Serum MMP-9 Research Articles

Cinobufotalin effect and mechanism on serum MMP-2, MMP-9, Beclin1, LC3-II in advanced NSCLC patients.

This study was conducted to explore cinobufotalin's effects and related mechanisms on serum MMP-2, MMP-9, Beclin1, and LC3-II in advanced non-small-cell lung cancer (NSCLC) patients. For this purpose, 150 patients with advanced NSCLC in our hospital from Jan. 2020 to Feb. 2022 were chosen as participants in the research study. Using a random number table method, the 150 patients were divided evenly into two groups - a control group (C) and an observation group (O). Group C received conventional NP regimen chemotherapy, while Group O received cinobufotalin capsules based on the control group. The follow-up was conducted for 4 months, and the differences in serum MMP-2, MMP-9, Beclin1, LC3-II and chemotherapy resistance rates were compared. Results showed that There was no statistically significant difference in MMP-2, MMP-9, Beclin1, and LC3-II levels between the two before treatment (P>0.05); 4 months later, Group O's MMP-2, MMP-9, Beclin1, and LC3-II levels were lower than those before treatment and Group C during the same period, with a statistically significant difference (P<0.05); At 4 months after treatment, the clinical efficacy of Group O was better and its ORR was higher, with a statistically significant difference (P<0.05); Using Pearson correlation analysis, a weak positive correlation was identified between MMP-2, Beclin1, LC3-II, and chemotherapy resistance (r=0.167, 0.197, 0.273, P<0.05), a positive correlation between MMP-2 and MMP-9, Beclin1, LC3-II (r=0.592, 0.852, 0.665, P<0.01), a positive correlation between MMP-9 and Beclin1, LC3-II (r=0.552, 0.472, P<0.01), and a positive correlation between Beclin1 and LC3-II (r=0.647, P<0.01). It was concluded that cinobufotalin has an inhibitory effect on the serum MMP-2, MMP-9, Beclin1, and LC3-II levels in advanced NSCLC patients, which can promote clinical efficacy improvement and reduce the risk of chemotherapy resistance by downregulating MMP-2, Beclin1, and LC3-II levels.

Ubiquinol attenuates γ-radiation induced coronary and aortic changes via PDGF/p38 MAPK/ICAM-1 related pathway

Endothelial vascular injury is one of the most pivotal disorders emerging during radiotherapy. It is crucial to rely on strong antioxidants to defend against vascular damage. The current study was carried out to investigate the ameliorative effect of ubiquinol (Ubq) against gamma (γ)-radiation induced aortic and coronary changes, with highlighting its role in suppression of p38 mitogen activated protein kinase (MAPK). Exposure to γ-radiation was adopted as a potent detrimental model that induces vascular tissue damage. Concisely, male albino rats were irradiated at a dose level of 7 Gy and treated daily with Ubq (10 mg/kg/day, p.o.) for 7 days pre-and post-irradiation. At the end of the experiment, lipid profile, 8-hydroxydeoxyguanosine (8-OHdG), gene expression of intercellular adhesion molecule (ICAM-1), platelet derived growth factor (PDGF), p38 MAPK and matrix metalloproteinase-9 (MMP-9) were estimated. Exposure to radiation significantly deteriorates aortic and coronary tissues. Conversely, administration of Ubq significantly reduced serum t-cholesterol, LDL and triglycerides (p = 0.001). In addition, Ubq prevented oxidative DNA damage (8-OHdG) (p = 0.1) and reduced serum MMP-9 (p = 0.001) which contributed to the endothelial cells damage. The positive impact of Ubq was more apparent in suppression of both PDGF (p = 0.001) and p38 MAPK (p = 0.1) protein concentrations, leading subsequently in reduction of ICAM-1 (p = 0.001) gene expression. As a conclusion, vascular endothelial damage brought on by γ-radiation is one of the leading causes of coronary and aortic deteriorations which could be successfully mitigated by Ubq.

Retracted: Clinical Value of Pleural Effusion and Serum MMP-3 and CYFRA21-1 Combined with ADA in Differential Diagnosis of Pleural Exudative Effusion.

[This retracts the article DOI: 10.1155/2022/1615058.].

Clinical value of serum MMP-3 in chronic kidney disease

BackgroundChronic kidney disease (CKD) is defined as the progressive deterioration of renal parenchyma and decline in renal unit function. In the early stages of CKD(G1 + G2), symptoms are usually not obvious and cannot be effectively recognized on the basis of available clinical markers. Progression to the middle and late stages of CKD results in severe kidney damage with multiple complications causing adverse outcomes, including death. Therefore, the early diagnosis and monitoring of CKD is critical. Matrix metalloproteinase-3 (MMP-3), an extracellular matrix–degrading enzyme, plays an important role in kidney diseases. However, the clinical significance of serum MMP-3 levels in CKD has rarely been reported. MethodsWe quantified the serum MMP-3 levels of 237 patients with CKD and 96 healthy individuals by using a highly sensitive time-resolved fluorescence immunoassay and analyzed differences in MMP-3 levels among the stages of CKD and the correlations of these changes with clinical indicators. ResultsThe serum MMP-3 concentrations of patients with CKD (171.76 ± 165.22 ng/mL) were significantly higher than those of healthy controls (34.05 ± 22.93 ng/mL; P < 0.0001). In CKD, serum MMP-3 levels were significantly correlated with estimated glomerular filtration rate (eGFR) (r = − 0.5804, P < 0.0001), serum creatinine (CREA) (r = 0.5823, P < 0.0001), blood urea nitrogen (BUN) (r = 0.6106, P < 0.0001), and protein-to-creatinine ratio (r = 0.4992, P < 0.0001). Randomized forest analysis finds CREA, BUN, and MMP-3 most significant influences on CKD disease severity. The critical value of MMP-3 concentration of 40.39 ng/mL combined with eGFR was effective in diagnosing positive patients in the early (G1 + G2) stage of CKD and showed a positivity rate of 73.45 %. Moreover, in the early stages of CKD, patients with CKD who had serum MMP-3 concentration > 100 ng/mL had more severe renal impairment and inflammation than those with CKD who have lower serum MMP-3 concentrations. ConclusionElevated serum MMP-3 levels are correlated with decreased kidney function in CKD progression, and patients with concomitant inflammation may express high levels of serum MMP-3. Serum MMP-3 may assist eGFR in improving the diagnosis of patients with early CKD.

Matrix metalloproteinase-1 serum level in association with the occurrence of striae distensae

Introduction: Striae distensae are fine atrophic scar tissue on the skin. They are formed on areas with dermal collagen rupture due to excessive stretching of the skin. Matrix metalloproteinase-1 (MMP-1) is an enzyme that degrades collagen types I and III. An imbalance in the expression of MMP-1 and transforming growth factor-beta (TGF-β), cytokine that trigger the synthesis of new collagen, leads to imperfect dermis remodeling process in atrophic scar tissue, which is a clinical appearance of striae distensae. This study aimed to determine the association between serum MMP-1 level and striae distensae. Methods: We conducted an observational cross-sectional study on 40 females with striae distensae and 40 controls. History taking, physical and dermatological examination, followed by blood sampling analysis of serum MMP-1 level with ELISA method were conducted in all subjects. Results: The mean serum MMP-1 levels in the striae distensae group were 51.54±28.03 ng/dL. All subjects in the striae distensae group had striae albae and only 7 subjects (17.5%) had striae rubrae. The most common location of striae distensae is the combination of femoral and gluteus regions (25%). The results of this study showed a relationship between high MMP-1 levels and the risk of striae distensae by 4.89 times (p = 0.002). Conclusion: There was an association between serum MMP-1 levels and striae distensae.

Serum and Urinary Matrix Metalloproteinase-9 Concentrations in Dehydrated Horses.

Matrix metalloproteinase-9 is increased in renal tissue in human kidney disease, but its role as a biomarker for kidney disease has not been fully evaluated yet. The aim of this study was to evaluate serum MMP-9 (sMMP-9) and urinary MMP-9 (uMMP-9) concentrations in dehydrated horses. Dehydrated horses were prospectively included. Blood and urinary samples were taken at admission, and after 12, 24, and 48 h (t0, t12, t24, t48), an anti-equine MMP-9 sandwich ELISA was used. Four healthy horses served as the controls. Serum creatinine, urea, symmetric dimethylarginine (SDMA), urine-specific gravity, urinary protein concentration, fractional sodium excretion, and urinary gamma-glutamyl transferase/creatinine ratio (uGGT/Cr) were measured. Statistical analysis included a repeated measures ANOVA and mixed linear regression model. Overall, 40 dehydrated horses were included (mild dehydration 13/40, moderate 16/40, severe 11/40). Acute kidney injury was found in 1/40 horses; 7/40 horses showed elevated serum creatinine, 11/40 horses elevated serum SDMA, and 5/28 elevated uGGT/Cr at presentation. In dehydrated horses, sMMP-9 concentrations were significantly higher on t0 (median: 589 ng/mL, range: 172-3597 ng/mL) compared to t12 (340 ng/mL, 132-1213 ng/mL), t24 (308 ng/mL, 162-1048 ng/mL), and t48 (258 ng/mL, 130-744 ng/mL). In healthy horses, sMMP-9 (239 ng/mL, 142-508 ng/mL) showed no differences over time or compared to patients. uMMP-9 and uMMP-9/creatinine did not differ over time or to the controls. No differences were found between dehydration groups. Urinary casts (p = 0.001; estimate = 135) and uGGT/Cr (p = 0.03; estimate = 6.5) correlated with sMMP-9. Serum urea was associated with uMMP-9/Cr (p = 0.01, estimate 0.9). In conclusion, sMMP-9 was elevated at arrival in dehydrated patients compared to later measurements. Correlations to uGGT/Cr and urinary casts need further evaluation.

Predictive role of glycocalyx components and MMP-9 in cardiopulmonary bypass patients for ICU stay

BackgroundShedding of glycocalyx is relevant to worse prognosis in surgical patients, and elevated levels of serum matrix metalloproteinase-9 (MMP-9) are associated with this phenomenon. This study aimed to investigate the dynamic alterations of serum glycocalyx components and MMP-9 during cardiopulmonary bypass (CPB), and evaluate their predictive capacities for prolonged intensive care unit (ICU) stay, as well as their correlation with coagulation dysfunction. MethodsThis retrospective study analyzed serum levels of syndecan-1, heparan sulfate (HS), and MMP-9 at different time points during CPB, and assessed their association with prolonged ICU stay and coagulation dysfunction. ResultsSyndecan-1, HS, and MMP-9 exhibited divergent changes during CPB. Serum levels of syndecan-1 (AUC = 78.0 %) and MMP-9 (AUC = 78.4 %) were validated as reliable predictors for prolonged ICU stay, surpassing the predictive value of creatinine (AUC = 70.0 %). Syndecan-1 (rho = 0.566, P < 0.01 at T1 and rho = 0.526, P < 0.01 at T2) and HS (rho = 0.403, P < 0.05 at T4) exhibited correlations with activated partial thromboplastin time (APTT) ratio beyond the normal range. ConclusionsOur findings advocate the potential efficacy of serum glycocalyx components and MMP-9 as early predictive indicators for extended ICU stay following cardiac surgery with CPB. Additionally, we observed a correlation between glycocalyx disruption during CPB and coagulation dysfunction. Further studies with expansive cohorts are warranted to consolidate our findings and explore the predictive potential of other glycocalyx components.

Exercise training reduces systemic inflammation and improves general health status in female migraineurs: a randomised controlled trail.

The objectives of this study were to assess the effect of 8 weeks of moderate-intensity aerobic training on permeability inflammatory indicators of matrix metalloproteinases (MMPs) and specific tissue inhibitors of MMPs in female migraineurs. Female migraineurs (n = 28, age 32 ± 6) were randomised into two groups: migraine with exercise training (EXE + Mig, n = 13) and migraine without exercise training (NON-EXE + Mig, n = 15). Matched healthy women were also recruited as a healthy control group (CON, n = 15). The EXE-Mig group performed 8weeks of aerobic training. Pre and post intervention, serum matrix metalloproteinases (MMP-2 and 9) and specific tissue inhibitors of MMPs (TIMP-1 and 2) were measured. In addition, body composition indices and VO2max were determined. Exercise training reduced serum MMP-9 in female migraineurs with between-group changes and a time x group interaction (p < 0.05). In addition, exercise training reduced the serum MMP-9/TIMP-1 ratio in female migraineurs with between-group changes and time x group interaction(p < 0.05). However, no training-induced effect was observed in serum TIMP-1, TIMP-2, MMP-2 contents (p > 0.05) and MMP-2/TIMP-2 ratio (p > 0.05). Finally, exercise training reduced body fat content, WHR and BMI, and improved VO2max (p < 0.01). Our results demonstrated beneficial effects of aerobic exercise training on some circulatory inflammation factors (MMP9, MMP-9/TIMP-1) and some health indicators in female migraineurs, suggesting that such training can be employed as a non-pharmacological therapeutic method.

Clinical Characteristics and Prognosis of Biliary Atresia with Low Serum Matrix Metalloproteinase-7 Levels

PurposeSerum matrix metalloproteinase-7 (MMP-7) levels can precisely differentiate biliary atresia (BA) from non-BA cholestasis. However, serum MMP-7 levels of some BA patients were within normal range or slightly elevated. This study aimed to investigate the clinical characteristics and prognosis of biliary atresia with low serum MMP-7 levels. MethodThis is a retrospective cohort study. Cases of BA from July 2020 to December 2022 were consecutively enrolled. They were divided into low-MMP-7 group (MMP-7 ≤ 25 ng/ml) and high-MMP-7 group (MMP-7 > 25 ng/ml) according to serum MMP-7 levels preoperatively. The perioperative clinical characteristics, the 3-month and 6-month jaundice clearance rate post-Kasai procedure, and the native liver survival were compared between the two groups. ResultsA total of 329 cases were included in this study, 40 of which were divided into the low-MMP-7 group. Preoperative GGT and direct bilirubin levels in the low-MMP-7 group were significantly lower than those in the high-MMP-7 group (258.6 U/L, interquartile range [IQR]: 160.4411.6 vs. 406.8 IU/L, IQR: 215,655.0, P = 0.0076; 103.8 μmol/L, IQR: 79.0,121.4 vs. 115.3 μmol/L, IQR: 94,138.8, P = 0.0071), while the gender, the day at surgery and preoperative ALT, AST, TBA, total bilirubin levels showed no significant differences (P > 0.05). The 3-month and 6-month jaundice clearance rate post-Kasai procedure in the low-MMP-7 group were lower than those in the high-MMP-7 group (29.73% vs. 53.09%, P = 0.049; 32.14% vs. 54.73%, P = 0.023). The 1-year native liver survival rate was 29.63% for the low-MMP-7 group and 53.02% for the high-MMP-7 group (P = 0.022). ConclusionPreoperative clinical characteristics were similar between low-MMP-7 group and high-MMP-7 group, while patients with low serum MMP-7 levels showed worse prognosis, indicating that this might be listed as a new clinical subtype of BA which could contribute to designing new treatment strategies for BA in the future. Study TypeCohort Study. Level of EvidenceLevel II.

The Protective Role of L-carnitine on Psychosocial Stress-induced Changes in Gene Expression and Protein Levels of Matrix Metalloproteinases, Serum Corticosterone in a Rat Model.

Psychosocial stress (STS) is a common stress in modern societies. Chronic STS is associated with the impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in memory. Matrix metalloproteinases (MMPs), a protein family of zinccontaining endopeptidases, are essential in neuro-inflammation and involved in neurodegenerative diseases. L-Car possessed neuroprotective, antioxidant, and anti-inflammatory properties and was shown to modulate MMPs. The current study aimed to examine the protective effect of L-Carnitine (L-CAR) on STSinduced changes in serum corticosterone levels, MMP-2, -9, and -12 protein and mRNA expression in the hippocampus as a possible mechanism for L-CAR protective effect on STS-induced memory impairment. The chronic STS and L-CAR (300 mg/kg/day, i.p) were simultaneously administered for 6 weeks to adult male Wistar rats. Serum corticosterone and protein levels of MMP-2, -9 and -12 were evaluated using ELISA. Real-Time PCR techniques were used to determine the mRNA levels of MMP-2, -9 and -12 in the hippocampus. The findings showed that serum corticosterone levels and MMP-2 and -9 protein levels were significantly increased (p<0.05) in the STS group compared to the control. Similarly, RT-PCR findings showed that the mRNA of those proteinases significantly increased (p<0.05) following the intruder method. On the other hand, the administration of L-CAR restored the alterations in corticosterone levels and MMPs gene and protein expression induced by chronic STS. STS induced elevations in corticosterone and MMP-2 and -9 levels in the hippocampus. L-CAR, on the other hand, exhibited protective effects against the STS-induced changes in MMP-2 and -9.

Biochemical markers assessing rate of reparative processes in patients with infiltrative pulmonary tuberculosis

Theeffectiveness of chemotherapy for infiltrative pulmonary tuberculosis (ITL) is determined by proper timing and adequacy of treatment. The speed of reparative changes in the pulmonary parenchyma is associated with the effectiveness of therapy. Different classes of proteinases are involved in extracellular matrix remodeling. The aim of the study was to evaluate a potential of using the markers of proteinase/inhibitors axis for predicting effectiveness of therapy in patients with ITL due to varying resistance ofMycobacterium tuberculosisto anti-tuberculosis drugs (PTP).Materials and methods.A retrospective study included 60 and 55 ITL patients with the drug sensitive (DS) and drug resistance (DR) Mtb strains, respectively. Patients were divided into two groups according to therapy effectiveness. The levels of blood serum matrix metalloproteinase MMP-1, MMP-3, MMP-8, MMP-9 and their TIMP-1 inhibitor, neutrophil elastase (NE), alpha-2 macroplobulin (MG) and proteinase inhibitor (PI) were determined. Statistica 10.0 and R software packages were used.Results. According to the model of discriminant analysis, the pattern of host inflammatory response in ITL was accounted for not only by varying pathogen resistance, but also by the different size of lung damage. Patients with a limited and widespread process with the DS of the pathogen strains were assigned to group I and II, and DR — to group III and IV group, respectively. The decisive in the speed of tissue repair was the number of neutrophils bearing various levels of proteinase MMP-8, MMP-9 (I group) or TIMP-1 and PI inhibitors (II group). Only combining biochemical data with the those on radiation methods are possible for prognosis in a group of patients with DR (III and IV).Conclusions.Combinations of the markers of the proteinase/inhibitors axis are informative in assessing a rate of reparative changes in ITL and differ not only depending on the pathogen DS strains, but also from the size of destructed pulmonary parenchyma. Differences in parameter combinations are accounted for by history of a specific disease.

Relation of STAT3 rs1053005 Variation and miR-452-3p with Osteoarthritis Susceptibility and Severity and the Clinical Response to High-Molecular-Weight Hyaluronic Acid Injection in Osteoarthritis Patients

Polymorphisms in the 3′ untranslated region of STAT3 mRNA can derange STAT3 gene expression via modifying the microRNA-binding site. This study aimed to examine the impact of STAT3 rs1053005 variation and miR-452-3p expression on osteoarthritis (OA) susceptibility and severity and the efficacy of intra-articular high-molecular-weight hyaluronic acid (HMW-HA) injection as a therapy option for knee OA. Two hundred and fifty-eight OA patients and 200 healthy controls were enrolled in the study. STAT3 genotyping and STAT3 and miR-452-3p expression were carried out using allelic-discrimination PCR and quantitative real-time PCR. Functional assessment and pain evaluation were performed for all patients. Eighty-three patients received HMW-HA injections, and multiple follow-up visits were performed. STAT3 mRNA was upregulated, and expression was positively associated with plasmin, TNF-α, MMP-3, and STAT3 serum levels, whereas miR-452-3p was downregulated and negatively associated with the previously mentioned parameters in OA patients. Osteoarthritis patients had a lower prevalence of the minor allele of the rs1053005 variant (p &lt; 0.001). Plasmin, TNF, MMP-3, and STAT3 mRNA and protein levels were significantly decreased, and miR-452-3p expression was significantly increased in the GG genotype compared to AG and AA genotypes. HMW-HA injection improved OA patients’ clinical scores with concomitant decreased STAT3 levels and enhanced expression of miR-452-3p. More efficient improvement was observed in rs1053005 AG + GG genotype carriers vs. AA genotype carriers. The G allele of STAT3 rs1053005 (A/G) polymorphism was associated with decreased OA susceptibility and severity and enhanced clinical response to HMW-HA injection, possibly via enhancing miR-452-3p binding and a subsequent decrease in STAT3 expression.

Neuropeptide Y, a potential marker for lupus, promotes lupus development

ObjectiveRelationship between neuropeptide Y (NPY) serum levels, NPY genetic mutation with systemic lupus erythematosus (SLE) pathogenesis is yet to be clarified, and role of NPY in development of SLE needs elucidation. MethodThis study included 460 SLE patients, 472 non-SLE cases, 500 healthy volunteers. Serum NPY, matrix metalloproteinase-1 (MMP-1) and MMP-8 levels were tested by ELISA. Genotyping 7 NPY single nucleotides polymorphisms (SNPs) (rs5573, rs5574, rs16129, rs16138, rs16140, rs16147, rs16478) was obtained by Kompetitive Allele-Specific PCR (KASP) method. Pristane-induced lupus mice were treated with NPY-Y1 receptor antagonist, and histological analysis, serological changes of the mice were evaluated. ResultsNPY serum concentrations were significantly increased in SLE patients when compared to that in healthy volunteers, non-SLE cases. Rs5573 G allele, rs16129 T allele, rs16147 G allele frequencies were significantly different between SLE cases and healthy controls. Rs5574 TT + TC genotypes were related to levels of IgG, C3, C4 and erythrocyte sedimentation rate, and rs16138 GG + GC genotypes correlated with SLE cases with anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA) (+). Serum MMP-1, MMP-8 concentrations were higher in SLE patients, and NPY levels were significantly related to MMP-1, MMP-8 levels. After treatment of lupus mice with NPY-Y1 receptor antagonist, damage of liver, spleen and kidney was alleviated, production of autoantibodies (anti-nuclear antibody (ANA), total IgG, anti-dsDNA) and MMP-1, MMP-8 was down-regulated, and differentiation of CD3+, CD8+ T cells, B cells, monocytes, macrophages, T helper 1 (Th1), Th2, Th17 cells was reversed. ConclusionNPY may be a biomarker for lupus, which may promote occurrence and development of lupus.

Correlation analysis of serum MMP-1 and MMP-2 levels with lower extremity deep venous thrombosis after operation for lower limb fracture

To investigate the relationship between serum matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-2(MMP-2) and the formation of deep venous thrombosis(LDVT) in lower extremity patients after surgery for lower extremity fracture, and to analyze the value of MMP-1 and MMP-2 in predicting the occurrence of LDVT after lower extremity fracture. From June 2018 to December 2021, 352 patients who planned to receive surgical treatment of lower limb fracture in our hospital were selected as the research objects. Venous blood was collected at 1, 2 and 3 days after surgery, respectively, and serum MMP-1 and MMP-2 levels were detected. The incidence of LDVT during hospitalization was analyzed, and the risk factors of postoperative LDVT in patients with lower limb fracture surgery and the predictive value of MMP-1 and MMP-2 for LDVT were analyzed. LDVT occurred in 40 patients (LDVT group), the incidence of LDVT was 11.36%, and 312 patients did not occurred(no occurred group). The serum levels of MMP-1 and MMP-2 in LDVT group increased gradually after surgery; the serum levels of MMP-1 and MMP-2 in the no occurred group increased slightly after surgery at 2 days and then decreased at 3 days after surgery (P<0.01);the serum levels of MMP-1 and MMP-2 in LDVT group were higher than those in the no occurred group at 2 days and 3 days after surgery (P<0.05). Serum levels of MMP-1 and MMP-2 were positively correlated with serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor -α (TNF-α) in LDVT patients at 2 days and 3 days postoperatively (P<0.05). Operative time, MMP-1 and MMP-2 postoperative 3 days were related to the occurrence of LDVT after lower limb fracture (P<0.01). The area under the curve(AUC) predicted by MMP-1 and MMP-2 postoperative 3 days for LDVT after lower limb fracture was 0.738 and 0.744 respectively, and the AUC predicted by combined MMP-1 and MMP-2 was 0.910, which was higher than that predicted by single indicator(Z=2.819 and 2.025, P<0.05). High levels of MMP-1 and MMP-2 after lower extremity fracture are closely related to the occurrence of LDVT, and 3 d mMP-1 and MMP-2 after surgery maybe used as evaluation indexes for LDVT risk prediction.

Incident Breakthrough Seizures, Serum Matrix Metalloproteinase-9 and Perfusion Magnetic Resonance Imaging Parameters in a Cohort of Children and Adolescents With Neurocysticercosis: A Longitudinal Observational Study

BackgroundThe current study estimated incident breakthrough seizures, serum matrix metalloproteinase-9 (MMP-9), and perfusion magnetic resonance imaging (MRI) parameters in five- to 18-year-olds with neurocysticercosis (NCC) from colloidal or vesicular through calcified stages over at least 24 months’ follow-up. MethodsSingle, colloidal, or vesicular parenchymal NCC cases were treated with albendazole and steroids and followed at a tertiary care north Indian hospital. Serum MMP-9 was estimated in colloidal or vesicular treatment-naive state and in a subset of calcified cases at six-month follow-up. The same subset of calcified cases also underwent perfusion MRI of the brain at six-month follow-up. ResultsAmong 70 cases, 70% calcified at six-month follow-up. Over a median follow-up of 30 months, the incidence of breakthrough seizures was 48.6% (61.2% in calcified and 19.2% in resolved, P = 0.001; 32.9% early [within six months] and 15.7% late [beyond six months], P = 0.02).Serum MMP-9 levels were higher in colloidal and vesicular compared with calcified stage (242.5 vs 159.8 ng/mL, P = 0.007); however, there was no significant association with breakthrough seizures and/or calcification in follow-up. In a subgroup of calcified cases (n = 31), the median relative cerebral blood volume on perfusion MRI in and around the lesion was lower in those with seizures (n = 12) than in those without (n = 19) (10.7 vs 25.2 mL/100 g, P = 0.05). ConclusionsIn post-treatment colloidal or vesicular NCC, incident breakthrough seizures decrease beyond six months. In calcified NCC with remote breakthrough seizures, significant perilesional hypoperfusion is seen compared with those without seizures.

Role of circadian clock system in the mitochondrial trans-sulfuration pathway and tissue remodeling.

Previous studies from our laboratory revealed that the gaseous molecule hydrogen sulfide (H2S), a metabolic product of epigenetics, involves trans-sulfuration pathway for ensuring metabolism and clearance of homocysteine (Hcy) from body, thereby mitigating the skeletal muscle's pathological remodeling. Although the master circadian clock regulator that is known as brain and muscle aryl hydrocarbon receptor nuclear translocator like protein 1 (i.e., BMAL 1) is associated with S-adenosylhomocysteine hydrolase (SAHH) and Hcy metabolism but how trans-sulfuration pathway is influenced by the circadian clock remains unexplored. We hypothesize that alterations in the functioning of circadian clock during sleep and wake cycle affect skeletal muscle's biology. To test this hypothesis, we measured serum matrix metalloproteinase (MMP) activities using gelatin gels for analyzing the MMP-2 and MMP-9. Further, employing casein gels, we also studied MMP-13 that is known to be influenced by the growth arrest and DNA damage-45 (GADD45) protein during sleep and wake cycle. The wild type and cystathionine β synthase-deficient (CBS-/+) mice strains were treated with H2S and subjected to measurement of trans-sulfuration factors from skeletal muscle tissues. The results suggested highly robust activation of MMPs in the wake mice versus sleep mice, which appears somewhat akin to the "1-carbon metabolic dysregulation", which takes place during remodeling of extracellular matrix during muscular dystrophy. Interestingly, the levels of trans-sulfuration factors such as CBS, cystathionine γ lyase (CSE), methyl tetrahydrofolate reductase (MTHFR), phosphatidylethanolamine N-methyltransferase (PEMT), and Hcy-protein bound paraoxonase 1 (PON1) were attenuated in CBS-/+ mice. However, treatment with H2S mitigated the attenuation of the trans-sulfuration pathway. In addition, levels of mitochondrial peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC 1-α) and mitofusin-2 (MFN-2) were significantly improved by H2S intervention. Our findings suggest participation of the circadian clock in trans-sulfuration pathway that affects skeletal muscle remodeling and mitochondrial regeneration.

Measurement of MMP-7 in micro-volume peripheral blood: development of dried blood spot approach.

Serum matrix metalloproteinase-7 (MMP-7) is significant in differentiating biliary atresia (BA). This study aims to develop a new peripheral blood quantitative collection device to detect MMP-7 levels via dried blood spot (DBS). This is a diagnostic accuracy test. Serum and DBS MMP-7 concentrations were measured using an ELISA kit. Intraoperative cholangiography and subsequent histological examinations were used to confirm BA diagnoses. A total of 241 infants with obstructive jaundice were enrolled, among whom 168 were BA. Linear regression showed DBS MMP-7 correlated well with serum MMP-7 (R = 0.93, P < 0.001). The best cut-off value of serum MMP-7 for BA was 25.9 ng/ml, achieving the area under the ROC curve (AUC) of 0.962 (95% CI: 0.941, 0.983), and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 86.9%, 94.5%, 97.3% and 75.8%, respectively. The best cut-off value of DBS MMP-7 for BA was 12.5 ng/ml, achieving the AUC of 0.922 (95% CI: 0.888, 0.956), and the sensitivity, specificity, PPV, and NPV were 86.9%, 89.0%, 94.8%, and 74.7%, respectively. The dried blood spots were intervened under different storage conditions, including 1-5 days at room temperature, 2 or 3 days at 30 °C and 2 or 3 days at 37 °C. The DBS MMP-7 concentration under different storage conditions had good correlation and consistency with that at -80 °C. Serum and DBS MMP-7 correlate well, both of which have high accuracy in the diagnosis of BA, while the requirements for the storage of DBS are low.

Mechanism of gemcitabine combined with lobaplatin in interventional treatment of locally advanced cervical cancer.

In order to investigate the mechanism of gemcitabine combined with lobaplatin in the interventional treatment of locally advanced cervical cancer (LACC), 90 patients with LACC were divided into control group (oxaliplatin + gemcitabine) and experimental group (lobaplatin + gemcitabine) according to different perfusion drugs and embolization drugs, 45 cases in each group. They were treated with arterial chemotherapy and arterial embolization. Postoperative recurrence, metastasis, and survival, as well as changes in serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) levels before and after treatment were observed in both groups. The results showed that the recurrence rate of cervical cancer at 0.5, 1, 2, 3, 4, and 5 years after operation in the experimental group was significantly lower than that in the control group, P < 0.05; there was no significant difference in the postoperative cervical cancer metastasis rate, P > 0.05. Before treatment, the serum VEGF in the experimental group and the control group were (642.76 ± 216.67) ng/L and (626.30 ± 275.43) ng/L, respectively, and MMP-9 were (580.61 ± 194.12) ng/L and (575.28 ± 202.55) ng/L, respectively. After treatment, the serum VEGF levels in the experimental group and the control group were (429.24 ± 132.69) ng/L and (554.63 ± 178.11) ng/L, respectively, and MMP-9 levels were (357.60 ± 123.11) ng/L and (461.83 ± 144.45) ng/L, respectively. There was no significant difference in the serum VEGF and MMP-9 levels between the two groups before treatment ( P > 0.05); after treatment, the serum VEGF and MMP-9 levels in the experimental group were significantly lower than those in the control group, P < 0.05. Therefore, gemcitabine combined with lobaplatin interventional therapy can improve the cure rate of LACC by reducing VEGF and MMP-9 levels in the serum of patients.

Efficacy of phentolamine combined with milrinone on severe pneumonia in children, and its effect on serum levels of MMP-9, TIMP-1 and sICAM-1

Purpose: To investigate the effect of the co-administration of phentolamine and milrinone on severe pneumonia in children, as well as on serum MMP-9, TIMP-1 and sICAM-1 levels.&#x0D; Methods: From January 2021 to January 2022, 100 patients diagnosed with severe pneumonia were randomly divided into 2 groups; the control group received oxygen inhalation and other symptomatic treatment, while the study group received phentolamine concurrently with milrinone, Serum MMP-9, TIMP-1, sICAM-1 levels and clinical efficacy were determined in the two groups before and after treatment.&#x0D; Results: After treatment, there were significant differences in IL-6, IL-10, and TNF-α levels between the study group and the control group. Furthermore, IgA, IgG, and IgM levels in both groups were significantly higher after treatment than before treatment (p &lt; 0.05). The study group exhibited significant differences in MMP-9, TIMP-1, and sICAM-1 levels after treatment compared to control group (p &lt; 0.05). Healing and therapeutic effectiveness in the study group was 76 %, which was significantly greater than in the control group (48 %; p = 0.000). Additionally, total treatment effectiveness in the study group was 92 %, which was significantly higher than in the control group (80 %; p = 0.015). After treatment, the PEF, FRC, and TEF25 % in the study group were significantly higher than in the control group (p &lt; 0.05).&#x0D; Conclusion: Co-administration of phentolamine and milrinone is highly effective for the treatment of severe pneumonia in children, and significantly reduces the levels of serum MMP-9, TIMP-1 and sICAM-1. However, multi-center clinical trials should be carried out prior to the adoption of this treatment mode in clinical practice.

Changes and clinical significance of serum MMP-9, TIMP-1, COX-2, and immune levels in patients with asthma

Objective: To detect serum metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases (TIMP-1), cyclooxygenase-2 (COX-2), and T helper cells 1–T helper cells 2 (Th1–Th2) levels in asthma patients and assess their clinical significance. Methods: A total of 72 patients experiencing acute asthma (acute group), 66 stable asthma patients (stable group), and 60 healthy volunteers (control group) were included in this study. The levels of TIMP-1, COX-2, and Th1–Th2 in patients with acute asthma were measured following treatment with budesonide aerosol inhalation. In addition, the levels of MMP-9, TIMP-1, COX-2 and Th1–Th2 were compared in patients with different severity of acute asthma before and after treatment. Results: The serum levels of MMP-9, TIMP-1, and COX-2 showed an increasing trend in the control, stable, and acute groups, while levels of Th1–Th2 showed a sequential decreasing trend, and the differences were statistically significant. Comparison of lung function indexes among the three groups of patients established a negative correlation between serum MMP-9 and its forced vital capacity% predicted (FEV%pred), TIMP-1, and COX-2, and FEV%pred and forced expiratory volume in 1 s–forced vital capacity (FEV1/FVC) levels, but a positive correlation between Th1–Th2 and FEV1/FVC levels in the acute group. A significant difference was observed on comparing the levels of serum MMP-9, TIMP-1, COX-2, and Th1–Th2 in patients with different conditions in the acute group. Specifically, as the condition worsened, a significant increase in serum MMP-9, TIMP-1, and COX-2 levels but a significant decrease in Th1–Th2 levels was observed. After treatment, we observed a significant decrease in serum MMP-9, TIMP-1, and COX-2 levels but a significant increase in Th1–Th2 levels in the acute group. Conclusion: The serum levels of MMP-9, TIMP-1, COX-2, and Th1–Th2 are valuable indicators reflecting the condition of asthma patients and could be considered promising clinical monitoring indicators.