Serum MMP-9 Research Articles

WITHDRAWN: The Bufei Nashen pill inhibits the PI3K/AKT/HIF-1 signaling pathway to regulate extracellular matrix deposition and improve COPD progression

Ethnopharmacological relevanceAccording to the theory and practice of traditional Chinese medicine (TCM), chronic obstructive pulmonary disease (COPD) can be classified as “cough,” “dyspnea,” or “lung distention disease.” Bufei Nashen pill (BFNSP) is a classic Chinese herbal formula with certain activity against the above syndromes. FNSP has previously been shown to improve clinical symptoms (cough, lumbar and knee weakness, tinnitus) in patients with occupationally related interstitial lung disease. Aim of the studyThere is a lack of convincing evidence supporting the use of BFNSP for the treatment of COPD. This study aimed to investigate the effect of BFNSP on COPD and explore its underlying mechanisms. Materials and methodsLiquid chromatography-mass spectrometry (LC/MS) was used to analyze the main components of BFNSP and BFNSP-containing serum. A COPD rat model was generated, and the rats were treated with different doses of BFNSP. Lung function indices were analyzed by a pulmonary function testing system, and lung histopathology was assessed by HE staining and scanning electron microscopy. The levels of TGF-β1, IL-6, IL-8, IL-1β, MMP3, MMP-9, and TIMP1 in BALF and the levels of MMP3, MMP-9, TIMP1, and HA in serum were detected by ELISA. Immunohistochemical staining was performed to determine the expression of Col-I, Col-III, and LN in lung tissues. RT‒qPCR was performed to detect the mRNA expression of PI3K, Akt, HIF-1α, MMP-9, TGF-β1, TIMP1, and ERK1/2 in lung tissue, and Western blotting was performed to detect the protein expression of PI3K, p-PI3K, Akt, p-Akt, HIF-1α, MMP-9, TGF-β1, TIMP1, and p-ERK1/2 in lung tissue. In addition, in vitro cellular assays were performed for validation. ResultsThe results showed that BFNSP effectively improved the functional status of pulmonary ventilation, attenuated pathological damage in lung tissue, inhibited the release of inflammatory factors, reduced extracellular matrix deposition, and inhibited the activation of the PI3K/AKT/HIF-1 signaling pathway in lung tissue in COPD rats (P<0.05) and may alleviate COPD progression by inhibiting the PI3K/AKT/HIF-1 signaling pathway. ConclusionBFNSP inhibits the PI3K/AKT/HIF-1 signaling pathway to regulate extracellular matrix deposition and improve COPD progression.

To Investigate the Mechanism of Qinpi Tongfeng Formula in Treating Acute Gouty Arthritis by UHPLC-Q-Orbitrap-MS, Network Pharmacology and Experimental Validation.

Acute gouty arthritis (AGA) is characterized by the accumulation of monosodium urate crystals within the joints, leading to inflammation and severe pain. Western medicine treatments have limitations in addressing this condition. Previous studies have shown the efficacy of Qinpi Tongfeng formula (QPTFF) in treating AGA, but further investigation is needed to understand its mechanism of action. We used ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS) to identify compounds in QPTFF. Target proteins regulated by these compounds were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction Database. AGA-related targets were searched and screened from various databases, including Genecards, PharmGKB, Drugbank, etc. Intersection targets of QPTFF and AGA were analyzed for protein-protein interaction networks, GO function enrichment, and KEGG pathway enrichment. We then verified QPTFF's mechanism of action using an AGA rat model, assessing pathological changes via H&E staining and target expression via ELISA, RT-qPCR, and Western blot. UHPLC-Q-Orbitrap-MS identified 207 compounds in QPTFF, with 55 selected through network pharmacology. Of 589 compound-regulated targets and 1204 AGA-related targets, 183 potential targets were implicated in QPTFF's treatment of AGA. Main target proteins included IL-1β, NFKBIA, IL-6, TNF, CXCL8, and MMP9, with the IL-17 signaling pathway primarily regulated by QPTFF. Experimental results showed that medium and high doses of QPTFF significantly reduced serum inflammatory factors and MMP-9 expression, and inhibited IL-17A, IL-6, IKK-β, and NF-κB p65 mRNA and protein expression in AGA rats compared to the model group. Key targets of QPTFF include IL-1β, NFKBIA, IL-6, TNF-α, CXCL8, and MMP9. QPTFF effectively alleviates joint inflammation in AGA rats, with high doses demonstrating no liver or kidney toxicity. Its anti-inflammatory mechanism in treating AGA involves the IL-17A/NF-κB p65 signaling pathway.

The correlation between pentraxin-3, matrix metalloproteinase-9, and estimated glomerular filtration rate in patients with chronic kidney disease

Background: Chronic kidney disease (CKD) is diagnosed when there is a sustained decrease in the estimated glomerular filtration rate (EGFR) over a period of more than 3 months. While Pentraxin-3 (PTX-3) and Matrix Metalloproteinase-9 (MMP-9) levels increase during the acute phase of the kidney injury, chronic conditions often exhibit alteration in the epithelial mesenchymal transition (EMT).Objectives: This study aimed to elucidate the correlation between serum PTX-3, MMP-9, and eGFR in patients with CKD. Method: Thirty hypertensive patients with CKD stages 3, 4, and 5, aged between 16 and 65 years, were enrolled in the study (15 males and 15 females). Diagnosis of CKD was based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria, utilizing serum creatinine, and CKD-epidemiology Collaboration (CKD-EPI) estimates. Subsequently, serum MMP-9 and PTX-3 levels were quantified. Result: Patients with CKD exhibited significantly higher serum levels of PTX3 and MMP9. Furthermore. a significant negative connection between PTX-3, MMP-9, and EGFR was observed. Additionally, CKD patients displayed a correlation between PTX-3 and MMP-9 concentrations.Conclusion: Plasma levels of PTX-3 and MMP-9 serve as unique, promising, and important markers that contribute to the pathogenesis of CKD.

Causal effect of serum matrix metalloproteinase levels on venous thromboembolism: a Mendelian randomization study.

Serum matrix metalloproteinase (MMP) levels are associated with cardiovascular diseases. However, the causal associations between serum levels of specific MMPs and venous thromboembolism (VTE) remain unclear. The present study sought to explore the causal relationship between serum MMP levels and VTE by using the Mendelian randomization (MR) method. In this study 2-sample MR study, the exposure data on serum MMP levels were derived from genome-wide association studies involving 21,758 individuals from 13 cohorts of European descent. The outcome data on VTE, including deep vein thrombosis and pulmonary embolism, were derived from the FinnGen research project. The primary method used was the inverse-variance weighting method. The MR-Egger intercept test and the Cochran Q test were used to evaluate pleiotropy and heterogeneity. Using the inverse-variance weighting method, higher serum MMP-12 levels were found to be associated with an increased risk of VTE (odds ratio, 1.04; 95% confidence interval, 1.01 to 1.07; p=0.001). Moreover, there was a weak association between the levels of certain MMPs and VTE. Sensitivity analyses revealed no significant heterogeneity and pleiotropy in our study, and the Steiger directionality test did not reveal a significant reverse causation association. There is a causal association between MMP-12 levels and VTE, which may have substantial implications for the diagnostic and therapeutic strategies used for VTE.

Time trajectories and within-subject correlations of matrix metalloproteinases 3, 8, 9, 10, 12, and 13 serum levels and their ability to predict mortality in polytraumatized patients: a pilot study

BackgroundManaging polytrauma victims poses a significant challenge to clinicians since applying the same therapy to patients with similar injury patterns may result in different outcomes. Using serum biomarkers hopefully allows for treating each multiple injured in the best possible individual way. Since matrix metalloproteinases (MMPs) play pivotal roles in various physiological processes, they might be a reliable tool in polytrauma care.MethodsWe evaluated 24 blunt polytrauma survivors and 12 fatalities (mean age, 44.2 years, mean ISS, 45) who were directly admitted to our Level I trauma center and stayed at the intensive care unit for at least one night. We determined their MMP3, MMP8, MMP9, MMP10, MMP12, and MMP13 serum levels at admission (day 0) and on days 1, 3, 5, 7, and 10.ResultsMedian MMP8, MMP9, and MMP12 levels immediately rose after the polytrauma occurred; however, they significantly decreased from admission to day 1 and significantly increased from day 1 to day 10, showing similar time trajectories and (very) strong correlations between each two of the three enzyme levels assessed at the same measurement point. For a two-day lag, autocorrelations were significant for MMP8 (− 0.512) and MMP9 (− 0.302) and for cross-correlations between MMP8 and MMP9 (− 0.439), MMP8 and MMP12 (− 0.416), and MMP9 and MMP12 (− 0.307). Moreover, median MMP3, MMP10, and MMP13 levels significantly increased from admission to day 3 and significantly decreased from day 3 to day 10, showing similar time trajectories and an (almost) strong association between every 2 levels until day 7. Significant cross-correlations were detected between MMP3 and MMP10 (0.414) and MMP13 and MMP10 (0.362). Finally, the MMP10 day 0 level was identified as a predictor for in-hospital mortality. Any increase of the MMP10 level by 200 pg/mL decreased the odds of dying by 28.5%.ConclusionsThe time trajectories of the highly varying individual MMP levels elucidate the involvement of these enzymes in the endogenous defense response following polytrauma. Similar time courses of MMP levels might indicate similar injury causes, whereas lead–lag effects reveal causative relations between several enzyme pairs. Finally, MMP10 abundantly released into circulation after polytrauma might have a protective effect against dying.

Serum MMP-8 and TIMP-1 concentrations in a population-based cohort: effects of age, gender, and health status

BackgroundMatrix-degrading proteinases and their regulators, such as matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), may contribute to various pathological events. Elevated MMP-8 concentrations have been associated with e.g., cardiovascular diseases and periodontitis. However, there is little knowledge on physiological concentrations of these molecules in serum, or the effect of demographic or lifestyle factors on their levels.Design and methodsWe investigated the effect of various demographic characteristics and behavioral habits, such as aging, sex, smoking, and BMI, on serum concentrations of MMP-8 and TIMP-1. We used the FINRISK97 cohort (n = 8,446), which has comprehensive information on demographic and lifestyle factors, clinical data, laboratory measurements, and register data available. Further, we investigated the concentrations of MMP-8, TIMP-1, and the MMP-8/TIMP-1 ratio in different age groups of healthy and diseased participants. T-test was used to compare log-transformed mean levels in different groups and linear regression was used to evaluate the association between MMP-8 and TIMP-1 and selected diseases and background variables.ResultsMMP-8 levels decreased with increasing age in the whole population and for women, while TIMP-1 concentration increased slightly with age for the whole population and both genders separately (p for linear trend &amp;lt;0.001). The concentrations of MMP-8 were lower and TIMP-1 higher in men compared to women (p &amp;lt; 0.001). Additionally, significant positive association was found for MMP-8 and smoking, CRP, and inverse association with obesity and fasting time. For TIMP-1, significant positive associations were found with smoking, CRP and obesity, and an inverse association with prevalent diabetes.ConclusionThe association of serum MMP-8 and TIMP-1 concentrations with cardiometabolic risk is frequently investigated. MMP-8 levels decrease significantly with age and fasting time. In addition, sex, smoking, and obesity are associated with both MMP-8 and TIMP-1 concentrations. These factors should be carefully considered in epidemiological studies on serum MMP-8 and TIMP-1.

Investigation on the relationship between serum periostin, MMP-7, TGF-β, and IL-18 levels and the clinical course and prognosis of COVID-19.

Cytokines are involved in the inflammatory/anti-inflammatory balance and have been shown to play an important role in the course of COVID-19. This study aimed to evaluate the relationship of periostin, transforming growth factor-beta (TGF-β), interleukin-18 (IL-18), and matrix metalloproteinase 7 (MMP-7) levels with clinical course and mortality in patients with early COVID-19 pneumonia. A total of 150 hospitalized patients were diagnosed with COVID-19 between June and October 2021, and a control group of 30 healthy individuals were included in our study. The COVID-19 patients were divided into those who developed macrophage activation syndrome (MAS) in Group 1 and those who did not in Group 2. Serum periostin, MMP-7, TGF-β, and IL-18 levels were measured from blood samples obtained at admission using enzyme-linked immunosorbent assay (ELISA). Periostin, MMP-7, and IL-18 levels were significantly higher in COVID-19 patients compared to the control group (p<0.001 for all). Periostin and MMP-7 levels were also significantly higher in Group 1 than in Group 2 (p<0.001 for both). Periostin, MMP-7, IL-18, and TGF-β levels were significantly higher in non-surviving patients compared to survivors (p=0.04, p<0.001, p<0.001, and p<0.001, respectively). In the receiver operating characteristic (ROC) curve analysis, MMP-7 was found to have high sensitivity (90%) at a predictive value of 2.66 ng/mL. It is still not possible to predict which patients with early COVID-19 pneumonia will go on to develop MAS despite receiving standard treatment. The results of our study suggest that elevation of periostin and MMP-7 levels in the early period may predict the development of macrophage activation syndrome.

Association of Serum Macrophage Migration Inhibitory Factor with 3-Month Poor Outcome and Malignant Cerebral Edema in Patients with Large Hemispheric Infarction.

We aimed to investigate the associations of macrophage migration inhibitory factor (MIF), toll-like receptors 2 and 4 (TLR2/4), and matrix metalloproteinase 9 (MMP9) with 3-month poor outcome, death, and malignant cerebral edema (MCE) in patients with large hemispheric infarction (LHI). Patients with LHI within 24h of onset were enrolled consecutively. Serum MIF, TLR2/4, and MMP9 concentrations on admission were measured. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3months. MCE was defined as a decreased level of consciousness, anisocoria and midline shift > 5mm or basal cistern effacement, or indications for decompressive craniectomy during hospitalization. The cutoff values for MIF/MMP9 were obtained from the receiver operating characteristic curve. Of the 130 patients with LHI enrolled, 90 patients (69.2%) had 3-month poor outcome, and MCE occurred in 55 patients (42.3%). Patients with serum MIF concentrations ≤ 7.82ng/mL for predicting 3-month poor outcome [adjusted odds ratio (OR) 2.827, 95% confidence interval (CI) 1.144-6.990, p = 0.024] also distinguished death (adjusted OR 4.329, 95% CI 1.841-10.178, p = 0.001). Similarly, MMP9 concentrations ≤ 46.56ng/mL for predicting 3-month poor outcome (adjusted OR 2.814, 95% CI 1.236-6.406, p = 0.014) also distinguished 3-month death (adjusted OR 3.845, 95% CI 1.534-9.637, p = 0.004). Lower serum MIF and MMP9 concentrations at an early stage were independently associated with 3-month poor outcomes and death in patients with LHI. These findings need further confirmation in larger sample studies.

Correlation Between HIF1-A Expression and Airway Remodeling in COPD.

Airway remodeling is a significant pathological characteristic of chronic obstructive pulmonary disease (COPD). In recent years, hypoxia-inducible factor 1-α (HIF-1α), a member of the hypoxia-inducible factor protein family, has gained attention. However, the potential correlation between HIF-1α and COPD airway remodeling remains unclear. This study explored the expression patterns of HIF-1α in patients with COPD and its association with airway remodelling. This investigation aims to furnish novel insights for the clinical identification of prospective therapeutic targets for ameliorating COPD-related airway remodelling. A total of 88 subjects were included, consisting of 28 controls and 60 COPD patients. Various staining methods were employed to observe the pathological changes in airway tissues. Immunohistochemistry was utilized to detect the expression of HIF-1α and MMP9 (matrix metalloproteinase 9) in airway tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration in serum of HIF-1α and MMP9. Computed tomography (CT) airway parameters were measured in all participants to assess airway remodeling. The relationship between serum HIF-1α and MMP9 concentrations and airway parameters was analyzed. Staining of airway structures in COPD patients revealed significant pathological changes associated with airway remodelling, including mixed cilia and subepithelial fibrosis. The expression of HIF-1α and MMP9 was significantly higher in both human airway tissue and serum compared to controls. Chest CT scans exhibited typical imaging features of airway remodeling and increased airway parameters. The findings suggest a correlation between increased HIF-1α expression and COPD airway remodelling. This study provides novel evidence that HIF-1α may be a potential biomarker for airway remodelling in COPD patients.

Clinical value of KiSS-1 and MMP-2 expression levels in breast cancer tissue in evaluating prognosis of elderly breast cancer patients after modified radical mastectomy.

We attempted to clarify clinical value of KiSS-1 and MMP-2 levels in breast cancer (BC) tissue in evaluating prognosis of elderly BC patients after modified radical mastectomy (MCM). The data of 192 elderly female BC patients receiving MCM in our hospital from January 2018 to December 2022 were collected. According to prognosis, patients received division into poor prognosis group (n = 43) and good prognosis group (n = 149). The serum CEA level and KiSS-1 and MMP-2 levels in BC tissue received measurement in both groups. The predictive value of KiSS-1 and MMP-2 alone and jointly in adverse prognosis of elderly BC patients after MCM received assessment. Results showed that No statistical significance was exhibited between both groups in general data (P > 0.05). The serum CEA level and MMP-2 expression in BC tissue in poor prognosis group exhibited elevation relative to those in good prognosis group, and KiSS-1 expression in BC tissue in poor prognosis group exhibited depletion relative to that in good prognosis group, indicating statistical significance (P < 0.05). The high-level KiSS-1 might be a protective element for adverse prognosis of elderly BC patients after MCM, and high-level CEA and MMP-2 might be an independent risk element for adverse prognosis of elderly BC patients after MCM (P < 0.05). KiSS-1 and MMP-2 alone and jointly predicted AUC of adverse prognosis in elderly BC patients after MCM were 0.93, 0.802 and 0.958, with certain predictive values; when cutoff values of KiSS-1 and MMP-2 were 6.15 and 2.26, the predictive value was the best. In conclusion, KiSS-1 and MMP-2 levels in BC tissue possess relation to adverse prognosis of MCM. KiSS-1 and MMP-2 levels in elderly BC patients before surgery may be detected in the future to assist in prognosis evaluation of elderly BC patients after MCM.

Вміст сироваткової матриксної металопротеїнази-1 та тканинного інгібітора матриксної металопротеїнази-1 у новонароджених від матерів із недиференційованою дисплазією сполучної тканини

Laboratory markers of undifferentiated connective tissue dysplasia (UCTD) are indicators of the matrix metalloproteinases (MMP) system, which are involved in the remodeling of connective tissue components, morphogenesis, inflammation. Purpose - to analyze the correlation between signs of UCTD in postpartum women and the level of serum MMP-1, tissue inhibitor of MMP-1 (TIMP-1) and the MMP-1/TIMP-1 ratio in newborns. Materials and methods. We examined 122 women in labor and their 122 newborn children with a gestational age (GA) of 28-42 weeks, a body weight (BW) of 1270-4070 g. Clinical and anamnestic data and biochemical markers (level of serum MMP-1, TIMP-1, MMP-1/TIMP-1) were investigated in children. Clinical signs of UCTD in women in labor were registered. The main group (n=82) involved women with ≥3 UCTD markers, the control group (n=40) consisted of women with ≤2 UCTD features and their newborns. Accordingly, the main group of newborns - children from mothers with ≥3 markers of UCTD, the control group - babies from mothers with ≤2 signs of UCTD. For statistical analysis, Mann-Whitney (U) test and Cramer’s coefficient (φc) were used. Results. Newborns of the main group had a longer GA (U=1069.5; p=0.002), a lower Apgar score (U=1522.5; p=0.04), a smaller weight-for-age ratio (U=1511.0; p=0.038), higher concentrations of MMP-1 (U=55.0; p=0.000013) and higher values of the MMP-1/TIMP-1 (U=76.0; p=0.000323). The optimal range of MMP-1 in newborns is 2.72-3.91 ng/ml, TIMP-1 - 16.08-17.49 ng/ml, MMP-1/TIMP-1 - 0.16-0.24. MMP-1 concentration ranges ≥4.51 ng/ml and MMP-1/TIMP-1 values ≥0.31 were more typical for full-term infants (p&lt;0.01) than prematurely born, and for children with lower BW (p&lt;0.01). UCTD-associated obstetric complications were related to ranges of MMP-1 ≥4.51 ng/ml (p&lt;0.001-0.05), TIMP-1 ≤16.07 ng/ml (p&lt;0.05), MMP-1/TIMP-1 ≥0.31 (p&lt;0.001-0.05) in children. Conclusions. UCTD in parturient mothers is an unfavorable factor in the formation of small weight-for-age ratio (p=0.038), a low postnatal adaptation (p=0.04), imbalance of serum MMP-1 (p=0.000013) and MMP-1/TIMP-1 (p=0.000323) in children. The optimal level of serum MMP-1 for newborns is 2.72-3.91 ng/ml, TIMP-1 - 16.08-17.49 ng/ml, MMP-1/TIMP-1 - 0.16-0.24. The values of MMP-1 ≥4.51 ng/ml and MMP-1/TIMP-1 ≥0.31 are markers of delayed physical development of the fetus (p&lt;0.01). UCTD-associated obstetric complications are prognostically unfavorable for imbalance of MMP-1, TIMP-1, MMP-1/TIMP-1 in newborns. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of an institution. The informed consent to participate in the study was obtained from each mother. No conflict of interests was declared by the authors.

Abstract 5979: Recombinant N-acetylgalactosamine-4-sulfatase (arylsulfatase B; ARSB) inhibits lung metastases in murine B16F10 syngeneic tumor model

Abstract Activity of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B: ARSB), which removes the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate (C4S) and dermatan sulfate, is reduced in several malignant cell lines and human tissues, including melanomas, mammary, prostate, and colon. Following tail vein injection of B16F10 melanoma cells in 12-week-old female C57BL/6J mice (n=11) and subsequent treatment by tail vein injection of bioactive, recombinant human ARSB (0.2 mg/kg), on days 2 and 7, development of metastatic lung lesions was markedly reduced. The average number of lesions declined from mean value of 114 (range: 10-278; n=5) to mean value of 2.5 (range: 0-9; n=6). These findings are consistent with our previous report of significant increase in survival and decrease in size of B16F10 subcutaneous melanomas in C57BL/6J mice treated with exogenous ARSB. The underlying mechanisms leading to inhibition of melanoma proliferation have profound impact on vital signaling pathways and transcriptional events. These pathways involve more or less binding with C4S when ARSB activity is modified. Notably, galectin-3 binding with C4S increases following exogenous ARSB, leading to decline in free nuclear galectin-3. This leads to reduced expression of the melanoma biomarker chondroitin sulfate proteoglycan CSPG)-4; also known as melanoma-associated chondroitin sulfate proteoglycan (MCSP). Expression of Programmed Death-Ligand 1 (PD-L1) is also reduced, declining from 1.34 ± 0.23 ng/mg protein (n=5) to 0.50 ± 0.05 ng/mg protein (n=6) following ARSB treatment. Inverse to the effect on galectin-3, SHP2, the ubiquitous non-receptor tyrosine phosphatase (PTPN11), binds less to C4S following treatment with exogenous ARSB. The resulting activation of SHP2 impacts on MAPK signaling, reducing phospho-ERK1/2 and phospho(T180/Y182)-p38-MAPK. These effects contribute to decline in matrix metalloproteinases MMP2 and MMP9 and thereby restrain invasiveness and metastasis. Following treatment with exogenous ARSB, the serum MMP2 declined from 267 ± 38 (ng/ml; n=5) to 121 ± 16 ng/ml (n=6), consistent with the observed decline in melanoma lesions. The impact of ARSB on signaling pathways and transcriptional events demonstrates how modification of a critical sulfation and the resulting impact on binding with C4S influences vital cell processes and can suppress tumor development. Recombinant human ARSB is an approved agent for the treatment of Mucopolysaccharidosis VI and is used safely and effectively for this congenital deficiency of ARSB. Exogenous ARSB may become an effective treatment for acquired deficiency of ARSB in melanoma. Citation Format: Joanne Kramer Tobacman, Sumit Bhattacharyya, Insug O-Sullivan. Recombinant N-acetylgalactosamine-4-sulfatase (arylsulfatase B; ARSB) inhibits lung metastases in murine B16F10 syngeneic tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5979.

Retracted: Correlation Analysis of Acute Coronary Syndrome with Serum IL-18, MMP-9, hs-CRP, and Plasma FIB.

[This retracts the article DOI: 10.1155/2022/5984184.].

The implication of miR-200a and miR-132 expression and their correlations with NF-κB/TNF-alpha signaling in adults with diabetic nephropathy

AimThe primary factor causing chronic renal failure is diabetic nephropathy (DN) worldwide. However, the current biomarkers for DN have limited diagnostic utility. Thus, this work aimed to clarify the implications of microRNA-200a (miR-200a) and microRNA-132 (miR-132) and their correlation with NF-κB (nuclear factor- kappa beta), and, TNF-α (tumor necrosis factor –alpha) signaling to identify biomarkers able to distinguish late-stage from early- stage DN. MethodsFifty healthy controls, and 271 type 2 diabetic (T2D) patients (166 male plus 105 female) were enrolled. Participants were stratified into seven groups according to along with the estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c%), healthy controls, diabetes without DN (G1), diabetes with mild renal impairment (G2), and four DN grades (G3a, G3b, G4, and G5). ResultsCompared to healthy controls, the DN groups exhibited linear increases in serum miR-200a, TNF-α, NF-κB, matrix metalloproteinase (MMP-9) and interleukin-6 (IL-6) levels and reductions in miR-132 serum expression. Among the patients, NF-κB and TNF-α produced a negative correlation with miR-132, while, positive correlation has been discovered with miR-200-a. The operating characteristic of the receiver curve (ROC), proved that, miR-200a also miR-132 had good diagnostic performance in distinguishing early from advanced DN. ConclusionMiR-200a as well as miR-132 expression levels, and their correlations with NF-κB/TNF-alpha signaling, were able to differentiate between DN patients with lower eGFR, suggesting their utility as diagnostic and prognostic biomarkers.

Matrix metalloproteinases are associated with severity of disease among COVID-19 patients: A possible pharmacological target.

COVID-19 is a devastating disease and imbalanced matrix metalloproteinase (MMP) activity may contribute to its pathophysiology. This exploratory study examined whether increased circulating concentrations of MMP-2 and MMP-9, and their endogenous inhibitors, the tissue inhibitors of MMP (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4 are persistently found in patients 2 weeks after their recovery from severe or critical COVID-19 as compared with those in healthy controls. Subjects who had severe (n= 26) or critical (n= 25) PCR-confirmed COVID-19 and healthy controls (n= 21) had blood samples drawn 2 weeks after recovery and serum MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were determined using two Human Luminex® Discovery Assays. Circulating MMP activity was also determined by gel zymography. Patients who had severe or critical COVID-19 had increased circulating MMP-9 and MMP-2 concentrations, with increased MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios indicating increased MMP activity, confirmed by gel zymography (all p< 0.05). Higher circulating MMP-9 (but not MMP-2) concentrations were found in critical versus severe COVID-19 (p< 0.05). We found increased circulating MMP-9 and MMP-2 concentrations and activity many days after recovery from the acute disease, with MMP-9 levels associated with disease severity. These biochemical alterations suggest that MMP-2 and MMP-9 may be important pharmacological targets in COVID-19.

Probiotics combined with Budesonide and Ipratropium bromide for chronic obstructive pulmonary disease: A retrospective analysis.

To explore the effect of probiotics combined with budesonide and ipratropium bromide in the treatment of chronic obstructive pulmonary disease (COPD) on lung function and gut microbiota. This was a retrospective study of prospectively collected clinical data of 118 patients with COPD admitted to our hospital between January 2020 and December 2022. According to the treatment records, 59 patients received budesonide and irpratropium bromide (control group), and 59 patients received probiotics combined with budesonide and irpratropium bromide (observation group). The lung function, inflammatory factor levels, airway remodeling, and gut microbiota before and after treatment were compared between the 2 groups. After treatment, FVC, MMEF, PEF, and FEV1 in the 2 groups were higher than before treatment, and the values in the observation group were higher than those in the control group (P < .05). After treatment, the serum levels of TNF-α, IL-6, and PCT in the 2 groups were lower than before treatment, and the levels in the observation group were lower than those in the control group (P < .05). After treatment, the levels of serum MMP-9, VEGF, basic fibroblast growth factor, and NGF in the 2 groups were lower than before treatment, and the levels in the observation group were lower than those in the control group (P < .05). After treatment, the levels of lactobacilli and bifidobacteria in the 2 groups increased compared to those before treatment, and the observation group had a higher level, while the levels of Enterobacteriaceae and Enterococcus were lower in the observation group than those before treatment (P < .05). Based on budesonide and irpratropium bromide, probiotic treatment of COPD is more conducive to reducing the degree of inflammatory reactions, inhibiting airway remodeling, regulating the level of gut microbiota, and promoting the recovery of lung function.

Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort.

High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated the accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort. MMP-7 was measured in serum samples of 399 infants with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays. The discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an AUROC of 0.90 (CI: 0.87-0.94). At cutoff 52.8ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77-0.86), stool color = 0.68 (CI: 0.63-0.73), and pathology = 0.84 (CI: 0.76-0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+gamma-glutamyl transferase AUROC to 0.91 (CI: 0.88-0.95). Serum concentrations produced by time resolved fluorescence energy transfer differed from single-plex, with an optimal cutoff of 18.2ng/mL. Results were consistent within each assay technology and generated similar AUROCs. Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in the evaluation of infants with cholestasis may simplify diagnostic algorithms and shorten the time to hepatoportoenterostomy.

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis

BackgroundBronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. MethodsThis study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. ResultsThe current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia

BackgroundInflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology.MethodsThe study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function.ResultsSerum TNF-α and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F = 4.289, P = 0.016; F = 4.682, P = 0.011, respectively). Bonferroni correction demonstrated that serum TNF-α levels were significantly elevated in CMS patients (P = 0.022) and MMP-2 levels were significantly higher in TRS patients (P = 0.014) compared to healthy controls. In TRS patients, TNF-α was negatively correlated with age (r=-0.435, P = 0.015) and age of onset (r=-0.409, P = 0.022). In CMS patients, MMP-2 and TNF-α were negatively correlated with PANSS negative and total scores, and TNF-α was negatively correlated with PANSS general psychopathology scores (all P < 0.05). MMP-2 levels were positively correlated with TNF-α levels (P < 0.05), but not with cognitive function (P > 0.05).ConclusionThe results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.

Effectiveness of Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg ethanol extract in suppressing inflammation and cartilage degeneration in animal models of osteoarthritis

Context: Osteoarthritis (OA) is a degenerative joint disease characterized by an inflammatory reaction and cartilage degradation. Artocarpus altilis is a well-known traditional medicine with various phenolic and flavonoid content. Several pharmacological properties of A. altilis extract (AAE) have been reported, but its effectiveness in osteoarthritis is unknown. Aims: To investigate the potential of AAE as an anti-osteoarthritis. Methods: The Wistar rats induced OA with mono-iodoacetate (MIA). The OA model rats were treated with AAE with three dose levels (100, 200, and 400 mg/kg) for 28 days. As a positive control used Na-diclofenac (20 mg/kg). Serum IL-1β, IL-10, MMP-3, and MMP-13 levels and histopathological profiles were compared to the MIA group and normal control (5% Na-CMC). Results: The experimental results showed that AAE could significantly suppress the production of inflammatory mediator factor IL-1β, matrix-degrading proteinase MMP-3, MMP-13, and cartilage degeneration. In addition, AAE increased the production of the anti-inflammatory mediator IL-10, improved synovial inflammation, and increased cartilage thickness. Conclusions: A. altilis extract has the potential to be developed as an anti-osteoarthritis therapeutic agent from natural medicine.