Search Results (288)

Galectins are a class of lectins that are extensively expressed in all organisms. Galectins are involved in a range of functions, including early development, tissue regeneration, cancer and inflammation. It has been shown that galectin-8 is expressed in the villous and extravillous trophoblast (EVT) cells of the human placenta; however, its physiological role in pregnancy establishment has not been elucidated. Taking these factors into account, we investigated the functional role of galectin-8 in HTR-8/SVneo cells—a human EVT cell line—and human primary cytotrophoblast cells isolated from a first-trimester placenta. We analyzed the effects of recombinant human galectin-8 (rh galectin-8) on the adhesion, migration and invasion of HTR-8/SVneo cells. We used qPCR, cell-based ELISA (cELISA) and gelatin zymography to study the effects of galectin-8 on mediators of these processes, such as integrin subunits alpha-1 and beta-1 and matrix metalloproteinases (MMPs)-2 and -9, on the mRNA and protein levels. Further, we studied the effects of galectin-8 on primary cytotrophoblast cells’ invasion. Galectin-8 stimulated the adhesion, migration and invasion of HTR-8/SVneo cells, as well as the invasion of primary cytotrophoblasts. In addition, the MMP-2 and -9 levels were increased, while the expression of integrins alpha-1 and beta-1 was not affected. Galectin-8 has the ability to positively affect EVTs’ invasion, so it can be considered a significant factor in the trophoblast cell invasion process. Full article

Skin aging is characterized by reactive oxygen species (ROS) accumulation, principal players in triggering events associated with aging. Our recent data on the ability of an innovative poly-component formulation (KARISMA Rh Collagen^® FACE: K formulation) to suppress the biomolecular events associated with oxidative stress-induced aging prompted us to deepen the mechanisms underlying the observed effects on aged human dermal fibroblasts (HDFs). Here, we evaluated K’s ability to perform a direct free radical-scavenging action and modulate anti-oxidant systems by counteracting the inflammatory process in an H₂O₂-induced cellular senescence model. Standard methods were used to measure scavenging capacity and enzymatic anti-oxidant system activities. Nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) levels were analyzed by Western blot. We assessed pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and advanced glycation end-products (AGEs). Our results show that K counteracted stress-induced aging in a dose-dependent manner by exerting a direct scavenging action and increasing anti-oxidant systems, such as superoxide dismutase (SOD) and catalase (CAT) up to control values. These findings could be associated with increased phospho-Nrf2 (p-Nrf2) expression, generally reduced in aged HDFs following exposure to different concentrations of K formulation. Moreover, K formulation caused a reduction of pro-inflammatory cytokines, interleukin-1β and -6, MMP-1 and -9, and AGE levels, events related to a downregulation of p-NF-κB level. The results indicate that K formulation re-established the normal physiology of HDFs by reducing p-NF-κB expression and restoring Nrf2 activation, thus supporting its efficacious reparative and regenerative action in treating skin aging. Full article

Genetic factors play a significant role in the pathogenesis of mitral valve diseases, including mitral valve prolapse (MVP) and mitral valve regurgitation. Genes like Fibrillin-1 (FBN1), Filamin A (FLNA), matrix metalloproteinase 2 (MMP2), and SRY-box transcription factor 9 (SOX9) are known to influence mitral valve pathology but knowledge of the exact mechanism is far from clear. Data regarding serum parameters, transesophageal echocardiography, and genetic and histopathologic parameters were investigated in 54 patients who underwent cardiovascular surgery for mitral valve regurgitation. The possible association between Fibrillin-1, Filamin A, MMP2, and SOX9 gene expressions was checked in relationship with the parameters of systemic inflammatory response. The mRNA expression levels (RQ—relative quantification) were categorized into three distinct groups: low (RQ < 1), medium/normal (RQ = 1–2), and high (RQ > 2). Severe fibrosis of the mitral valve was reflected by high expression of FBN1 and low expression of MMP2 (p < 0.05). The myxoid degeneration level was associated with the mRNA expression level for FBN1 and a low lymphocyte-monocyte ratio was associated with an increased mRNA expression of FBN1 (p < 0.05). A high number of monocytes was associated with high values of FBN1 whereas the increase in the number of lymphocytes was associated with high levels of MMP2. In addition, we observed that the risk of severe hyalinization was enhanced by a low mRNA expression of FLNA and/or SOX9. In conclusion, a lower FLNA mRNA expression can reflect the aging process that is highlighted in mitral valve pathology as a higher risk for hyalinization, especially in males, that might be prevented by upregulation of the SOX9 gene. FBN1 and MMP2 influence the inflammation-related fibrotic degeneration of the mitral valve. Understanding the genetic base of mitral valve pathology can provide insights into disease mechanisms, risk stratification, and potential therapeutic targets. Full article

Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1β, TNF-α, TGF-β, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action. Full article

In identifying biomarkers for anticancer drugs, the lack of objectivity in selecting candidate factors makes interpretation difficult. We performed preclinical analysis and a translational validation study to identify candidate biomarkers for regorafenib efficacy in metastatic colorectal cancer (mCRC). Using in silico COMPARE analysis with a human cancer cell line panel, JFCR39, we selected candidate biomarkers whose expression correlates with regorafenib sensitivity. We validated predictive values in mCRC patients receiving regorafenib (discovery, n = 53) and FTD/TPI (control, n = 16). Blood samples were obtained at baseline (BL), before the second cycle (2nd), and at progressive disease (PD), and biomarker levels were measured using ELISA. Our analysis showed that high matrix metalloproteinase (MMP)-14 expression was associated with a high sensitivity to regorafenib. In the discovery cohort, high MMP-14 levels at BL and PD were correlated with tumor shrinkage and longer progression-free survival (PFS). A subsequent analysis of other related factors further indicated that the patients with decreased MMP-9 levels at the 2nd had higher disease control rates, tumor shrinkage, longer PFS, and overall survival than those with increased changes. These findings were not observed in the control cohort. Our study suggests MMP-14 and MMP-9 may serve as prognostic markers for regorafenib and provide insights into novel combination therapies with anti-MMP-9 agents or FTD/TPI. Full article

Background: Matrix metalloproteinases (MMPs) play an important role in the pathophysiology of atherosclerosis. Reportedly, statins can decrease MMP activity in patients with atherosclerotic cardiovascular disease, but this effect has not been studied in healthy individuals. Methods: MMPs 2, 7, and 9 and several other parameters were measured before and after a four-week course of moderate-dose atorvastatin (20 mg/day) in 21 healthy individuals. Results: Atorvastatin treatment resulted in lower total cholesterol, LDL-cholesterol, non-HDL-cholesterol, and triglycerides (p < 0.001 for all), but higher levels of plasma enzymes AST, ALT, CK, and LDH (p < 0.05 for all). No effect of atorvastatin on plasma MMP median concentrations was recorded. Before treatment, moderate positive significant correlations were found between MMP-7 and age, blood lipids, and blood count-derived inflammatory markers. Pre-treatment MMP-7 was best predicted by the total cholesterol-to-HDL cholesterol ratio in a remnant cholesterol-weighted least squares regression model. After atorvastatin treatment, MMP-7 no longer correlated with these markers. Conclusions: While the effect of statins on plasma MMPs in atherosclerosis is controversial, short-term moderate-dose atorvastatin treatment does not seem to affect levels of MMPs 2, 7, and 9 in healthy individuals. However, an intriguing correlation between MMP-7 and atherosclerosis-related blood lipids and neutrophil-associated inflammatory biomarkers seems to be disrupted by atorvastatin independently of hsCRP, possibly via pleiotropic effects. Full article

Teff (Eragrostis tef), a gluten-free cereal crop cultivated originally in Northeast Africa, is increasingly utilized due to its nutritional and health benefits. The aim of the present study was to investigate the effects of ethanol extract obtained from raw and thermally treated teff, referred to as RTE and TTE, respectively, on uncontrolled growth and activated metastasis using human cancer cell lines. Both RTE and TTE contained flavones, such as orientin (luteolin 8-C-glucoside) and vitexin (apigenin 8-C-glucoside), and phenolic acids, such as protocatechuic acid and p-coumaric acid. TTE showed higher total phenol, protocatechuic acid, and p-coumaric acid contents, but lower orientin content compared to RTE. RTE and TTE significantly suppressed cell growth of H1299 human lung cancer cells, with TTE exhibiting more pronounced effects than RTE, while both extracts had only minimal effects on the growth of non-malignant human umbilical vein endothelial cells. The growth-inhibitory activities of RTE and TTE in H1299 cells were associated with apoptosis induction and cell cycle arrest at the G2/M phase. TTE produced an additional effect on inducing cell cycle arrest at the S phase in H1299 cells, potentially contributing to its stronger growth-inhibitory effects. Moreover, both RTE and TTE effectively inhibited key events in metastasis, such as invasion, migration, and adhesion, in H1299 cells under non-cytotoxic conditions, with TTE showing stronger effects. In HCT116 human colon cancer cells, a similar pattern of inhibition was demonstrated against the metastatic events, accompanied by reduced levels of matrix metalloproteinase-2 and -9. Our results indicate that teff extracts exhibit in vitro anti-growth and anti-metastatic activities, which are enhanced by thermal treatment of teff. Full article

Background: 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). Methods: 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. Results: 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. Conclusions: 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. Full article

Gastric inflammation-related disorders are commonly observed digestive system illnesses characterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E₂ (PEG₂) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric inflammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol extract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal human gastric mucosa epithelial cells (GES-1). The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE₂ and MMP-9 proteins induced by TNF-α to examine the anti-inflammatory properties of Lj extracts. The results indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG₂ and MMP-9 activity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflammation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG₂ and MMP-9 through the activation of TNFR–ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH exhibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation. Full article

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, β-citronellol (β-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-β1 to induce fibrogenesis were co-treated with crude KL extract and β-CIT. Gene expression was analyzed by real-time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The release of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein–ligand interactions. The results showed that both crude KL extract and β-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of β-CIT. This study demonstrates the ability of KL extract and β-CIT to inhibit HSC activation during TGF-β1-induced fibrogenesis, suggesting a promising role of β-CIT in anti-hepatic fibrosis therapies. Full article

Diabetic neuropathy and nephropathy are common complications of type 1 diabetes (T1D). The symptoms are often elusive in the early stages, and available diagnostic methods can be improved using biomarkers. Matrix metalloproteinase 3 (MMP-3) has been identified in the kidneys and is thought to be involved in diabetic nephropathy. Growth differentiation factor 15 (GDF-15) has been suggested to have positive effects in diabetes, but is otherwise associated with adverse effects such as cardiovascular risk, declined kidney function, and neurodegeneration. This study aims to investigate plasma MMP-3 and GDF-15 as systemic biomarkers for diabetic neuropathy and nephropathy in T1D. The study involves patients with childhood-onset T1D (n = 48, age 38 ± 4 years) and a healthy control group (n = 30, age 38 ± 5 years). Neurophysiology tests, evaluations of albuminuria, and measurements of routine biochemical markers were conducted. The neuropathy impairment assessment (NIA) scoring system, where factors such as loss of sensation and weakened reflexes are evaluated, was used to screen for symptoms of neuropathy. MMP-3 and GDF-15 concentrations were determined in heparinized plasma using ELISA kits. In total, 9 patients (19%) had albuminuria, and 25 (52%) had diabetic neuropathy. No significant differences were found in MMP-3 concentrations between the groups. GDF-15 levels were higher in T1D, with median and interquartile range (IQR) of 358 (242) pg/mL in T1D and 295 (59) in controls (p < 0.001). In the merged patient group, a positive correlation was found between MMP-3 and plasma creatinine, a negative correlation was found between MMP-3 and estimated glomerular filtration rate (eGFR; rho = −0.358, p = 0.012), and there was a positive correlation between GDF-15 and NIA (rho = 0.723, p < 0.001) and high-sensitive C-reactive protein (rho = 0.395, p = 0.005). MMP-3 was increased in macroalbuminuria and correlated positively with NIA only in the nine T1D patients with albuminuria (rho = 0.836, p = 0.005). The present study indicates that high MMP-3 is associated with low eGFR, high plasma creatinine, and macroalbuminuria, and that GDF-15 can be a biomarker for diabetic neuropathy in T1D. MMP-3 may be useful as biomarker for neuropathy in T1D with albuminuria. Full article

Growth differentiation factor 9 (GDF-9) contributes to early ovarian development and oocyte survival. Higher concentrations of GDF-9 in follicular fluid (FF) are associated with oocyte nuclear maturation and optimal embryo development. In in vitro fertilization (IVF), GDF-9 affects the ability of the oocyte to fertilize and subsequent embryonic development. Bone morphogenetic protein 15 (BMP-15) is involved in the regulation of ovarian function and affects oocyte development. During IVF, BMP-15 contributes to the formation of competent blastocysts. BMP-15 may play a role in embryo implantation by affecting endometrial receptivity. Bone morphogenetic protein 4 (BMP-4) is involved in the regulation of follicle growth and development and affects granulosa cell (GC) differentiation. In relation to IVF, BMP-4 is important for embryonic development, influences cell fate and differentiation, and plays a role in facilitating embryo–endometrial interactions during the implantation process. Extracellular matrix metalloproteinase inducer (EMMPRIN) is associated with ovulation and follicle rupture, promotes the release of mature eggs, and affects the modification of the extracellular matrix of the follicular environment. In IVF, EMMPRIN is involved in embryo implantation by modulating the adhesive properties of endometrial cells and promotes trophoblastic invasion, which is essential for pregnancy to occur. The purpose of the current article is to review the studies and recent findings of GDF-9, BMP-15, BMP-4 and EMMPRIN as fundamental factors in normal follicular development and in vitro fertilization. Full article

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

Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium damage and myocardial fibrosis. The aim of our study was to assess endothelial damage and myocardial fibrosis in the early period after RT on the basis of cardiac biomarkers and in relation to the radiation dose applied to individual heart structures in patients treated for non-small-cell lung cancer. This single-center prospective study included consecutive patients with lung cancer (LC) who were referred for treatment with radiochemotherapy (study group) or chemotherapy (control group). The study protocol included performing an echocardiographic examination, a standard ECG examination, and collecting blood samples for laboratory tests before starting treatment for lung cancer in the first week after completing RT (after four cycles of chemotherapy in the control group) and after 12 weeks from the end of treatment. The study included 23 patients in the study group and 20 patients in the control group. Compared to the baseline values, there was a significant increase in total cholesterol concentration in the study group immediately after the end of RT, which persisted for three months after the end of therapy. After taking into account the use of statins in the analysis, it was found that an increase in total cholesterol concentration after oncological treatment was observed only among patients who did not use statins. Taking into account the assessment of myocardial fibrosis markers, there were no significant changes in the concentration of matrix metallopeptidase 9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in the study group. In patients treated with radiochemotherapy, there was a significant increase in the concentration of intercellular adhesion molecule 1 (ICAM-1) immediately after RT, when compared to the baseline. After taking into account the use of statins, an increase in ICAM-1 concentration immediately after RT was observed only in patients who did not use statins. There was also a significant correlation between the radiation dose received by the left anterior descending coronary artery (LAD) and left circumferential coronary artery, and vascular cell adhesion protein 1 (VCAM-1) concentration measured at three months after the end of RT. Immediately after completion of radiotherapy, a significant increase in the level of ICAM-1 is observed indicating endothelial damage. The radiation dose to coronary arteries should be minimized, as it correlates with the concentration of VCAM-1. The use of statins may prevent the increase in total cholesterol and ICAM-1 concentration after irradiation for lung cancer; however, further studies designed for this specific purpose are necessary to confirm the effectiveness of statins in this area. Full article

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1β, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1β and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes. Full article