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International Journal of Environmental... Jun 2024The hypothesis that physiological changes in women can affect periodontal tissues is the subject of this study, and inflammatory markers such as matrix...
The hypothesis that physiological changes in women can affect periodontal tissues is the subject of this study, and inflammatory markers such as matrix metalloproteinase-8 can measure susceptibility to inflammation. The study aimed to analyze MMP-8 levels in periodontal sites of postpartum women and women without a history of pregnancy, comparing health parameters and periodontal disease. This is a case-control study with 40 participants, 20 cases (women in the postpartum period) and 20 controls (women without any pregnancy), who underwent clinical periodontal examination and the collection of crevicular gingival fluid. The ELISA test was used to detect MMP-8 levels. Postpartum women had worse periodontal parameters, such as bleeding index on probing, number of sites with CAL ≥ 3, and fewer teeth present. In the group of women without a history of pregnancy, a significantly lower MMP-8 level was observed in healthy sites and a higher one was observed in periodontal pockets ( < 0.01). In contrast, in postpartum women, MMP-8 levels were elevated in both healthy sites and periodontal pockets ( > 0.01). The MMP-8 levels in gingival fluid appear to be related to periodontal clinical parameters and may be a possible marker of enzymatic changes involved in periodontal tissue destruction in postpartum women.
Topics: Humans; Female; Matrix Metalloproteinase 8; Adult; Case-Control Studies; Postpartum Period; Gingival Crevicular Fluid; Pregnancy; Periodontal Diseases; Biomarkers; Young Adult
PubMed: 38928985
DOI: 10.3390/ijerph21060739 -
International Journal of Molecular... Jun 2024The levels of the MMPs in the biological samples of confirmed patients with gastric cancer are significantly elevated compared to those found in healthy people....
Determination of Matrix Metalloproteinase 2 in Biological Samples Using a 3D Stochastic Microsensor Based on Graphene Oxide/AuNanoparticles/(Z)-N-(pyridin-4-yl-methyl) Octadec-9-enamide.
The levels of the MMPs in the biological samples of confirmed patients with gastric cancer are significantly elevated compared to those found in healthy people. Therefore, a novel 3D stochastic microsensor based on graphene oxide, modified with gold nanoparticles and (Z)-N-(pyridin-4-yl-methyl) octadec-9-enamide (namely N2-AuNP/GO), was designed for the determination of MMP-2 in biological samples, and validated for the screening tests of biological samples in order to be used for the early diagnosis of gastric cancer. The proposed sensor presents a low limit of quantification (1.00 × 10 g mL), high sensitivity (1.84 × 10 s g mL), and a wide working concentration range (1.00 × 10-1.00 × 10 g mL). Recovery values higher than 99.15% were recorded for the assay of MMP-2 in whole blood, gastric tissue tumors, saliva, and urine samples.
Topics: Graphite; Humans; Matrix Metalloproteinase 2; Metal Nanoparticles; Gold; Stomach Neoplasms; Biosensing Techniques
PubMed: 38928425
DOI: 10.3390/ijms25126720 -
International Journal of Molecular... Jun 2024Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium...
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.
Topics: Humans; Male; Female; Lung Neoplasms; Middle Aged; Aged; Prospective Studies; Fibrosis; Carcinoma, Non-Small-Cell Lung; Endothelium, Vascular; Matrix Metalloproteinase 9; Myocardium; Radiotherapy; Tissue Inhibitor of Metalloproteinase-1; Cardiomyopathies; Cholesterol; Biomarkers
PubMed: 38928407
DOI: 10.3390/ijms25126705 -
International Journal of Molecular... Jun 2024The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery...
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 ( < 0.001), while IL-12 showed a direct relationship with CAL gain ( = 0.005) and PPD reduction ( = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes.
Topics: Humans; Gingival Crevicular Fluid; Male; Female; Middle Aged; Biomarkers; Adult; Regeneration; Matrix Metalloproteinase 8; Phenotype; Matrix Metalloproteinase 9; Inflammation; Treatment Outcome; Interleukin-1beta; Aged
PubMed: 38928390
DOI: 10.3390/ijms25126687 -
International Journal of Molecular... Jun 2024Prostate cancer (PC) is the most common cancer diagnosed in men worldwide. Currently, castration-resistant prostate cancer (CRPC), which is resistant to androgen...
Prostate cancer (PC) is the most common cancer diagnosed in men worldwide. Currently, castration-resistant prostate cancer (CRPC), which is resistant to androgen deprivation therapy, has a poor prognosis and is a therapeutic problem. We investigated the antitumor effects on PC of an antibody neutralizing secreted disintegrin and metalloproteinase domain-containing protein 9 (sADAM9), which is a blood-soluble form. We performed proliferation assays, wound healing assays, invasion assays, Western blot (WB), and an in vivo study in which a sADAM9 neutralizing antibody was administered intratumorally to PC-bearing mice. In invasion assays, the sADAM9 neutralizing antibody significantly inhibited invasion in all cell lines (TRAMP-C2: = 0.00776, LNCaP: = 0.000914, PC-3: = 0.0327, and DU145: = 0.0254). We examined epithelial-mesenchymal transition (EMT) markers, one of the metastatic mechanisms, in WB and showed downregulation of Slug in TRAMP-C2, LNCaP, and DU145 and upregulation of E-cadherin in TRAMP-C2 and PC-3 by sADAM9 neutralization. In mouse experiments, the sADAM9 neutralizing antibody significantly suppressed tumor growth compared to controls (1.68-fold in TRAMP-C2, 1.89-fold in LNCaP, and 2.67-fold in PC-3). These results suggested that the sADAM9 neutralizing antibody inhibits invasion, migration, and tumor growth in PC. Previous studies examined the anti-tumor effect of knockdown of total ADAM9 or sADAM9, but this study used the new technology of neutralizing antibodies for sADAM9. This may be novel because there was no animal study using a neutralizing antibody for sADAM9 to see the relationship between ADAM9 expression and prostate cancer.
Topics: Male; Epithelial-Mesenchymal Transition; Animals; Humans; Cell Movement; ADAM Proteins; Mice; Cell Line, Tumor; Prostatic Neoplasms; Antibodies, Neutralizing; Cell Proliferation; Membrane Proteins; Xenograft Model Antitumor Assays
PubMed: 38928352
DOI: 10.3390/ijms25126646 -
International Journal of Molecular... Jun 2024Aneurysms pose life-threatening risks due to the dilatation of the arteries and carry a high risk of rupture. Despite continuous research efforts, there are still no...
Aneurysms pose life-threatening risks due to the dilatation of the arteries and carry a high risk of rupture. Despite continuous research efforts, there are still no satisfactory or clinically effective pharmaceutical treatments for this condition. Accelerated inflammatory processes during aneurysm development lead to increased levels of matrix metalloproteinases (MMPs) and destabilization of the vessel wall through the degradation of the structural components of the extracellular matrix (ECM), mainly collagen and elastin. Tissue inhibitors of metalloproteinases (TIMPs) directly regulate MMP activity and consequently inhibit ECM proteolysis. In this work, the synthesis of TIMP-1 protein was increased by the exogenous delivery of synthetic TIMP-1 encoding mRNA into aortic vessel tissue in an attempt to inhibit MMP-9. In vitro, TIMP-1 mRNA transfection resulted in significantly increased TIMP-1 protein expression in various cells. The functionality of the expressed protein was evaluated in an appropriate ex vivo aortic vessel model. Decreased MMP-9 activity was detected using in situ zymography 24 h and 48 h post microinjection of 5 µg TIMP-1 mRNA into the aortic vessel wall. These results suggest that TIMP-1 mRNA administration is a promising approach for the treatment of aneurysms.
Topics: Tissue Inhibitor of Metalloproteinase-1; Matrix Metalloproteinase 9; RNA, Messenger; Animals; Humans; Rats; Aneurysm; Aorta; Male; Arteries; Matrix Metalloproteinase Inhibitors
PubMed: 38928311
DOI: 10.3390/ijms25126599 -
International Journal of Molecular... Jun 2024Breast cancer, known for its diverse subtypes, ranks as one of the leading causes of cancer-related deaths. Prostate-specific membrane antigen (PSMA), primarily...
Breast cancer, known for its diverse subtypes, ranks as one of the leading causes of cancer-related deaths. Prostate-specific membrane antigen (PSMA), primarily associated with prostate cancer, has also been identified in breast cancer, though its role remains unclear. This study aimed to evaluate PSMA expression across different subtypes of early-stage breast cancer and investigate its correlation with clinicopathological factors. This retrospective study included 98 breast cancer cases. PSMA expression was examined in both tumor cells and tumor-associated blood vessels. The analysis revealed PSMA expression in tumor-associated blood vessels in 88 cases and in tumor cells in 75 cases. Ki67 expression correlated positively with PSMA expression in blood vessels ( < 0.0001, RSpearman 0.42) and tumor cells ( = 0.010, RSpearman 0.26). The estrogen and progesterone receptor expression correlated negatively with PSMA levels in blood vessels ( = 0.0053, R Spearman -0.26 and = 0.00026, R Spearman -0.347, respectively). Human epidermal growth factor receptor 2 (HER2) status did not significantly impact PSMA expression. We did not detect any statistically significant differences between breast cancer subtypes. These findings provide evidence for a heterogenous PSMA expression in breast cancer tissue and suggest its correlation with tumor aggressiveness. Despite the limited sample size, the study provides valuable insights into the potential of PSMA as a prognostic, diagnostic, and therapeutic target in the management of breast cancer.
Topics: Humans; Breast Neoplasms; Female; Glutamate Carboxypeptidase II; Middle Aged; Antigens, Surface; Aged; Biomarkers, Tumor; Retrospective Studies; Immunohistochemistry; Neoplasm Staging; Adult; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Aged, 80 and over
PubMed: 38928224
DOI: 10.3390/ijms25126519 -
International Journal of Molecular... Jun 2024Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought...
Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought to be biomarkers of preeclampsia. The aim of this study was to assess the correlation between concentrations of Gal-13 and laeverin measured in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic assessment of the fetoplacental measurements. Fetal biometric data and placental volume and perfusion indices were measured in 62 singleton pregnancies. Serum and amniotic levels of Gal-13 and laeverin levels were measured using a sandwich ELISA. Both amniotic fluid and serum Gal-13 levels expressed a negative correlation to the plasma laeverin level in mid-pregnancy. Serum laeverin level correlated positively with the gestational length at delivery (β = 0.39, < 0.05), while the amniotic laeverin level correlated well with the abdominal circumference of the fetus (β = 0.44, < 0.05). Furthermore, laeverin level in the amnion correlated positively with the estimated fetal weight (β = 0.48, < 0.05) and with the placental volume (β = 0.32, < 0.05). Logistic regression analyses revealed that a higher circulating Gal-13 level represents a slightly significant risk factor (OR: 1.01) for hypertension-related diseases during pregnancy. It is a novelty that laeverin can be detected in the amniotic fluid, and amnion laeverin concentration represents a potential biomarker of fetoplacental growth.
Topics: Humans; Pregnancy; Female; Adult; Galectins; Placenta; Amniotic Fluid; Biomarkers; Pre-Eclampsia; Fetal Development; Gestational Age; Pregnancy Proteins; Metalloproteases
PubMed: 38928055
DOI: 10.3390/ijms25126347 -
Genes May 2024X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the...
X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the gene. The diagnosis of individuals with mild phenotypes can be challenging and often delayed. Here, we describe a three-generation family with a very mild clinical presentation of XLH. The diagnosis was unexpectedly found in a 39-year-old woman who was referred for genetic testing due to an unclear childhood diagnosis of a tubulopathy. Genetic testing performed by next-generation sequencing using a kidney disease gene panel identified a novel non-canonical splice site variant in the gene. Segregation analysis detected that the consultand's father, who presented with hypophosphatemia and decreased tubular phosphate reabsorption, and the consultand's son also carried this variant. RNA studies demonstrated that the non-canonical splice site variant partially altered the splicing of the gene, as both wild-type and aberrant splicing transcripts were detected in the two male members with only one copy of the gene. In conclusion, this case contributes to the understanding of the relationship between splicing variants and the variable expressivity of XLH disease. The mild phenotype of this family can be explained by the coexistence of transcripts with aberrant and wild-type splicing.
Topics: Humans; PHEX Phosphate Regulating Neutral Endopeptidase; Adult; Female; Familial Hypophosphatemic Rickets; Male; Pedigree; RNA Splice Sites; RNA Splicing; Phenotype; Genetic Diseases, X-Linked; Mutation
PubMed: 38927615
DOI: 10.3390/genes15060679 -
Anticancer Research Jul 2024The activity and expression of matrix metalloproteinase-7 (MMP7) have been found to be upregulated in the late stages of endometriosis. However, the contribution of MMP7...
BACKGROUND/AIM
The activity and expression of matrix metalloproteinase-7 (MMP7) have been found to be upregulated in the late stages of endometriosis. However, the contribution of MMP7 genotype to endometriosis has seldom been examined. This study aimed to investigate the role of MMP7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes in determining personal susceptibility to endometriosis in a Taiwanese cohort.
PATIENTS AND METHODS
In this hospital-based case-control study, MMP7 genotypes were analyzed in 153 endometriosis and 636 individuals without endometriosis using typical polymerase chain reaction-restriction fragment length polymorphism methodology.
RESULTS
The statistical analysis revealed that MMP7 rs11568818 genotypes were differentially distributed between the endometriosis and control groups (p for trend=0.0048). Specifically, the MMP7 rs11568818 homozygous variant GG was associated with endometriosis risk compared to the wild-type AA genotype (OR=4.59, 95% CI=1.46-14.48, p=0.0136). However, the MMP7 rs11568818 heterozygous variant AG was not associated with endometriosis risk (OR=1.57, 95% CI=0.97-2.53, p=0.0854). The frequency of than variant allele G of MMP7 rs11568818 was 12.7% in the endometriosis group, significantly higher than the 7.2% observed in the control group (OR=1.90, 95% CI=1.27-2.82, p=0.0021).
CONCLUSION
MMP7 rs11568818 GG genotype was found to be a novel marker for endometriosis risk in Taiwanese.
Topics: Humans; Endometriosis; Female; Matrix Metalloproteinase 7; Taiwan; Genetic Predisposition to Disease; Adult; Case-Control Studies; Polymorphism, Single Nucleotide; Genotype; Risk Factors; Promoter Regions, Genetic; Gene Frequency
PubMed: 38925847
DOI: 10.21873/anticanres.17118