Serum MMP-9 Research Articles

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.

Serum MMP3 and IL1-RA levels may be useful biomarkers for detecting asthma and chronic obstructive pulmonary disease overlap in patients with asthma

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) is characterized by concurrent features of asthma and COPD. Since disease pathogenesis, severities, and treatments differ between asthma and ACO, it is important to differentiate them. ObjectiveTo clarify and compare the characteristics of ACO and asthma and identify the serum biomarkers for differentiating them, especially in older patients. MethodsThis study used the data of 639 participants from the nationwide cohort study, the NHOM-Asthma study, an asthma registry in Japan, with complete information on smoking history, respiratory function, and serum biomarkers. ACO was defined as the self-reported comorbidity of COPD or emphysema, or with obstructive pulmonary function and smoking history (pack-years≥10). The clinical characteristics of patients with ACO and asthma without COPD were compared. The serum biomarkers for differentiation were examined using receiver operating characteristic curves and multivariable analysis. The associations between the biomarkers and age were also analyzed. ResultsOf the 639 asthma patients, 125 (19.6%) were diagnosed with ACO; these patients were older and male-dominant and had a higher prevalence of comorbidities such as hypertension, diabetes, and stroke. Among the serum biomarkers that were significantly different between ACO and asthma without COPD, the YKL-40/CHI3L1, MMP3, and IL-1RA levels showed a high area under the curve for discriminating ACO. Only the MMP3 and IL-1RA levels were significantly higher among ACO patients, regardless of age and sex; the YKL-40/CHI3L1 levels were not different due to the effect of age. ConclusionMMP3 and IL-1RA may be useful serum biomarkers for distinguishing ACO from asthma.

Synthesis of Au-decorated boron nitride nanotubes and its application to pretreatment-free electrochemical biosensor for matrix metalloproteinase9 in clinical sample

As matrix metalloproteinase-9 (MMP-9) is a biomarker for several diseases such as inflammatory, cardiovascular, and lung diseases, determining its level in human serum is vital for the detection of such diseases. However, accurately detecting MMP-9 in serum requires a time-consuming and expensive pre-treatment process with filters. To minimize the diagnosis process, the authors constructed a pre-treatment-free electrochemical biosensor for determining MMP-9 in clinical sample. To fabricate the biosensor, Au-decorated boron nitride nanotubes (Au@BNNTs) were synthesized to improve the sensor's performance. The synthesis of Au@BNNTs was confirmed through transmission electron microscopy (TEM), energy dispersive spectrometer (EDS), and Fourier-transform infrared spectroscopy (FT-IR) experiments. Then, the MMP-9 aptamer was immobilized on the Au@BNNTs-modified round Au micro-gap integrated printed circuit board (PCB) chip. The electrochemical biosensor's performance was validated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Based on this, the electrochemical signal amplification ability of Au@BNNTs is confirmed, and its potential is demonstrated. In addition, the fabricated biosensor can detect the MMP-9 in 100% human serum. The linear detection range test yielded a wider concentration range (0.1–10,000 ng∙mL−1) and a lower limit of detection (0.0218 ng∙mL−1) for MMP-9 compared to previous research. Finally, through a selectivity test and clinical patient sample test, it is confirmed that the proposed biosensor specifically detects only MMP-9 well. The proposed Au@BNNT biosensor with aptamer has potential applications in MMP-9 detection and diagnosis of various diseases without the need for pretreatment.

The magnetic resonance imaging and age-adjusted matrix metalloproteinase-7 assist the diagnosis of biliary atresia.

We investigated the utilities of the liver-to-psoas apparent diffusion coefficient ratios (LTPAR) yielded by diffusion-weighted magnetic resonance imaging (DWMRI) and the age-adjusted serum matrix metalloproteinase-7 (MMP-7) for the diagnosis of biliary atresia (BA) in cholestatic infants. In total, 170 cholestatic infants were recruited, of whom 50 (29.41%) were diagnosed with BA after cholestatic workups. The LTPAR and MMP7 levels were assessed. The LTPAR was significantly lower in BA infants, and the age-adjusted MMP7 ratio was significantly higher, compared to other cholestatic infants (both p < 0.001). Receiver operating characteristic curve analysis yielded a cutoff > 0.1ng/mL.day for the age-adjusted MMP-7 ratio, and an LTPAR < 1.01 for the optimal prediction of BA (both p < 0.001). Univariate logistic regression analysis revealed that both an age-adjusted MMP-7 ratio > 0.1ng/mL.day and an LTPAR < 1.01 were significant predictors of BA among cholestatic infants (odds ratio = 30.98 and 13.28; p < 0.001 and < 0.001, respectively). The significance of the age-adjusted MMP-7 ratio and the LTPAR persisted on multivariate logistic regression analysis after adjusting for sex and the serum gamma-glutamyl transferase level (p < 0.001 and < 0.001, respectively). The negative predictive values (NPVs) for BA were 91.49% and 94.17%, respectively, for the LTPAR and age-adjusted MMP-7 ratio. The age-adjusted MMP-7 ratio and the LTPAR are both significant non-invasive predictors of BA. The consideration of both serum and imaging parameters may enhance BA diagnostic performance in cholestatic infants.

D-dimer, C-reactive protein and matrix metalloproteinase 9 for prediction of type A aortic dissection patient survival.

Acute type A aortic dissection (ATAAD) is a life-threatening condition requiring prompt diagnosis and treatment. Surgery is an effective treatment for ATAAD, but the in-hospital mortality rate in the 30day perioperative period is still as high as 9-30%. It is critical to identify biological factors for preoperative assessment of post-operative survival in patients with ATAAD. This is a retrospective study, investigating the association of combined measurements of d-dimer, C-reactive protein (CRP), and matrix metalloproteinase 9 (MMP9) for 1year of survival in patients with ATAAD. Data from 247 patients who underwent surgery were analysed, including 89 patients who did not survive and 158 patients who survived within 1year after surgery. Pearson's correlation analysis was carried out to determine the correlations between CRP in whole blood, d-dimer in plasma, and CRP in whole blood. Receiver operating characteristic (ROC) analysis was used to analyse the value of preoperative whole blood CRP, plasma d-dimer, and serum MMP9 concentration and the combined detection model in predicting death of patients with ATAAD. Deceased patients with ATAAD exhibited higher age, hypertension prevalence, systolic blood pressure, white blood cell count, whole blood CRP, plasma d-dimer, and serum MMP9 levels compared with survivors. Preoperative CRP, d-dimer, and MMP9 levels were significantly higher in patients with ATAAD compared with healthy controls. Positive correlations were observed between CRP and d-dimer, CRP and MMP9, and d-dimer and MMP9 in patients with ATAAD. ROC analysis showed that the combined detection model of CRP, d-dimer, and MMP9 had the highest predictive value for 1year of survival (area under the curve=0.88). Combined measurement of CRP, d-dimer, and MMP9 is associated with 1year of survival in patients with ATAAD.

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival.

The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosinstaining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-β1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-β1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.

The disruption of blood-brain barrier induced by long-term arsenic exposure is associated with the increase of MMP-9 and MMP-2: The characteristics are similar to those caused by senescence

Accumulating evidence suggests that Matrix metalloproteinase-9 (MMP-9) and −2 (MMP-2) are involved in the neuropathological processes by contributing to breaking the extracellular matrix and the tight junctions that constitute the blood-brain barrier (BBB). However, the influences of arsenic (As) on these two MMPs were inconsistent. In the cross-sectional study of 500 adults, serum MMP-2 and MMP-9 positively correlated with urine arsenic. And the positive correlation between urine tAs and serum MMP-9/2 was found in people older than 59 years. In vivo studies, we found that arsenic exposure or senescence might decrease number of neurons and neuritic density and increase serum and cortical MMP-9/2 levels. Furthermore, arsenic exposure or senescence could disrupt the tight junction of BBB and elevate MMP-9 and MMP-2 expression in the cerebral microvascular endothelium. The MMP-9 and MMP-2 are of particular interest when researching the link between arsenic exposure and nerve damage.

Serum matrix metalloproteinase-9 (MMP9) and amyloid-beta protein precursor (APP) as potential biomarkers in children with Fragile-X syndrome: A cross sectional study

IntroductionFragile-X syndrome(FXS) is a neurological disease caused by abnormal repeats in the 5′untranslated region of the FMR1 gene leading to a defective fragile-X-messenger-ribonucleoprotein-1 (FMRP). Although relatively common in children, it is usually under-diagnosed especially in developing countries where genetic screening is not routinely practiced. So far, FXS lacks a laboratory biomarker that can be used for screening, severity scoring or therapeutic monitoring of potential new treatments. Methods110 subjects were recruited; 80 male children with suspected FXS and 30 matched healthy children. We evaluated the clinical utility of serum matrix metalloproteinase-9(MMP9) and amyloid-beta protein precursor(APP) as potential biomarkers for FXS. ResultsOut of 80 suspected children, 14 had full mutation, 8 had the premutation and 58 children had normal genotypes. No statistically-significant difference was detected between children with different genotypes concerning age of onset(P = 0.658), main clinical presentation(P = 0.388), clinical severity-score(P = 0.799), patient’s disease-course(P = 0.719) and intellectual disability(P = 0.351). Both MMP9 and APP showed a statistically significant difference when comparing different genotype subgroups(P = 0.019 and < 0.001, respectively). Clinically, MMP9 levels were highest in children presenting with language defects, while APP was highest in children with neurodevelopmental delay. In receiver operating curve analysis, comparing full and premutation with the normal genotype group, MMP9 has an area-under-the-curve of 0.701(95 % CI 0.557–0.845), while APP was marginally better at 0.763(95 % CI 0.620–0.906). When combined together, elevated MMP9 or APP had excellent sensitivity > 95 % for picking-up FXS cases in the clinical setting. ConclusionsScreening for circulating biomarkers in the absence of FXS genetic diagnosis is justified. Our study is the first to evaluate both MMP9 and APP in FXS suspected children in a clinical setting and to assess their correlation with disease presentation and severity.

Chonggu Granules Improve Cartilage Matrix Metabolism in Knee Osteoarthritis via the miR-148a-3p/Wnt/β-Catenin Pathway.

This study aims to explore the effect and underlying mechanism of Chonggu Granules (CGG) in knee osteoarthritis (KOA) in rats. A papain-induced KOA model was established in rats. The pathological alterations of extracellular matrix in rat cartilage tissues were observed through hematoxylin and eosin (H&E) staining, followed by Mankin score for quantitative scoring. The ultrastructure of cartilage extracellular matrix was examined under a transmission electron microscopy (TEM). ELISA was used to measure the levels of IL-6, TNF-α, and IL-1β in rat serum. Immunofluorescence was performed for assessing the levels of MMP-3, MMP-13, and Col2al in rat cartilage. Western blot was used to identify the protein expressions of wnt1, GSK-3β, β-catenin, and Aggrecan in rat cartilage. The mRNA relative expressions of miR-148a-3p, wnt1, β-catenin, and GSK-3β in rat cartilage were detected by RT-PCR. Luciferase reporter gene was used to detect the target genes of miR-148a-3p. CGG significantly improved articular cartilage tissue and extracellular matrix metabolism compared to the model group as indicated by H&E, Mankin score, and TEM data. Moreover, low, medium, and high doses of CGG reduced the levels of IL-6, TNF-α, IL-1β, MMP-3, and MMP-13 in serum to varying degrees but increased the levels of Col2al and Aggrecan. Mechanistically, CGG targeted wnt1 by increasing the expression of miR-148a-3p in a dose-dependent manner, thereby downregulating the mRNA and protein expressions of β-catenin in cartilage tissue and upregulating the mRNA and protein expressions of GSK-3β. CGG may control the miR-148a-3p/wnt/β-catenin signaling pathway to decrease the levels of its downstream target genes MMP-13 and MMP-3, increase the expressions of Col2al and Aggrecan, and downregulate the contents of inflammatory cytokines IL-6, TNF-α, and IL-1β, thereby improving the metabolism of cartilage extracellular matrix and alleviating the degeneration of articular cartilage in KOA.

Abdominal aortic diameter as a predictor of peripheral atherosclerosis progression in 40-64-year-old patients with cardiovascular risk factors

Aim. To study the prognostic significance of abdominal aorta (AA) diameter in progression of peripheral atherosclerosis in patients aged 40-64 years and without abdominal aortic dilation.Materials and Methods. The study included 157 outpatients aged 40-64 years who underwent Doppler ultrasonography of brachiocephalic arteries, lower extremity arteries, and abdominal aorta in order to assess cardiovascular risk. Upon the serum collection, we measured lipid fractions, creatinine, glycated hemoglobin, high-sensitivity C-reactive protein, pentraxin-3 and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-10). The criteria for the progression of peripheral atherosclerosis were: 1) the appearance of a new atherosclerotic plaque; 2) stenosis increase by ≥ 10%; 3) carotid plaque area increase by ≥ 0.106 cm2.Results. We found that 116 (73.9%) patients initially had low to moderate cardiovascular risk. Abdominal aortic diameter directly correlated with the level of glycated hemoglobin (r = 0.298; p = 0.003) and serum MMP-2 (r = 0.240; p = 0.041), whilst aortic size index directly correlated with serum MMP-9 (r = 0.319; p = 0.029). Repeated Doppler ultrasonography was performed in 120 (76.4%) patients, with the median period between two examinations was 14.4 (12.3; 20.8) months, and progression of peripheral atherosclerosis was identified in 26 (21.6%) patients. An increase in abdominal aortic diameter &gt; 1.64 cm could predict atherosclerosis progression with sensitivity of 53.8% and specificity of 74.1%. According to Cox regression analysis, an increase in abdominal aortic diameter &gt; 1.64 cm was associated with a 2.31-fold increased risk of atherosclerosis progression (95% CI = 1.06 - 5.00, p = 0.034).Conclusion. Abdominal aortic diameter can be considered as a predictor of peripheral atherosclerosis progression.

Secreted proteins encoded by super enhancer-driven genes could be promising biomarkers for early detection of esophageal squamous cell carcinoma

BackgroundEarly detection of cancer remains an unmet need in clinical practice, and high diagnostic sensitivity and specificity biomarkers are urgently required. Here, we attempted to identify secreted proteins encoded by super-enhancer (SE)-driven genes as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). MethodsWe conducted an integrative analysis of multiple data sets including ChIP-seq data, secretome data, CCLE data and GEO data to screen secreted proteins encoded by SE-driven genes. Using ELISA, we further identified up-regulated secreted proteins through a small size of clinical samples and verified in a multi-centre validation stage (345 in test cohort and 231 in validation cohort). Receiver operating characteristic curves were used to calculate diagnostic accuracy. Artificial intelligence (AI) method named gradient boosting machine (GBM) were applied for model construction to enhance diagnostic accuracy. ResultsSerum EFNA1 and MMP13 were identified, and showed significantly higher levels in ESCC patients compared to normal controls. An integrated Five-Biomarker Panel (iFBPanel) established by combining EFNA1, MMP13, carcino-embryonic antigen, Cyfra21-1 and squmaous cell carcinoma antigen had AUCs of 0.881 and 0.880 for ESCC in test and validation cohorts, respectively. Importantly, the iFBPanel also exhibited good performance in detecting early-stage ESCC patients (0.872 and 0.864). Furthermore, the iFBPanel was further empowered by AI technology which showed excellent diagnostic performance in early-stage ESCC (0.927 and 0.907). ConclusionsOur study suggested that serum EFNA1 and MMP13 could potentially assist ESCC detection, and provided an easy-to-use detection model that might help the diagnosis of early-stage ESCC.

The Role of Matrix Metalloproteinase 13 and Vitamin D in Osteoarthritis: A Hospital-Based Observational Study.

Introduction Osteoarthritis (OA) is the most common form of degenerative joint disease characterized by the progressive degeneration of articular cartilage, osteophyte formation, and joint space narrowing. Matrix metalloproteinases (MMPs) are potential biomarkers for osteoarthritis. Aims and objective The study's aim is the estimation of serum and synovial fluid matrix metalloproteinase (MMP) 13 and serum vitamin D levels in the grade 3 and grade 4 stages of osteoarthritis according to the Kellgren and Lawrence (KL) system of classification. Materials and methods A total of 100 subjects were included; of them, 25 patients with grade 3 and 25 patients with grade 4 knee osteoarthritis diagnosed clinically and radiologically according to the Kellgren and Lawrence criteria have been enrolled in the study, and 50 patients with knee pain having a diagnosis other than degenerative OA of the knee were taken as controls. Venous blood and synovial fluid have been collected from all of them for the estimation of MMP-13 and vitamin D. The enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) methods were used for the estimation of MMP-13 and vitamin D, respectively. Results The mean value of synovial fluid MMP-13 was found to be elevated in grade 4 as compared to grade 3 and the control group, whereas the mean value of serum MMP-13 was found to be elevated in grade 3 as compared to grade 4 and control. The level of serum vitamin D was found deficient in OA patients as compared to control. The Kruskal-Wallis test was performed to compare these groups, and there was a significant difference between these groups(p-value of <0.05). Summary and conclusion High synovial and serum MMP-13 is associated with knee structural abnormalities in patients with knee OA as compared to the control groupsuggesting that MMP-13 can be a biomarker in knee OA, whereas the decreased level of vitamin D may be associated with an increased risk for the progression of OA; hence, serum vitamin D may be a good indicator for the prediction of the initiation of OA.

Matrix Metalloproteinase-9, Neuron-specific Enolase, S100 B and Tau Protein Levels in the Patients with Carbon monoxide Poisoning

Background: S100B, NSE, MMP-9, and Tau protein levels increase in cases causing hypoxic cell damage. The diagnosis of the severity of carbon monoxide (CO) poisoning in the early period of these parameters was studied. Material and Method: COHb level measurement was made using a signal capture CO-pulse oximeter (Masimo's SET Rainbow, Masimo's Co, USA) at the first admission of the patients. Then, COHb levels were confirmed by arterial blood gas(ABG) analysis. The patients were divided into two groups as mild and moderate-severe, according to their Glasgow coma scores (GCS) [Mild (14–15); Moderate (9–13) or Severe (3–8)]. The control group was composed of 16 healthy and non-smoking volunteers. Results: The serum S100B protein and MMP-9 values at 0 hr of admission in the hospital and 3hr of treatment were not significantly different in the patient group as compared to the control group. Tau protein levels were significantly higher in the patient group at 0 and 3 hours (p&gt; 0.05) as compared to healthy person. Conclusion: There was no relationship between CO poisoning and MMP-9 and S100B protein levels. NSE and Tau protein were significantly higher in the patient group than the control group. Tau protein may be more useful marker as compared to neuron-specific enolase.

Extracellular matrix metalloproteinases inducer gene polymorphism and reduced serum matrix metalloprotease-2 activity in preeclampsia patients.

Preeclampsia increases the risk of pregnancy-related complications, nevertheless a successful spiral vessel remodeling, and trophoblast invasion reduces disorders of pregnancy. Matrix metalloproteinase-2 (MMP-2) clears the path for trophoblast invasion, and activation of MMP-2 largely depends on extracellular matrix metalloproteinases inducer (EMMPRIN) protein. This study aimed to investigate EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia patients. Archival whole blood and serum samples of 74 preeclampsia and 66 normotensive pregnant women age-matched were used in this case-control study. Genomic DNA was extracted from the whole blood samples and EMMPRIN gene amplified with specific primers following fragments sequence mutation analysis. Serum MMP-2 activity was determined using enzyme-linked immunosorbent assay (ELISA) and socio-demographic data of participants retrieved from the database. Age of preeclampsia patients (32.78 ± 6.39) years and body mass index (BMI) (33.09 ± 7.27) kg/m2 compared with the normotensive counterparts (32.33 ± 5.56) years and (32.33 ± 5.56) kg/m2,respectively, were not statistically significant (P > 0.05). Serum matrix metalloprotease-2 (MMP-2) activity was significantly reduced in preeclampsia group (16.34 ± 7.07) compared with the normotensives (25.63 ± 4.56) (P < 0.001), and rs424243T/G variant (55.6%) was overrepresented among the cases compared with the normotensives (16.7%). The single-nucleotide polymorphism T/G was found to be associated with preeclampsia (odds ratio [OR] = 7.63; 95% confidence interval [CI] = 3.95-14.75; P < 0.0001). Decreased activity of MMP-2 and rs424243T/G SNP of EMMPRIN gene was reported in preeclampsia. These preliminary data warrant a further investigation into the relationship between EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia.

Imbalance of the protease-antiprotease system against the background of chronic obstructive pulmonary disease in combination with ischemic heart disease

The aim of the study: to evaluate the clinical value of the violation of the expression level of MMP-9 and TIMP against the background of chronic obstructive pulmonary disease (COPD) in combination with ischemic heart disease (IHD). Materials and methods. In accordance with the set goal of the study, 26 people with COPD + IHD and 22 practically healthy people were under observation. The average age of patients was 56.68 ± 1.21 years; 76.92 % were men. In the control group, the average age was 54.37 ± 1.84 years, 72.73 % were men. The object of the study was ischemic heart disease: angina pectoris. Research methods: external respiration function study, six minute walk test, determination of heart rate variability, the concentration of MMP-9 and TIMP in blood serum was determined by the method of solid-phase enzyme immunoassay. Results. The analysis of the level of expression of proteases and its inhibitor shows that patients with comorbid IHD on the background of COPD demonstrated 8.11 times higher activity of MMP-9 (p &lt; 0.05) compared to a cohort of practically healthy people. Indicators of TIMP activity in patients with IHD on the background of COPD are 1.46 ± 0.03 μg/ml, which is statistically significantly lower by 53.21 % (p &lt; 0.05) compared to healthy people (3.12 ± 0.01 μg/ml). The presence of reliable correlations between the MMP-9 level and the FEV1 indicator (r = -0.67, p &lt; 0.05), the LF/HF parameter (r = -0.74, p &lt; 0.05) indicates, that when the level of expression of MMP-9 is elevated, there is a more pronounced violation of the function of external respiration and a shift in the sympatho-parasympathetic balance in the direction of sympathetic activation and a decrease in vagal tone in heart rate modulation. The analysis of the meeting frequency with the analysis of conjugation tables showed that in persons in the upper quartile of MMP-9, prognostically negative parameters of the function of external breathing – an isolated decrease in the Tifno index (χ2 = 5.2 at p = 0.03), as well as the expressiveness of shortness of breath – were recorded more often ≥6 points on the Borg scale when assessing exercise tolerance during the 6-minute walk test (χ2 = 7.3 at p = 0.02). Conclusions. The obtained data demonstrate that patients with IHD on the background of COPD have a pronounced proteolytic imbalance and disruption of fibrotic processes compared to practically healthy individuals.

Serum proteomics identifies S100A11 and MMP9 as novel biomarkers for predicting the early efficacy of sublingual immunotherapy in allergic rhinitis

BackgroundAllergic rhinitis (AR) is a chronic inflammatory disorder, and sublingual immunotherapy (SLIT) is an important therapy. However, SLIT exhibits a wide range of fluctuations and lacks objective monitoring indicators. Therefore, exploring biomarkers for early prediction of the efficacy of SLIT is urgently needed. MethodsWe recruited two independent cohorts. In the discovery cohort, house dust mite (HDM) -induced AR patients underwent SLIT for at least 1 year, and were categorized into response and no response groups based on early efficacy. Serum proteomics was conducted to detect variations in protein expression levels between the two groups. The candidate proteins were confirmed in the validation cohort with enzyme-linked immunosorbent assay (ELISA), and their predictive values and levels of change before and after treatment were evaluated. ResultsSerum proteomics identified a total of 113 differential proteins between the two groups, including 41 proteins upregulated and 72 downregulated in the no response group than the response group. The top 5 up- and down-regulated proteins were selected for further validation, and ELISA results revealed that serum CCL14, LTA4H, S100A11 and MMP9 levels were significantly elevated, and TGFBI and MASP1 were decreased in the response group than those in the no response group(P < 0.05). Moreover, receiver operating characteristic curves revealed that serum S100A11 and MMP9 exhibited greater ability in predicting the early effectiveness of SLIT (AUC > 0.7, P < 0.05). Furthermore, these two biomarkers exhibited significant reductions 1 year after SLIT, particularly in those patients who responded positively to the treatment (P < 0.05). ConclusionSerum S100A11 and MMP9 have the potential to serve as biomarkers for early prediction of the effectiveness of SLIT and monitoring the therapeutic effects. The circulating proteomic alterations might contribute to guiding treatment and understanding the mechanism of SLIT in AR patients.