Differential biological activity of two extracts of ripe fruits of Carica candamarcensis Hook on human neutrophils / Actividad biologica diferencial de dos extractos de frutos maduros de Carica candamarcensis Hook en neutrófilos humanos

We evaluated the effect of the total macerate (TM) and seed oil (SO) of mature Carica candamarcensis fruits, on the release of Matrix metalloproteinase 9 (MMP9) and the phosphorylation of MAPK in neutrophils. The antioxidant capacity of these extracts was evaluated by ABTS assay. Neutrophils stimulated with different dilutions of TM or SO were analyzed for cytotoxicity, MMP9 release, and MAPK phosphorylation, using trypan blue exclusion assays, zymography, and immunoblotting, respectively. Both extracts show antioxidant activity, being higher in TM; none presented cytotoxic effect. The 5% and 2.5% dilutions of TM significantly reduced MMP9 release, and all decreased MAPK phosphorylation. SO significantly increased the release o f MMP9 and MAPK phosphorylation, the effect being greater when they were prestimulated with lipopolysaccharide.TM may have anti - inflammatory potential, while SO could have a priming effect that needs to be confirmed

Evaluamos el efecto del macerado total (MT) y aceite de semillas (AV) de frutos maduros de Carica candamarcensis , en la liberación de Matriz metaloproteinasa 9 (MMP9) y la fosfor ilación de MAPK en neutrófilos. La capacidad antioxidante de estos extractos se evaluó por ensayo ABTS. En neutrófilos estimulados con diferentes diluciones de MT o AV se analizó la citotoxicidad, liberación de MMP9 y fosforilación de MAPK, mediante ensayo s de exclusión con azul de tripano, zimografía e inmunotransferencia, respectivamente. Ambos extractos muestran actividad antioxidante, siendo mayor en MT; ninguno presentó efecto citotóxico. Las diluciones 5% y 2,5% de MT redujeron significativamente la l iberación de MMP9, y todas disminuyeron la fosforilación de MAPK. El AV incrementó significativamente la liberación de MMP9 y la fosforilación de MAPK, el efecto fue mayor cuando se preestimularon con lipopolisacárido. El MT puede tener potencial antiinfla matorio, mientras que el AV podría tener un efecto "priming" que necesita ser corroborado.

The predictive value of serum MMP-9 and sTREM-1 in postoperative urinary tract infection in patients with ureteral calculi / 国际检验医学杂志

Objective To investigate the predictive value of serum matrix metalloproteinase-9(MMP-9)and soluble triggering receptor expressed on myeloid cells-1(sTREM-1)in postoperative urinary tract infec-tion(UTI)in patients with ureteral calculi.Methods Among the ureteral calculi patients admitted to the De-partment of Urology in a hospital from October 2021 to October 2022,68 patients with postoperative UTI(UTI group)and 68 patients without UTI(non-UTI group)were selected as the study objects.Serum MMP-9 and sTREM-1 levels were detected by enzyme-linked immunosorbent assay(ELISA).Spearman method was used to analyze the correlation between serum MMP-9 and sTREM-1 levels and clinical data in UTI group,and the predictive value of serum MMP-9 and sTREM-1 levels in postoperative UTI in ureteral calculi patients was analyzed by receiver operating characteristic curve.The influencing factors of postoperative UTI in ureter-al calculi patients were analyzed by multivariate Logistic regression.Results Compared with non-UTI group,serum MMP-9 and sTREM-1 levels in UTI group were significantly increased,with statistical significance(P＜0.05).Correlation analysis showed that serum MMP-9 and sTREM-1 levels were positively correlated in UTI group(r=0.585,P＜0.001).The combined prediction of the area under the curve(AUC)for postopera-tive UTI in ureteral calculi patients was 0.961(95％CI:0.934-0.988).The sensitivity and specificity were 73.36％and 85.68％,respectively.The AUC predicted by MMP-9 and sTREM-1 was higher than that predic-ted by MMP-9 and STREM-1 alone(Z=25.420,P＜0.001;Z=21.531,P＜0.001).The levels of MMP-9 and sTREM-1 were the influencing factors of postoperative UTI in ureteral calculi patients(P＜0.05).Conclusion The serum levels of MMP-9 and sTREM-1 in postoperative UTI in ureteral calculi patients are increased,and the detec-tion of both levels has important predictive value for the occurrence of postoperative UTI in ureteral calculi patients.

To evaluate the predictive value of multimodal ultrasound combined with serum matrix metalloproteinase-9 in the recurrence of breast cancer after breast-conserving surgery / 中华内分泌外科杂志

Objective:To explore the predictive value of multimodal ultrasound features combined with serum matrix metalloproteinase-9 (MMP-9) detection for tumor recurrence of breast cancer after breast-conserving surgery.Methods:A total of 194 patients with breast cancer who underwent breast-conserving surgery in Affiliated Hospital of Jining Medical College from Jan. 2017 to May. 2018 were selected. Routine ultrasound, automated breast volume imaging and contrast-enhanced ultrasound were performed before surgery. Logistic regression equation was used to analyze the risk factors affecting local tumor recurrence after breast-conserving surgery, and ROC curve was drawn to analyze the predictive value of multimodal ultrasound features combined with serum MMP-9 for local tumor recurrence after breast-conserving surgery.Results:After 5 years of follow-up, 29 out of 194 breast cancer patients who underwent breast-conserving surgery had local recurrence and metastasis. There were no significant differences in tumor diameter, spiculation sign, convergence sign, Alder blood flow grade, enhancement sequence, pattern and enhancement intensity between the two groups ( P>0.05 t=1.48, P=1.451; χ2=0.55, P=0.460; χ2=0.50, P=0.478; χ2=0.60, P=0.439; χ2=0.50, P=0.780; χ2=0.04, P=0.981; χ2=0.13, P=0.716). Logistic regression analysis showed that irregular tumor shape, small calcification,Peripheral radial enhancement, perfusion defect and abnormal elevation of serum MMP-9 were independent risk factors for local recurrence of breast cancer after breast-conserving surgery ( P=0.034, 95%CI=1.177~62.266; P=0.048, 95%CI=1.022~58.397; P=0.045, 95%CI=1.100~56.756; P=0.043, 95%CI=1.079~ 60.937; P=0.044, 95%CI=1.000~1.026). ROC curve showed that the AUC of multimodal ultrasound features combined with serum MMP-9 in predicting local tumor recurrence after breast-conserving surgery was 0.970, and the sensitivity and specificity were 98.63% and 91.67%, respectively. Conclusions:Multimodal ultrasound features combined with serum MMP-9 detection have high application value in the evaluation of local tumor recurrence after breast-conserving surgery, and provide a new idea for the clinical diagnosis and treatment of breast cancer.

Expression and pathological diagnostic value of extracellular matrix metalloproteinase inducer,ma-trix metalloproteinase-9 and lysine demethylase 6B in invasive breast cancer / 新乡医学院学报

Objective To investigate the expressions of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-9(MMP-9),lysine demethylase 6B(KDM6B)proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.Methods The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People's Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens＞1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic(ROC)curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.Results The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues(P＜0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＞0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer(P＞0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer(P＞0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis(TNM)staging of invasive breast cancer(P＜0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P＜0.05).In the WHO grades Ⅰ,Ⅱ,and Ⅲ of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages Ⅲ-Ⅳ were significantly higher than those in stages Ⅰ-Ⅱ(P＜0.05),while the relative expression of KDM6B protein was significantly lower than that in stages Ⅰ-Ⅱ(P＜0.05).In the group of invasive breast cancer with diameter≤2 cm,2 to 5 cm,and＞5 cm,the relative expression of MMP-9 protein increased sequentially(P＜0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues(r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein(r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein(r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve(AUC)of EMMPRIN protein for diagnosing invasive breast cancer was 0.875[95％confidence interval(CI):0.823-0.926,P＜0.05],with an optimal threshold of 10.043,sensitivity of 79.0％,and specificity of 76.8％;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863(95％CI:0.808-0.917,P＜0.05),with an optimal threshold of 10.070,sensitivity of 74.2％,and specificity of 76.8％;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267(95％CI:0.196-0.338,P＜0.05),with an optimal threshold of 11.003,sensitivity of 71.0％,and specificity of 98.6％.Conclusion EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.

The therapeutic effect of dual microcatheter technology on acute intracranial wide necked aneurysms / 中国医师杂志

Objective:To explore the therapeutic effect of dual microcatheter technology on acute intracranial wide necked aneurysms and its impact on serum levels of matrix metalloproteinase-9 (MMP-9), neuron specific enolase (NSE), and central nervous system specific protein (S100β).Methods:A prospective study was conducted on 80 patients with acute intracranial wide neck aneurysms admitted to the Affiliated Suzhou Hospital of Anhui Medical University from January 2020 to March 2023. They were randomly divided into an observation group and a control group, with 40 cases in each group, using a random number table method. The control group patients were treated with stent assisted spring coil intervention embolization, while the observation group patients were treated with dual microcatheter technology intravascular intervention embolization. We compared the perioperative conditions of two groups, including changes in serum MMP-9, NSE, and S100β, as well as short-term prognosis, changes in the National Institutes of Health Stroke Scale (NIHSS) score, Barthel Index (BI) score, and incidence of complications.Results:The observation group had shorter surgical and hospital stay than the control group, and the difference was statistically significant (all P<0.05); At 7 days after surgery, the serum levels of MMP-9, NSE, and S100β in the observation group were lower than those in the control group, and the differences were statistically significant (all P<0.05); The short-term good prognosis rate of the observation group was 55.00%(22/40), significantly higher than the control group′s 32.50%(13/40), and the difference was statistically significant (all P<0.05); At one month after surgery, the NIHSS score in the observation group was lower than that in the control group, while the BI score was higher than that in the control group, with statistically significant differences (all P<0.05); There was no statistically significant difference in the total incidence of postoperative complications between the two groups ( P>0.05). Conclusions:The dual microcatheter technique has a significant therapeutic effect on acute intracranial wide neck aneurysms, reducing the increase in serum MMP-9, NSE, and S100β levels after surgery, promoting postoperative recovery, and is worthy of clinical promotion.

Title correlation analysis of chitinase-3 like-protein-1, matrix metalloproteinase-9 and imaging markers in middle aged and elderly patients with cerebral small vessel disease / 中华老年医学杂志

Objective:This study aimed to investigate the correlation between serum chitinase-3 like-protein-1(YKL-40), matrix metalloproteinase-9(MMP-9), and imaging markers in middle-aged and elderly patients with cerebral small vessel disease(CSVD).It also sought to elucidate the mechanism underlying the onset and development of CSVD.Methods:A case-control study was conducted with 130 CSVD patients and 20 age-matched controls admitted to the Department of Neurology of the Second Affiliated Hospital of Zhengzhou University between December 2020 and November 2022.Based on their white matter hyperintensity(WMH)and enlarged perivascular spaces(EPVS)scores, CSVD patients were categorized into mild, moderate, and severe groups.Cerebral microbleeds(CMBs)were classified into non-lacunar, lacunar, non-CMBs, and CMBs groups.Patients' general data were collected, and serum levels of YKL-40 and MMP-9 were measured using ELISA.Results:The results showed 34 cases in the severe WMH group, 35 cases in the EPVS severe group, 90 cases in the group with lacunar and 65 cases in the group with CMBs.Statistically significant differences(both P<0.05)in serum YKL-40 and MMP-9 in WMH severe groups compared to age control group.Statistically significant differences(both P<0.05)in serum YKL-40 and MMP-9 in EPVS severe groups compared to age control group.The increase of serum YKL-40 and MMP-9 levels was an independent risk factor for the severity of WMH( OR=1.25, 95% CI: 0.164-0.289, P<0.05)( OR=1.13, 95% CI: 0.090-0.160, P<0.05)and EPVS( OR=1.05, 95% CI: 0.021-0.076, P<0.05)( OR=1.02, 95% CI: 0.006-0.026, P<0.05).There was no significant different in the serum YKL-40 and MMP-9 levels between lacunar group and non-lacunar group( P>0.05).The serum YKL-40 and MMP-9 levels in the group with CMBs were significantly higher than those in the group without CMBs( P<0.05).The ROC curve showed that the optimal cutoff point of YKL-40 was 0.38, the area under the curve was 0.669(95% CI: 0.569-0.768, P<0.01), the optimal cutoff point of MMP-9 was 0.40, and the area under the curve was 0.746(95% CI: 0.644-0.848, P<0.01). Conclusions:Changes in serum YKL-40 and MMP-9 levels in middle-aged and elderly patients with CSVD were found to be associated with various imaging markers, potentially contributing to the onset and development of CSVD.These findings may aid in early CSVD diagnosis and provide insights for potential interventions.

Clinical study of timolol maleate combined with cryotherapy for infantile cutaneous hemangioma / 局解手术学杂志

Objective To explore the clinical effect of timolol maleate combined with cryotherapy for infantile cutaneous hemangioma.Methods A total of 240 infants with cutaneous hemangioma were randomly divided into the control group(120 cases)and the combined group(120 cases).The control group was treated with timolol maleate,and the combined group was treated with timolol maleate combined with cryotherapy.The clinical efficacy,tumor diameter,levels of serum matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)and the occurrence of adverse reactions of the two groups were compared.Results The total effective rate of the combined group was significantly higher than that of the control group(P<0.05).Compared with before treatment,the tumor diameter 3 months and 6 months after treatment in the two groups gradually decreased(P<0.05),and the tumor diameter 3 months and 6 months after treatment in the combined group decreased more obviously(P<0.05).Compared with before treatment,the levels of serum MMP-9 and VEGF 3 months and 6 months after treatment in the two groups gradually decreased(P<0.05),and the levels of serum MMP-9 and VEGF 3 months and 6 months after treatment in the combined group were significantly lower than those in the control group(P<0.05).There was no statistically significant difference in the total incidence of adverse reactions such as eczema,ulcer,erosion or redness between the two groups(P>0.05).Conclusion Timolol maleate combined with cryotherapy for infantile cutaneous hemangioma has significant curative effect,which can effectively reduce the levels of serum MMP-9 and VEGF,and shrink the tumor body,with safety and effectiveness.

Effects of ICMT gene silencing on the invasion and migration of human salivary adenoid cystic carcinoma cells in vitro / 口腔疾病防治

Objective @#To investigate the effect of isoprene cysteine carboxymethyltransferase (ICMT) gene on the migration and invasion of salivary adenoid cystic cancer cells (SACC) and the related mechanism, to provide experimental evidence for molecular targeted therapy of SACC.@*Methods@# Adenoid cystic cancer cells SACC-LM and SACC-83 were cultured in vitro, and siRNA was transfected into human SACC-LM and SACC-83 cells (experimental group) by transient transfection of a liposome vector. A blank control group and negative control group were set up respectively (transfected NC-siRNA). qRT-PCR was peformed to measure the mRNA expression of ICMT and RhoA in each group after transfection and to determine the silencing efficiency. The expression of ICMT, membrane RhoA, total RhoA, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and Rho associated with coiled helical binding protein kinase 1 (ROCK1) in each group was detected by Western blot. The proliferation abilityies of SACC cells was detected by CCK-8 assay. The migration and invasion ability of SACC cells were detected by comparing the relative healing area of cell scratch assay and the number of Transwell assay cells. @*Results@#After transfection of ICMT-siRNA into SACC-LM and SACC-83 cells, the expression of ICMT gene and protein in the experimental group was significantly decreased compared with the negative control group and blank control group (P<0.05), but there were no significant differences in the expression of RhoA gene and total protein among all groups (P>0.05). The expression of RhoA membrane proteins, ROCK1, MMP-2, MMP-9 in the experimental group was significantly decreased compared with that in the negative control group and blank control group (P<0.05). Cell proliferation ability was significantly decreased (P<0.05). The migration and invasion abilities were significantly decreased (P<0.05). @*Conclusion @#In vitro silencing of ICMT gene can effectively inhibit the migration and invasion of human SACC-LM and SACC-83 cells, and the mechanism may be related to RhoA-ROCK signaling pathway.

Effect of Modified Zhenwutang on Interstitial Fibrosis in Rats with Chronic Renal Failure Based on IL-6/MMP-9/COL-Ⅳ Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the modulatory effect of modified Zhenwutang on the interleukin-6 （IL-6）， matrix metallopeptidase-9（MMP-9）， type Ⅳ collagen（COL-Ⅳ） in rats with chronic renal failure （CRF） and to investigate the potential mechanism of its treatment of CRF. MethodFifty male SD rats were randomly divided into a modeling group of 40 rats and a normal group of 10 rats， and the modeling group was prepared by continuous adenine gavage for 12 weeks. After successful modelling， the modelling group was divided into the model group， the low dose （7.2 g·kg-1·d-1） group， the medium dose （14.4 g·kg-1·d-1） group， the high dose （28.8 g·kg-1·d-1） group and the Benadryl hydrochloride （10 mg·kg-1·d-1） group for gavage according to the random number table method， In the normal group and the model group， equal volume of distilled water was administered by gavage for 4 weeks. After the administration， the levels of blood creatinine （SCr）， blood urea nitrogen （BUN） and 24 h urine protein （24 h-UTP） were measured， the levels of serum IL-6 were measured by enzyme linked immunosorbent assay（ELISA）. Immunohistochemistry （IHC） was used to detect intercellular cell adhesion molecule-1 （ICAM-1）， IL-6， MMP-9， and other molecules in the rat kidney. The expression of ICAM-1 mRNA， IL-6 mRNA， MMP-9 mRNA and COL-Ⅳ mRNA in rat kidney tissues was measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression levels of ICAM-1， IL-6， MMP-9 and COL-Ⅳ in rat kidney tissues were measured by Western blot. ResultCompared with the normal group， the levels of SCr， BUN and 24 h-UTP were significantly increased in the model group （P<0.01）； the serum IL-6 level was significantly increased （P<0.01）， the tubular lumen was dilated with atrophy， the tubular epithelial cells were necrotic， swollen and vacuolated， the interstitium was infiltrated by a large number of inflammatory cells and collagen fibers were deposited， the levels of IL-6， ICAM-1 and COL-Ⅳ were strongly positive in the tubular interstitium of the model group （P<0.01）， The levels of ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA were significantly increased （P<0.01） and MMP-9 mRNA was significantly decreased （P<0.05） in the model rats. ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly increased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01） in the renal tissue， and MMP-9 protein expression was significantly decreased （P<0.01）. Compared with the model group， the 24 h-UTP， SCr and BUN levels of rats were significantly reduced after treatment with modified Zhenwutang （P<0.01）， the serum IL-6 level was significantly decreased （P<0.01）， the renal lesions of rats were significantly improved and collagen fiber deposition was reduced； the expression of IL-6， ICAM-1 and COL-Ⅳ in renal tubules and interstitium was weakened， and MMP-9 in ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA levels were significantly reduced （P<0.01） and MMP-9 mRNA levels were significantly increased （P<0.05）， ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly reduced （P<0.01） and MMP-9 protein expression was significantly The expression of ICAM-1， IL-6 and COL-Ⅳ proteins was significantly decreased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01）. ConclusionModified Zhenwutang may regulate the IL-6/MMP-9/COL-Ⅳ signaling pathway， thereby reducing proteinuria， improving renal function， reducing renal pathological damage and delaying the progression of CRF interstitial fibrosis.

The role of Nrf2 in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated MMP9 / 中华劳动卫生职业病杂志

Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.

Identification the key factor of pulmonary fibrosis following silica nanoparticles exposure based on bioinformatics analysis / 中华劳动卫生职业病杂志

Objective: To investigate the main mechanisms of pulmonary fibrosis following silica nanoparticles (SiNPs) exposure through constructing the macrophage-fibroblast model in vitro, which simulated the process of pulmonary fibrosis. Methods: In January 2021, human mononuclear leukemia cells (THP-1) were treated with 0, 25, 50, 100 μg/ml SiNPs for 24 h. The supernatant of THP-1 cells was collected and applied to human embryonic lung fibroblast cells (MRC-5) which divided into control and low, medium and high dose groups at the logarithmic growth stage for 24 h. MRC-5 cell viability was detected by CCK8. The hydroxyproline (Hyp), interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) expression were detected in the supernatants of MRC-5. The changed proteins were detected by liquid-phase mass spectrometry in high dose group. GeneCard database were applied to identity the differential pulmonary fibrosis proteins in high dose group. Gene Ontology (GO) was performed to identity the key biological process in differential pulmonary fibrosis proteins of high dose group. The String database was used to construct the protein-protein interactions (PPI) network of differential pulmonary fibrosis proteins. The APP of CytoHubba was applied to calculate the key protein of differential pulmonary fibrosis proteins in PPI network. Correlation coefficients between key differential pulmonary fibrosis proteins were calculated using Pearson correlation analysis. Western blotting was applied to detect the expression of key proteins of differential pulmonary fibrosis proteins in different groups. Results: CCK8 results showed that MRC-5 cell viability was increasing in low, medium and high dose groups compared with control group (P<0.05). The expression levels of Hyp and IL-1β in different group were increased compared with control group, the expression levels of IL-6 and TNF-α were increased in high dose group compared with control group (P<0.05). GeneCard database identified 26 differential pulmonary fibrosis proteins, which were mainly involved in extracellular matrix hydrolysis, cell inflammatory response, tissue repair, cell proliferation, inflammation response by GO analysis. The APP of CytoHubba was calculated that matrix metalloproteinase 9 (MMP9) and tissue inhibitor metalloproteinase 1 (TIMP1) played an important role in PPI network. The results of correlation analysis showed that MMP9 was correlated with the expression of matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3), TIMP1 and epidermal growth factor receptor (EGFR) (r=0.97, 0.98, 0.94, 0.93, P<0.05). Western blotting results showed that TIMP1 protein expression was increased in low, medium and high dose groups, while MMP9 protein expression was increased only in high dose group (P<0.05) . Conclusion: Differential expression proteins related with pulmonary fibrosis in MRC-5 cells mainly regulate biological processes of extracellular matrix hydrolysis, tissue repair, and cellular inflammation response following SiNPs exposure. MMP9 and TIMP1 may be the key proteins, which affected the fibrosis process in vitro pulmonary fibrosis model.

Matrix metalloproteinase-9 and cerebral small vessel disease / 国际脑血管病杂志

Cerebral small vessel disease (CSVD) is a series of clinical syndrome characterized by the damage of small blood vessels in the brain caused by a variety of causes. Although the pathophysiological mechanisms of CSVD are not fully understood, increasing evidence suggests that matrix metalloproteinase-9 plays an important role in the occurrence and development of CSVD.

Evaluation of CT perfusion imaging parameters and serum CTRP-3,LDL-C and MMP-9 on the hemorrhage transformation after acute cerebral infarction / 中国医学装备

Objective:To explore the evaluations of computed tomography(CT)perfusion imaging parameters and serum complement C1q/tumor necrosis factor related protein-3(CTRP-3),low density lipoprotein cholesterol(LDL-C),matrix metalloproteinase-9(MMP-9)on hemorrhagic transformation(HT)after acute cerebral infarction(ACI).Methods:A total of 206 ACI patients who admitted to the People's Hospital of Jianyang from August 2019 to July 2022 were retrospectively selected as the study objects.The patients were divided into HT group(45 cases)and non-HT group(161 cases)according to whether occurred HT after intravenous thrombolysis.The CT perfusion imaging parameters[blood flow(BF),blood volume(BV),mean transit time(MTT),permeability surface(PS)],CTRP-3,LDL-C,MMP-9 were compared between two groups.Receiver operating characteristic(ROC)curve model was used to analyze the area under curve(AUC)values,sensitivities and specificities of CT perfusion imaging parameters,CTRP-3,LDL-C and MMP-9 in diagnosing HT.Results:The BF and BV of HT group were lower than those of non-HT group,while the MTT and PS of HT group were higher than those of non-HT group,and the differences were statistically significant(t=-5.941,t=-5.777,t=5.863,t=6.954,P<005),respectively.The CTRP-3 and LDL-C of HT group were respectively lower than those of non-HT group,while the MMP-9 of HT group was higher than that of non-HT group,with statistical significances(t=-3.788,t=-5.835,t=6.935,P<0.05).The ROC curve analysis showed that the AUC values of BF,BV,MTT,PS,CT comprehensive parameters,CTRP-3,LDL-C and MMP-9 were respectively 0.790,0.779,0.738,0.775,0.949,0.692,0.777 and 0.785(P<0.05).The sensitivities of them were respectively 88.90%,100.00%,53.30%,66.70%,100.00%,88.90%,66.70%and 78.60%.The specificities of them were respectively 64.60%,51.60%,91.30%,77.60%,81.40%,47.80%,78.90%and 75.80%.The differences of the AUC values between CT comprehensive parameters and CTRP-3,and between that and LDL-C,and between that and MMP-9 were significant(Z=6.202,Z=4.563,Z=3.704,P<0.05),respectively.Conclusion:CT perfusion imaging parameters,serum CTRP-3,LDL-C and MMP-9 levels have close correlation with HT after ACI.The monitoring of the change degrees of them is helpful to provide important references for predicting the occurrence of HT in ACI patients after thrombolytic therapy.

Study on the analysis on the clinical effect of hyperbaric oxygen chamber in treating the postoperatively malignant brain edema of craniocerebral trauma / 中国医学装备

Objective:To study the clinical effect of NBYY-BXDR-001 hyperbaric oxygen chamber in treating the postoperatively malignant brain edema of craniocerebral trauma,and the effects of that on the levels of matrix metalloproteinase-9(MMP-9),neutrophil gelatinase-associated lipocalin(NGAL),tenascin-C(TNC)and tumor necrosis factor-ɑ(TNF-ɑ).Methods:A total of 84 patients with postoperatively malignant brain edema of craniocerebral trauma who admitted to the hospital were selected,and they were divided into an observation group(45 cases received the interventional treatment of hyperbaric oxygen within postoperative 1-3 days)and a control group(39 cases received interventional treatment of hyperbaric oxygen within postoperative 4-10 days)according to the different therapeutic times of postoperative hyperbaric oxygen.The levels of serum MMP-9,NGAL,TNC and TNF-ɑof the two groups of patients were compared.The Glasgow Coma Scale(GCS)scores and the duration of brain edema of patients before and after treatment were recorded,and the mortality rates of the two groups of patients also were recorded.Results:There was no statistically significant difference in postoperative mortality rates between the two groups.The overall efficacy of the observation group was significantly better than that of the control group,and the difference was statistically significant(Z=-2.203,P<0.05).The GCS scores of the patients of the observation group at the 1st week,2nd week,3rd week and 4th week after surgery were significantly higher than that at the 1st d after surgery,and the differences were statistically significant(t=5.236,t=5.687,t=6.354,t=6.782,P<0.05),respectively.The serum MMP-9,NGAL,TNC and TNF-ɑ levels of the two groups of patients at the 1st week,2nd week,3rd week and 4th week after surgery were significantly lower than those at the 1st day after surgery,and the differences were statistically significant(Fobservation group= 125.127,F=98.224,F=137.791,F=105.226,Fcontrol group=113.370,F=73.363,F=115.520,F=84.069,P<0.05),respectively.At the 2nd,3rd and 4th week after surgery,the GCS scores of the observation group were significantly higher than those of the control group,and the serum MMP-9,NGAL,TNC and TNF-ɑ of the observation group were significantly lower than those of the control group,and the differences were statistically significant(tMMP-9=5.689,t=6.879,t=8.253,tNGAL=8.658,t=9.657,t=8.658,tTNC=6.587,t=6.354,t=6.859,tTNF-ɑ=7.898,t=8.654,t=8.256,P<0.05),respectively.Compared with the control group,the peak time and duration of brain edema of the observation group were significantly shortened,and the differences of them between two groups were statistically significant(t=2.064,t=-2.084,P<0.05),respectively.Conclusion:Early interventional treatment of hyperbaric oxygen in patients with postoperatively malignant brain edema of craniocerebral trauma can contribute to relieve postoperative brain edema and improve the treatment effect,which is related to the adjustment of hyperbaric oxygen for serum MMP-9,NGAL,TNC and TNF-ɑ levels.

An in vitro study of the effect of Mycobacterium tuberculosis infection on the expression of bone destruction-related factors in osteoclasts / 中国脊柱脊髓杂志

Objectives:To establish a model of Mycobacterium tuberculosis infection of osteoclasts(OC)and explore the mechanism of Mycobacterium tuberculosis infection on OC.Methods:Peripheral blood mononuclear cells(peripheral blood mononuclear cells,PBMCs)were isolated from healthy volunteers.Receptor activator of nuclear factor-KB ligand(RANKL)and macrophage-colony stimulating factor(M-CSF)were used to make PBMCS into OC,and tartrate resistant acid phosphatase(TRAP)staining was performed on the cells.The constructed kanamycin resistant H37Rv pMV261-GFP green fluorescent strain was resuscitated and cultured with 10％oleic albumin dextrose catalase(OADC),7H9 and kanamycin containing Mycobacterium tuberculosis special liquid medium in an incubator at 37℃ until the optical density(OD)value was about 0.5 at 600nm.The OC cells cultured alone were set as the blank control group.And OC cells were also infected with Mycobacterium tuberculosis at different multiplicity of infection(MOI)for 24h,and MTT colorimetric method was used to detect cell survival rate.The MOI with the highest cell survival rate was selected as experimental MOI,and OC cells infected with H37Rv at experimental MOI were set as the experimental group.Fluorescence microscopy and Mycobacterium tuberculosis acid-fast staining were used to observe the transfection of Mycobacterium tuberculosis at the experimental MOI.Quantitative real-time PCR(qRT-PCR)was used to detect the expressions of non-receptor tyrosine kinase C-src,cathepsin K(CK),carbonic anhydrase 2(CA2),Integrin-β3 and matrix metalloproteinase-9(MMP-9).Immunohistochemistry was used to detect the expressions of P-src,CK,CA2,Integrin-β3 and MMP-9 on the cell surface.Western blot(WB)was used to detect the protein expression levels of P-src,CK,CA2,Integrin-β3,and MMP-9.Results:TRAP staining showed that more than 90％of the cells were OC after 15d of culture,which could be used for experiments.The results of MTT colorimetric assay showed that the cell survival rate was the highest when the MOI was 20:1(P＜0.05).This transfection multiplicity can be used as the concentration of experimental group.Fluorescence microscopy showed that when the transfection multiplicity ratio was 20:1,the green fluorescent Mycobacterium tuberculosis entered the OC and was successfully transfected into the OC.The results of acid-fast staining after infection of OC with Mycobacterium tuberculosis showed that when the MOI was 20:1,the acid-fast Mycobacterium tuberculosis stained red entered OC and was also successfully transfected into OC.The results of qRT-PCR,cell immunohistochemistry,and WB showed that the expressions of MMP-9,CK,C-src,CA2,and Integrin-β3 in the experimental group were higher than those in the blank control group(P＜0.05).Conclusions:Mycobacterium tuberculosis can transfect OC;Compared with the blank control group,the levels of five bone destruction factors in the experimental group transfected with OC by Mycobacterium tuberculosis were increased,suggesting that bone destruction of spinal tuberculosis may be related to this,which may provide a new exploration direction for the diagnosis and treatment of bone tuberculosis diseases.

The level and significance of CD64 index, matrix metalloproteinase-9 and serum amyloid A in peripheral blood of patients with severe carbapenem resistant Enterobacteriaceae infection / 中国医师杂志

Objective:To investigate the level and significance of CD64 index, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) in peripheral blood of patients with severe carbapenem resistant Enterobacteriaceae (CRE) infection.Methods:A total of 61 patients with severe CRE infection who were admitted to the neurosurgery department of Kashgar First People′s Hospital from January 2019 to January 2022 were selected as the CRE group, and 100 patients with severe carbapenem sensitive Enterobacteriaceae (CSE) infection were selected as the CSE group. The difference in clinical data between the two groups was compared, and the difference in clinical data between the dead and surviving patients in the CRE group was compared. The value of CD64 index, MMP-9 and SAA in differential diagnosis of CRE was analyzed. Logistic regression was used to analyze the influencing factors of prognosis in patients with CRE infection.Results:The age, hypertension, lung disease, liver and kidney disease, comorbidities≥2, antibiotic use≥2 combinations, antibiotic use time>10 days, proportion of carbapenem use, CD64 index, MMP-9, and SAA of the CRE group patients were significantly higher than those of the CSE group patients (all P<0.05). The area under the receiver operating characteristic (ROC) curve for CD64 index, MMP-9, and SAA differential diagnosis of CRE was 0.857, 0.701, and 0.655, respectively (all P<0.05). In the CRE group, the age , the score of Acute Physiological and Chronic Health Status Ⅱ (APACHE Ⅱ) score at admission, diabetes, liver and kidney diseases, comorbidities≥2, the proportion of carbapenems, CD64 index, MMP-9 and SAA of dead patients were significantly higher than those of survivors (all P<0.05). Logistic regression analysis showed that age, APACHE Ⅱ score at admission, comorbidities≥2, CD64 index, MMP-9, and SAA were influencing factors for the prognosis of severe CRE patients (all P<0.05). Conclusions:The peripheral blood CD64 index, MMP-9, and SAA have certain application value in the diagnosis of neurological severe CRE infection, and are also influencing factors for the prognosis of CRE infected patients.

High mobility group box-1 inhibition reduces expression of matrix metalloproteinase-9 in astrocytes in rats after spinal cord injury / 中华创伤骨科杂志

Objective:To investigate the role and underlying mechanisms of inhibiting high mobility group box-1 (HMGB1) in the expression of matrix metalloproteinase-9 (MMP-9) in spinal cord astrocytes (AS) in rats after spinal cord injury (SCI).Methods:After an SCI model was established in Sprague-Dawley (SD) rats using a modified Allen's Weight-Dropping method and ethyl pyruvate (EP) or glycyrrhizin (GL) was used to inhibit the effect of HMGB1, the rats were divided into a sham group, an SCI group, an SCI+EP (50 mg/kg) group, and an SCI+GL (100 mg/kg) group. The expression levels of glial fibrillary acid protein (GFAP) and MMP-9 in spinal cord AS were observed. After the spinal cord AS in SD rats was cultured and incubated by the oxygen-glucose deprivation/reoxygenation (OGD/R) procedure, the expression of MMP-9 protein was detected at 6 h/R 6 h, 12 h, 24 h, and 48 h after OGD. The time point with the highest expression was chosen in the subsequent experiments as an OGD/R group. HMGB1 was inhibited by HMGB1 shRNA or EP to observe the effect of HMGB1 on the expression of MMP-9 protein in AS treated with OGD/R. Then, toll-like receptor 4 (TLR4) inhibitor, TIR-domain-containing adaptor inducing interferon- β (TRIF) inhibitor, and nuclear factor-kappa B (NF- κB) inhibitor were used to investigate the effects of TLR4/TRIF/NF- κB signaling pathway during the regulation of HMGB1 on MMP-9 in vitro. Results:Western blot showed that the expression of MMP-9 protein in the spinal cord was significantly increased in rats at 1 d after SCI, and the expression of MMP-9 protein in the SCI+EP group and the SCI+GL group was significantly lower than that in the SCI group ( P<0.001). Immunofluorescence showed that GFAP and MMP-9 proteins were co-localized in the spinal cord after SCI, and the expression of GFAP and MMP-9 proteins in the SCI+EP and SCI+GL groups was significantly lower than that in the SCI group ( P<0.05). Since the expression of MMP-9 protein in the spinal cord AS cultured in vitro was significantly higher in the OGD 6h/R 12h group than that in the normal group and the OGD 6h/R 6h, 24, and 48 h groups, the OGD 6h/R 12h was taken as the OGD/R group. The MMP-9 protein expression in AS in the OGD/R+HMGB1 shRNA group and the OGD/R+EP group was significantly lower than that in the OGD/R group ( P<0.001). In the cultured AS, moreover, inhibiting TLR4, TRIF, and NF- κB reduced MMP-9 protein expression after OGD 6 h/R 12 h when compared with that in the OGD/R group ( P<0.001). Conclusions:HMGB1 inhibition may result in a reduction in MMP-9 expression both in the spinal cord AS in SCI rats and in AS after OGD/R treatment in vitro. HMGB1 may regulate MMP-9 protein expression in AS after OGD/R treatment via the TLR4/TRIF/NF- κB signal pathway.

Association of Circulating Matrix Metalloproteinase-9 and the Risk of Coronary Heart Disease in Young Smokers

@#Introduction: Smoking causes cardiovascular risk which may alter the stability between the production and degradation of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is a zinc-containing endopeptidase that degrades the extracellular matrix and plays a vital role in tissue remodeling. As a result, elevated serum MMP-9 levels produced by smoking, particularly at young age, raise the risk of future CHD. So this study aims to find out the possible relationship between circulating MMP-9 and the risk of cardiovascular disease in young smokers. Methods: The study was conducted on smokers with CHD subjects attending cardiology and medicine OP of the SRM Medical College Hospital and research center Tamil Nadu, India. The study group was divided into three groups. Group 1 includes 120 healthy controls as nonsmokers, Group 2 includes 120 smokers with Coronary heart disease (CHD), and Group 3 includes 120 smokers with diabetes and CHD subjects in the age group of 20-55 years. Serum MMP-9, hs-CRP, and APO-E levels were measured using the ELISA method and the lipid level was measured enzymatically using AU480 automatic analyzer (back man coulter). Results: The mean serum MMP-9, hs-CRP, and APO-E levels were significantly higher in both groups (p<0.05) when compared to controls. The study also shows a significant positive association between MMP-9 with hs-CRP, APO-E, smoking burden, and smoking intensity. Conclusion: The study concludes a significant association exists between cigarette smoking with MMP-9 and also relative exposure to circulating inflammation markers plays a potential role in the pathogenesis of CHD.

Changes of biomarkers in plasma of patients with occupational silicosis and their diagnostic value / 中国职业医学

{L-End}Objective To analyze the changes of seven potential biomarkers in plasma of patients with occupational silicosis (hereinafter referred to as "silicosis"), and explore their clinical value in determining the stage of silicosis. {L-End}Methods A total of 100 male silicosis patients were selected as the silicosis group (63 cases in stage Ⅰ and 37 cases in stage Ⅱ subgroups), and 100 male healthy individuals were selected as the control group using the 1∶1 matched case-control study. Enzyme-linked immunosorbent assay was used to analyze the level of interleukin-17 (IL-17), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), Krebs von den Lungen-6 (KL-6), connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), and histone H4 in plasma. Their clinical value for diagnosing silicosis was evaluated using receiver operating characteristic (ROC) curve, discriminant analysis stepwise method, and Fisher discriminant function analysis. {L-End}Results The levels of IL-17, MCP-1, MMP-9, KL-6, CTGF, PDGF, and histone H4 in the plasma of the silicosis group, silicosis stage Ⅰ subgroups, and stage Ⅱ subgroups were higher than those in the control group (all P<0.05). The levels of IL-17, MCP-1, and MMP-9 in the plasma of the stage Ⅱ subgroup decreased (all P<0.05), while the levels of KL-6, CTGF and histone H4 increased (all P<0.05) compared with the stage Ⅰ subgroup. The area under the ROC curve for diagnosing silicosis using these seven potential biomarkers ranged from 0.761 to 1.000 (all P<0.01), with the sensitivity of 0.640-1.000, the specificity of 0.840-0.990, and the Youden index of 0.540-0.990. The Fisher discriminant function was formed by stepwise discriminant analysis, and the results showed that the coincidence rate was 99.5%, and the misdiagnosis rate was 0.5% for diagnosing and staging silicosis with these seven potential biomarkers. The coincidence rate of diagnosing control group, silicosis stageⅠsubgroup and the silicosis stage Ⅱ subgroup was 100.0%, 98.4% and 100.0%, respectively. {L-End}Conclusion IL-17, MCP-1, MMP-9, KL-6, CTGF, PDGF and histone H4 in plasma can be used as biomarkers for the diagnosis of silicosis, and the Fisher discriminant function based on the combination of these seven biomarkers can assist in staging silicosis.

Structural distribution and mechanism of elastic fibers and collagen fibers in ventricular interstitium of aged rats / 解剖学报

Objective To investigate the structural distribution features and mechanism of elastic fibers and collagen fibers in ventricular interstitium of aged rats. Methods Five young SD rats (24 weeks) and five old SD rats (104 weeks) were used,and their cardiac function was examined by echocardiography. Modified Weigert elastic fiber staining, immunohistochemistry, immunofluorescence and Western blotting techniques were used to detect the expression changes of type I and IH collagen fibers and their proteins, elastic fibers and their proteins, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 2 (TIMP-2), respectively. Results The type I and type IH collagen in the ventricular interstitium of aged rats was very sufficient and wrapped around the cardiomyocytes. Compared with the young rats, the content of collagen protein in the ventricular interstitium of the aged rats significantly increased (P<0. 05). Elastic fibers in the ventricular interstitium of the aged rats were and widely distributed. Compared with the young rats, the number of elastic fibers and the level of elastin in the ventricular interstitium of the aged rats significantly decreased (P<0. 05), and the expression levels of MMP-2 and MMP-9 in ventricular muscle of aged rats increased, and the)' were correlated with the level of elastin. The level of TIMP-2 in ventricular muscle of aged rats decreased with age. Conclusion The number of collagen fibers and elastic fibers in ventricular interstitium of aged rats is fluctuated with each other. With the increase of age, the contents of TIMP-2 and elastic fibers in the ventricular interstitium gradually decreased, and the ratio of collagen fibers to elastic fibers is out of balance.