Serum Levels Of MMP-9 Research Articles

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.

The value of serum MMP-7 and SOX9 levels in the diagnosis and prognosis of biliary atresia

IntroductionTo investigate the diagnostic value of serum MMP-7 and SOX9 levels in patients with biliary atresia (BA) and to further analyze their relationship with the liver fibrosis and prognosis. MethodsSixty-eight patients hospitalized for jaundice and underwent surgical treatment from March 2019 to February 2022 were retrospectively analyzed, including 44 patients with BA and 24 patients with other cholestatic liver diseases as disease controls (DC). Serum levels of MMP-7 and SOX9 were detected using enzyme-linked immunosorbent assay (ELISA). The diagnostic value of MMP-7 and SOX9 for BA was evaluated using the receiver operating characteristic (ROC) curve. ResultsSerum levels of MMP-7 and SOX9 were higher in the BA group compared to the DC group (P = 0.0002, P = 0.0006). The AUC for the combined diagnosis of serum MMP-7, SOX9 and GGT was 0.888 (95 % CI:0.788–0.952, P < 0.0001), which was significantly different from the diagnosis of MMP-7 or SOX9 alone (P = 0.034, P = 0.030). Serum levels of MMP-7 and SOX9 were significantly positively correlated with the liver fibrosis score (rs = 0.41, P = 0.006; rs = 0.58, P < 0.0001). BA patients who maintained native liver survival had lower preoperative serum levels of MMP-7 and SOX9 (P = 0.008, P = 0.0008). ConclusionsThe combined diagnosis of BA by MMP-7, SOX9 and GGT has better accuracy than MMP-7 or SOX9 alone. Serum SOX9 levels can assess the severity of BA liver fibrosis and correlate with BA native liver survival, but more sample data are needed to further investigate its predictive value.

Omentin-1 May Be One Treatment Factor for Intravenous Thrombolysis of Acute Cerebral Infarction Through the Inhibition of NLRP3 Ubiquitination by AMPK Function: Preliminary Findings.

Acute cerebral infarction (ACI) is a common neurological disease that is associated with high morbidity, disability and mortality rates. At present, antiplatelet therapy is a necessary treatment for ACI. The present study aimed to investigate the effects of omentin-1 on the intravenous thrombolysis of ACI. The present study aimed to investigate the effects of omentin-1 on the intravenous thrombolysis of ACI. The mouse model of ACI was induced using male C57BL/6 mice through middle cerebral artery occlusion (MCAO). Meanwhile, the murine BV2 microglial cells were pretreated with 0.1 mg/ml of lipopolysaccharide (LPS), and then induced with 2 mM of adenosine triphosphate (ATP). The omentin-1 mRNA expression in patients receiving intravenous thrombolysis for ACI was down-regulated compared with the normal group. Additionally, the serum level of omentin-1 was negatively correlated with National Institute of Health Stroke Scale (NIHSS) score or serum level of IL-1β or MMP-2 in patients receiving intravenous thrombolysis for ACI. Meanwhile, the serum mRNA expression of omentin-1 was positively correlated with Barthel index or high-sensitivity C-reactive protein (hs-CRP) in patients undergoing intravenous thrombolysis for ACI. As observed from the in vitro model, Omentin-1 reduced inflammation, promoted cell growth, alleviated ROS-induced oxidative stress, and enhanced AMPK activity through activating NLRP3 ubiquitination. Omentin-1 presented ACI in the mouse model of ACI. Regulating AMPK activity contributed to controlling the effects of Omentin-1 on the in vitro model. Omentin-1 reduced neuroinflammation and ROS-induced oxidative stress in the mouse model of ACI, which was achieved by inhibiting NLRP3 ubiquitination through regulating AMPK activity. Therefore, omentin-1 may serve as a treatment factor for the intravenous thrombolysis of ACI in further clinical application.

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.

Warm Acupuncture Reduces Pain and Inflammation in Rats with Lumbar Disc Herniation Induced by Autologous Nucleus Pulposus Transplantation via Regulating p38MAPK/NF-κB Pathway.

: Warm acupuncture (WA) has analgesic and anti-inflammatory effects. However, the underlying mechanism of these effects remain unclear. : To explore the analgesic and anti-inflammatory effects of WA and the potential underlying mechanism in male Sprague-Dawley rats with non-compressive lumbar disk herniation (LDH) caused by autologous nucleus pulposus (NP) transplantation. : We used low-frequency (2 Hz) electrical stimulation and WA (40℃) to treat GB30 and BL54 acupoints in rats for 30 mins per day. We monitored the paw withdrawal threshold of rats during the experiment and measured serum cytokine levels using commercial kits. Dorsal root ganglion (DRG) tissue pathology was analyzed via H&E staining. We used qRT-PCR to measure the mRNA expression levels of IL-1β, IL-6, and TNF-α genes in DRG. Western blot was used to analyze the expression levels of IL-1β, IL-6, TNFα, P-p38MAPK, p38MAPK, P-IκBα, IκB α, and NF-κB p65 proteins. : WA treatment significantly increased the pain threshold of rats, reduced serum IL-6, PEG2, NO, SP, NP-Y, and MMP-3 levels, and effected histopathological improvements in the DRG in rats. Moreover, WA treatment significantly downregulated the expression levels of inflammation-associated genes (Il-1β, Il-6, and Tnf-α) and proteins (IL-1β, IL-6, TNF-α, P-p38MAPK, P-IκBα, and NF-κB p65) in the DRG of non-compressive LDH rats. : WA can alleviate pain and inhibit inflammatory response in rats with non-compressive LDH caused by autologous NP transplantation, and these effects are likely associated with the inhibition of the p38MAPK/NF-κB pathway.

Relationship of MMP-9 with the clinical course of apical periodontitis and the main bacterial species in the oral microbiota.

Bacterial products, host immune cells and cytokines have been reported to play an important role in the pathogenesis of apical periodontitis (AP). This study aimed to determine the main bacterial species in the microbiota as gram positive and negative and to compare the relationship between matrix metalloproteinase (MMP)-9 and tumor necrosis factor (TNF)-α with controlled patient groups. 60 patients with AP and extraction indication were included in the study. 30 systemically healthy volunteers without AP were selected as the control group. After access cavity preparation, an initial microbiologic sample (S1) was taken from the root canal. After atraumatic extraction of the tooth, a second microbial sample (S2) was taken from the extraradicular region. After bacterial DNA extraction, 16S rRNA gene primer was designed for sequence analysis. Bacterial community profiling was made by Sanger sequencing of the PCR products. In addition, serum MMP-9 and TNF-α levels were measured from all patients. TNF-α levels of the AP group were higher than the control group, while MMP-9 levels were found to be lower (p = 0.0264 and p = 0.0146, respectively). There was no difference in the main bacterial species isolated from the samples taken from the intracanal and extraradicular region of the tooth with AP (p = 0.714). The main bacterial species in the intracanal region of the tooth with AP are similar to the main bacterial species in the extraradicular region. The pathophysiology of the tooth with AP is associated with low MMP-9 and high TNF-α, independent of the bacterial species in the intracanal and extraradicular regions.

MMP9 and pancreatic cancer.

Pancreatic carcinoma is one of the most severe oncological diseases of the gastrointestinal tract. At the time of diagnosis, up to 28% of patients have metastatic liver damage, and only 5% of patients survive five years. Scientific research focuses on non-invasive markers that could help screen for the disease and identify patients more quickly. Potential biomarkers also include matrix metalloproteinases, which play arole in oncogenesis. We prospectively followed 46 patients with pancreatic cancer and benign pancreatic diseases from September 2022 to March 2023. We determined the level of MMP9 in serum and tissue biopsied during surgeries. As aresult, MMP9 levels were elevated from the T2 stage. The correlation between disease stage and MMP9 level was not confirmed in lower stages, possibly due to the small group of patients. MMP9 seems suitable for detecting late stages of pancreatic cancer, possibly for secondary prevention. We could not confirm acorrelation between MMP9 levels and the initial stages of the disease (Tab.1, Fig. 3, Ref. 21). Text in PDF www.elis.sk Keywords: pancreatic cancer, MMP9, marker, non-invasive, screening.

Traditional Chinese Manual Therapy (Tuina) Improves Knee Osteoarthritis by Regulating Chondrocyte Autophagy and Apoptosis via the PI3K/AKT/mTOR Pathway: An in vivo Rat Experiment and Machine Learning Study.

Knee osteoarthritis (KOA) is on the rise due to lifestyle changes, obesity, and aging, yet effective treatments are lacking. Traditional Chinese manual therapy (Tuina) is promising for KOA. However, its mechanism remains unclear. This study aims to determine the effects of Tuina on a rat KOA model, focusing on the role of chondrocyte apoptosis and autophagy mechanisms. KOA was induced in rats by intra-articular injection of L-cysteine-activated papain into the right knee. Thirty-six male Sprague Dawley (SD) rats were randomly divided into blank, model control, Tuina, and positive drug groups. Paw withdrawal threshold tests, knee joint swelling, and passive range of motion assessed knee behavior. Cartilage tissue cytology, cytokine contents, and the mRNA and protein expression of PI3K/AKT/mTOR signaling pathway components were analyzed using HE and TUNEL staining, ELISA, RT-qPCR, and Western blotting, respectively. In addition, we used machine learning methods to conduct a secondary analysis of the dataset from the in vivo experiments in rats to verify the findings. Tuina significantly relieved pain and joint swelling, and improved range of motion. Staining showed reduced articular cartilage destruction and apoptosis. Tuina reduced the serum levels of IL-1β, IL-17, MMP-3, and MMP-13. Tuina downregulated Bax, ULK1, Beclin-1, LC3-II/I and upregulated PI3K, AKT, mTOR, and BCL-2 in cartilage tissue. The machine learning results indicated an 83.33% accuracy for the prediction model, remaining stable through both uni- and multivariate analyses. Tuina yielded the best comprehensive efficacy on KOA as well as better rat behavior and PI3K/AKT/mTOR signaling pathway improvement effect than positive drugs, while its cytokine-reducing ability was comparable to that of positive drugs. Tuina can alleviate cartilage tissue injury in KOA, relieve inflammation, and reduce chondrocyte apoptosis and autophagy, the underlying mechanisms of which may be associated with activation of the PI3K/AKT/mTOR signaling pathway.

Correlation between neurofilament, HMGB1, MMP9, ds DNA blood levels and cognitive impairment in patients with neuropsychiatric systemic lupus erythematosus.

Diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is challenging due to nonspecific biomarkers. High serum levels of neurofilament protein light subunit (NFL), high mobility group box 1 (HMGB1), Matrix metalloproteinase-9 (MMP-9) and have been reported in several autoimmune diseases. The aim of this study was to examine whether their plasma levels could serve as a diagnostic or prognostic biomarker for NPSLE. There were 90 SLE patients enrolled in this cross-sectional study (87.8% women and 12.2% men with a mean age of 41.67±11.05 years). We assessed the mental status of patients, also we measured the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/ACR (SLICC/ ACR) Damage Index or SDI scores. Serum levels of NFL, HMGB1, MMP9, and ds-DNA were investigated to find a role in the pathophysiology of NPSLE. Among the 90 patients with SLE, 63 (70%) met the criteria of NPSLE syndrome. Our results have shown a notable difference concerning SEDIAC-2k score, SDI score, PANS, MoCA, and Beck anxiety depression, between the two groups (p < 0.05). Although serum level of all measured serum biomarkers (NFL, MMP-9, HMGB1, dsDNA) were higher in patients with NPSLE, the difference was not statistically significant. Interestingly, our results showed that the serum level of NFL was correlated with the serum level of HMGB-1 and MMP-9. (r: 0.411, P=0.003). Serum level of NFL, HMGB-1 and MMP-9 may be used to detect abnormal mental status in patients with SLE.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Successful endodontic treatment reduces serum levels of cardiovascular disease risk biomarkers-high-sensitivity C-reactive protein, asymmetric dimethylarginine, and matrix metalloprotease-2.

To investigate serum biomarkers of inflammation 2 years following non-surgical root canal re-treatment (Re-RCT) and peri-apical surgery (PS). The results were correlated with signs and symptoms, treatment outcome, metabolic syndrome factors, infection with severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 (COVID-19) infection and COVID-19 vaccination. Subjects from our previous study were recalled for 2 years post-treatment follow-up. Changes to the patient's history (medical, dental, social) were noted. Periapical health of the treated teeth was examined both clinically and radiographically. Blood pressure, fasting HbA1C and low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides and total cholesterol (TC) levels were measured. Serum inflammatory marker levels were assayed using a Bio-Rad Bio-Plex 200 analyser and values at different time points within the same group were compared using a Wilcoxon signed-rank test and differences between groups with a Mann-Whitney test. Linear associations were tested using Pearson's correlations. The recall percentage at 2 years was 56.9% (n = 37), with a 100% radiographic success rate using periapical radiographs. In total, 21 cases (56.8%) were completely healed, and 16 cases (43.2%) were healing. Higher matrix metalloprotease 2 (MMP2) levels were present in the healing group compared to the healed group. Serum levels of high-sensitivity C-reactive protein (hs-CRP), asymmetric dimethylarginine (ADMA) and MMP-2 were significantly reduced (p ≤ .001) whereas other biomarkers showed significant increases at 2 year compared to pre-operative levels, while FGF-23 and ICAM-1 were not significantly increased. HbA1C (p = .015), TC (p = .003), LDL (p = .003) and HDL (p = .003) reduced significantly at 2 years post-treatment compared to their preoperative levels. COVID infection showed a significant association with MMP-9 (p = .048). hs-CRP, ADMA and MMP-2 can be regarded as prognostic biomarkers of successful Re-RCT and PS as they reduced at 2 year recall in cases which showed evidence of clinical and radiographic success. The successful treatment of chronic apical periodontitis is correlated with improvements in metabolic syndrome indicators, better glycemic control, and reduction at 2 year of some systemic inflammatory markers which are related to risks of cardiovascular disease events.

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

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

Prognostic value of different forms of serum MMP-2 and MMP-9 in dogs with mammary tumors; a longitudinal study

Gelatinases (MMP-2 and MMP-9) are related to tumor invasion and metastasis. In humans, the diagnostic value of serum levels of gelatinases has been confirmed in breast cancer, but their diagnostic value in canine mammary tumors is still unknown. This study aimed to determine the serum level of gelatinases in dogs with mammary tumors in order to determine their value in the diagnosis of malignancy or benign tumors and also in predicting the possibility of metastasis and recurrence. Frequent measurement of MMP-2 and MMP-9 by gelatin zymography in serum before and after surgical treatment has not previously been studied for monitoring mammary tumors in dogs. Thus, the serum levels of MMP-2 and MMP-9 in 26 dogs with mammary tumors before surgical treatment and then 1, 4 and 12 months after surgery were evaluated by gelatin zymography. Serum samples of 26 healthy dogs with normal conditions were used as control.Dogs with benign and malignant mammary tumors showed bands of pro-MMP-2, pro-MMP-9 and active MMP-9. However, only pro-MMP-2 and pro-MMP-9 bands appeared in the serum of control group. Our results showed that the presence of active MMP-9, regardless of its level, was prognostically important for metastasis and or recurrence (M/R). However, the presence of active MMP-2 band was more important for M/R than active MMP-9, as its presence coincides with definitive M/R. It seems that serum gelatin zymography could possibly be used at regular intervals before and after surgery to evaluate the probability of M/R in dogs with mammary tumors. More research is needed in this regard.

Prognosticating acute traumatic spinal cord injury using Neurofilament (NF), Neuron Specific Enolase (NSE), Matrix Metalloproteinases (MMPs), and S-100B as biomarkers.

Spinal cord injury (SCI) can result in lifelong disability. Currently, the literature suggests that biomarkers are helpful in prognosticating SCI, but there is no specific biomarker to date. This is the first study that predicted the prognosis dynamically using biomarkers. To elucidate the role of biomarkers in prognosticating acute traumatic SCI. Blood samples were obtained from 35 patients of acute traumatic SCI at presentation, immediate post-op, and at 6 weeks. At 6 months follow-up, patients were divided into two groups, i.e, improved and non-improved based on the improvement in the ASIA grade compared to presentation. A non-parametric test was used for comparing mean NSE, MMP-2, S100-B, and NF serum levels at presentation, immediate post-op, and 6 weeks post-op follow-up between the two groups. There was a significant difference (p = 0.03) in the NF values at presentation between the two groups. The difference of NSE values at 6 weeks was also significant(p = 0.016) between the two groups. S-100B levels were also significantly different between both groups at presentation (p=0.016), and at the immediate post-op stage (p=0.007). MMP-2 levels neither displayed any specific trend nor any significant difference between the two groups. Higher NF values at presentation, and higher S-100B levels at presentation and immediate post-operative period correlated with poor outcome. Also, increased NSE valuesafter surgery are indicativeof no improvement. These levels can be used at various stages to predict the prognosis. However, further studies are required on this topic extensively to know the exact cut-off values of these markers to predict the prognosis accurately. REF/2020/01/030616.