macrophage heterogeneity,which is mediated via the p38 MAPK pathway by delivery of DUSP2 and DUSP3,and might be a promising candidate for tendinopathy therapy.
