NLRP3 Inflammasome in the Pathogenesis of Miscarriages.

Despite significant advances in prenatal medicine, spontaneous miscarriage remains one of the most common and serious pregnancy complications, affecting an increasing number of women. Since many aspects of the pathogenesis of spontaneous miscarriage remain unexplained, the aim of this study has been to assess the involvement of the NLRP3 inflammasome as a potential causative factor. The concentrations of NLRP3, IL-1ß, IL-18, and cytochrome C in the serum of patients after miscarriage were measured by means of the immunoenzymatic method. In the placental tissue, the expression of NLRP3, IL-1ß, IL-18, and Caspase-1 as well as that of the classical apoptosis biomarkers Fas, FasL, Bcl-2, and Ca was evaluated by means of immunohistochemistry techniques. Additionally, in whole blood, the concentrations of elements crucial for pregnancy progression, such as Ca, K, Mg, and Na, were examined by means of the ICP-OES method. Significantly higher concentrations of NLRP3 and IL-18 were demonstrated in the serum of patients with miscarriage as compared to the control group. In the placental tissue samples, a higher expression of IL-1ß, IL-18, and Caspase-1 proteins was noted in women who had experienced miscarriage as compared to the control group. At the same time, a significantly lower expression of FasL and Bcl-2 proteins as well as Ca deposits was observed in women after miscarriage as compared to those with a normal pregnancy outcome. Significantly lower concentrations of Ca and K were recorded in the blood of patients with spontaneous miscarriage as compared to pregnant women. The analysis of the results x indicated a greater involvement of the inflammasome in women with spontaneous miscarriage associated with oxidative-antioxidative imbalance than in the case of miscarriage related to NET formation. Our research has provided evidence for the involvement of the inflammasome in the process of spontaneous miscarriage and identifies a new direction for diagnostics that includes NLRP3 as a preventive element in prenatal care, particularly in light of the steadily declining number of pregnancies and the increasing number of reproductive failures.

Enhanced Pain Relief and Function Improvement in Children with Osgood-Schlatter Disease: Leukocyte-Rich Platelet-Rich Plasma (LR-PRP) as a Complementary Treatment to Standard Conservative Therapy.

BACKGROUND Osgood-Schlatter disease (OSD) causes pain and loss of function of the knee in growing children. This study aimed to evaluate pain and function of the knee joint in 152 growing children with chronic OSD before and after treatment with LR-PRP when used with standard conservative treatment. MATERIAL AND METHODS Treatment efficacy was evaluated using the VAS, Tegner, Lyshom, and KOOS scales. Patient satisfaction, post-surgery athletic performance, and X-ray assessment were also used to determine the success of the procedure. RESULTS We found that 75% of the subjects were satisfied with the results of the treatment, and 72% of the subjects returned to full physical activity. The analysis showed a significant decrease in the median VAS score after treatment compared to the pre-treatment score (P<0.05), and an increase in the median scores of the Tegner, Lysholm, and KOOS scales compared to the pre-treatment score (P<0.05; P<0.05; P<0.05, respectively). The results showed that the shorter the duration of the disease, the better the treatment results were received. Return to activity and patient satisfaction were highest in the study group previously rehabilitated. CONCLUSIONS LR-PRP injection of the tibial tuberosity in patients with chronic OSD with open growth cartilage is an effective and uncomplicated method. We did not observe any adverse effects, which suggests the relatively high safety of the procedure. The use of PRP in the earlier phase of the disease and additional rehabilitation before treatment significantly increases the effectiveness of treatment.

Importance of Metalloproteinase Enzyme Group in Selected Skeletal System Diseases.

Bone tissue is a dynamic structure that is involved in maintaining the homeostasis of the body due to its multidirectional functions, such as its protective, endocrine, or immunological role. Specialized cells and the extracellular matrix (ECM) are responsible for the remodeling of specific bone structures, which alters the biomechanical properties of the tissue. Imbalances in bone-forming elements lead to the formation and progression of bone diseases. The most important family of enzymes responsible for bone ECM remodeling are matrix metalloproteinases (MMPs)-enzymes physiologically present in the body's tissues and cells. The activity of MMPs is maintained in a state of balance; disruption of their activity is associated with the progression of many groups of diseases, including those of the skeletal system. This review summarizes the current understanding of the role of MMPs in bone physiology and the pathophysiology of bone tissue and describes their role in specific skeletal disorders. Additionally, this work collects data on the potential of MMPs as bio-markers for specific skeletal diseases.

CXC ELR-Positive Chemokines as Diagnostic and Prognostic Markers for Breast Cancer Patients.

As the most common type of malignant lesison, breast cancer is a leading challenge for clinicians. Currently, diagnosis is based on self-examination and imaging studies that require confirmation by tissue biopsy. However, there are no easily accessible diagnostic tools that can serve as diagnostic and prognostic markers for breast cancer patients. One of the possible candidates for such markers is a group of chemokines that are closely implicated in each stage of tumorigenesis. Many researchers have noted the potential of this molecule group to become tumor markers and have tried to establish their clinical utility. In this work, we summarize the results obtained by scientists on the usefulness of the ELR-positive CXC group of chemokines in ancillary diagnosis of breast cancer.

CXCL12 and CXCR4 as Potential Early Biomarkers for Luminal A and Luminal B Subtypes of Breast Cancer.

Purpose: Breast cancer is the most common type of malignancy in women. Factors that increase the risk of occurrence include chronic inflammation, with chemokines as its mediators. Therefore, the purpose of the present study was to determine the diagnostic utility of CXCL12 and CXCR4 as modern tumor markers in patients with early-stage luminal A and luminal B subtype of breast cancer and also to compare the results with the routinely used marker - CA 15-3. Patients and Methods: The study included 100 patients with early breast cancer of luminal A and B subtypes, 50 women with benign breast lesion and 50 healthy women. The levels of CXCL12 and CXCR4 concentrations were determined by enzyme-linked immunosorbent assay (ELISA), comparative marker CA 15-3 - by electrochemiluminescence method (ECLIA). Results: Concentrations of CXCL12 were significantly lower, while CXCR4 and CA 15-3 - significantly higher among patients with early-stage breast cancer than healthy women. CXCL12 also showed lower concentrations among fibroadenoma patients in comparison to healthy women, while CXCR4 - lower concentrations among fibroadenoma patients than cancer group. CXCL12 showed significantly higher values of sensitivity (79%), specificity (82%), positive predictive value (89.72%), negative predictive value (80%), diagnostic accuracy (80%) and diagnostic power (AUC = 0.8196) in the whole breast cancer group compared to the CA 15-3 marker (58%; 72%; 80.56%; 46.15%, 62.67%, 0.6434, resp.). Analysis of combined parameters resulted in increased sensitivity, negative predictive value and power of the test with a slight decrease in positive predictive value and a more significant decrease in specificity, reaching the best values for the three-parameter test CXCL12+CXCR4+CA15-3 (96%; 85.71%; AUC = 0.8812; 78.69%; 48%, resp.). Conclusion: The results indicate the preliminary usefulness of CXCL12 and CXCR4 as early biomarkers in the diagnosis of breast cancer, especially in the combined panel with CA 15-3.

Plasma Levels of Metalloproteinase 3 (MMP-3) and Metalloproteinase 7 (MMP-7) as New Candidates for Tumor Biomarkers in Diagnostic of Breast Cancer Patients.

Matrix metalloproteinases (MMPs) are a group of enzymes that mediate both physiological and pathological processes such as carcinogenesis. The role of matrix metalloproteinase-3 (MMP-3) and (MMP-7) in the pathogenesis of breast cancer (BC) has been demonstrated, suggesting that they may be considered as potential markers of this condition. The aim of this study was to assess plasma concentrations and diagnostic utility of MMP-3 and MMP-7 in 100 patients with early-stage breast cancer with Luminal A subtype or Luminal B HER-negative subtype, before and after surgical treatment, and in the following control groups: patients with a benign tumor (fibroadenoma) and healthy subjects. The concentrations of MMP-3 and MMP-7 were referenced to the levels of the widely recognized marker for BC diagnosis CA 15-3. MMP-3 and MMP-7 was measured by ELISA method and CA 15-3 by CMIA. Plasma levels of MMP-7 were significantly higher in Luminal A and Luminal B HER2-negative subtype breast cancer patients as compared to the healthy group. MMP-7 demonstrated comparable but mostly higher to CA 15-3 or MMP-3 values of diagnostic sensitivity, specificity, positive and negative predictive values and AUC (0.6888 for Luminal A subtype; 0.7612 for Luminal B HER2-negative; 0.7250 for BC total group, respectively) in the groups tested. The combined use of the tested parameters resulted in a further increase in diagnostic criteria and AUC. These results suggest the usefulness of combining MMP-7 with CA 15-3 in the diagnostics of breast cancer, especially in Luminal B HER2-negative subtypes patients, as a new candidate for tumor markers.

Utility of Matrix Metalloproteinases in the Diagnosis, Monitoring and Prognosis of Ovarian Cancer Patients.

Ovarian cancer is one of the most common gynecologic malignancies. It is characterized by a high mortality rate, which is mainly due to the asymptomatic course of the disease. In light of the high mortality rate and increasing morbidity, new diagnostic methods are being explored to enable earlier detection, better monitoring, and improved prognosis. Such diagnostic methods include the assessment of tumor markers in various biological samples. Among the markers currently being investigated, extracellular matrix metalloproteinases (MMPs) are of particular interest. The objective of this article was to compile the existing knowledge of MMPs in ovarian cancer patients and to describe their potential diagnostic utility. Additionally, this article provides an overview of the symptoms, complications, and risk factors associated with ovarian cancer and the role of MMPs in physiology and pathology. Preliminary results indicate that tissue expression and blood and body fluid levels of MMPs may be different in ovarian cancer patients than in healthy women. The expression and concentration of individual MMPs have been shown to be correlated with cancer stage and disease severity. In addition, the preliminary value of some of these enzymes in predicting prognosis is discussed. However, as the amount of data is limited, more studies are needed to fully evaluate the potential function of individual MMPs in ovarian cancer patients. Based on the knowledge gathered for this article, it seems that MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, are tentatively the most useful. A thorough evaluation of their utility as modern biomarkers in ovarian cancer requires further investigation.

Plasma Levels of CXC Motif Chemokine 1 (CXCL1) and Chemokine 8 (CXCL8) as Diagnostic Biomarkers in Luminal A and B Breast Cancer.

Chemokines are involved in the regulation of immune balance and in triggering an immune response. CXCL1 and CXCL8 belong to the ELR-motif-containing group of CXC chemokines, which, in breast cancer (BC), stimulate angiogenesis and increase migration and invasiveness of tumor cells. The aim of this study was to evaluate CXCL1, CXCL8 and comparative marker CA 15-3 plasma concentrations in BC patients with luminal subtypes A and B. The study group consisted of 100 patients with BC, and the control group of 50 subjects with benign breast lesions and 50 healthy women. Chemokines concentrations were determined by ELISA method; CA15-3-by CMIA. Concentrations of CXCL8 and CA15-3 were significantly higher in BC total group and luminal B (for CA15-3 also in luminal A) subtype of BC than in healthy controls and subjects with benign lesions. In the total BC group, the highest SE, PPV and NPV were observed for CXCL8 (70%, 77.78%, 50%, resp.). A combined analysis of tested chemokines with CA 15-3 increased SE and NPV values (96%, 69.23%, resp.). The diagnostic power of the test (measured by area under ROC curve (AUC)) showed the highest value for CXCL8 in the total BC group (0.6410), luminal A (0.6120) and B subgroup of BC (0.6700). For the combined parameter, the AUC was increasing and reached the highest value for CXCL1 + CXCL8 + CA15-3 combination (0.7024). In light of these results, we suggest that CXCL8 could be used as an additional diagnostic marker that would positively influence the diagnostic utility of CA 15-3, especially in luminal B subtype of BC.

The diagnostic potential of novel biomarkers of hypertension in men.

Introduction: The present study aimed to evaluate the diagnostic usefulness of selected novel parameters as biomarkers of hypertension: miR-145-5p, miR-1-3p, miR-423-5p, PCSK9, MyBPC3, NOX1, and CYBb, and NCF2, DNase 1, anti-MPO and anti-PR3 antibodies. Methods: We present the data of men with normal blood pressure, diagnosed hypertension, confirmed hypertension, and hypertension and coexisting coronary artery disease. Results: Elevated levels of miR-145-5p, miR-1-3p, and miR-423-5p and high levels of PCSK9, MyBPC3, and DNase 1 were observed in all groups of hypertensive men. We showed decreased levels of NOX1 and CYBb, and an elevated level of NCF2. Conclusions: PCSK9 shows the greatest potential as an early biomarker of screening-detected hypertension.

Plasma Levels and Diagnostic Utility of VEGF in a Three-Year Follow-Up of Patients with Breast Cancer.

Breast cancer is the most common malignancy in women globally. The increasing worldwide incidence of this type of cancer illustrates the challenge it represents for healthcare providers. Therefore, new tumor markers are constantly being sought. The aim of this study was to assess plasma concentrations and the diagnostic power of VEGF in 100 patients with early-stage breast cancer, both before and after surgical treatment and during a three-year follow-up. The control groups included 50 subjects with benign breast tumors (fibroadenoma) and 50 healthy women. The VEGF concentration was determined using enzyme-linked immunosorbent assay (ELISA) and the CA 15-3 concentration was determined by chemiluminescent microparticle immunoassay (CMIA). We observed significantly higher preoperative plasma concentrations of VEGF and CA 15-3 in patients with breast cancer. VEGF, similar to CA 15-3, demonstrated high diagnostic utility in the assessment of the long-term efficacy of surgical removal of the tumor. Determinations of VEGF had the highest diagnostic usefulness in the detection of breast cancer recurrence (SE 40%, SP 92%, PPV 67%, NPV 79%). Additionally, the highest values of SE, NPV and AUC were observed during the combined analysis with CA 15-3 (60%; 84%; 0.7074, respectively). Our study suggests a promising diagnostic utility of VEGF in the early stages of breast cancer and in the evaluation of the efficacy of the surgical treatment of breast cancer as well as the detection of breast cancer recurrence, particularly in a combined analysis with CA 15-3 as a new diagnostic panel.

Gut Microbiome in Chronic Coronary Syndrome Patients.

Despite knowledge of classical coronary artery disease (CAD) risk factors, the morbidity and mortality associated with this disease remain high. Therefore, new factors that may affect the development of CAD, such as the gut microbiome, are extensively investigated. This study aimed to evaluate gut microbiome composition in CAD patients in relation to the control group. We examined 169 CAD patients and 166 people in the control group, without CAD, matched in terms of age and sex to the study group. Both populations underwent a detailed health assessment. The microbiome analysis was based on the V3-V4 region of the 16S rRNA gene (NGS method). Among 4074 identified taxonomic units in the whole population, 1070 differed between study groups. The most common bacterial types were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Furthermore, a higher Firmicutes/Bacteroidetes ratio in the CAD group compared with the control was demonstrated. Firmicutes/Bacteroidetes ratio, independent of age, sex, CAD status, LDL cholesterol concentration, and statins treatment, was related to altered phosphatidylcholine concentrations obtained in targeted metabolomics. Altered alpha-biodiversity (Kruskal-Wallis test, p = 0.001) and beta-biodiversity (Bray-Curtis metric, p < 0.001) in the CAD group were observed. Moreover, a predicted functional analysis revealed some taxonomic units, metabolic pathways, and proteins that might be characteristic of the CAD patients' microbiome, such as increased expressions of 6-phospho-ß-glucosidase and protein-N(pi)-phosphohistidine-sugar phosphotransferase and decreased expressions of DNA topoisomerase, oxaloacetate decarboxylase, and 6-beta-glucosidase. In summary, CAD is associated with altered gut microbiome composition and function.