<strong>Background:</strong> <span style="font-family:Verdana;">Invasive breast cancer is the most common type of malignancy in women worldwide. Matrix Metalloproteinase</span><spa...<strong>Background:</strong> <span style="font-family:Verdana;">Invasive breast cancer is the most common type of malignancy in women worldwide. Matrix Metalloproteinase</span><span style="font-family:""><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">9 is a member of degrading enzymes required for tumor metastasis.</span><b><span style="font-family:Verdana;"> Aim: </span></b><span style="font-family:Verdana;">To assess the prognostic significance of the Matrix Metalloproteinase</span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">9 expression in invasive breast cancer and its association with the clinicopathological features.</span><b><span style="font-family:Verdana;"> Patients and Methods: </span></b><span style="font-family:Verdana;">Cross-sectional study was conducted at the Oncology and Nuclear Therapy Unit, Suez Canal University Hospital. The study involved 33 females that were registered between January 1</span><sup><span style="font-family:Verdana;">st</span></sup><span style="font-family:Verdana;">, 2008 and December, 31</span><sup><span style="font-family:Verdana;">st</span></sup><span style="font-family:Verdana;">, 2012. The eligible participants had a confirmed non-metastatic invasive ductal carcinoma, underwent surgery that their paraffin blocks containing tumor were available. The participants’ tissue specimens were immune stained for Matrix Metalloproteinase</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">9 expression level in the hospital pathology lab. Survival analysis and correlation models were conducted to explore the association between Matrix Metalloproteinase</span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">9 expression level with clinicopathological parameters and survival.</span><b><span style="font-family:Verdana;"> Results</span></b><span style="font-family:Verdana;">: The mean age of participants was 51.2 ± 9.9 years. The mortality rate was 18.2%. The mean Matrix Metalloproteinase</span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">9 expression was 5.42 (±3.37);57.6% showed high expression level. There was no significant correlation with clinicopathological features. Nottingham Prognostic Index was a significant predictor of mortality. Overall survival and disease-free survival were insignificantly different among cases with low and high MMP-9 expression.</span><b><span style="font-family:Verdana;"> Conclusion: </span></b><span style="font-family:Verdana;">Tissue Matrix Metalloproteinase</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">9 expression level does not play a significant role in disease progression. However, Nottingham Prognosis Index is a significant predictor of mortality among studied breast cancer cases.</span></span>展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly underst...Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke- prone spontaneously hypertensive rats by intragastric administration of high-sodium water (1.3% NaC1) for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone sponta- neously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregula- tion is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodi- um water-induced focal cerebral infarction.展开更多
文摘<strong>Background:</strong> <span style="font-family:Verdana;">Invasive breast cancer is the most common type of malignancy in women worldwide. Matrix Metalloproteinase</span><span style="font-family:""><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">9 is a member of degrading enzymes required for tumor metastasis.</span><b><span style="font-family:Verdana;"> Aim: </span></b><span style="font-family:Verdana;">To assess the prognostic significance of the Matrix Metalloproteinase</span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">9 expression in invasive breast cancer and its association with the clinicopathological features.</span><b><span style="font-family:Verdana;"> Patients and Methods: </span></b><span style="font-family:Verdana;">Cross-sectional study was conducted at the Oncology and Nuclear Therapy Unit, Suez Canal University Hospital. The study involved 33 females that were registered between January 1</span><sup><span style="font-family:Verdana;">st</span></sup><span style="font-family:Verdana;">, 2008 and December, 31</span><sup><span style="font-family:Verdana;">st</span></sup><span style="font-family:Verdana;">, 2012. The eligible participants had a confirmed non-metastatic invasive ductal carcinoma, underwent surgery that their paraffin blocks containing tumor were available. The participants’ tissue specimens were immune stained for Matrix Metalloproteinase</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">9 expression level in the hospital pathology lab. Survival analysis and correlation models were conducted to explore the association between Matrix Metalloproteinase</span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">9 expression level with clinicopathological parameters and survival.</span><b><span style="font-family:Verdana;"> Results</span></b><span style="font-family:Verdana;">: The mean age of participants was 51.2 ± 9.9 years. The mortality rate was 18.2%. The mean Matrix Metalloproteinase</span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">9 expression was 5.42 (±3.37);57.6% showed high expression level. There was no significant correlation with clinicopathological features. Nottingham Prognostic Index was a significant predictor of mortality. Overall survival and disease-free survival were insignificantly different among cases with low and high MMP-9 expression.</span><b><span style="font-family:Verdana;"> Conclusion: </span></b><span style="font-family:Verdana;">Tissue Matrix Metalloproteinase</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">9 expression level does not play a significant role in disease progression. However, Nottingham Prognosis Index is a significant predictor of mortality among studied breast cancer cases.</span></span>
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
基金supported by the China Medical Board Project,No.82-143
文摘Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke- prone spontaneously hypertensive rats by intragastric administration of high-sodium water (1.3% NaC1) for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone sponta- neously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregula- tion is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodi- um water-induced focal cerebral infarction.