Zinc, Copper, and Iron in Selected Skin Diseases.

Trace elements are essential for maintaining the body's homeostasis, and their special role has been demonstrated in skin physiology. Among the most important trace elements are zinc, copper, and iron. A deficiency or excess of trace elements can be associated with an increased risk of skin diseases, so increasing their supplementation or limiting intake can be helpful in dermatological treatment. In addition, determinations of their levels in various types of biological material can be useful as additional tests in dermatological treatment. This paper describes the role of these elements in skin physiology and summarizes data on zinc, copper, and iron in the course of selected, following skin diseases: psoriasis, pemphigus vulgaris, atopic dermatitis, acne vulgaris and seborrheic dermatitis. In addition, this work identifies the potential of trace elements as auxiliary tests in dermatology. According to preliminary studies, abnormal levels of zinc, copper, and iron are observed in many skin diseases and their determinations in serum or hair can be used as auxiliary and prognostic tests in the course of various dermatoses. However, since data for some conditions are conflicting, clearly defining the potential of trace elements as auxiliary tests or elements requiring restriction/supplement requires further research.

Importance of Metalloproteinase 8 (MMP-8) in the Diagnosis of Periodontitis.

Periodontitis is a complex condition. Left untreated, it leads to tooth loss and the need for prosthetic treatment. The incidence of periodontitis is steadily increasing, so new methods are being sought to aid in the diagnosis of the disease. Among the methods postulated is the determination of concentrations of bioactive compounds which include extracellular matrix metalloproteinases (MMPs). These enzymes are present in various structural elements of the stomatognathic system. The most promising enzyme of this group appears to be metalloproteinase 8 (MMP-8). MMP-8 assays are performed in gingival fluid or saliva, and MMP-8 levels have been shown to be higher in patients with periodontitis compared to healthy subjects and correlated with some clinical parameters of the condition and the severity of the disease. In addition, the preliminary usefulness of this enzyme in evaluating the effectiveness of periodontal treatment and doxycycline therapy has been demonstrated. Determination of the active form of MMP-8 (aMMP-8) in oral rinse fluid using off-the-shelf assays shows the highest potential. Despite reports about aMMP-8 and promising data on the role of MMP-8 in periodontal diagnosis, a clear determination of the usefulness of this enzyme requires further research.

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.

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.

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.

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 potential of cannabinoids and inhibitors of endocannabinoid degradation in respiratory diseases.

The global incidence of respiratory diseases and complications is increasing. Therefore, new methods of treatment, as well as prevention, need to be investigated. A group of compounds that should be considered for use in respiratory diseases is cannabinoids. There are three groups of cannabinoids - plant-derived phytocannabinoids, synthetic cannabinoids, and endogenous endocannabinoids including the enzymes responsible for their synthesis and degradation. All cannabinoids exert their biological effects through either type 1 cannabinoid receptors (CB1) and/or type 2 cannabinoid receptors (CB2). In numerous studies (in vitro and in vivo), cannabinoids and inhibitors of endocannabinoid degradation have shown beneficial anti-inflammatory, antioxidant, anti-cancer, and anti-fibrotic properties. Although in the respiratory system, most of the studies have focused on the positive properties of cannabinoids and inhibitors of endocannabinoid degradation. There are few research reports discussing the negative impact of these compounds. This review summarizes the properties and mechanisms of action of cannabinoids and inhibitors of endocannabinoid degradation in various models of respiratory diseases. A short description of the effects selected cannabinoids have on the human respiratory system and their possible use in the fight against COVID-19 is also presented. Additionally, a brief summary is provided of cannabinoid receptors properties and their expression in the respiratory system and cells of the immune system.

Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to coronavirus disease 2019 (COVID-19) which, in turn, may be associated with multiple organ dysfunction. In this review, we present advantages and disadvantages of cannabidiol (CBD), a non-intoxicating phytocannabinoid from the cannabis plant, as a potential agent for the treatment of COVID-19. CBD has been shown to downregulate proteins responsible for viral entry and to inhibit SARS-CoV-2 replication. Preclinical studies have demonstrated its effectiveness against diseases of the respiratory system as well as its cardioprotective, nephroprotective, hepatoprotective, neuroprotective and anti-convulsant properties, that is, effects that may be beneficial for COVID-19. Only the latter two properties have been demonstrated in clinical studies, which also revealed anxiolytic and antinociceptive effects of CBD (given alone or together with Δ9-tetrahydrocannabinol), which may be important for an adjuvant treatment to improve the quality of life in patients with COVID-19 and to limit post-traumatic stress symptoms. However, one should be aware of side effects of CBD (which are rarely serious), drug interactions (also extending to drugs acting against COVID-19) and the proper route of its administration (vaping may be dangerous). Clearly, further clinical studies are necessary to prove the suitability of CBD for the treatment of COVID-19.

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats.

Cannabidiol (CBD) is known for its vasorelaxant (including in the human pulmonary artery), anti-proliferative and anti-inflammatory properties. The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on monocrotaline (MCT)-induced pulmonary hypertension (PH) rats. PH was connected with elevation of right ventricular systolic pressure; right ventricle hypertrophy; lung edema; pulmonary artery remodeling; enhancement of the vasoconstrictor and decreasing vasodilatory responses; increases in plasma concentrations of tissue plasminogen activator, plasminogen activator inhibitor type 1 and leukocyte count; and a decrease in blood oxygen saturation. CBD improved all abovementioned changes induced by PH except right ventricle hypertrophy and lung edema. In addition, CBD increased lung levels of some endocannabinoids (anandamide, N-arachidonoyl glycine, linolenoyl ethanolamide, palmitoleoyl ethanolamide and eicosapentaenoyl ethanolamide but not 2-arachidonoylglycerol). CBD did not affect the cardiopulmonary system of control rats or other parameters of blood morphology in PH. Our data suggest that CBD ameliorates MCT-induced PH in rats by improving endothelial efficiency and function, normalization of hemostatic alterations and reduction of enhanced leukocyte count determined in PH. In conclusion, CBD may be a safe, promising therapeutic or adjuvant therapy agent for the treatment of human pulmonary artery hypertension.

The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease.

Cannabidiol (CBD) is a non-intoxicating and generally well-tolerated constituent of cannabis which exhibits potential beneficial properties in a wide range of diseases, including cardiovascular disorders. Due to its complex mechanism of action, CBD may affect the cardiovascular system in different ways. Thus, we reviewed the influence of CBD on this system in health and disease to determine the potential risk of cardiovascular side effects during CBD use for medical and wellness purposes and to elucidate its therapeutic potential in cardiovascular diseases. Administration of CBD to healthy volunteers or animals usually does not markedly affect hemodynamic parameters. Although CBD has been found to exhibit vasodilatory and antioxidant properties in hypertension, it has not affected blood pressure in hypertensive animals. Hypotensive action of CBD has been mainly revealed under stress conditions. Many positive effects of CBD have been observed in experimental models of heart diseases (myocardial infarction, cardiomyopathy, myocarditis), stroke, neonatal hypoxic ischemic encephalopathy, sepsis-related encephalitis, cardiovascular complications of diabetes, and ischemia/reperfusion injures of liver and kidneys. In these pathological conditions CBD decreased organ damage and dysfunction, oxidative and nitrative stress, inflammatory processes and apoptosis, among others. Nevertheless, further clinical research is needed to recommend the use of CBD in the treatment of cardiovascular diseases.