Matrix Metalloproteinase-9 Levels Research Articles

Photoprotective effects of quercetin on photoaging-induced rats

Purpose Photoaging is characterised by cutaneous changes caused by exposure to ultraviolet light over time. Quercetin is a bioflavanoid with antioxidant, antineoplastic, and anti-inflammatory effects. This study investigated the therapeutic effects of topical quercetin on photoaging, a phenomenon not previously studied in ultraviolet A (UVA)-induced photoaging. Methods A total of 40 rats were randomly categorised into 5 groups, each comprising 8 rats. A photoaging model was induced by applying UVA to the dorsal region of all rats, except for the negative control group. Topical 0.1% retinoic acid was applied to one UVA group, topical 0.3% quercetin to another UVA group, and both agents were applied in combination to yet another UVA group 5 days a week for 8 weeks. Subsequently, wrinkle values were measured, reactive oxygen species (ROS) and matrix metalloproteinase-1 (MMP-1) levels were analysed, and histopathological parameters were examined. Results The wrinkle value of the UVA group was found to be significantly higher than that of the UVA + Quercetin group. Collagen damage was lower in the UVA + Quercetin group than in the UVA group, although this difference was not statistically significant. Compared with the UVA + Retinoic Acid group, the UVA + Quercetin group exhibited a more significant decrease in inflammation. MMP-1 values were considerably higher in the UVA + Retinoic Acid and UVA + Quercetin + Retinoic Acid groups as well as in the UVA + Quercetin group compared with the control and UVA groups. Conclusion The present study showed that quercetin can be utilised in the treatment of photoaging, especially when combined with retinoic acid.

Elevated visfatin levels illuminate the inflammatory path in bronchopulmonary dysplasia

Background. Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants caused by an imbalance between lung injury and lung repair in the developing immature lungs of the newborn. Pulmonary inflammation is an important feature in the pathogenesis of BPD. The aim of this study was to evaluate the relationship between the inflammatory microenvironment and the levels of visfatin and nesfatin-1, which are among the new adipocytokines, in BPD patients. Methods. The groups consisted of 30 patients with BPD and 30 healthy children. Plasma levels of visfatin and nesfatin-1 and inflammation-related markers including interleukin-4 (IL-4), interleukin-10 (IL-10), nuclear factor kappa B (Nf-κB) and matrix metalloproteinase-9 (MMP-9) were determined by enzyme-linked immunosorbent assay (ELISA). RT-PCR was performed to evaluate the change in mRNA expression of visfatin and nesfatin-1 in the groups. Results. Visfatin levels were significantly higher in the BPD group compared to the healthy control (7.05±4.07 ng/ml vs. 2.13±1.66 ng/ml, p<0.0001). There was a 1.36±0.12 fold increase in visfatin mRNA expression (p<0.05) in the BPD group. There was no significant difference in plasma levels of nesfatin-1, IL-4, and IL-10 between the groups. Although MMP-9 and Nf-κB levels were significantly higher in the BPD group (p<0.0001), there was no correlation between visfatin levels and MMP-9 and Nf-κB levels in BPD patients. Conclusions. This study showed that significant changes in visfatin levels in BPD patients might be associated with the risk of developing inflammation in BPD.

Derivatives of D(-)-glutamine-based MMP-2 inhibitors as an effective remedy for the management of chronic myeloid leukemia-Part-III: Synthesis, biological screening and in silico binding interaction analysis.

Tyrosine kinase inhibitors (TKIs) have markedly improved the overall survival rate of patients with chronic myeloid leukemia (CML), enabling them to achieve a normal life expectancy. However, toxicity, relapse, and drug resistance continue to pose major challenges in the clinical treatment of CML. The progression of leukemia is directly connected to higher expression levels and enzymatic actions of matrix metalloproteinase-2 (MMP-2). It is also associated with increased expression and enzymatic actions of matrix metalloproteinase-9 (MMP-9). From this perspective, MMP-2 and MMP-9 offers a promising strategy for developing novel therapeutic molecules that could be effective in treating CML. This study is the Part-III of D(-)-glutamine-based MMP-2 inhibitors series for the management of chronic myeloid leukemia. Fourteen newly synthesized p-tosyl-D(-)-glutamine derivatives were examined in cell culture-based antileukemic assays and also evaluated for their ability to inhibit MMPs. The lead compounds 5g and 5j demonstrated the most promising antileukemic potential. Compounds 5g and 5j are safe for normal cells and effectively block gelatinases (MMP-2 and MMP-9). The best active molecule 5g induced significant apoptosis. Compound 5g reduced MMP-2 levels in the K562 cell line. It also had strong antiangiogenic effects in the ACHN cell line. The strongest MMP-2 inhibitor, 5g, had stable binding at the MMP-2 active site, which is linked to its effective inhibition of MMP-2. In conclusion, these p-tosyl-D(-)-glutamine derivatives are promising MMP-2 inhibitors. They have strong anti-CML effects and should be studied more for future CML treatment.

Eucalyptol Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

Background One of the leading causes of acute brain injury is cerebral ischemia/reperfusion (I/R) injury. It is an ailment that occurs when the brain does not receive enough oxygen-rich blood supply, which damages brain cells. Oxidative stress is recognized as a significant mechanism that causes I/R injury and is a critical focal point for therapy. Apoptosis and inflammation are all pathogenic processes underpinning I/R damage. Eucalyptol (EU), a plant-derived substance, protects neuronal damage. We postulate that EU inhibits apoptosis and oxidative stress after focal cerebral I/R damage in mice. Purpose Thus, the present work sought to examine the neurological protective benefits of EU in mice models of cerebral ischemia/reperfusion (CI/R) injury. Methods The measurement of neurological function, infarct volume, and the amount of water in the brain were evaluated subsequently. The brain tissue was examined to assess the activities of oxidative stress, inflammatory cytokines, and matrix metalloproteinases (MMP) levels, and histopathology was determined. Using enzyme-linked immunosorbent assay (ELISA), apoptotic marker expression was used to measure the levels of B-cell lymphoma 2 (Bcl-2), caspase-3, and Bcl-2 associated X-protein (Bax) proteins that exist as indicators of apoptosis. Results EU treatment malondialdehyde (MDA) levels decreased while glutathione (GSH), superoxide dismutase (SOD), A-TOC, and catalase (CAT) activity increased. Following EU therapy dramatically reduced cerebral dysfunction, which was supported by reduced histological damage in I/R injury. Furthermore, with lower levels of MMP-2 and 9, EU treatment could be a novel approach for preventing CI/R injury. EU-treated mice had a notable reduction in cleaved Bax, caspase-3, and increased Bcl-2 protein activities. EU therapy shields the brain against CI/R injury by inhibiting cell death. Conclusion According to the present study’s findings, EU is a promising neuroprotective agent that can be used to treat CI/R injury in mice. By focusing on these aspects, nurses can provide comprehensive care to patients involved in studies on the effects of EU on CI/R injury, promoting better outcomes through careful monitoring, supportive interventions, and education.

Higher serum cystatin C and matrix metalloproteinase 9 levels effectively predict in-stent restenosis after stent implantation for intracranial and extracranial arterial stenosis

ObjectiveThis paper was performed to unravel the predictive value of serum cystatin C (Cys C) and matrix metalloproteinase 9 (MMP-9) levels before vascular stent implantation for in-stent restenosis (ISR) 6-12 months after stent implantation for intracranial and extracranial arterial stenosis. MethodsOne hundred and ninety-eight patients who underwent dilatation stenting for intracranial and extracranial arterial stenosis and completed Digital Subtraction Angiography or head and neck CT- Angiography review were selected for the study and were divided into ISR group (n = 33) and no ISR (NISR) group (n = 165) according to the presence or absence of ISR. Serum levels of Cys C, MMP-9, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), creatinine (Cr), homocysteine (Hcy), fibrinogen (FIB), total bilirubin (TBIL), endothelin-1 (ET-1), nitric oxide (NO), angiotensin II (Ang II), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) levels before vascular stent implantation were examined and compared between groups. ROC curves were employed for analyzing the predictive value of serum Cys C and MMP-9 alone or in combination for ISR. Pearson test was utilized for analyzing the serum Cys C and MMP-9 with vasoactive substances and inflammatory cytokines in patients in the ISR group. Logistic regression analysis was implemented to analyze the factors influencing ISR 6-12 months after stent implantation for intracranial and extracranial arterial stenosis. ResultsCys C, MMP-9, LDL, UA, Cr, Hcy, FIB, ET-1, NO, Ang II, IL-6, TNF-α, and CRP were higher in the ISR group than in the NISR group, and TBIL was lower than in the NISR group (P < 0.05). The AUC of the combined serum Cys C and MMP-9 (AUC = 0.900) was greater than that of Cys C (AUC = 0.685) or MMP-9 (AUC = 0.870) alone (P < 0.05). Cys C and MMP-9 levels were positively correlated with ET-1, NO, Ang II, IL-6, TNF-α, and CRP (r > 0, P < 0.05). Increased levels of Cys C, MMP-9, LDL-C, UA, Cr, Hcy, FIB, ET-1, NO, Ang II, IL-6, TNF-α, and CRP, and diabetes were risk factors for the development of ISR (OR > 1, P < 0.05), and TBil was protective factor (OR < 1, P < 0.05). ConclusionSerum Cys C combined with MMP-9 levels are effective in predicting ISR.

MMP-2, MMP-9 and TIMP-2 expression in pituitary neuroendocrine tumors and their relationship with cavernous sinus invasion

Objective: To evaluate the expression of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in pituitary tumors, and investigate their correlation with circulating plasma proteins and cavernous sinus invasion. Additionally, the Ki-67 index was also assessed. Methods: Seventy-four patients (37 females) with pituitary adenomas were included, with preoperative peripheral blood collected in 29 cases. Tumor samples were evaluated for MMP-2, MMP-9, TIMP-2, and Ki-67 expression by immunohistochemistry. Protein plasma was semi-quantitatively detected using a commercial membrane antibody array. Results: Sixteen patients presented tumors invading the cavernous sinus. MMP-2 and TIMP-2 were slightly increased in these tumors compared to the non-invasive group, but the difference was not statistically significant. MMP-9 and TIMP-2 plasma concentrations did not correlate with tumor protein expression and also did not differ between the two groups. MMP-2 was not detected in plasma in any case. No statistically significant difference was observed when different tumors subtypes were considered. A significant difference was observed in tumor size [3.4 cm (2.8-4.9) vs. 1.9 cm (1.3-2.6); p &lt; 0.001] and in the Ki-67 index [1.8% (0.3-2.5) vs. 0.5% (0.2-1.0); p = 0.01] between the invasive and non-invasive groups, respectively. Conclusions: In this cohort, we found no significant correlation between tissue and plasma levels of MMP-2, MMP-9, and TIMP-2 and cavernous sinus invasion in pituitary tumors. Further investigation is needed to elucidate the potential role of these markers in invasiveness of pituitary tumors.

Cannabiorcol as a novel inhibitor of the p38/MSK-1/NF-κB signaling pathway, reducing matrix metalloproteinases in osteoarthritis

BackgroundThe bioactivity and potential medicinal applications of cannabiorcol, a lesser-known derivative of Cannabis sativa, require further investigation. Osteoarthritis (OA) is a chronic joint condition marked by gradual degradation of the cartilage and commonly associated with elevated levels of matrix metalloproteinases (MMPs). However, the influence of cannabiorcol on OA and its underlying mechanisms remains unclear. MethodsIn silico analysis investigated the key transcription factors that regulate MMP expression. A chondrocyte cell model [interleukin (IL)-1β and IL-1⍺-treated C20A4 cell line] was established and treated with cannabiorcol. Associated cytotoxicity was assessed using a WST-8 assay. A monoiodoacetate-induced OA rat model was established and treated with cannabiorcol. Protein translocation and transactivation analyses were conducted using immunofluorescence and dual-luciferase reporter assays, respectively. Western blotting and real-time PCR analyzed relevant markers to examine cannabiorcol's effects on OA and its fundamental mechanisms. ResultsCannabiorcol inhibits the expression of IL-1β-induced MMPs compared to other cannabis-related compounds. In silico analysis revealed that the nuclear factor-kappa β (NF-κβ) and mitogen-activated protein kinase (MAPK) pathways are associated with MMP expression as key regulators. In vitro, cannabiorcol inhibits the NF-κB and p38 MAPK pathways independently cannabinoid receptors and transient receptor potential vanilloids. In vivo, cannabiorcol reduces MMP expression and ameliorates monoiodoacetate-induced OA traits in rats. ConclusionCannabiorcol inhibits IL-1β-induced MMP expression in vitro and alleviates OA in an MIA-induced OA rat model by reducing MMP expression and inhibiting the p65/p38 axis.

Plasma levels of matrix metalloproteinases in early psychosis, anxiety and depression: Evidence from the ALSPAC cohort

BackgroundConverging evidence supports the role of Matrix Metalloproteinases (MMPs) in psychiatric disorders. Originally identified as regulators of the extracellular matrix (ECM), MMPs’ functions span multiple processes, including inflammation, synaptic plasticity, neuronal migration, and blood–brain barrier maintenance. Tissue Inhibitors of Metalloproteinases (TIMPs) are major regulators of MMPs. In the present study we examined the associations of plasma MMPs and TIMPs with mental disorders in young adults aged 24 years in the Avon Longitudinal Study of Parents and Children (ALSPAC). MethodsThe present study was a nested case control study within the Avon Longitudinal Study of Parents and Children and comprised 374 participants who met criteria for psychiatric disorders (35 met the criteria for psychotic disorder, 201 for mild/moderate depressive disorder, and 266 for generalised anxiety disorder) and 401 controls. All cases and controls had were selected from the group of 4019 participants who had attended at age 24 years, completed psychiatric assessments and provided plasma samples. Plasma concentrations of MMP2, MMP3, MMP9 and TIMP-4 were quantified using proximity extension assays available on Olink® Cardiovascular Panel III. Logistic regression analysis compared standardised MMPs and TIMPs levels in cases and controls. Models were adjusted for sex, body mass index, and cigarette smoking. ResultsThere was evidence for an association between MMP3 and depressive disorder (Odds ratio [OR] 1.35, 95 % confidence interval [CI] 1.06–1.73). There was evidence for an association between TIMP4 and depressive disorder (OR 1.51, 95 % CI 1.22–1.88) and generalised anxiety disorder (OR 1.43, 95 % CI 1.19–1.72). There was no evidence for an association between MMPs and psychotic disorders. ConclusionsThe study revealed that 24-year-olds with depressive and anxiety disorders exhibited elevated plasma concentrations of TIMP-4 compared to controls. There was evidence for an association between MMP3 and depressive disorder. These findings provide further support for the involvement of metalloproteinases as biomarkers in the pathophysiology of mental disorders during early adulthood.

Montelukast inhibits abdominal aortic aneurysm formation in mice via activating the AMPK/mTOR signalling pathway

ObjectiveTo investigate the mechanism by which Montelukast inhibits abdominal aortic aneurysm (AAA) formation through the AMPK/mTOR signaling pathway in mice.MethodsMice were randomly assigned to the Normal group, Model group, Montelukast group, and Montelukast + compound C (C.C) group. The Model, Montelukast, and Montelukast + C.C groups were induced with AAA by continuous infusion of 1000 ng/kg/min of Ang II. The Montelukast group received daily oral administration of 10 mg/kg Montelukast, while the Montelukast + C.C group received 10 mg/kg Montelukast and 10 mg/kg C.C orally for 28 days. Abdominal aortas were isolated, and their diameters and AAA occurrence were measured using a micrometer. Histological analysis was performed using Hematoxylin-Eosin (HE) staining to assess the morphological changes. TUNEL staining was conducted to measure cell apoptosis levels in the abdominal aortas. Western Blot was employed to evaluate protein expressions of Bax, Bcl-2, MMP-2, MMP-9, α1-AT, p-AMPK, AMPK, p-mTOR, mTOR in the abdominal aortic tissues. qRT-PCR was used to assess the expression of IL-6, TNF-α, IFN-γ in the mouse abdominal aortas.ResultsCompared to the Normal group, the Model group showed significantly increased abdominal aortic diameter, AAA occurrence, TUNEL positivity, Bax/Bcl-2 ratio, IL-6, TNF-α, IFN-γ, MMP-2, MMP-9, p-mTOR/mTOR, and decreased α1-AT, p-AMPK/AMPK (P < 0.05). The Montelukast group exhibited significant decreases in abdominal aortic diameter, AAA occurrence, TUNEL positivity, Bax/Bcl-2 ratio, IL-6, TNF-α, IFN-γ, MMP-2, MMP-9, p-mTOR/mTOR, and increases in α1-AT, p-AMPK/AMPK compared to the Model group (P < 0.05). The Montelukast + C.C group showed opposite trends compared to the Montelukast group (P < 0.05). The Normal group exhibited intact abdominal aortic wall structure with orderly arranged cells. The Model group showed thickened aortic walls, plaque formation, and inflammatory cell infiltration. The Montelukast group demonstrated reduced aortic wall thickening, approaching a morphology closer to the Normal group. The Montelukast + C.C group exhibited a morphology between the Model and Montelukast groups.ConclusionMontelukast can inhibit AAA formation in mice, possibly through the downregulation of cell apoptosis, inflammatory response, and matrix metalloproteinase levels via the AMPK/mTOR signaling pathway.

Betanin inspired zinc oxide nanoparticles: The potential antioxidant and anticancer activity against human lung cancer cell line (A549)

Background informationLung cancer is the most frequently reported disease on a global scale. The bioactive substances are less successful in specifically destroying cancer cells. To prevent early inactivation and ensure targeted delivery of bioactive chemicals to cancer cells. Betanin is known as nitrogenous water-soluble molecule which possess anti-inflammatory, hepatoprotective, antioxidant, and anticancer properties. Aim of the studyThis work evaluates the anti-cancer and anti-oxidant properties of Betanin coated zinc oxide nanoparticles on the A549 lung cancer cell line. Materials and methodsIn the current work, Betanin coated Zinc oxide nanoparticles (Betanin coated ZnO NPs) were made utilizing Betanin, a phytochemical. SEM, FTIR, DLS, and UV–Vis were used to evaluate their properties. Trypan blue and MTT were used to confirm cell survival and cytotoxicity of ZnO nanoparticles at various dosages. The morphological evaluation of A549 cells was investigated by phase contrast microscopy and apoptosis by propidium iodide staining. The membrane integrity of mitochondria was investigated by rhodamine 123 staining and observed under fluorescence microscope. The anti-oxidant ability of ZnO nanoparticles was analyzed by level of catalase, glutathione, nitric oxide, lipid peroxidation, and superoxide dismutase using UV spectrophotometric analysis. Studies on gene expression (Bcl2, P53and BAX) were conducted to assess the molecular mechanism of apoptosis mediated by synthesized nanoparticle and level of matrix metalloproteinase −2 (MMP-2) by gelatin zymography. ResultsAt the peak of 383 nm in the UV band, zinc oxide NP synthesis was confirmed. The FT-IR data demonstrated that zinc oxide nanoparticles were effectively coated with Betanin and by dynamic light scattering analysis confirmed particle size to be 100.8 nm. The presence of cubic, spherical, and platelet-shaped zinc oxide nanoparticles has been observed by SEM analysis. The nanoparticles of zinc oxide (ZnO) were synthesized chemically and exhibited decreasing cell viability and increasing cytotoxicity and apoptosis in dose dependent manner. The levels of LPO activity increased significantly and NO, antioxidant enzymes (GSH, SOD, and CAT) activity decreased significantly (P <0.0001). Our results demonstrated that A549 cells treated with Betanin loaded ZnO nanoparticles to prevent oxidation by scavenging free radicals and increased levels of gene expression related to apoptotic proteins BAX, p53 and decreased level of expression in Bcl2. Further, level of matrix metalloproteinase −2 (MMP-2) decreased with increase in concentration of nanoparticle. ConclusionAs per the research described above, lung cancer cells were effectively targeted by the anticancer and antioxidant abilities of ZnO nanoparticles inspired by Betanin (A549).

The Annexin A1 Protein Mimetic Peptide Ac2-26 prevents cellular senescence of CHON-001 chondrocytes against tumor necrosis factor-α via the Nrf2/NF-κB pathway.

Osteoarthritis (OA) is a degenerative joint disorder characterized by progressive cartilage degradation. Excessive oxidative stress (OS), inflammatory responses, extracellular matrix breakdown, and cellular senescence of chondrocytes play crucial roles in the pathological development of OA. Currently, curing OA remains a significant challenge. In this study, we aimed to elucidate the protective effects of Annexin A1 protein Mimetic Peptide (Ac2-26) against tumor necrosis factor-α (TNF-α)-induced damage in CHON-001 chondrocytes by assessing cellular senescence, OS, and the expression levels of matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4. Our results show that Ac2-26 mitigated the reduction of telomerase activity and the exacerbation of cellular senescence induced by TNF-α in CHON-001 chondrocytes. Treatment with TNF-α led to decreased expression of the human telomerase reverse transcriptase gene and increased expression of the telomeric repeat-binding factor 2 gene, which were reversed by Ac2-26 treatment. The TNF-α-induced increases in the gene and protein expressions of p53 and p16 were restored by Ac2-26 in a dose-dependent manner. Additionally, we found that TNF-α caused elevations in the mRNA and protein levels of MMP-13 and ADAMTS-4, which were reduced by Ac2-26 in a dose-dependent fashion. Furthermore, TNF-α triggered the activation of nuclear factor κ-B (NF-κB) by increasing the levels of phosphorylated NF-κB p65 and the luciferase activity of NF-κB. Notably, Ac2-26 alleviated OS by reducing mitochondrial reactive oxygen species levels and promoting the activation of NF-E2-related factor 2 (Nrf2) in TNF-α-challenged CHON-001 chondrocytes. Silencing Nrf2 abolished the Ac2-26-induced activation of NF-κB and cellular senescence in CHON-001 chondrocytes. Collectively, these findings offer new insights into the potential therapeutic use of Ac2-26 for treating OA.

Inhibition of lysine-specific histone demethylase 1A suppresses adenomyosis through reduction in ectopic endometrial stromal cell proliferation, migration, and invasion

Objective: Deep endometriosis is now referred to as adenomyosis externa, whereas adenomyosis is once known as endometriosis interna. Lysine-specific histone demethylase 1A (KDM1A, commonly LSD1) is a lysine demethylase that targets histone and non-histone proteins. This study aimed to assess how KDM1A affects the migration, invasion, and proliferation of adenomyosis-derived endometrial stromal cells (ESCs). Material and Methods: Immunocytochemistry staining was used to identify primary ectopic endometrial stromal cells (EESCs) and eutopic endometrial stromal cells (EuESCs) were isolated and purified from patients with complete hysterectomy for adenomyosis. Cell counting kit-8 assay, colony formation, wound scratch, and transwell assays were used to investigate the effect of silencing KDM1A on the inhibition cell viability, colony, migration, and invasion, respectively. Mechanistic investigations were carried out by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Results: Vimentin staining was highly positive and cytokeratin staining was nearly negative in EESCs and EuESCs. KDM1A silencing reduced the ability of EESCs and EuESCs to proliferate (P &lt; 0.001). The proliferation, motility, and invasiveness of EESCs and EuESCs were markedly reduced when KDM1A was silenced (P &lt; 0.001). KDM1A silencing substantially downregulated invasion- and migration-related proteins or genes according to Western blot and qRT-PCR analysis (P &lt; 0.05). EESCs and EuESCs with KDM1A silencing showed a higher reduction in these proteins than the control group (P &lt; 0.05). Conclusion: In adenomyosis, silencing KDM1A can limit the motility, invasiveness, and proliferation of EuESCs and EESCs. These outcomes could potentially correlate with the decreased expression levels of matrix metalloproteinases (MMP)-2, MMP-9, Fascin, and Erzin proteins.

Syringin ameliorates dextran sulphate colitis via alteration oxidative stress, inflammation NF-κB signalling pathway and gut microbiota.

The objective of the current study was to investigate the potential effects of syringin against dextran sulphate colitis (DSS)-induced ulcerative colitis (UC) in mice. In vitro study was performed on the RAW 264.7 cells and cytokines and inflammatory level were estimated. The oxidative stress, inflammatory cytokines, apoptosis and inflammatory parameters were estimated. The mRNA expression and faecal samples were estimated in the colon tissue. Syringin treatment enhanced the body weight, colon length and reduced the disease activity index (DAI), spleen index. Syringin treatment remarkably suppressed the level of nitric oxide (NO), myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) along with alteration of antioxidant parameters. Syringin treatment also altered level of cytokines in the serum and colon tissue; inflammatory parameters viz., platelet-activating factor (PAF), cyclooxygenase-2 (COX-2), prostaglandin (PGE2), inducible nitric oxide synthetase (iNOS), nuclear factor κ-B (NF-κB); matrix metalloproteinases (MMP) level. Syringin significantly (p < 0.001) enhanced the level of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). Syringin remarkably altered the relative abundance of gut microbiota like Firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia and Actinobacteria. Syringin exhibited the protective effect against DSS-induced UC in mice via alteration of NF-κB signalling pathway.

Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model.

Colon cancer (CC) is one of the most common malignant tumors in the gastrointestinal system. Overall, CC had the third highest incidence but the second highest mortality rate globally in 2020. Nowadays, CC is mainly treated with capecitabine chemotherapy regimen, supplemented by radiotherapy, immunotherapy and targeted therapy, but there are still limitations, so Chinese medicine plays an important role. To investigate the effects of invigorating-spleen and anticancer prescription (ISAP) on body weight, tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling pathway in CC mice model. The CC mice model were established and the mice were randomly divided into 5 groups, including the control group, capecitabine group, the low-dose, medium-dose and high-dose groups of ISAP, with 8 mice in each group, respectively. After 2 weeks of intervention, the body weight and tumor inhibition rate of mice were observed, and the expression of RAS, ERK, phosphorylated ERK (p-ERK), C-MYC and matrix metalloproteinase 2 (MMP2) proteins in the tissues of tumors were detected. Compared with the control group, the differences of body weight before and after treatment was much smaller in the groups of ISAP, with the smallest difference in the high-dose group of ISAP, while the capecitabine group had the greatest difference, indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice. The expression of RAS protein was decreased in the low- and medium-dose groups of ISAP, and the change of p-ERK was significant in the medium- and high- dose groups of ISAP. MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP. There were no significant changes in ERK in the ISAP group compared to the capecitabine group, while RAS, MMP2, and C-MYC protein expression were reduced in the ISAP group. The expression level of C-MYC protein decreased after treated with ISAP, and the decrease was the most significant in the medium-dose group of ISAP. ISAP has a potential inhibiting effect on transplanted tumor in mice, and could maintain the general conditions, physical strength and body weight of mice. The expression levels of RAS, p-ERK, MMP2 and c-myc were also decreased to a certain extent. By inhibiting the expression of upstream proteins, the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased. Therefore, it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.

Pinus densiflora Root Extract Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Cartilage Degradation in Interleukin-1β and Monosodium Iodoacetate-Induced Osteoarthritis Models.

Osteoarthritis (OA) is a common degenerative joint condition caused by an imbalance between cartilage synthesis and degradation, which disrupts joint homeostasis. This study investigated the anti-inflammatory and joint-improving effects of Pinus densiflora root extract powder (PDREP) in both in vitro and in vivo OA models. In an in vitro OA model, in which SW1353 human chondrosarcoma cells were treated with interleukin (IL)-1β, PDREP treatment significantly reduced the mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 while enhancing collagen type II alpha 1 (Col2a1) mRNA level, and decreased IL-6 and prostaglandin E2 (PGE2) levels. In addition, PDREP inhibited the phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), p38, nuclear factor-kappa B (NF-κB), and the expression of inducible nitric oxide synthase (iNOS). In a monosodium iodoacetate (MIA)-induced OA rat model, the administration of PDREP resulted in decreased OA clinical indices, improved weight-bearing indices and gait patterns, reduced histological damage, and lowered serum inflammatory cytokine and MMPs expression. Furthermore, PDREP downregulated the phosphorylation of ERK, JNK, p38, and NF-κB, as well as the expression of iNOS, consistent with the in vitro findings. These results suggest that PDREP exhibits anti-inflammatory and joint-improving effects and has potential as a therapeutic strategy or functional food for the treatment of OA.

Antioxidant Effect of a Plant-Derived Extracellular Vesicles' Mix on Human Skin Fibroblasts: Induction of a Reparative Process.

Plant-Derived Extracellular Vesicles extracellular vesicles (PDEVs) from organic agriculture (without the use of pesticides and microbicides) contain high levels of antioxidants. Organic PDEVs have shown an increased antioxidant power compared to PDEVs from single plants, suggesting a synergistic effect of the bioactives constitutively expressed in the PDEVs from single fruits. With this study, we wanted to investigate the beneficial effects of a mix of PDEVs on human skin cells. We found detectable levels of citric acid, ascorbic acid, glutathione, catalase, and SOD in a mix of PDEVs deriving from five different fruits (grape, red orange, papaya, pomegranate, and tangerine). We then treated H2O2-conditioned fibroblasts with the mix of PDEVs. The results showed that the PDEVs' mixture reverted the H2O2-induced redox imbalance, restoring mitochondrial homeostasis, with a strong reduction of mitochondrial anion superoxide and an increase in sirtuin levels. The antioxidant action was consistent with wound repair on a lesion produced in a fibroblast's monolayer. This result was consistent with an increased level of vimentin and matrix metalloproteinase-9, whose expression is directly related to the efficiency of the reparative processes. These data support a beneficial role of PDEVs in both preventing and treating skin injuries through their potent antioxidant and reparative activities.

Clinical trial of arthroscopic debridement combined with functional exercise in the treatment of advanced knee osteoarthritis: A retrospective observational study.

Advanced knee osteoarthritis (KOA) impacts both knees, resulting in pain, deformity, and substantial restrictions in joint mobility. This study aims to examine the effectiveness of combining arthroscopic debridement with functional exercise in treating advanced KOA. A total of 296patients diagnosed with advanced KOA were divided into two groups: the observation group (n= 152) received arthroscopic debridement combined with functional exercise, while the control group (n= 144) underwent arthroscopic debridement only. The study compared and observed the outcomes between the two groups. There were no significant differences in knee joint function, inflammation level, and oxidative stress between the two groups before treatment (P> 0.05). Following treatment for six months, the observation group exhibited significantly lower visual analog scale (VAS) score, tissue inhibitors of metalloproteinase-1 (TIMP-1), tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), matrix metalloproteinase-3 (MMP-3), and malondialdehyde (MDA) levels compared to the control group (P< 0.05). Meanwhile, the observation group showed significantly higher levels of Lysholm score, hospital for special surgery (HSS) score, range of motion (ROM) of knee, peak torque (PT) and total work (TW) for knee extension and flexion, superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione (GSH) compared to the control group (P< 0.05). Besides, the effective treatment rate in the observation group was notably higher than that in the control group (80.92% vs. 69.44%, P< 0.05). The combination of arthroscopic debridement with functional exercise is an effective treatment for advanced KOA. This approach not only enhances the function and strength of knee joint and reduces inflammatory response but also boosts the body's antioxidant capacity. The treatment exhibits encouraging outcomes and warrants broad implementation.

Serum integrin accumulation during asthma exacerbation: The role of matrix metalloproteinases.

The inflammation caused by asthma exacerbation can lead to permanent changes in the airways and loss of lung function. Integrins are membrane receptors that interact with components of the extracellular matrix and cell adhesion molecules. It is known that these receptors can be found in soluble form in some conditions such as asthma, but it is unknown if exacerbation during asthma leads to soluble integrins. Our results indicated that asthma patients showed higher levels of soluble α1, α2, and β2 integrin subunits in their serum compared to controls, as confirmed by both ELISA and western blot. During asthma exacerbation, the levels of α2 and β2 integrin subunits increased even more compared to non-exacerbation and controls, while the α1 integrin subunit decreased. Western blot analysis identified two β2 integrin subunits, one at 75 kDa and another at 120 kDa; the 120 kDa subunit increased during asthma exacerbation. The activity of matrix metalloproteinase 9 (MMP9) increased during exacerbation, while MMP2 remained unchanged. Lower forced expiratory volume in 1 second (FEV1) values were associated with higher expression levels of α2, β1, and β2 integrin subunits. Active and latent MMP9 were correlated with the levels of the β2 integrin subunit, which means that at low levels of active and latent MMP9, there are lower levels of β2 integrin subunit. In conclusion, asthma exacerbation leads to the presence of soluble integrins, particularly the β2 subunit, most likely due to MMP9-induced proteolytic cleavage.

Pre-transplant Screening for MMP-9 in Allogeneic HSCT Candidates

Purpose: InflammaDry® (Quidel Eye Health, San Diego, California), an FDA-approved point-of-care commercial test, measures matrix metalloproteinase-9 (MMP-9) levels in the tear film. MMP-9 is an inflammatory biomarker that is elevated in response to ocular surface stress, particularly observed in ocular graft-versus-host disease (oGVHD). The purpose of this study is to assess the prevalence of MMP-9 positivity and a score &gt;4 on the OSDI-6 questionnaire in patients before allogeneic hematopoietic stem cell transplant (HSCT). Methods: A prospective, observational, cross-sectional single center pilot study was conducted among 23 patients (46 eyes) undergoing planned allogenic HSCT. InflammaDry® results, OSDI-6 questionnaire results, and development of oGVHD were collected. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and chi-square test were calculated. Results: InflammaDry® demonstrated high sensitivity (1.0) but low specificity (0.1429) for oGVHD development. The PPV was 0.25, while the NPV was 1.0. No statistical significance was found between InflammaDry® result and development of oGVHD (p-value&gt; 0.05). Conclusion: InflammaDry® is not an effective tool for detecting the onset or predicting the risk of developing oGVHD. A significant percentage of patients exhibited ocular inflammation before allogeneic HSCT, suggesting that initiating prophylactic treatment could be valuable in reducing oGVHD development.

Utility of Serum Matrix Metalloproteinase-7 as a Biomarker in Cholestatic Infants with Congenital Heart Disease.

Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH. This is a single-center cross-sectional study including infants < 180days of age with cholestasis and serum MMP-7 levels collected from 2019 to 2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test. A total of 149 patients were included. Patients with CHD had significantly elevated MMP-7 levels relative to the non-CHD cohort (50 vs. 34ng/mL, p = 0.009). Sub-analysis comparing infants with and without PH revealed significantly elevated median MMP-7 levels in those with clinically significant PH (125 vs. 39ng/mL, p = 0.010). CHD patients with PH had greater median MMP-7 compared to CHD patients without PH (154 vs 43ng/mL, p = 0.028). Serum MMP-7 levels in infants with congenital heart disease with cholestasis (CHD-C) were significantly elevated compared to those with cholestasis alone. MMP-7 may help identify non-BA cholestatic infants who have concurrent clinically significant pulmonary hypertension. Larger, prospective studies are needed to validate this finding and establish CHD-specific MMP-7 cut-offs.