Matrix Metalloproteinase-9 Concentrations Research Articles

Airway MMP-12 and DNA methylation in COPD: an integrative approach

BackgroundIn COPD, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] is shifted towards excessive degradation, reflected in bronchoalveolar lavage (BAL) as increased MMP concentrations. Because of their critical role in lung homeostasis, MMP activity is tightly regulated, but to what extent this regulation occurs through epigenetic mechanisms remains unknown.MethodsTo explore the interplay between MMPs, TIMPs, and DNA methylation (DNAm) we (1) analysed MMP-9, -12, and TIMP-1 concentrations in BAL fluid, and profiled DNAm in BAL cells from 18 COPD and 30 control subjects, (2) estimated protein–COPD relationships using multivariable regression, (3) identified protein quantitative trait methylation loci (pQTMs) with COPD as a potential modifier in a separate interaction model, and (4) integrated significant interactions with a previous COPD GWAS meta-analysis.ResultsCOPD was associated with higher levels of BAL MMP-12 (p = 0.016) but not with MMP-9 or TIMP-1. Further examination of MMP-12 identified association with DNAm at 34 loci (pQTMs), with TGFBR2 (p = 2.25 × 10–10) and THBS4 (p = 1.11 × 10–9) among the top ten pQTM genes. The interaction model identified 66 sites where the DNAm–MMP-12 association was significantly different in COPD compared to controls. Of these, one was colocalized with SNPs previously associated with COPD.ConclusionsOur findings indicate that airway MMP-12 may partially be regulated by epigenetic mechanisms and that this regulation is disrupted in COPD. Furthermore, integration with COPD GWAS data suggests that this dysregulation is influenced by a combination of environmental factors, disease processes, and genetics, with the latter potentially playing a lesser role.

Renal Clearable Chiral Manganese Oxide Supraparticles for In Vivo Detection of Metalloproteinase-9 in Early Cancer Diagnosis.

In this study, polypeptide TGGGPLGVARGKGGC-induced chiral manganese dioxide supraparticles (MnO2 SPs) are prepared for sensitive quantification of matrix metalloproteinase-9 (MMP-9) in vitro and in vivo. The results show that L-type manganese dioxide supraparticles (L-MnO2 SPs) exhibited twice the affinity for the cancer cell membrane receptor CD47 (cluster of differentiation, integrin-associated protein) than D-type manganese dioxide supraparticles (D-MnO2 SPs) to accumulate at the tumor site after surface modification of the internalizing arginine-glycine-aspartic acid (iRGD) ligand, specifically reacting with the MMP-9, disassembling into ultrasmall nanoparticles (NPs), and efficiently underwent renal clearance. Furthermore, L-MnO2 facilitates the quantification of MMP-9 in mouse tumor xenografts, as demonstrated by circular dichroism (CD) and magnetic resonance imaging (MRI) within 2 h. A strong linear relationship is observed between MMP-9 concentration and both CD and MRI intensity, ranging from 0.01 to 10ngmL-1. The corresponding limits of detection (LOD) are 0.0054ng mL-1 for CD and 0.0062ng mL-1 for MRI, respectively. hese SPs provide a new approach for exploring chiral advanced biosensors for early diagnosis of cancer.

Matrix Metalloproteinase-9 as a Predictor of Healing in Diabetic Foot Ulcers.

Background Wound healing in diabetic foot ulcers (DFUs) is hindered by several physiological and biochemical abnormalities, including prolonged inflammation, an imbalance in extracellular matrix (ECM) synthesis and degradation, insufficient neovascularization, and reduced macrophage activity. In DFUs, excessive and uncontrolled matrix metalloproteinases (MMPs) degrade the ECM and impede wound healing. Matrix metalloproteinase-9 (MMP-9) concentration plays a key role in inflammation and ECM degradation. This study explores the relationship between wound type in DFUs and MMP-9 levels, hypothesizing that a high MMP-9 environment may indicate inflammation and impaired wound healing. Materials and methods Forty individuals with type 2 diabetes and foot ulcers were recruited for the study. The participants were divided into two groups: nonhealing and healing, with 20 patients in each group. Biopsy samples were homogenized, and MMP-9 activity was measured using an ELISA. Results The MMP-9 concentration was significantly higher in nonhealing ulcers compared to healing ulcers. Receiver operating characteristic analysis revealed that MMP-9 measurement was the most accurate predictor of wound healing, with an area under the curve value of 0.945 and high sensitivity and specificity. Although there was a weak correlation between MMP-9 concentration and glycosylated hemoglobin, it was not statistically significant. Conclusions MMP-9 expression serves as a marker of poor wound healing. MMP-9 levels in the wound at the time of presentation may predict the healing trajectory and help tailor a specific treatment plan for each DFU patient.

Intraoperative Use of Sodium Bicarbonate Ringer's Solution Instead of Sodium Lactate Ringer's Solution to Reduce Endothelial Glycocalyx Degradation and Improve Postoperative Recovery During Cardiopulmonary Bypass Cardiac Surgery: A Single-Center Prospective Cohort Study.

To investigate the effect of sodium bicarbonate Ringer's solution (BRS) on the degradation of endothelial glycocalyx components in patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, and to evaluate its impact on endothelial glycocalyx preservation and postoperative recovery. A total of eight patients scheduled for elective CPB heart surgery were included and randomly divided into two groups: the sodium lactate Ringer's solution (LRS) group and the BRS group. ELISA was used to measure plasma concentrations of syndecan-1, matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-3 (MMP-3), IL-6, IL-8, TNF-α, and TGF-β at predefined time points: T0 (before induction of anesthesia), T3 (immediately after weaning from CPB), T5 and T6 (24 and 72hours postoperatively). Serum creatinine concentrations were measured within 48hours postoperatively. The incidence of postoperative delirium (POD) was assessed three days after surgery. Postoperative mechanical ventilation time, duration of stay in the intensive care unit and hospital stay were also documented. The BRS group had significantly lower plasma concentrations of syndecan-1 at T3 (7.98 [7.43, 8.92] ng/mL vs 9.54 [8.4, 10.73] ng/mL, P < 0.001) and T5 (4.20 [3.31, 4.96] ng/mL vs 5.40 [3.95, 6.55] ng/mL, P = 0.001) in comparison with the LRS group (P<0.01). Syndecan-1 levels in both groups were similar at T6 (3.18 [2.88, 3.5]ng/mL vs 3.12 [2.77, 3.45] ng/mL, P > 0.05). Additionally, MMP-9, MMP-3, IL-6 and IL-8 were significantly lower at T3 and T5 in the BRS group (P<0.05 and P<0.01, respectively). However, no significant differences were observed between the two groups in the incidence of acute kidney injury (AKI) or POD (P > 0.05). BRS has the potential to reduce glycocalyx degradation in patients undergoing heart valve surgery with CPB. However, both groups demonstrated similar post-postoperative clinical outcomes, including the rates of AKI and POD.

Sensitive Fluorescent Determination of Matrix Metalloproteinase-2 (MMP-2) Using the Inner Filter Effect (IFE) with Carbon Dots and Aggregated Gold Nanoparticles

Matrix metalloproteinase-2 (MMP-2) is a key biomarker involved in various pathological processes, so its sensitive and selective detection is of great clinical significance. A fluorescent sensor for the detection of MMP-2 was successfully designed based on the inner filter effect (IFE) between carbon dots (CDs) and gold nanoparticles (AuNPs). In the presence of MMP-2, peptide chains are hydrolyzed, releasing short peptides that contain thiol groups and positive charges, thereby inducing the aggregation of AuNPs. This aggregation disrupts the IFE between AuNPs and CDs, leading to a significant enhancement of the fluorescence. By monitoring the change in fluorescence intensity of CDs, the concentration of MMP-2 was accurately determined. The sensor exhibited a linear response across the concentration range from 1.0 to 150 ng/mL, with a detection limit as low as 0.23 ng/mL, which is lower than those of previously reported methods. Furthermore, the sensor demonstrated minimal interference from coexisting biochemical substances for MMP-2 in human serum. Notably, the sensor was successfully applied to determine MMP-2 in human serum, showing satisfactory recovery rates ranging from 98.8 to 1106.0%. In conclusion, this fluorescent sensor offers high selectivity and sensitivity for MMP-2 detection, making it a promising tool for clinical diagnosis of related diseases.

Abnormal proteolytic activity profile in plasma of blood donors according to anti-SARS-CoV-2 IgG titer

This work aims to study whether there is a relationship between titer values of anti-SARS-CoV-2 IgG and changes in proteolytic processes. To confirm this hypothesis, we analyzed the content and activity of Matrix Metalloproteinases (MMPs) as well as the concentration and composition of circulating peptide pools in the plasma of blood donors divided into groups on the basis of anti-SARS-CoV-2 IgG titers. The results of gelatin zymography showed the presence of active MMP-2 in donors’ plasma who recovered from COVID-19. In contrast, collagenases and their complexes were detected in the plasma of donors with no anti-SARS-CoV-2 IgG, while their activity was undetectable in some groups of COVID-19 convalescent individuals. The content of MMPs also differed among the donors with different titers of anti-SARS-CoV-2 IgG. Plasma peptide content was identical among the donors' groups, but there were more peptide fractions in plasma peptide pools of COVID-19 convalescent individuals; furthermore, they all were characterized by the presence of peptides with molecular weights less than 920 Da and greater than 1530 Da. We hypothesized a link between proteolytic alterations and peptide fraction composition. Our data need further validation to confirm the relationship between the titer values of anti-SARS-CoV-2 IgG and the severity of the proteolytic imbalance.

The possible role of serum NGAL and MMP-9 in the assessment of kidney impairment and cardiovascular risk in children and adolescents with type 1 diabetes mellitus or obesity.

Type 1 diabetes mellitus (DM1) and obesity represent two chronic pediatric diseases characterized by increased risk for renal impairment and cardiovascular disease. The potential usefulness of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9), two novel biomarkers, for predicting early kidney injury or increased cardiovascular risk in children and adolescents with DM1 or obesity, was investigated in this cross-sectional study. Serum samples were obtained from children and adolescents aged 12.7 ± 3.8 years old with DM1 (n = 38) or obesity (n = 34) and normal renal function, as well as from healthy controls (n = 24). NGAL and MMP-9 concentrations were measured using commercially available sandwich ELISA kits (NGAL: DY1757-05, MMP-9: DMP900; R&D systems, Minneapolis, MN, USA). NGAL serum values were found significantly higher in patients with obesity but not in those with DM1. A positive correlation was found in patients with DM1 with diabetes duration, and in the total population with body mass index (BMI) z-score. Also, serum MMP-9 levels were significantly increased in patients with DM1 and in patients with obesity compared to controls. Circulating NGAL and MMP-9 levels may prove useful as surrogate biomarkers to creatinine, glomerular filtration rate (GFR), and albumin excretion rate for early detection of kidney injury and cardiovascular complications in children and adolescents with DM1 or obesity.

MMP-9 as a clinical marker for endometriosis: a meta-analysis and bioinformatics analysis.

This study systematically evaluated the potential efficacy of serum matrix metalloproteinase-9 (MMP-9) concentration as a diagnostic marker for endometriosis through meta-analysis. Early and accurate diagnosis of endometriosis, a common gynecological disease, is crucial for improving patient prognosis. Hence, this study aimed to comprehensively analyze the data from multiple studies to assess the diagnostic value of serum MMP-9 concentration for endometriosis. Articles investigating the association between MMP-9 and endometriosis, published from the inception of the databases until February 2024, were systematically retrieved from multiple databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and CNKI. Download and analyze the GSE7305, GSE23339, and GSE51981 datasets. Statistical analyses of all eligible studies were conducted using RevMan 5.4, Stata 11.0, and R software version 4.3.3. Fifteen studies fully met the inclusion criteria for the meta-analysis. The concentration of MMP-9 in the blood of patients with endometriosis was significantly higher compared to that of the control group (p < 0.0001). Subgroup analysis based on different stages of endometriosis revealed a trend towards significantly higher serum MMP-9 concentrations in patients, whether in stages I-II or III-IV. Bioinformatics analysis revealed differences in the expression of MMP-9 in endometrial tissue between EMT patients and healthy controls in the GSE7305 and GSE23339 datasets. Additionally, in the GSE51981 dataset, we found significant differences between the normal group and both mild and severe cases of endometriosis. Both the current meta-analysis and bioinformatics analysis indicate differences in MMP-9 concentration levels between endometriosis patients and healthy individuals, with potentially elevated MMP-9 concentrations in serum samples from patients with endometriosis. https://www.crd.york.ac.uk/prospero, identifier CRD42024525864.

Особливості показників гуморального імунітету в новонароджених дітей із маркерами недиференційованої дисплазії сполучної тканини

Connective tissue dysplasia can affect the immune response in children. The study of humoral immunity indicators in newborns with locomotor and biochemical markers of undifferentiated connective tissue dysplasia (UCTD) is very relevant. Aim - study the correlations between anthropometric, laboratory markers of UCTD and indicators of the B-cell link of immunity in newborns. Materials and methods. We examined 122 newborns: 79 full-term and 43 premature infants. In them, the perinatal history data were analyzed, anthropometric and biochemical (matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1)) markers of UCTD were studied, and the ratio of MMP-1/TIMP-1 was calculated. The absolute number of B-lymphocytes and the levels of immunoglobulins of classes A (IgA), M (IgM), G (IgG) in the blood were also investigated. The main group (n=82) consisted of newborns with elevated values of ≥2 anthropometric markers of UCTD, the control group (n=40) included children without deviation from the norm of any anthropometric index. Results. Children with signs of UCTD are more likely to be born from ≥2 births, with a body weight of 2499-2000 g and ≤1999 g, and have lower levels of serum IgA, IgM than children of the control group. Such perinatal factors as operative delivery and parity of more than two births can be considered prognostically unfavorable for a lower absolute number of B-lymphocytes, lower levels of IgA and IgM in the blood of newborns. Serum content of MMP-1≥4.51 ng/ml, values of MMP-1/TIMP-1≥0.31 are associated with a higher absolute number of B-lymphocytes and lower level of IgA, also the concentration of TIMP-1≥16.08 ng/ml is associated with higher levels of IgA, IgM, IgG. The content of serum immunoglobulins correlates with the gestational age. Conclusions. Therefore, newborns with anthropometric markers of UCTD and an imbalance of biochemical markers (MMP-1, TIMP-1, index MMP-1/TIMP-1) have lower levels of serum IgA and IgM. The concentration of MMP-1≥4.51 ng/ml, MMP-1/TIMP-1≥0.31, TIMP-1≤16.07 ng/ml are prognostically unfavorable factors regarding changes in the B-cell immunity in newborns. The lowest concentrations of immunoglobulins of all classes were recorded in children with a gestational age of 31-28 weeks. The study was carried out according to the principles of the Declaration of Helsinki. The study protocol was accepted by the Local Ethical Committee of these institutions. The informed consent of the children's parents was obtained for the research. The authors declare no conflict of interest.

Microfluidic-SERS sensing system based on dual signal amplification and aptamer for gastric cancer detection.

Studies have found that matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) play an important role in tumorigenesis. In order to detect MMP-9 and IL-6 concentrations with high sensitivity and specificity, an efficient microfluidic-SERS sensing system was prepared based on surface-enhanced Raman scattering (SERS). The aptamer recognition-release mechanism and the dual signal amplification strategy were applied in the sensing system. The sensor system was developed using two kinds of nanomaterials with excellent SERS properties, namely gold-coated iron tetroxide particles (Fe3O4@AuNPs) and gold nanocages (AuNCs). In addition, Fe3O4@AuNPs also has magnetic adsorption properties. In the sensing system, single-stranded DNA1 (ssDNA1) and aptamer were modified on Fe3O4@AuNPs. Single-stranded DNA2 (ssDNA2) and Raman tags were modified on AuNCs. When the target was present, the aptamer bound to the target and detached from the Fe3O4@AuNPs, andssDNA2 bound to the exposed ssDNA1. At this time, the Fe3O4@AuNPs@AuNCs@SERS tag complex was formed, and the SERS signal was enhanced for the first time. Under the action of an external magnet on the microfluidic chip, the complex was magnetized and enriched. The SERS signal was enhanced for the second time. Due to the high affinity between the aptamer and the target object, the sensing system has a strong specificity. The double amplification of the SERS signal gave the system excellent sensitivity. The limit of detection (LOD) relative to MMP-9 and IL-6 were as low as 0.178pg/mL and 0.165pg/mL, respectively. The microfluidic-SERS sensing system has a feasible prospect in the early screening of gastric cancer.

Levels of Matrix Metalloproteinase-9 (MMP-9) and its gene polymorphism of Hydatid Cyst Disease in an Infected Patients

Hydatid cystic disease is an economic burden in Iraq since it decreases the productivity of sheep, goats, cows, and camels by making the organs unpalpable for human consumption, hence weight-loss and ill health. This is one of the most common zoonosis diseases shared between human beings and animals and appears in man hosts inlcuded some organes, such as liver and lung as hydatid cyst . it causes many complications that may lead to death in repured parasites. Now there are no safe and effective in the fight against this parasite, and the search for such medications is in research. The Matrix Metalloproteinase-9 is a one of the enzymes that belong to the family of matrix metalloproteinases (MMPs), which play a crucial role in the proteolytic degradation of the extracellular matrix (ECM). These enzymes have a zinc ion in the active site that is important for their proteolytic activity. MMP-9, also known as Gelatinase B, catalyzes gelatin and degrades components of the ECM, including abundant type IV collagen in basement membranes. MMP-9 plays an important role in various biological processes, including tissue remodeling, angiogenesis, and tissue inflammation. The objective of the study is to determine the impact of MMP-9 serum levels and specific single nucleotide polymorphisms (SNPs) rs17576 and rs76070157 on patients with hydatid disease, in comparison to a control group of healthy individuals. A total of (62) patients diagnosed with hydatid disease, consisting of 18 males and 44 females, were compared to a control group of(75) individuals, comprising 29 males and 46 females .The study examined the MMP-9 rs17576 and rs76070157 )SNPs( in patients with hydatid disease, comparing them to a control group of healthy individuals. The study revealed no statistically significant difference in the average age between the two groups at a significance level of 0.05. Additionally, the study found higher concentrations of MMP-9 in the sera of the infected group (20.40 ± 1.52 pg/µl) compared to the control group (19.49 ± 1.62 pg/µl). The rs17576 )SNPs( data indicated that the TT genotype and T allele exhibited a slightly higher frequency percentage in the group of patients with hydatid disease compared to the healthy group, however this difference was not statistically significant. The values are (98.4% and 99.0%) the value of pc is 0.001. The elevated odds ratio (OR) associated with the TT genotype and T allele may serve as a potential risk factor for hydatid disease. The rs17576 SNPs displayed genotypes that were not in accordance with Hardy-Weinberg equilibrium. However, these genotypes were consistent with those observed in a control group. The GG genotype showed a significant increase in frequency compared to the control group (100.0% vs. 100.0%), while the G allele exhibited a non-significant increase in frequency. The odds ratio (OR) for the TG genotype was 3.68, and the p-value (pc) was 0.05.Elevated value could potentially increase the risk of hydatid disease. The presence of the TG genotype was shown to considerably increase the frequency percentage in the group of patients with hydatid disease. The odds ratio (OR) value of 1.6 suggests that it may be a risk factor for hydatid disease, with a frequency of 98.4% compared to 0.99 % in the control group. The p-value of 0.001 indicates a statistically significant association. The GG genotype was present in (0%) of the affected group but absent (100.0%) in the healthy group. The odds ratio (OR) of 3.68, with a p-value of 0.001, suggests that the GG genotype is associated with a significantly lower risk of hydatid disease.

Proteolytic imbalance in plasma of patients with multiple sclerosis following COVID-19

Background. The present research was conducted with the following objectives: 1) to determine the plasma levels of five matrix metalloproteinases (MMPs), namely MMP-1, -2, -3, -8, -10, and tissue inhibitor of metalloproteinase-1 (TIMP-1); 2) to analyze protease activity profiles in plasma using a zymographic method; and 3) to perform preliminary analysis on plasma peptide pool composition in patients with multiple sclerosis (MS) with and without COVID-19 history. Materials and methods. We examined 97 patients with MS: 41 had been diagnosed with COVID-19 in the past 4–6 months (MS + COVID group), and 56 did not suffer from SARS-CoV-2 infection previously (MS group). The plasma of healthy volunteers (n = 30) with no evidence of disease was used as control. The enzyme-linked immunosorbent assay was used to measure MMP and TIMP-1 concentrations. Plasma MMP activity was verified by gelatin-substrate zymography. Peptide pools were extracted from the plasma of MS patients and healthy subjects. Then size exclusion chromatography was used to identify separate fractions present in peptide pools. Results. We found that plasma concentration of MMP-2 was remarkably increased in the MS group compared with healthy controls, while in the MS + COVID patients, the levels of two other MMPs, MMP-1 and -10, were elevated. Zymography showed four dominant gelatinolytic bands of 92, 84, 72, and 62 kDa in MS plasma samples, whereas only traces of MMP were detected in healthy subjects. Most of MS plasma samples showed MMP-2 lytic activity, but only a few contained MMP-9. Finally, we determined the concentration of circulating peptides. The levels of plasma peptides were higher in patients from both the MS and MS + COVID group compared to control subjects. According to our results, the development of MS was accompanied by changes in both quantity and quality of peptide pool composition compared to healthy controls. Conclusions. Thus, an advanced understanding of the role of MMPs in MS pathogenesis following infection is important in developing optimized interventions to improve health and clinical outcomes during COVID-19.

Electrochemical detection of MMP-2 with enhanced sensitivity: Utilizing T7 RNA polymerase and CRISPR-Cas12a for neuronal studies

This study introduces a novel electrochemical biosensor for detecting Matrix Metalloproteinase-2 (MMP-2), a key biomarker in cancer diagnostics and tissue remodeling. The biosensor is based on a dual-amplification strategy utilizing T7 RNA polymerase isothermal amplification and CRISPR-Cas12a technology. The principle involves the release of a DNA template in the presence of MMP-2, leading to RNA synthesis by T7 RNA polymerase. This RNA activates CRISPR-Cas12a, which cleaves a DNA probe on the electrode surface, resulting in a measurable electrochemical signal.The biosensor demonstrated exceptional sensitivity, with a detection limit of 2.62 fM for MMP-2. This high sensitivity was achieved through the combination of transcriptional amplification and the collateral cleavage activity of CRISPR-Cas12a, which amplifies the signal. The sensor was able to detect MMP-2 across a wide dynamic range from 2 fM to 1 nM, showing a strong linear correlation between MMP-2 concentration and the electrochemical signal. In practical applications, the biosensor accurately detected elevated levels of MMP-2 in cell culture supernatants from HepG2 liver cancer cells, distinguishing them from normal LO2 liver cells. The use of an MMP-2 inhibitor confirmed the specificity of the detection. These results underscore the biosensor's potential for clinical diagnostics, particularly in early cancer detection and monitoring of tissue remodeling activities. The biosensor's design allows for rapid, point-of-care testing without the need for complex laboratory equipment, making it a promising tool for personalized healthcare and diagnostic applications.

A protocol for a single center, randomized, controlled trial assessing the effects of spectacles or orthokeratology on dry eye parameters in children and adolescents

BackgroundThe prevalence of myopia among adolescents is increasing precipitously in China, and the popularity of orthokeratology (OK) lenses as an effective treatment for controlling myopia progression is rising. This protocol assessed and compared the clinical dry eye parameters in children and adolescents with myopia treated with spectacles or OK lenses. Methods and analysisThis single-masked randomized control trial will include 300 participants (aged 8–17 years) with myopia treated with OK lens (study group) or spectacles (control group). We will record the ocular surface disease index, visual analog scale score, noninvasive tear breakup time, tear meniscus height, meibomian gland score, ocular redness score, visual acuity, tear Matrix Metalloproteinase-9 concentration, tear Lymphotoxin alpha levels at baseline, and after 1-, 3-, 6-, and 12-month. DiscussionThis study will be a standardized, scientific, clinical trial designed to evaluate the dry eye parameters in children and adolescents with myopia treated with OK lenses for myopia control. Ethics and disseminationThis study has been approved by the Ethics Committee of He Eye Specialist Hospital [ethics approval number: IRB(2023)K024.01]. Before participating in the trial, written informed consent will be obtained from all patient's parents or guardians. The findings of this study will be showcased at both local and international conferences and will also be submitted for publication in reputable peer-reviewed journals. Trial registration numberClinicaltrials.gov: NCT06023108 {2a, 2b}

Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits

Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

NDRG2 Deficiency Exacerbates UVB-Induced Skin Inflammation and Oxidative Stress Damage.

UVB radiation induces inflammatory and oxidative stress responses, contributing to skin damage, yet the underlying mechanisms are not fully understood. N-Myc downstream-regulated gene 2 (NDRG2), an emerging stress-associated gene, remains unexplored in UVB-induced skin injury. In this study, we detected skin NDRG2 expression after UVB irradiation for the first time and further used Ndrg2 knockout mice to clarify the role of NDRG2 in UVB-induced skin injury. Three-month-old male Ndrg2+/+ and Ndrg2-/- mice (16-18g) were exposed to UVB to induce acute skin damage, and then dorsal skin samples were collected for subsequent analyses. UVB-induced skin damage was scored. Western Blot Analysis, immunofluorescence (IF) double labeling, and immunohistochemistry (IHC) were employed to assess NDRG2 expression and/or distribution. The concentrations of TNF-α, IL-6, IL-1β, MPO, MMP8, superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining were employed to determine pathological changes. RNA sequencing and analysis were performed to estimate transcript expression levels and analyze mRNA expression. DESeq2 software was employed to identify differentially expressed genes (DEGs). DEGs were visualized using volcanic and heat maps. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to identify primary biological functions, metabolic pathways, or signal transduction pathways associated with DEGs. UVB-challenged Ndrg2-/- mice exhibited significantly exacerbated skin damage (erythema, edema, and erosion), neutrophil infiltration, and apoptosis compared to Ndrg2+/+ mice. Furthermore, UVB-challenged Ndrg2-/- mice displayed significantly elevated pro-inflammatory cytokines, myeloperoxidase (MPO), matrix metalloproteinase-8 (MMP8), and reduced antioxidant expression. RNA sequencing identified 1091 significantly differentially expressed genes enriched in inflammation, immune response, and oxidative stress pathways. In conclusion, the deficiency of Ndrg2 markedly exacerbated UVB-induced skin damage by promoting inflammatory responses and inhibiting antioxidant responses. This suggests that stabilizing NDRG2 expression holds promise as a therapeutic strategy for protecting against UVB-induced skin damage.

The effects of SGLT-2 inhibitors on echocardiographic indices and antioxidative properties in patients with heart failure with reduced ejection fraction and diabetes mellitus.

Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are a new class of drugs that lower blood glucose and reduce mortality in heart failure patients with reduced ejection fraction (HFrEF). They also have antioxidant effects. The exact mechanism of SGLT-2i is unknown. This study investigated the effects of SGLT-2i on asprosin, matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP-1) concentrations and echocardiographic measurements of strain in the left heart chamber. This prospective follow-up study included 56 patients with HFrEF and diabetes mellitus (DM) who did not initially receive SGLT-2 inhibitors. The control group consisted of 30 healthy individuals. Patients with HFrEF were administered either empagliflozin (n=28) or dapagliflozin (n=28) in addition to their treatment. The patient group was evaluated for left ventricular global longitudinal strain (LVGLS), left atrial (LA) strain, and LA volumes at the beginning and third month of the study. The control group had blood collected once, while the patient group had it twice: at the start of the trial, on the same day as the echocardiographic evaluation, and at the end of the third month after starting an SGLT-2i. Serum levels of asprosin, MMP-1 and TIMP-1 were assessed. LVGLS increased significantly in HFrEF patients at the third-month assessment compared to baseline (-8.6±2.3% vs. -9±2.5%, respectively; p<0.001), but there was no significant difference in LVEF (p=0.593). A substantial increase was observed in the left atrial ejection fraction (LAEF) compared to baseline values (36.3±9.4% vs. 42.1±8.7%, respectively; p<0.001), driven by a reduction in minimal LA volume [32.5 (19-96) ml vs. 32 (20-86) ml, respectively; p=0.018]. Compared to baseline evaluation, LA reservoir [13 (6-25) vs. 16.5 (2-26), respectively; p<0.001] and contraction strain (7.7±4.3 vs. 9.4±5.6, respectively; p=0.014) values were also enhanced at the third month. Between the baseline and the 3rd month, the patient group's LA conduit strain (p=0.122) and LA maximum volume (p=0.716) remained unchanged. Serum asprosin significantly increased (11.7±5.1 ng/mL vs. 14±9.4 ng/mL, respectively; p=0.032); however, no statistically significant alteration was detected in MMP (p=0.278) and TIMP-1 levels (p=0.401). SGLT-2i are associated with elevated levels of LVGLS, LAEF, LA contraction strain, and LA reservoir strain. SGLT-2i medications may improve plasma asprosin levels to boost energy metabolism, reduce oxidative stress and reactive oxygen radicals.

Matrix Metalloproteinase 9 (MMP-9) and Interleukin-8 (IL-8) in Gingival Crevicular Fluid after Minimally Invasive Periodontal Surgery with or without Er:YAG and Nd:YAG Laser Application.

This study aimed to evaluate alterations in the concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) within gingival crevicular fluid (GCF) extracted from the intrabony periodontal defect site before and after minimally invasive regenerative surgery, with or without supplemental laser application. The surgical procedure was performed using the modified minimally invasive surgical technique (M-MIST). Thirty-eight patients, each presenting with a single vertical defect, were randomly assigned to either the test (M-MIST + Er:YAG + Nd:YAG) or the control group (M-MIST). IL-8 and MMP-9 levels (primary outcomes of the study) were assessed prior to therapy, after 2 and 4 weeks, and 6 months following the surgical procedure by means of dedicated ELISA kits. Both procedures were clinically effective as evidenced by probing depth (PD) reduction and clinical attachment level (CAL) gain at the 6-month follow-up. No statistical differences were observed in the levels of MMP-9 and IL-8 between the groups at any time point assessed. The changes in the level of MMP-9 and IL-8 over time were not statistically significant in any group. IL-8 was positively correlated with MMP-9 in the control group throughout the study and in the test group 2 weeks and 6 months post-op. Within the limitations of this study, the additional application of Er:YAG + Nd:YAG lasers alongside the M-MIST procedure did not enhance the clinical and biochemical treatment outcomes compared to M-MIST alone.

Serum Concentrations of Matrix Metalloproteinase-1 and Procollagen Type I Carboxy Terminal Propeptide Discriminate Infarct-Like Myocarditis and Non-ST-Segment-Elevation Myocardial Infarction.

Biomarkers simplifying the diagnostic workup by discriminating between non-ST-segment-elevation myocardial infarction (NSTEMI) and infarct-like myocarditis are an unmet clinical need. A total of 105 subjects were categorized into groups as follows: ST-segment-elevation myocardial infarction (n=36), NSTEMI (n=22), infarct-like myocarditis (n=19), cardiomyopathy-like myocarditis (n=18), and healthy control (n=10). All subjects underwent cardiac magnetic resonance imaging, and serum concentrations of matrix metalloproteinase-1 (MMP-1) and procollagen type I carboxy terminal propeptide (PICP) were measured. Biomarker concentrations in subjects presenting with acute coronary syndrome and non-ST-segment-elevation, for example NSTEMI or infarct-like myocarditis, categorized as the non-ST-segment-elevation acute coronary syndrome-like cohort, were of particular interest for this study. Compared with healthy controls, subjects with myocarditis had higher serum concentrations of MMP-1 and PICP, while no difference was observed in individuals with myocardial infarction. In the non-ST-segment-elevation acute coronary syndrome-like cohort, MMP-1 concentrations discriminated infarct-like myocarditis and NSTEMI with an area under the receiver operating characteristiccurve (AUC) of 0.95 (95% CI, 0.89-1.00), whereas high-sensitivity cardiac troponin Tperformed inferiorly (AUC, 0.74 [95% CI, 0.58-0.90]; P=0.012). Application of an optimal MMP-1 cutoff had 94.4% sensitivity (95% CI, 72.7%-99.9%) and 90.9% specificity (95% CI, 70.8%-98.9%) for the diagnosis of infarct-like myocarditis in this cohort. The AUC of PICP in this context was 0.82 (95% CI, 0.68-0.97). As assessed by likelihood ratio tests, incorporating MMP-1 or PICP with age and C-reactive protein into composite prediction models enhanced their diagnostic performance. MMP-1 and PICP could potentially be useful biomarkers for differentiating between NSTEMI and infarct-like myocarditis in individuals with non-ST-segment-elevation acute coronary syndrome-like presentation, though further research is needed to validate their clinical applicability.

Therapeutic Efficacy of Baicalein Green Biomolecule in Methicillin-Resistant Staphylococcus aureus Murine Mastitis Model

Methicillin-resistant Staphylococcus aureus (MRSA) mastitis poses a significant threat to dairy herds worldwide, given its resistance to methicillin and other β-lactam antibiotics, which often leads to treatment failure. Consequently, there is an urgent need for safe and effective alternative therapeutic approaches. Recent investigations have highlighted the potential of baicalein, a natural flavonoid known for its potent anti-inflammatory and antibacterial properties, especially its synergistic effects with β-lactam antibiotics against MRSA. However, the limited solubility and bioavailability of baicalein hinder its biomedical utility. The present study assessed the therapeutic efficacy of encapsulated baicalein in chitosan, forming a tricomplex with a β-lactam antibiotic, using a murine model of MRSA-induced mastitis. The experimental design comprised seven groups, each consisting of six mice. We evaluated the ability of various treatment regimens to mitigate histopathological alterations and bacterial burden induced by MRSA infection, aiming to elucidate underlying mechanisms. Our results revealed that tricomplex treatment significantly reduced bacterial load in mammary tissue and preserved tissue integrity, resulting in decreased inflammatory responses post-MRSA inoculation. In addition, tricomplex treatment markedly reduced mean leukocyte and neutrophil counts in blood and suppressed the matrix metalloproteinase-9 (MMP-9) concentration and C-reactive protein (CRP) response. Notably, the synergistic interaction between baicalein and amoxicillin was particularly pronounced. Our findings suggest that chitosan-encapsulated baicalein combined with a β-lactam antibiotic holds promise as a therapeutic option for MRSA-induced mastitis. Further investigations, particularly in target animal species, are warranted to comprehensively evaluate its clinical feasibility.