Serum Levels Of MMP-9 Research Articles

A comprehensive study on mechanisms of action of fibroin, aloe vera, and ginger extracts through histochemical, inflammation biomarkers, and matrix metalloproteinases analysis against diabetic wounds

IntroductionDiabetes causes complications like delayed wound healing for a long time. Fibroin, aloe vera, and ginger extracts along with their combinations are used for diabetic wound healing. MethodsAfter induction of diabetes, The wound healing effects of fibroin (50 mg/ml), aloe vera gel (50 mg/ml), and ginger extract (30 mg/ml), individually and in combination, were assessed. The pro-inflammatory cytokines including tumor narcosis factor-α (TNF-α) interleukin (IL-6, IL-8, IL-1β), matrix metalloproteinases (MMP 2, MMP7, MMP 9), vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinases (TIMPs) levels were analyzed in the serum. ResultsA combination of fibroin + aloe vera gel + ginger extract (Fi + Al + Gi) healed the wounds in 11 days via wound contraction of 98.5 ± 0.9 % as compared to diabetic control (58.2 ± 0.7 %) and positive control (73.3 ± 0.6 %) groups. However, the wounds of the Polyfax and the diabetic control groups were healed in 17 and 19 days, corresponding to a contraction of: 96.7 ± 1.4 % and 96.3 ± 1.1 %. The histological assay showed that the Fi + Al + Gi group indicated an increased growth of collagen fibers, fibroblasts, keratinocytes and blood vessels with lessened inflammation. The Fi + Al + Gi group alleviated the serum level of TNF-α (12.7 ± 0.9 pg/ml), IL-6 (9.6 ± 0.9 pg/ml), IL-8 (19.6 ± 1.0 pg/ml), MMP2 (217.0 ± 9.2 pg/ml), MMP7 (279.0 ± 9.8 pg/ml), and MMP9 (156.0 ± 11.6 pg/ml) significantly as compared to the diabetic control (P ≤ 0.05). TIMP serum level (202.0 ± 6.9 pg/ml) was significantly elevated as compared to the diabetes control group. ConclusionThe present study concludes that the biomaterials in their combinations possess high regenerative and healing abilities.

Candidate Biomarkers For Response To Treatment In Psoriatic Disease.

To determine whether biologic therapy alters serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in psoriatic arthritis (PsA) and psoriasis (PsC) patients, and whether baseline levels of these proteins predict response to treatment for PsA. We included PsA patients on TNF inhibitors (TNFi), Interleukin-17 inhibitors (IL-17i), methotrexate (MTX), and untreated with bDMARDs or csDMARDs (untreated) and PsC patients on bDMARDs and matched untreated. Serum samples at baseline and 3-6 months follow-up were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as: 1. Achieving low disease activity or remission (according to DAPSA), 2. 75% reduction in PASI, and 3. 50% reduction in actively inflamed joint count. In PsA, TNFi reduced serum levels of all five proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA (p<0.05). There were no significant differences between treated or untreated PsC patients. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (AUC>0.8) for response to biologics in PsA patients. Biologics treatment and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in PsA patients. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.

Serum metalloproteinase-7 as a biomarker of progressive pulmonary fibrosis

IntroductionProgressive pulmonary fibrosis (PPF) corresponds to any fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) that presents clinical, physiological and/or radiological evidence of disease progression similar to IPF. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis and are associated with disease progression and reduced survival in IPF and other fibrotic ILDs.AimThis study aimed to investigate the role of the serum levels of MMP-1 and MMP-7 in patients with fibrotic non-IPF ILD as possible biomarkers of patients at risk of developing PPF.MethodsNewly diagnosed patients with fibrotic non-IPF ILD were included in this study. Serum levels of MMP-1 and MMP-7 were quantified at baseline, and disease progression was monitored. PPF was defined according to the recent ATS/ERS/JRS/ALAT Clinical Practice Guidelines.ResultsSeventy-nine patients with fibrotic non-IPF ILDs were included and classified as having PPF or non-PPF. Significantly higher levels of MMP-7, but not MMP-1, were detected in the PPF group (p=0.01). MMP-7 was independently associated with PPF (aOR=1.263; 95% CI 1.029—1.551, p=0.026) after adjustment for sex, age and smoking history. A cut-off value of 3.53 ng·mL−1for serum MMP-7 levels had a sensitivity of 61% and a specificity of 74% for predicting PPF in non-IPF ILDs.ConclusionsIn patients with fibrotic non-IPF ILDs, serum MMP-7 levels were significantly greater in the subgroup of patients meeting the PPF criteria at follow-up. This can be considered and further investigated as a possible biomarker to identify fibrotic ILD patients at risk of PPF.

High-intensity intermittent exercise increases serum levels of chitinase 3-like protein-1 and matrix metalloproteinase-9 in persons with multiple sclerosis

The study aimed to evaluate the effect of high-intensity intermittent exercise (HIIE) on serum levels of MMP-9 and CHI3L1 in multiple sclerosis. Study group received HIIE twice a week for 12 weeks, while control group received no treatment. In intra-group comparison, study group showed a significant increase in MMP-9 and CHI3L1 levels, while control group showed no significant difference. In intergroup comparison, a significant difference was found only in CHI3L1 levels after treatment. The increase in MMP-9 and CH3L-1 concentrations in study group suggests that these biomarkers may play a role in regulating specific skeletal muscle adaptations due to HIIE.

UV-spectrophotometric and spectroscopic observed Vachellia nilotica and Nigella sativa formulations regularized the histopathological and biochemical parameters during wound contraction.

Diabetes mellitus causes impaired diabetic wounds which is linked to a number of pathological alterations that impede the healing of wounds. In the current research, Swiss albino mice were given alloxan monohydrate to induce diabetes and excision wounds of approximately 6 mm using biopsy punch. The diabetic wounds were treated with various biomaterials including Vachellia nilotica extract (VN), Nigella sativa extract (NS), V. nilotica nanoparticles (VNNPs) and N. sativa nanoparticles (NSNPs). Their effects were determined by evaluating the percent wound contraction, healing time, and histopathological analysis. The serum level of various biochemical parameters that is, pro-inflammatory cytokines, Matrix metalloproteinases (MMPs) and tissue inhibitor matrix metalloproteinases (TIMPs) were also determined. VNNPs group provided the best outcomes, with wound contraction 100% on 12th day. According to histopathological examination, VNNPs group reduced inflammation and encouraged the formation of blood vessels, fibroblasts, and keratinocytes. VNNPs group significantly alleviated the serum level of pro-inflammatory cytokines that are, TNF-α (19.4 ± 1.5 pg/mL), IL-6 (13.8 ± 0.6 pg/mL), and IL-8 (24.8 ± 1.2 pg/mL) as compared with the diabetic mice. The serum level of MMP2 (248.2 ± 7.9 pg/mL), MMP7 (316 ± 5.2 pg/mL), and MMP9 (167.8 ± 12.1 pg/mL) in the same group VNNPs were also observed much less than the diabetic mice. The serum level of TIMPs (176.8 ± 2.9 pg/mL) in the VNNPs group was increased maximally with respect to diabetic mice. It is concluded that nanoparticles and biomaterials possess healing properties and have the ability to repair the chronic/diabetic wound. RESEARCH HIGHLIGHTS: UV-spectrophotometric and Fourier transform infrared spectroscopy observation for functional group analysis and possible linkage between conjugates Optimization of the histopathological and biochemical markers after application of the formulations Microscopic analysis of epithelial tissues for evaluation of healing mechanisms Speedy contraction of wounds as the alleviation of the inflammatory and necrotic factors.

Level of some matrix metalloproteinases in blood serum in relation to their genetic polymorphism depending on age

The article presents data on the state of the proteolysis system and genes for the regulation of matrix metalloproteinases in 180 conditionally healthy women and men of young, middle, elderly and senile ages. A single sampling of the material (buccal epithelium) was performed in patients. PCR examination of the buccal epithelium for the analysis of polymorphisms of the genes MMP-1 rs1799750 and MMP-3 rs 3025058 was carried out on the instrument base of the DNA amplifier Bio-Rad CFX96. Serum levels of MMP-1, MMP-3 were studied by the sandwich variant of solid-phase enzyme immunoassay. Statistical processing of the obtained results was carried out using the IBM SPSS Statistics 26 program using nonparametric statistics methods. The results of the study. The values of MMP-1 and MMP-3 in the group of conditionally healthy women at a young age were lower than the values of middle age, whereas in old age their serum levels varied in different directions: MMP-1 decreased, and MMP-3 increased. When analyzing polymorphisms of the MMP-1 rs1799750 gene, the homozygous genotype -/- with low expression of the MMP-1 gene prevailed in young and middle-aged women, and in women over 75 years of age, the carriage of the G/G homozygote with active gene expression was recorded. When evaluating the expression of the MMP-3 rs 3025058 gene, it was found that young women significantly more often had 5A/5A polymorphism with high gene activity, but with a lower level of MMP- 3. In middle and old age, 65% have a heterozygous 5A/6A allele with reduced gene expression activity. In conditionally healthy men, the level of MMP-1 in blood serum increased in the middle-aged and senile groups, the values of MMP-3 in the group under 45 years of age were low compared with the elderly group (p = 0.041). MMP-1 rs1799750 in men under 75 years of age was identified in the -/G variant in the majority. Homozygous polymorphism of the MMP-3 rs 3025058 5A/5A gene with high activity of MMP-3 prevailed in groups of men under 60 years of age with serum levels of MMP-3 100.2 ng/mL and 92.5 ng/mL, respectively.

Diagnostic accuracy of serum biomarkers to identify giant cell arteritis in patients with polymyalgia rheumatica

IntroductionPolymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are frequently overlapping conditions. Unlike in GCA, vascular inflammation is absent in PMR. Therefore, serum biomarkers reflecting vascular remodelling could be used...

Exploring blood pressure dynamics and oxidative stress markers in an animal model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a hormonal disorder characterized by elevated androgen levels, heightened insulin secretion, and dysregulation of luteinizing hormone and follicle-stimulating hormone. This disorder results in metabolic disruptions, while the irregular estrous cycles associated with PCOS impact cellular functions like growth, movement, and alterations in cell adhesion within the tissue matrix. This study aims to identify the blood tension, serum malondialdehyde (MDA) levels, and serum Metalloproteinase-1 (MMP-1) in rat models of PCOS. The study was conducted using female Wistar rats aged 6 months weighing between 130 and 180 g. The rats were divided into three treatment groups: negative control, induction of testosterone propionate (TP) at a dose of 100 mg/kg BW IP for 12 days, and induction of estradiol valerate (EV) at a dose of 2 mg/kg BW IP for 2 days. Data were analyzed quantitatively using a one-way analysis of variance followed by a Posthoc Test using the least significant difference with a confidence level of 95%. The research results indicate that the average blood pressure of TP Group and EV Group did not differ significantly from the negative control (p > 0.05). Serum MDA levels were significantly different in the TP Group compared to the negative control (p < 0.05). On the other hand, MMP-1 levels showed no significant difference (p > 0.05) among all the treatment groups. The findings of this study suggest that TP induction in a rat model of PCOS can potentially contribute to oxidative stress and lipid peroxidation, but does not significantly affect blood pressure or serum MMP-1 levels.

Development of a diagnostic model for biliary atresia based on MMP7 and serological tests using machine learning.

To develop a machine learning diagnostic model based on MMP7 and other serological testing indicators for early and efficient diagnosis of biliary atresia (BA). A retrospective analysis was conducted on patient information from those hospitalized for pathological jaundice at Beijing Children's Hospital between January 1, 2019, and December 31, 2023. Patients with serum MMP7, liver stiffness measurements, and other routine serological tests were included in the study. Six machine learning models were constructed, including logistic regression (LR), random forest (RF), decision tree (DET), support vector machine classifier (SVC), neural network (MLP), and extreme gradient boosting (XGBoost), to diagnose BA. The area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the various models. A total of 98 patients were included in the study, comprising 64 BA patients and 34 patients with other cholestatic liver diseases. Among the six machine learning models, the XGBoost algorithm model and RF algorithm model achieved the best predictive performance, with an AUROC of nearly 100% in both the training and validation sets. In the training set, these two algorithm models achieved an accuracy, precision, recall, F1 score, and AUROC of 1. Through model interpretation analysis, serum MMP7 levels, serum GGT levels, and acholic stools were identified as the most important indicators for diagnosing BA. The nomogram constructed based on the XGBoost algorithm model also demonstrated convenient and efficient diagnostic efficacy. Machine learning models, especially the XGBoost algorithm and RF algorithm models, constructed based on preoperative serum MMP7 and serological tests can diagnose BA more efficiently and accurately. The most important influencing factors for diagnosis are serum MMP7, serum GGT, and acholic stools.

Impact of anti-human IgG hinge peptide antibodies on identification of patients with early seronegative rheumatoid arthritis.

The early diagnosis of seronegative rheumatoid arthritis (SNRA), characterised by the absence of rheumatoid factor and anti-citrullinated antibody, involves a greater challenge compared to seropositive RA (SPRA). This study aimed to assess the discriminatory potential of anti-human IgG hinge antibodies (AHAs) for patients with early SNRA. DMARDs-naive patients with SPRA (n=43), SNRA (n=21), and non-RA (n=49), with disease duration < 2 years, were included. Antigens comprised IgG1 or IgG4 F(ab')2 cleaved by pepsin or MMP-3 and their hinge peptide analogues. Eight IgG anti-hinge antibodies (AHAs) against these antigens were measured in sera from the patients and 58 healthy controls (HCs) using ELISA. Serum CRP and MMP-3 levels, and clinical disease activity index (CDAI), were obtained from medical records. The area under the curve (AUC) obtained from logistic regression and receiver operating characteristic curve analyses were used as a discriminant indicator. The levels of the IgG AHAs were as follows: SPRA≥SNRA≈non-RA>HC. None of the AHAs were effective in discriminating SNRA from non-RA. However, the combination of MMP-3 and AHAs against IgG4 hinge peptide analogues demonstrated the utility (AUC=0.94). Furthermore, combination of MMP-3, AHAs against IgG1 hinge peptide analogues and CDAI maximally exerted discriminatory power (AUC=0.997). Specific AHAs in combination with MMP-3 and CDAI are potentially useful to discriminate SNRA from non-RA.

Contribution of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 to Upper Tract Urothelial Cancer Risk in Taiwan.

Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were measured using ELISA and real-time PCR. Statistical analysis showed that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes were differently distributed between UTUC patients and controls (p = 0.0199 and 0.0020). The MMP-2 rs2285053 TT genotype was associated with higher UTUC risk compared to the CC genotype (OR = 2.20, p = 0.0190). Similarly, MMP-9 rs3918242 CT and TT genotypes were linked to increased UTUC risk (OR = 1.51 and 2.92, p = 0.0272 and 0.0054). In UTUC patients, TT carriers of MMP-2 rs2285053 and MMP-9 rs3918242 showed higher mRNA and protein levels (p < 0.01). These findings suggest that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes are significant markers for UTUC risk and metastasis in Taiwan.

- Correlation between dental fluorosis risk and bone specific alkaline phosphatase, osteocalcin, matrix metalloproteinase and parathyroid hormone in children

Objective Investigating the association between dental fluorosis occurrence in children and bone metabolism-related indicators including bone-specific alkaline phosphatase (BALP), osteocalcin (OC), matrix metalloproteinase (MMP-2, MMP-9, MMP-20), and parathyroid hormone (PTH).Methods A total of 189 cases of school-age children underwent health examinations in our hospital were enrolled, according to the presence or absence of dental fluorosis, they were divided into fluorosis group (n=97) and fluoride-free group (n=92), and the serum BALP, OC, MMP-2, MMP-9, MMP-20, and PTH levels of the two groups were compared, relevant clinical data were collected.In this study, multivariate logistic regression was employed to examine the factors associated with the development of dental fluorosis in children. Results The urine fluoride levels, BALP, MMP-2, and MMP-9 of the children influorosis group were higher thanfluoride-free group, and the mother's educational level, per capita annual household income, OC, and PTH were lower thanfluoride-free group (P&lt;0.05).Based on Spearman correlation analysis, a positive correlation was identified between the urinary fluoride level, the extent of dental fluorosis, and indicators such as BALP, MMP-2, and MMP-9. (r=0.618, 0.558, 0.567, 0.597, 0.602, 0.571, P&lt;0.001), and negatively correlated with OC and PTH (r=-0.580, -0.603, -0.549, -0.515, P&lt;0.001).As the urinary fluoride level and the extent of dental fluorosis increased, there was a gradual elevation in serum BALP, MMP-2, and MMP-9 levels in children, while OC and PTH levels gradually decreased (P&lt;0.05).After adjusting for confounding factors including urinary fluoride,maternal education level, and per capita annual household income, multivariate Logistic regression analysis showed that BALP, OC, MMP-2, MMP-9, PTH were independently associated with the risk of dental fluorosis (P&lt;0.05). Conclusion High BALP, MMP-2, MMP-9, low OC, and PTH are independent factors affecting the occurrence of dental fluorosis and are related tothe extent of dental fluorosis.

Association between matrix metalloproteinase-9-1562C/T gene polymorphism and MMP-9 serum level in rheumatoid arthritis

ABSTRACT Background Rheumatoid arthritis (RA) is an autoimmune disease indicated by joint inflammation and cartilage destruction. Matrix metalloproteinase (MMP) enzymes play an influential role in inflammation by affecting the invasion and degradation of anatomical barriers. In this way, the current study investigated the relationship between the MMP-9-1562C/T gene polymorphism and this enzyme’s serum level in RA. Methods The serum levels of MMP-9 in RA patients and healthy controls were measured using the enzyme-linked immunosorbent assay (ELISA). RA was confirmed using rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and C-reactive protein (CRP). Then the MMP-9-1562C/T gene polymorphism was analyzed utilizing polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Also, multivariate analysis investigated the connection between this polymorphism and the risk of RA. Results In this study, the increase of MMP-9 in patients due to the development of single nucleotide polymorphism in the promoter region of this gene (−1562 C→T) was confirmed by increasing the frequency of heterozygous genotype (CT). Logistic regression analysis also demonstrated that the chance of development of RA is higher in people with CT/CC genotype than in other alleles. Conclusions We demonstrated that MMP-9-1562C/T gene polymorphism can play a significant role in the occurrence of RA.

Diagnostic value of serum NLRP3, metalloproteinase-9 and interferon-γ for postoperative hydrocephalus and intracranial infection in patients with severe craniocerebral trauma.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. We unveiled the diagnostic value of serum NLRP3, metalloproteinase-9 (MMP-9) and interferon-γ (IFN-γ) levels in post-craniotomy intracranial infections and hydrocephalus in patients with severe craniocerebral trauma to investigate the high risk factors for these in patients with TBI, and the serological factors predicting prognosis, which had a certain clinical predictive value. Study subjects underwent bone flap resection surgery and were categorized into the intracranial infection/hydrocephalus/control (without postoperative hydrocephalus or intracranial infection) groups, with their clinical data documented. Serum levels of NLRP3, MMP-9 and IFN-γ were determined using ELISA kits, with their diagnostic efficacy on intracranial infections and hydrocephalus evaluated by receiver operating characteristic curve analysis. The independent risk factors affecting postoperative intracranial infections and hydrocephalus were analysed by logistic multifactorial regression. The remission after postoperative symptomatic treatment was counted. The intracranial infection/control groups had significant differences in Glasgow Coma Scale (GCS) scores, opened injury, surgical time and cerebrospinal fluid leakage, whereas the hydrocephalus and control groups had marked differences in GCS scores, cerebrospinal fluid leakage and subdural effusion. Serum NLRP3, MMP-9 and IFN-γ levels were elevated in patients with post-craniotomy intracranial infections/hydrocephalus. The area under the curve values of independent serum NLRP3, MMP-9, IFN-γ and their combination for diagnosing postoperative intracranial infection were 0.822, 0.722, 0.734 and 0.925, respectively, and for diagnosing hydrocephalus were 0.865, 0.828, 0.782 and 0.957, respectively. Serum NLRP3, MMP-9 and IFN-γ levels and serum NLRP3 and MMP-9 levels were independent risk factors influencing postoperative intracranial infection and postoperative hydrocephalus, respectively. Patients with hydrocephalus had a high remission rate after postoperative symptomatic treatment. Serum NLRP3, MMP-9 and IFN-γ levels had high diagnostic efficacy in patients with postoperative intracranial infection and hydrocephalus, among which serum NLRP3 level played a major role.

Association of Matrix Metalloproteinase-2 (MMP-2) and MMP-9 Promoter Variants, Their Serum Levels, and Activities with Aortic Valve Calcification (AVC) in a Population from Western Iran.

Background: Matrix metalloproteinase (MMP) enzyme gene polymorphisms MMP-2-1575G/A and MMP-9-1562C/T promoter polymorphism, their serum levels, and activity are associated with aortic valve calcification (AVC). Materials and Methods: The synergistic link between the risk of AVC and the alleles T and A of MMP-9 and MMP-2 was investigated, respectively. Ninety-two cases with AVC and 92 healthy individuals from the west of Iran were included, and MMP- 2-1575G/A and MMP-9-1562C/T promoter polymorphisms were detected using PCR-RFLP. The serum levels and activity of MMP-2 and -9 were assessed using ELISA and gelatin zymography methods, respectively. In addition, serum biochemical markers, including FBS, urea and creatinine, cholesterol, triglyceride, HDL, LDL, calcium, phosphorus, and blood pressure: systolic blood pressure and diastolic blood pressure were measured. Results: Heart valve calcification disease was associated with a comparatively higher frequency of the A allele of the MMP2-1575 variation (p = 0.002). In addition, the frequency of T allele of the MMP9-1562 variant was higher than the control group (p = 0.007). Conclusion: MMP-2 and MMP-9 serum levels and activities were observed to be considerably higher in the experimental group than in the control group (p < 0.001). Patients are more susceptible to cardiovascular disease than the control group due to elevated serum levels and activity of MMP-2 and MMP-9.

Assessment of serum inflammatory parameters in RRMS and SPMS patients

ABSTRACT Objectives Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Patients with relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS) differ in their responses to treatment; therefore, the correct diagnosis of the particular type of MS is crucial, and biomarkers that can differentiate between the forms of MS need to be identified. The aim of this study was to compare the levels of inflammatory parameters in serum samples from patients with RRMS and SPMS. Methods The study group consisted of 60 patients with diagnosed MS. The patients were divided into RRMS and SPMS groups. In the RRMS patients, the usage of disease-modifying treatment was included in our analysis. The serum levels of inflammatory parameters were evaluated. Results The serum levels of BAFF, gp130 and osteopontin were significantly higher in SPMS patients than in RRMS patients. The serum levels of BAFF correlated with age in both RRMS and SPMS patients. The serum levels of MMP-2 were significantly higher in RRMS patients than in SPMS patients and correlated with the number of past relapses. The serum levels of IL-32 were significantly higher in RRMS treatment-naïve patients than in RRMS patients treated with disease-modifying therapy. Discussion Significant differences were found in BAFF, gp130, MMP-2 and osteopontin levels between RRMS and SPMS patients. Serum IL-32 levels were statistically lower in RRMS patients treated with disease-modifying therapy than in treatment-naïve patients.

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.

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.

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.

Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of anabolic-androgenic steroids.

In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodelling and their association with hormones and echocardiographic myocardial pathology in weightlifters. In a cross-sectional study, 93 weightlifting AAS users, of whom 62 were current and 31 were past users, with at least 1-year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use), were compared with 54 non-using weightlifting controls (WLCs) using clinical interview, blood pressure measurements, and echocardiography. Serum levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF), interferon (IFN)-γ, growth differentiation factor (GDF)-15, and matrix metalloproteinase (MMP)-9, sex hormones, and lipids were analysed. It was found that serum levels of IL-8, GDF-15, and MMP-9 were significantly increased in current AAS users compared with former users and WLCs. Matrix metalloproteinase 9, but not IL-8, correlated consistently with sex hormone levels, and sex hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current vs. former AAS users and significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP-9 also correlated with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users. Long-term AAS is associated with increased levels of markers of inflammation and ECM remodelling, which seems to have a hormone-dependent (MMP-9) and a hormone-independent (IL-8) association with markers of myocardial dysfunction.