We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bi...We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen-B7 antigen was positive. Moreover, matrix metalloproteinase 3(MMP-3) was high. She was diagnosed with RS3 PE syndrome, and treatment with prednisolone(15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3 PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3 PE syndrome symptoms.展开更多
The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. ...The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. However like other MMPs, the molecular basis of ST3 function in vivo remains unclear due to the lack of information on its physiological substrates. Furthermore, ST3 has only weak activities toward all tested ECM proteins. Using thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we demonstrated previously that ST3 is important for apoptosis and tissue morphogenesis during intestinal remodeling. Here, we used yeast two-hybrid screen with mRNAs from metamorphosing tadpoles to identify potential substrate of ST3 during development. We thus isolated the 37 kd laminin receptor precursor (LR). We showed that LR binds to ST3 in vitro and can be cleaved by ST3 at two sites distinct from where other MMPs cleave. Through peptide sequencing, we determined that the two cleavage sites are in the extracellular domain between the transmembrane domain and laminin binding sequence. Furthermore, we demon strated that these cleavage sites are conserved in human LR. These results together with high levels of human LR and ST3 expression in carcinomas suggest that LR is a likely in vivo substrate of ST3 and that its cleavage by ST3 may alter cell-extracellular matrix interaction, thus, playing a role in mediating the effects of ST3 on cell fate and behavior ob- served during development and pathogenesis.展开更多
Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried ...Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried out in Ain Shams University hospital, Cairo, Egypt. 32 cases with vascular dementia were collected and classified into 2 subgroups;vascular dementia of multiinfarct type (VDMI) 14 patients, and vascular dementia of subcortical type (VDSC) 18 subjects. 23 cases with normal cognitive functions were collected as control group. Cases were subjected to comprehensive geriatric assessment, neurological examination, neuropsychological testing and brain CT scan. Blood sample was collected to analyze serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metalloproteinase 1 (TIMP1). Results: Mean serum level of TIMP1 (20.85 × 103 picogram/ml) was significantly lower than mean serum level of TIMP1 in control group (27.69 × 103 picogram/ml) (p = 0.018). The same finding was also evident when comparing VDMI subgroup mean serum TIMP1 (18.71 × 103 pc/ml) to control group (p = 0.025). There was no significant difference between mean serum MMP3 levels in cases group (mean = 67.39 × 103) as compared to control group (mean = 61.65 × 103 pc/ml) (p = 0.519). Conclusion: Patients with VD particularly VDMI has lower serum level of TIMP1 as compared to control group.展开更多
[Objectives] To observe the clinical effects of activating blood circulation to resolve blood stasis and glucosamine hydrochloride capsules therapy on post-traumatic knee osteoarthritis treatment,to measure the expres...[Objectives] To observe the clinical effects of activating blood circulation to resolve blood stasis and glucosamine hydrochloride capsules therapy on post-traumatic knee osteoarthritis treatment,to measure the expression of matrix metalloproteinase in post-traumatic knee osteoarthritis patients before and after treatment,and to explore its relevant molecular mechanisms. [Methods]A total of 60 patients with posttraumatic knee osteoarthritis in early stage in Affiliated Hospital of Shannxi University of Chinese Medicine from January 2015 to December2017 were selected and randomly divided into the control group( n = 30) and the observation group( n = 30). The control group was given oral administration of glucosamine hydrochloride capsules for 6 courses of the treatment. The observation group was using the activating blood circulation to resolve blood stasis therapy for 6 courses of treatment. The recovery of traumatic knee osteoarthritis and the symptom of traditional Chinese medicine( TCM) in 2 groups was compared before and after treatment. The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and the TCM symptom scores were recorded in both groups. And the synovial fluid and serum of patients were collected to detect the expression of matrix metalloproteinase. [Results]The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and TCM symptom scores of the 2 groups in the 1 st week,the 12 th week and the 24 th week after the treatment were significantly lower than those before the treatment,and the difference was statistically significant( P < 0. 05). Two therapeutic methods had certain therapeutic effects on the recovery from traumatic knee osteoarthritis,and could significantly improve the TCM syndrome. There were better therapeutic effects on oral decoction of traditional Chinese medicine than oral glycosaminoglycans hydrochloride capsules on treating traumatic knee osteogenesis( P < 0. 05). The expression level of MMP3 was decreased significantly in both groups( P <0. 001),while the expression level of MMP13 had no significant change in both groups( P >0. 05). The expression level of MMP1 was decreased significantly in the observation group( P < 0. 001),but there was no significant change in the control group after treatment( P >0. 05). [Conclusions]Two treatment methods have been effective in this clinical study. We found that the expression level of MMP3 was decreased significantly after treatment in 2 therapies,which can be clinically applied.展开更多
AIM:To investigate matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs) in pouch mucosa of pediatric onset ulcerative colitis(UC).METHODS:In this cross-sectional study,28 patients with pediatric onset UC...AIM:To investigate matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs) in pouch mucosa of pediatric onset ulcerative colitis(UC).METHODS:In this cross-sectional study,28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years(median) after proctocolectomy.Expression of MMPs-3,-7,-8,-9,-12 and-26 and TIMPs-1,-2 and-3 in samples was examined using immunohistochemichal methods,and another biopsy was used to evaluate the grade of histological inflammation.Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion,using a scale marking staining intensity as follows:0 = less than 20 positive cells;1 = 20-50 positive cells;2 = 50-200 positive cells;3 = over 20 positive cells.Fecal calprotectin and blood inflammatory markers [serum C-reactive protein(CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS:Of the 28 patients with pediatric onset UC,nine had not experienced pouchitis,whereas thirteen reported a single episode,and six had recurrent pouchitis(≥ 4 episodes).At the time of the study,six patients required metronidazole.In all of the others,the most recent episode of pouchitis had occurred over one month earlier,and none were on antibiotics.Only four samples depicted no sign of inflammation,and these were all from patients who had not had pouchitis.Two samples were too small to determine the grade of inflammation,but both had suffered pouchitis,the other recurrent.No sample depicted signs of colonic metaplasia.Most pouch samples showed expression of epithelial(e) and stromal(s) MMP-3(e,n = 22;s,n = 20),MMP-7(e,n = 28;s,n = 27),MMP-12(e,n = 20;s,n =24),TIMP-2(e,n = 23;s,n = 23) and MMP-3(e,n = 23;s,n = 28) but MMP-8(e,n = 0;s,n = 1),MMP-9(e,n = 0;s,n = 9) and MMP-26(e,n = 0;s,n = 3) and TIMP-1(n = 0,both) were lacking.In samples with low grade of inflammatory activity,the epithelial MMP-3 and MMP-7 expression was increased(r =-0.614 and r =-0.472,respectively,P < 0.05 in both).MMPs and TIMPs did not correlate with the markers of inflammation,fecal calprotectin,erythrocyte sedimentation rate,or CRP,with the exception of patients with low fecal calprotectin(< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMPor TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes.Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP-or TIMP-expression.CONCLUSION:The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease,but inflammation cannot be classified as a reactivation of the disease.展开更多
MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to...MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.展开更多
文摘We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen-B7 antigen was positive. Moreover, matrix metalloproteinase 3(MMP-3) was high. She was diagnosed with RS3 PE syndrome, and treatment with prednisolone(15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3 PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3 PE syndrome symptoms.
文摘The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. However like other MMPs, the molecular basis of ST3 function in vivo remains unclear due to the lack of information on its physiological substrates. Furthermore, ST3 has only weak activities toward all tested ECM proteins. Using thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we demonstrated previously that ST3 is important for apoptosis and tissue morphogenesis during intestinal remodeling. Here, we used yeast two-hybrid screen with mRNAs from metamorphosing tadpoles to identify potential substrate of ST3 during development. We thus isolated the 37 kd laminin receptor precursor (LR). We showed that LR binds to ST3 in vitro and can be cleaved by ST3 at two sites distinct from where other MMPs cleave. Through peptide sequencing, we determined that the two cleavage sites are in the extracellular domain between the transmembrane domain and laminin binding sequence. Furthermore, we demon strated that these cleavage sites are conserved in human LR. These results together with high levels of human LR and ST3 expression in carcinomas suggest that LR is a likely in vivo substrate of ST3 and that its cleavage by ST3 may alter cell-extracellular matrix interaction, thus, playing a role in mediating the effects of ST3 on cell fate and behavior ob- served during development and pathogenesis.
文摘Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried out in Ain Shams University hospital, Cairo, Egypt. 32 cases with vascular dementia were collected and classified into 2 subgroups;vascular dementia of multiinfarct type (VDMI) 14 patients, and vascular dementia of subcortical type (VDSC) 18 subjects. 23 cases with normal cognitive functions were collected as control group. Cases were subjected to comprehensive geriatric assessment, neurological examination, neuropsychological testing and brain CT scan. Blood sample was collected to analyze serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metalloproteinase 1 (TIMP1). Results: Mean serum level of TIMP1 (20.85 × 103 picogram/ml) was significantly lower than mean serum level of TIMP1 in control group (27.69 × 103 picogram/ml) (p = 0.018). The same finding was also evident when comparing VDMI subgroup mean serum TIMP1 (18.71 × 103 pc/ml) to control group (p = 0.025). There was no significant difference between mean serum MMP3 levels in cases group (mean = 67.39 × 103) as compared to control group (mean = 61.65 × 103 pc/ml) (p = 0.519). Conclusion: Patients with VD particularly VDMI has lower serum level of TIMP1 as compared to control group.
基金Supported by Shaanxi Administration of Traditional Chinese Medicine(LCPT034)
文摘[Objectives] To observe the clinical effects of activating blood circulation to resolve blood stasis and glucosamine hydrochloride capsules therapy on post-traumatic knee osteoarthritis treatment,to measure the expression of matrix metalloproteinase in post-traumatic knee osteoarthritis patients before and after treatment,and to explore its relevant molecular mechanisms. [Methods]A total of 60 patients with posttraumatic knee osteoarthritis in early stage in Affiliated Hospital of Shannxi University of Chinese Medicine from January 2015 to December2017 were selected and randomly divided into the control group( n = 30) and the observation group( n = 30). The control group was given oral administration of glucosamine hydrochloride capsules for 6 courses of the treatment. The observation group was using the activating blood circulation to resolve blood stasis therapy for 6 courses of treatment. The recovery of traumatic knee osteoarthritis and the symptom of traditional Chinese medicine( TCM) in 2 groups was compared before and after treatment. The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and the TCM symptom scores were recorded in both groups. And the synovial fluid and serum of patients were collected to detect the expression of matrix metalloproteinase. [Results]The symptoms and the quantitative assessment rating scale of knee osteoarthritis,the pain index of knee and TCM symptom scores of the 2 groups in the 1 st week,the 12 th week and the 24 th week after the treatment were significantly lower than those before the treatment,and the difference was statistically significant( P < 0. 05). Two therapeutic methods had certain therapeutic effects on the recovery from traumatic knee osteoarthritis,and could significantly improve the TCM syndrome. There were better therapeutic effects on oral decoction of traditional Chinese medicine than oral glycosaminoglycans hydrochloride capsules on treating traumatic knee osteogenesis( P < 0. 05). The expression level of MMP3 was decreased significantly in both groups( P <0. 001),while the expression level of MMP13 had no significant change in both groups( P >0. 05). The expression level of MMP1 was decreased significantly in the observation group( P < 0. 001),but there was no significant change in the control group after treatment( P >0. 05). [Conclusions]Two treatment methods have been effective in this clinical study. We found that the expression level of MMP3 was decreased significantly after treatment in 2 therapies,which can be clinically applied.
基金Supported by The Academy of Finland,Finska Lkaresllskapet,Helsinki University Central Hospital Research Fund,Finnish Cultural Foundation (to Mkitalo L)Biomedicum Helsinki Foundation (to Mkitalo L),Finland+2 种基金the Swedish Research Council,Sweden (to Saarialho-Kere U)the Pivikki and Sakari Sohlberg Foundation (to Kolho KL)the Finnish Pediatric Research Foundation (to Kolho KL)
文摘AIM:To investigate matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs) in pouch mucosa of pediatric onset ulcerative colitis(UC).METHODS:In this cross-sectional study,28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years(median) after proctocolectomy.Expression of MMPs-3,-7,-8,-9,-12 and-26 and TIMPs-1,-2 and-3 in samples was examined using immunohistochemichal methods,and another biopsy was used to evaluate the grade of histological inflammation.Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion,using a scale marking staining intensity as follows:0 = less than 20 positive cells;1 = 20-50 positive cells;2 = 50-200 positive cells;3 = over 20 positive cells.Fecal calprotectin and blood inflammatory markers [serum C-reactive protein(CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS:Of the 28 patients with pediatric onset UC,nine had not experienced pouchitis,whereas thirteen reported a single episode,and six had recurrent pouchitis(≥ 4 episodes).At the time of the study,six patients required metronidazole.In all of the others,the most recent episode of pouchitis had occurred over one month earlier,and none were on antibiotics.Only four samples depicted no sign of inflammation,and these were all from patients who had not had pouchitis.Two samples were too small to determine the grade of inflammation,but both had suffered pouchitis,the other recurrent.No sample depicted signs of colonic metaplasia.Most pouch samples showed expression of epithelial(e) and stromal(s) MMP-3(e,n = 22;s,n = 20),MMP-7(e,n = 28;s,n = 27),MMP-12(e,n = 20;s,n =24),TIMP-2(e,n = 23;s,n = 23) and MMP-3(e,n = 23;s,n = 28) but MMP-8(e,n = 0;s,n = 1),MMP-9(e,n = 0;s,n = 9) and MMP-26(e,n = 0;s,n = 3) and TIMP-1(n = 0,both) were lacking.In samples with low grade of inflammatory activity,the epithelial MMP-3 and MMP-7 expression was increased(r =-0.614 and r =-0.472,respectively,P < 0.05 in both).MMPs and TIMPs did not correlate with the markers of inflammation,fecal calprotectin,erythrocyte sedimentation rate,or CRP,with the exception of patients with low fecal calprotectin(< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMPor TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes.Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP-or TIMP-expression.CONCLUSION:The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease,but inflammation cannot be classified as a reactivation of the disease.
基金supported by Correlation between RECK and GH-type pituitary adenomas(No.21JR11RE027).
文摘MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.
