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Sebastian Majewski,1 Damian Tworek,2 Karolina Szewczyk,1 Justyna Kiszałkiewicz,3 Zofia Kurmanowska,1 Ewa Brzeziańska-Lasota,3 Hanna Jerczyńska,4 Adam Antczak,2 Wojciech Jerzy Piotrowski,1 Paweł Górski11Department of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland; 2Department of General and Oncological Pulmonology, Medical University of Lodz, Lodz, Poland; 3Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland; 4Central Scientific Laboratory (CoreLab), Medical University of Lodz, Lodz, PolandBackground: Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown.Objectives: To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD.Methods: Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated.Results: Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P

The PPARD gene codes protein that belongs to the peroxisome proliferator-activated receptor (PPAR) family engaged in a variety of biological processes, including lipid metabolism in muscle cells. In this study, we assess the relationship between PPARD gene expression lipid metabolism parameters and the variation of the PPARD gene expression before (T1) and after 12 hours of training (T2) sessions in a group of football players. Peripheral blood lymphocytes were obtained from 22 football players (17.5±0.7 years, 178±0.7 cm, 68.05±9.18 kg). The PPARD gene expression, analyzed by quantitative polymerase chain reaction (qPCR), was significantly higher after T2 (p = 0.0006). Moreover, at the end of the training cycle, there was a significant decrease in relative fat tissue (FAT) (%) (p = 0.01) and absolute FAT (kg) (p = 0.01). A negative correlation was observed between absolute FAT (kg) and PPARD gene expression level in T2 (p = 0.03). The levels of cholesterol and triglyceride (TG) fractions were not significantly different (p >0.05) before and after training. No significant relationship between PPARD expression and cholesterol or TG levels was found. We found that physical training affects PPARD expression. Moreover, the negative correlation between PPARD expression and absolute FAT (kg) level may be indicative of the contribution of PPARD in metabolic adaptation to increased lipid uptake that can be used to control the body composition of athletes.

Ultra-marathon (UM) running is an extreme endurance exercise. However, the mechanisms triggered with its practice remain unclear. While it is documented that strenuous physical activity activates immune responses and vitamin D plays a role in immune system suppression, data on the relationship between vitamin D status and cytokine profile in athletic populations are limited. To analyse the relative mRNA expression levels of selected pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, TNF-α), COX-2, vitamin D receptor and abundance of selected inflammatory microRNAs (Hsa-miR-21, -miR-146a, -miR-150, -miR-155, -miR-222, -miR-223) before and after a 100 km race in amateur runners in the presence or absence of vitamin D supplementation. Twenty runners aged 36–40years were divided into two groups: with and without vitamin D3 supplementation (10,000units daily). Blood samples were collected before and 12 h after the UM. The mRNA expression levels of selected cytokines, COX-2 and VDR in peripheral blood and abundance of serum exosomal miRNAs were investigated using q-RT-PCR. After UM, the significant up-regulation of TNF-α and hsa-miR-155 and down-regulation of IL-1β were observed in the group with vitamin D supplementation. In its absence, hsa-miR-155 and -miR-223 were significantly up-regulated. Additionally, a reverse correlation was observed between IL-6 expression level and abundance of hsa-miR-155 and -miR-223 in both groups. No statistical differences were noted when the other miRNAs and genes were examined in the groups and at the time points. The UM-induced mRNA expression pattern of pro-inflammatory cytokines could be influenced by vitamin D supplementation and/or miRNA. [ABSTRACT FROM AUTHOR]

The infectious agents may be the etiological factor of up to 15–20% of cancers. In stomach cancer, attention is paid to Helicobacter pylori and Epstein-Barr virus, both of which cause gastritis and can lead to tumor development. In co-infection, the inflammatory process is much more intense. We assessed the seroprevalence towards H. pylori and EBV in 32 patients with diagnosed gastric cancer. H. pylori antibodies were found in 69% patients, and anti-EBV – in all of them. The study confirmed that co-infection of H. pylori and EBV seems to be important in etiopathology of gastric cancer.

Introduction: The topic of increased intestinal permeability is associated with disruption of the intestinal barrier, leading to the "leaky gut" syndrome. Depressive disorders often coexist with abdominal obesity, metabolic syndrome, or its components and complications. Intestinal permeability has been proven to relate to all of the above., Methods: In this cross-sectional study, we aimed to assess the "leaky gut" blood biomarker - intestinal fatty acid-binding protein (I-FABP) - in 114 adult patients diagnosed with depressive disorders depending on abdominal obesity comorbidity, depression, anxiety, and stress level, or antidepressant use. The corrected p-value was set at 0.02. We analyzed patients' mental state, diet, anthropometric parameters, metabolic laboratory markers and I-FABP., Results: There was no difference in circulating I-FABP levels between obese and non-obese patients with depressive disorders (p = 0.648). Similarly, I-FABP levels were not different in patients with different emotional symptoms severity (p = 0.829 for self-assessed depression, p = 0.164 for anxiety, and p = 0.543 for stress). But, I-FABP levels differed significantly between patients treated and not treated with antidepressants (p = 0.011). In general linear model analysis treatment with antidepressants, anxiety severity level, their interaction, along with smoking status, drinks intake, and using dietary supplements were shown to significantly explain I-FABP variance (p < 0.001, R 2 adj  = 0.261)., Conclusions: Comorbid obesity did not increase intestinal permeability circulating marker, I-FABP, in the population of patients with depressive disorders. Treatment with antidepressants may be connected to higher I-FABP levels. Using dietary supplements, drinks intake, smoking status, or anxiety level may serve as explanatory factors., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Many types of cancer have infectious origins. Gastric cancer patients can demonstrate high seroprevalence of Helicobacter pylori (H. pylori). The aim of the present study was to assess the expression of SMOX gene in the group of Polish patients with gastric cancer. SMOX is believed to promote H. pylori-induced carcinogenesis via inflammation, DNA damage and activation of β-catenin signaling. We also assessed the mRNA expression of selected pro-inflammatory cytokines, i.e. IL-2, IFN-γ, TNF-α, and antimicrobial peptide, cathelicidin., Materials/methods: The study material consisted of gastric tissue samples collected during total gastrectomy from three different places in stomach: from primary tumor, 3 ​cm away from the primary lesion, and from the wall opposite to the primary tumor. After RNA isolation, qPCR reactions were performed for the relevant genes., Results: The obtained results confirmed an increased level of SMOX expression in gastric cancer patients with the history of H. pylori infection. And, as far as we know, this is the first study on SMOX gene expression conducted on tissue taken from a patient, not on a cell line. The levels of pro-inflammatory cytokines, i.e. IL-2, IFN-γ, TNF-α, were also increased, thus indicating their contribution to the specific inflammatory microenvironment of the tumor. Interestingly, the levels of CAMP, encoding antimicrobial peptide, were reduced in all tissue types., Conclusions: The findings confirm that SMOX plays a role in gastric carcinogenesis. However, further research is needed on the role of inflammatory and other factors involved in this process to identify targets for cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In lung cancer patients, two complementary abnormalities were found that can cause disruption of the mitochondrial network: increased fusion and impaired fission, manifested by reduced levels of FIS1, a mitochondrial division regulator, and increased expression of MFN1, a mitochondrial fusion mediator. Immunoexpression studies of MFN1 and FIS1 proteins were performed in serum samples obtained from 47 patients with non-small cell lung cancer (NSCLC) and 21 controls. In the NSCLC patients, the immunoexpression of the MFN1 protein was significantly higher, and the FIS1 protein level was significantly lower than in the control group ( p < 0.01; p < 0.001; UMW test). Patients with early, operable lung cancer had significantly lower levels of MFN1 immunoexpression compared to patients with advanced, metastatic lung cancer ( p < 0.05; UMW test). This suggests that early stages of the disease are characterized by greater fragmentation of damaged mitochondria and apoptosis. In contrast, lower FIS1 protein levels were associated with a worse prognosis. Increased mitochondrial fusion in the blood of lung cancer patients may suggest an increase in protective and repair mechanisms. This opens up questions about why these mechanisms fail in the context of existing advanced cancer disease and is a starting point for further research into why protective mechanisms fail in lung cancer patients.

The increasing prevalence of fungal strains showing acquired resistance and multidrug resistance is an increasing therapeutic problem, especially in patients with a severely weakened immune system and undergoing chemotherapy. What is also extremely disturbing is the similarity of the resistance mechanisms of fungal cells and other eukaryotic cells, including human cells, which may contribute to the development of cross-resistance in fungi in response to substances used in e.g. anticancer treatment. An example of such a drug is methotrexate, which is pumped out of eukaryotic cells by ABC transmembrane transporters - in fungi, used to remove azoles from fungal cells. For this reason, the aim of the study was to analyze the expression levels of genes: ERG11, MDR1 and CDR1, potentially responsible for the occurrence of cross-resistance in Candida albicans and Candida parapsilosis as a result of fungal exposure to methotrexate (MTX). In vitro exposure of C. albicans and C. parapsilosis strains to methotrexate showed a high increase in resistance to fluconazole and a partial increase in resistance to voriconazole. Analysis of the expression of resistance genes showed varied responses of the tested strains depending on the species. In the case of C. albicans, an increase in the expression of the MDR1 gene was observed, and a decrease in ERG11 and CDR1. However, for C. parapsilosis there was an increase in the expression of the CDR1 gene and a decrease in ERG11 and MDR1. We noted the relationship between the level of resistance to voriconazole and the level of ERG11 gene expression in C. albicans. This indicates that this type of relationship is different for each species. Our research confirms that the mechanisms by which fungi acquire resistance and develop cross-resistance are highly complex and most likely involve several pathways simultaneously. The emergence of multidrug resistance may be related to the possibility of developing tolerance to antimycotics by fungi., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Interactions between C. albicans and the microbiota play an important role in maintaining the balance between commensal and pathogenic organisms. Although the exact role of bacteria in reducing the pathogenicity of yeast remains poorly understood, a few examples have been documented so far: probiotics administration effectively reduces the formation of biofilm and bacterial metabolites inhibit the formation of hyphae. The aim of the study was to analyze C. albicans virulence levels based on the changes in the morphological structure and enzymatic profile in experimental cultures mixed with Escherichia coli. Viable cell abundance, cell pleomorphism and enzymatic profile were analyzed in single and mixed cultures (C. albicans + E. coli). The microscope analysis showed a large decrease in the number of viable C. albicans cells in mixed cultures with E. coli from 485.3±132.1 immediately after the establishment of the culture to 238.1±71.2 after an hour of incubation and 24.4±5.4 after 24 h. The length of C. albicans cells differed significantly between the single-species cultures and the mixed cultures for 24 h. Our present findings indicate a significant reduction in the secretion of several enzymes by fungi following contact with E. coli, including acid phosphatase, N-acetyl-β-glucosaminidase, naphthol-AS-BI-phosphohydrolase and leucine arylamidase. The interactions between fungi and bacteria appear to be extremely complex. On the one hand, during C. albicans with E. coli co-incubation, the bacteria stimulated the elongation of yeast cells, leading to the formation of a filamentous form; however, the number of yeast cells and their enzymatic activity decreased significantly. Therefore, it can be concluded that while E. coli stimulates some pathogenic properties, e.g. cell elongation, it also inhibits other virulence features, e.g. enzymatic activity of C. albicans., Competing Interests: Declaration of Competing Interest All authors have seen and approved the final version of the manuscript being submitted. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No funding was received for this work., (Copyright © 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Thyroid carcinoma is the primary endocrine malignancy worldwide. The preoperative examination of thyroid tissue lesion is often unclear. Approximately 25% of thyroid cancers cannot be diagnosed definitively without post-surgery histopathological examination. The assessment of diagnostic and differential markers of thyroid cancers is needed to improve preoperative diagnosis and reduce unnecessary treatments. Here, we assessed the expression of RASSF1A , DIRAS3 , and AKAP9 genes, and the presence of BRAF V600E point mutation in benign and malignant thyroid lesions in a Polish cohort (120 patients). We have also performed a comparative analysis of gene expression using data obtained from the Gene Expression Omnibus (GEO) database (307 samples). The expression of RASSF1A and DIRAS3 was decreased, whereas AKAP9 's was increased in pathologically changed thyroid compared with normal thyroid tissue, and significantly correlated with e.g., histopathological type of lesion papillary thyroid cancer (PTC) vs follicular thyroid cancer (FTC), patient's age, tumour stage, or its encapsulation. The receiver operating characteristic (ROC) analysis for the more aggressive FTC subtype differential marker suggests value in estimating RASSF1A and AKAP9 expression, with their area under curve (AUC), specificity, and sensitivity at 0.743 (95% CI: 0.548-0.938), 82.2%, and 66.7%; for RASSF1A , and 0.848 (95% CI: 0.698-0.998), 54.8%, and 100%, for AKAP9 . Our research gives new insight into the basis of the aggressiveness and progression of thyroid cancers, and provides information on potential differential markers that may improve preoperative diagnosis.

The importance of microbiota in developing and treating diseases, including lung cancer (LC), is becoming increasingly recognized. Studies have shown differences in microorganism populations in the upper and lower respiratory tracts of patients with lung cancer compared to healthy individuals, indicating a link between dysbiosis and lung cancer. However, it is not only important to identify "which bacteria are present" but also to understand "how" they affect lung carcinogenesis. The interactions between the host and lung microbiota are complex, and our knowledge of this relationship is limited. This review presents research findings on the bacterial lung microbiota and discusses the mechanisms by which lung-dwelling microorganisms may directly or indirectly contribute to the development of lung cancer. These mechanisms include influences on the host immune system regulation and the local immune microenvironment, the regulation of oncogenic signaling pathways in epithelial cells (causing cell cycle disorders, mutagenesis, and DNA damage), and lastly, the MAMPs-mediated path involving the effects of bacteriocins, TLRs signaling induction, and TNF release. A better understanding of lung microbiota's role in lung tumor pathology could lead to identifying new diagnostic and therapeutic biomarkers and developing personalized therapeutic management for lung cancer patients.

A thorough study of the exosomal proteomic cargo may enable the identification of proteins that play an important role in cancer development. The aim of this study was to compare the protein profiles of the serum exosomes derived from non-small lung cancer (NSCLC) patients and healthy volunteers (control) using the high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS) method to identify potentially new diagnostic and/or prognostic protein biomarkers. Proteins exclusively identified in NSCLC and control groups were analyzed using several bioinformatic tools and platforms (FunRich, Vesiclepedia, STRING, and TIMER2.0) to find key protein hubs involved in NSCLC progression and the acquisition of metastatic potential. This analysis revealed 150 NSCLC proteins, which are significantly involved in osmoregulation, cell-cell adhesion, cell motility, and differentiation. Among them, 3 proteins: Interleukin-34 (IL-34), HLA class II histocompatibility antigen, DM alpha chain (HLA-DMA), and HLA class II histocompatibility antigen, DO beta chain (HLA-DOB) were shown to be significantly involved in the cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) infiltration processes. Additionally, detected proteins were analyzed according to the presence of lymph node metastasis, showing that differences in frequency of detection of protein FAM166B, killer cell immunoglobulin-like receptor 2DL1, and olfactory receptor 52R1 correlate with the N feature according to the TNM Classification of Malignant Tumors. These results prove their involvement in NSCLC lymph node spread and metastasis. However, this study requires further investigation.

The C-C motif ligand 20 (CCL20) is a chemokine that specifically binds to the chemokine receptor 6 (CCR6) and the CCL20/CCR6 axis has been implicated in the non-small lung cancer (NSCLC) development and progression. Its expression is regulated by mutual interactions of non-coding RNAs (ncRNAs). This goals of presented study was to evaluate the expression level of CCR6/CCL20 mRNA in NSCLC tissue comparative to selected ncRNAs: miR-150, linc00673. The expression level of the studied ncRNAs was also assessed in serum extracellular vesicles (EVs). Thirty patients (n = 30) were enrolled as the study cohort. Total RNA was isolated from tumor tissue, adjacent macroscopically unchanged tissue and serum EVs. The expression level of studied genes and ncRNAs were estimated based on the qPCR method. Higher expression level of CCL20 mRNA but lower expression level of CCR6 mRNA were observed in tumor in comparison to control tissue. Relative to the smoking status, higher CCL20 (p < 0.05) and CCR6 mRNA (p > 0.05) expression levels were observed in current smokers than in never smokers. In serum EVs the expression level of miR-150 has a negative correlation with AJCC tumor staging, whereas the expression level of linc00673 positively correlated (p > 0.05). The lower expression level of miR-150 and higher expression level of linc00673 in serum EVs were observed in NSCLC patients with lymph nodes metastases (p > 0.05). Regarding the histopathological type, significantly lower expression level of miR-150 and higher expression level of linc00673 were observed in the serum EVs of patients with AC compared to patient with SCC. Our findings revealed that smoking significantly changed the expression level of CCL20 mRNA in NSCLC tissue. Changes in expression levels of miR-150 and linc00673 in the serum EVs of NSCLC patients in relation to presence of lymph node metastases and the stage of cancer development may serve as a non-invasive molecular biomarkers of tumor progression. Furthermore, expression levels of miR-150 and linc00673 may serve as non-intrusive diagnostic biomarkers differentiating adenocarcinoma from squamous cell carcinoma., (© 2023. The Author(s).)

Alterations in the expression of numerous genes and the miRNAs that are recognized as their regulators in the endometrial cells of women with endometriosis may disrupt the intracellular signaling pathways associated with epithelial-mesenchymal transition (EMT). So far, the functional role of BMP7 in endometrial physiology has been confirmed, especially in the context of fertility, but the role of the activation of a specific mechanism operating through the BMP-SMAD-CDH1 axis in the formation of endometrial lesions remains unexplored. The aim of this study was to evaluate the expression profile of miR-542-3p and the EMT markers ( BMP7 , SMAD4 , CDH1 ) in matched eutopic endometrium (EUE) and ectopic endometrium (ECE) samples from women with endometriosis in relation to healthy women. The levels of expression of the studied genes and miRNA in peripheral blood mononuclear cells (PBMCs) obtained from women diagnosed with endometriosis and those without the disease were also evaluated. Fifty-four patients (n = 54: with endometriosis-n = 29 and without endometriosis-n = 25) were included in the study. A comparative analysis of the relative mean expression values (RQ) of the studied mRNA and miRNA assessed by RT-qPCR demonstrated downregulation of BMP7 , SMAD4 , and CDH1 expression in ectopic lesions and upregulation in the eutopic endometrium compared with the control group. In the eutopic tissue of women with endometriosis, miR-542-3p expression was similar to that of the control but significantly lower than in endometrial lesions. We also confirmed a trend towards a negative correlation between miR-542-3p and BMP7 in ectopic tissue, and in PBMC, a significant negative correlation of miR-542-3p with further BMP signaling genes, i.e., SMAD4 and CDH1 , was observed. These results indicate that the miRNA selected by us may be a potential negative regulator of BMP7-SMAD4-CDH1 signaling associated with EMT. The different patterns of BMP7 , SMAD4 , and CDH1 gene expression in ECE, EUE, and the control endometrium observed by us suggests the loss of the endometrial epithelium phenotype in women with endometriosis and demonstrates their involvement in the pathogenesis and pathomechanism of this disease.

The molecular pathogenesis of endometriosis has been associated with pathological alterations of protein expression via disturbances in homeostatic genes, miRNA expression profiles, and signaling pathways that play an essential role in the epithelial-mesenchymal transition (EMT) process. TGF-β1 has been hypothesized to play a key role in the development and progression of endometriosis, but the activation of a specific mechanism via the TGF-β-SMAD-ILK axis in the formation of endometriotic lesions is poorly understood. The aim of this study was to assess the expression of EMT markers ( TGF-β1 , SMAD3 , ILK ) and miR-21 in ectopic endometrium (ECE), in its eutopic (EUE) counterpart, and in the endometrium of healthy women. The expression level of the tested genes and miRNA was also evaluated in peripheral blood mononuclear cells (PBMC) in women with and without endometriosis. Fifty-four patients ( n = 54; with endometriosis, n = 29, and without endometriosis, n = 25) were enrolled in the study. The expression levels (RQ) of the studied genes and miRNA were evaluated using qPCR. Endometriosis patients manifested higher TGF-β1 , SMAD3 , and ILK expression levels in the eutopic endometrium and a decreased expression level in the ectopic lesions in relation to control tissue. Compared to the endometrium of healthy participants, miR-21 expression levels did not change in the eutopic endometrium of women with endometriosis, but the RQ was higher in their endometrial implants. In PBMC, negative correlations were found between the expression level of miR-21 and the studied genes, with the strongest statistically significant correlation observed between miR-21 and TGF-β1 . Our results suggest the loss of the endometrial epithelial phenotype defined by the differential expression of the TGF-β1 , SMAD3 and ILK genes in the eutopic and ectopic endometrium. We concluded that the TGF-β1-SMAD3-ILK signaling pathway, probably via a mechanism related to the EMT, may be important in the pathogenesis of endometriosis. We also identified miR-21 as a possible inhibitor of this TGF-β1-SMAD3-ILK axis.

The aim of the study was to assess the impact of vitamin D supplementation and regular physical activity on 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and bone turnover marker concentrations in healthy male athletes. Twenty-five youth soccer players were divided into groups: non-supplemented (GN) and supplemented (GS) with a vitamin D dose of 20 000 IU twice a week for 8 weeks. The study was conducted during an 8-week preseason period, from mid-January to mid-March. At baseline (T1) and at the end of this period (T2), the serum concentrations of 25(OH)D, (PTH), osteocalcin (OC) and β-isomerized C-terminal telopeptide of type I collagen (β-CTx) were measured. At T2, 25(OH)D increased by 70% in GS ( p = 0.004) and by 6% in GN ( p > 0.05). Significant differences between GS and GN groups were observed throughout the study in the group-by-time interaction and changes of 25(OH)D ( p = 0.002; η 2 p = 0.36) and OC ( p = 0.008; η 2 p = 0.26). Increased OC (ES = 0.74; moderate) and β-CTx (ES = 1.31, large) in GN athletes who had an optimal baseline vitamin D level (GO) were observed. In GN, at T2, β-CTx positively correlated with PTH and OC ( p = 0.007 and p = 0.002). In GS, β-CTx positively correlated with OC at both time points (T1, p = 0.027 and T2, p = 0.037). A negative correlation between 25(OH)D and PTH was observed at T2 ( p = 0.018). The obtained results suggest that the 20 000 IU vitamin D3 dose applied twice a week for 8 weeks is effective for vitamin D compensation and sufficient to maintain the correct PTH concentration, as revealed by changes in the bone marker concentrations. In conclusion, the results suggest that the applied vitamin D supplementation dose in athletes leads to intensive bone remodelling and has protective effects on bone under intensive physical effort., Competing Interests: The authors declare that there is no conflict of interest for this manuscript., (Copyright © Biology of Sport 2022.)

One of the main treatment modalities for non-small-cell lung cancer (NSCLC) is cisplatin-based chemotherapy. However, the acquisition of cisplatin resistance remains a major problem. Existing chemotherapy regimens are often ineffective against cancer cells expressing aldehyde dehydrogenase (ALDH). As such, there is an urgent need for therapies targeting ALDH-positive cancer cells. The present study compares the anticancer properties of 36 structurally diverse isothiocyanates (ITCs) against NSCLC cells with the ALDH inhibitor disulfiram (DSF). Their potential affinity to ALDH isoforms and ABC proteins was assessed using AutoDockTools, allowing for selection of three compounds presenting the strongest affinity to all tested proteins. The selected ITCs had no impact on NSCLC cell viability (at tested concentrations), but significantly decreased the cisplatin tolerance of cisplatin-resistant variant of A549 (A549CisR) and advanced (stage 4) NSCLC cell line H1581. Furthermore, long-term supplementation with ITC 1-(isothiocyanatomethyl)-4-phenylbenzene reverses the EMT phenotype and migratory potential of A549CisR to the level presented by parental A549 cells, increasing E-Cadherin expression, followed by decreased expression of ABCC1 and ALDH3A1. Our data indicates that the ALDH inhibitors DSF and ITCs are potential adjuvants of cisplatin chemotherapy.

The aim of this study was to determine whether supplementation with vitamin D during eight weeks of high-intensity training influences muscle power and aerobic performance in young soccer players. A total of 25 athletes were divided into two groups: the supplemented group (GS; n = 12; vitamin D 20,000 IU, twice a week) and the non-supplemented group (GN; n = 13). A set of measurements, including sprint tests, explosive power test, maximal oxygen uptake (VO2max), and serum 25(OH)D concentration, were obtained before (T1) and after (T2) the intervention. A significant group x time interaction was found in the 25(OH)D serum levels ( p = 0.002; ES = 0.36, large). A significant improvement in VO2max was found in the TG ( p = 0.0004) and the GS ( p = 0.031). Moreover, a positive correlation between 25(OH)D and VO2max (R = 0.4192, p = 0.0024) was calculated. The explosive power tests revealed insignificant time interactions in the average 10-jump height and average 10-jump power ( p = 0.07, ES = 0.13; p = 0.10, ES = 0.11, respectively). A statistically insignificant trend was observed only in the group-by-time interaction for the sprint of 10 m ( p = 0.05; ES = 0.15, large). The present study provides evidence that vitamin D supplementation has a positive but trivial impact on the explosive power and locomotor skills of young soccer players, but could significantly affect their aerobic performance.

Although previous cases of ethyl alcohol production by microorganisms present in the intestines, referred to as auto-brewery syndrome (ABS), have been reported, a recent case in our practice was characterized by the production of alcohol in the oral cavity. Our research indicates that legally significant levels of ethyl alcohol can be detected in exhaled air in cases where there has been no alcohol consumption but where the subject has oral candidiasis. In such cases, following the consumption of foods containing carbohydrates, a fermentation process occurs in the mouth, the first stage of which is glycolysis, proceeding according to the Embden-Meyerhof-Parnas pathway, which is typical in eukaryotes. The main organic substrate in this case is glucose, which is formed in the oral cavity from disaccharides (maltose, sucrose) by the activity of α-amylase. Some mutated fungal strains of the genus Candida acquire the ability to break down sucrose and produce glucoamylase. Glucose is converted into glyceraldehyde 3-phosphate and then into pyruvate. The next stage of fermentation is the decarboxylation of pyruvate into acetaldehyde, a reaction catalyzed by pyruvate decarboxylase. The final stage is the reduction of acetaldehyde to ethanol by alcohol dehydrogenase. Such endogenous production of alcohol can be confused with its consumption, which can cause not only legal, but also social and medical problems., (Copyright © 2022 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

The chemokine receptor 7/C-C ligand 19 chemokine (CCR7/CCL19) has been implicated in the development and progression of NSCLC. Its expression is regulated by various epigenetic factors including miRNAs. The aim of this study was to assess the expression of CCR7/CCL19 in cancer tissue in relation to that of miRNAs (miR-let-7a, miR-335) as transcriptional regulators. The expression of the tested miRNAs was also evaluated in serum exosomes. Sixty patients ( n = 60) were enrolled in the study. The total expression of the studied mRNA and miRNAs were evaluated using qPCR. Tumor tissue fragments, macroscopically unchanged adjacent tissue, and serum were used as controls. Higher CCR7 and CCL19 mRNA expression levels were observed in tumor tissue compared to control. According to stages of the disease (AJCC tumor staging), the greatest expression level of the studied genes' mRNA was observed in patients with stage III. In NSCLC patients, lower miR let-7a expression level was observed in tumor tissue compared to serum; however, miR-335 expression level was higher ( p < 0.05). The expression level of miR-335 positively correlated with tumor size (T features according to pTNM staging) and AJCC tumor staging, while miR let-7a had a negative correlation ( p > 0.05) with liquid biopsy. Significantly greater miR-335 expression level and lower miR let-7a expression level in serum were observed in patients with metastases to lymph nodes. Our findings reveal a significant correlation between the expression levels of the mRNA of the studied genes and miRNAs. Changes in miR-335 and miR let-7a expression levels in the serum exosomes of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression.

The PPARδ gene codes protein that belongs to the peroxisome proliferator-activated receptor (PPAR) family engaged in a variety of biological processes, including carcinogenesis. Specific biological and clinical roles of PPARδ in non-small cell lung cancer (NSCLC) is not fully explained. The association of PPARα with miRNA regulators (e.g. miRNA-17) has been documented, suggesting the existence of a functional relationship of all PPARs with epigenetic regulation. The aim of the study was to determine the PPARδ and miR-17 expression profiles in NSCLC and to assess their diagnostic value in lung carcinogenesis. PPARδ and miR-17 expressions was assessed by qPCR in NSCLC tissue samples (n = 26) and corresponding macroscopically unchanged lung tissue samples adjacent to the primary lesions served as control (n = 26). PPARδ and miR-17 expression were significantly lower in NSCLC than in the control (p = 0.0001 and p = 0.0178; respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential in discriminating NSCLC from the control with an area under the curve (AUC) of 0.914 for PPARδ and 0.692 for miR-17. Significant increase in PPARδ expression in the control for current smokers vs. former smokers (p = 0.0200) and increase in miR-17 expression in control tissue adjacent to adenocarcinoma subtype (p = 0.0422) were observed. Overexpression of miR-17 was observed at an early stage of lung carcinogenesis, which may suggest that it acts as a putative oncomiR. PPARδ and miR-17 may be markers differentiating tumour tissue from surgical margin and miR-17 may have diagnostic role in NSCLC histotypes differentiation., (© 2021. The Author(s).)

Being one of the most common dermatological inflammatory disorders, psoriasis is a frequent subject of research. It is considered to be a T cell-dependent immune disease whose pathogenesis is influenced by cytokines, such as IL-10 , IL-17A , IL-17RA , IL-23A and IL-23R . The present study examines whether the expression of selected genes is correlated with the clinical course of psoriasis, assessed by the PASI, BSA and DLQI scales. Skin biopsies and blood from 60 patients with psoriasis and 24 healthy controls were obtained for RNA isolation. These were subjected to RT-PCR for IL-10 , IL-17A , IL-17RA , IL-23A and IL-23R genes. The results were presented as an RQ value. IL-17A and IL-23R expression levels were higher in psoriatic skin compared to controls, while IL-10 expression was lower. A positive correlation was also found between RQ for IL-23A and PASI index. Psoriatic skin is characterised by elevated expression of IL-17A and IL-23R and decreased expression of IL-10 . This indicates that the selected cytokines may be one of the factors involved in the pathogenesis and pathomechanism of psoriasis, but more studies need to be made before we can elucidate the exact reason for the unbalance in cytokine expression levels.

Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial-mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.

This study assesses the knowledge of medical students on the health effects of the use of psychoactive substances, in the context of their future role in prevention and treatment of addictions. The study was conducted using a questionnaire containing questions about classification, symptoms and effects of psychoactive substances, and the existing prevention programs. The study involved 430 students of medicine and allied faculties. Only 20.8% of medicine students and 12.5% of students of other faculties could correctly classify different psychoactive substances. Correct symptoms of drug misuse were mentioned by 20.4% of medicine students and 19.2% of students of other faculties. The overall knowledge of medical students was no greater than the knowledge of students of other allied faculties. Medical students showed insufficient knowledge about psychoactive substances and their effects on the human body, thus indicating the need to introduce into their study programme a more teaching in this area.

The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients ( n = 31) and control subjects ( n = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 ( p = 0.003, p = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a ( p = 0.0003), 0.733 for miR-let7i ( p = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker.

Tumours are characterised by an ability to avoid immune destruction and the presence of cancer-associated inflammation. Better understanding of the link between lung cancer and such inflammation is vital for early detection and personalized treatment. Thus, we examined the mRNA expression of interleukins IL-1β, IL-6, IL-17 and miR-9, miR-122 as potential useful biomarkers of NSCLC. Tumour tissues, non-cancerous tissue and blood samples were collected from 39 patients with primary NSCLC undergoing surgical treatment. The selected RNA was isolated from tissue samples and selected miRNAs from peripheral blood exosomes. This RNA was transcribed to cDNA and quantified using RT-qPCR. Significantly higher expression of the selected interleukins was observed in non-cancerous than tumour tissue, and IL-6 was significantly higher in the tumour tissue of patients with a history of ≤ 40 pack-years (PYs) (2.197, IQR: 0.821-4.415) than in those with > 40 PYs (0.461, IQR: 0.372-0.741; p = 0.037). It is clear that inflammatory processes play a role in NSCLC, as indicated by the upregulation of IL-1β and IL-6 in tumour and adjacent tissue, and that smoking has a strong influence on inflammation in tumourigenesis, demonstrated by the upregulation of IL-6 in tumour samples among patients with ≤ 40 PYs compared to > 40 PYs.

Lung cancer is a disease with a very low 5-year survival rate (6-13%) worldwide. The most frequently diagnosed histological type of this cancer is non-small cell lung cancer (NSCLC). Poor prognosis for lung cancer - including NSCLC - is mainly related to the fact that patients are diagnosed in the advanced stages of the disease. The aim of this study is to summarize data that concerns new directions of research regarding diagnostic biomarkers that could be used to support the routine diagnosis of this cancer. In recent years, proteomic analysis has become an important tool for cancer biology research, complementing genetic analysis. Among the numerous methods of proteomic analysis, mass spectrometry techniques enable the extremely accurate qualitative and quantitative identification of hundreds of proteins in small volumes of various biological samples. Such analyses may soon become the basis of improvement in lung cancer diagnostic procedures. This study presents the latest reports in proteomic research concerning the diagnosis of NSCLC. New potential proteomic biomarkers, whose presence indicates the development of a neoplastic process at an early stage, are presented. We describe biomarkers whose altered expression levels correlate with different stages of cancer. We also present protein biomarkers that help differentiate NSCLC subtypes. In the clinical workup of NSCLC patients, it is important not only to make an early diagnosis, but also to monitor the development of the neoplastic disease. Considering this fact, we also present examples of biomarkers whose abnormal expression may indicate a high risk of metastasis to the lymph nodes. This paper also emphasizes the need to conduct further research that would confirm the usefulness of the described biomarkers in clinical practice.

Objectives: As a chronic, recurrent, immunologically mediated systemic disease and a common cause of dermatological problems, psoriasis is often a subject of scientific research. Skin changes located on the hands can cause difficulties and limitations in the performance of professional activities, especially manual ones. The main role in pathogenesis is played by immunological factors - improper functioning of the components of the immune system, among others, T lymphocytes and cytokines like interleukin-12 (IL-12), interleukin-22 (IL-22) and interferon gamma (IFN-γ)., Material and Methods: The obtained tissue and blood were destined for RNA isolation. The RNA was then subjected to a reverse transcription reaction. The relative gene expression level was evaluated by the real-time polymerase chain reaction for IL-12B , IL-22 and IFN-γ genes, and presented as the relative quantification (RQ) value, relative to the reference gene GAPDH . In addition, a correlation analysis of the expression level of selected genes with the clinical course of the disease, as assessed by the Psoriasis Area and Severity Index (PASI), the Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI) scores was performed., Results: Statistical analysis confirmed a significant increase in RQ values for IL-12B , IL-22 and IFN-γ in the group of psoriatic patients vs. the control group. A positive correlation was also found between BSA and PASI and RQ for the IL-12B gene., Conclusions: Increased expression levels of IL-12B , IL-22 and IFN-γ genes in psoriatic skin confirm that selected cytokines play an important role in the initiation and sustenance of psoriasis. Int J Occup Med Environ Health. 2020;33(5):635-47., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

The growth hormone (GH)/insulin-like growth factor-1 axis is responsible for glucose homeostasis. In the present study we assessed the expression levels of miRNA-124, miRNA-210 and miRNA-375 and immunoexpression of IGFBP-3 in relation to the concentrations of IGF-1 and glucose in athletes performing different types of effort. Sixty-six young male athletes (age 25.4±4.1 years) were divided into: group EN (33 male athletes; age 25.6±4.4 years) with endurance-type efforts (disciplines: triathlon, long distance running, cycling) and group ST (33 male athletes; age 25.2±3.9 years) with strength-type efforts (disciplines: weightlifting, body building, CrossFit). The control group consisted of 28 non-training men (age 29.1±4.7 years). Statistically significantly higher IGF-1 concentration and lower glucose concentration (P<0.05) in serum were observed in the group of athletes (vs. controls). Immunoexpression of IGFBP-3 was higher in athletes (vs. controls), and a higher value of immunoexpression was obtained in athlete group ST vs. group EN (P>0.05). Levels of expression of miRNA-210 and miRNA-375 were higher in athletes vs. controls (P>0.05). The obtained data confirmed the importance of the somatotropic axis in the regulation of metabolic adaptation to physical exercise. The detected variation in the concentrations and expression levels of the studied molecules involved in the somatotropic axis in athletes confirmed the role of the somatotropic axis in adaptation to physical effort. Statistically significant reduction of glucose concentration and the highest expression of IGF-1in serum in athletes suggest the anabolic effect of IGF-1 through insulin receptors on many tissues under the influence of moderate physical exercises (mainly during resistance training)., Competing Interests: The authors declare that there is no conflict of interest for this manuscript., (Copyright © Biology of Sport 2020.)

A pro-inflammatory cytokine, IL-17A, is associated with increased risk of developing numerous cancers, including non-small cell lung cancer (NSCLC). IL-17A is a target gene for miR-9. This encouraged us to analyze these two genes in terms of their usefulness as prognostic markers in NSCLC. The expression levels of IL-17A gene and miR-9 was assessed in 26 NSCLC tissue samples and 26 unchanged lung tissue adjacent to lung tumors (control tissue), using qPCR. In both tissue groups, a decreased expression of IL-17A was observed in 100% of samples. Increased expression of miRNA-9 was observed in 92% of tumor samples, and in 100% of control samples. Neither statistical differences in the level of expression IL-17A depending on the patient's age, gender, smoking status, nor histopathology of the cancer was found. Regarding the presence of nodule metastasis ('N' value in TNM classification), significantly lower expression level of IL-17A was observed in cN2 as compared with cN1 group. Additionally, statistically lower IL-17A expression was found in III versus II tumor stage (cAJCC classification). Significant negative correlation between both studied genes was revealed in SCC subgroup. This leads to the conclusion that miRNA-9 can regulate the expression of IL-17A as an IL-17A mRNA antagonistic mediator. Inhibition of proinflammatory action of IL-17A in correlation with tumor progression can be related to various activity of Th17 cells on cancer development according to its immunogenicity, and also may suggest suppressive role of IL-17A in tumor progression. However, because of low number of analyzed samples, further studies on the functional role of IL-17A in development and/or progression NSCLC seem warranted.

Background: Lung cancer is one of the most common causes of death worldwide with a relatively high fatality rate and a mean 5-years survival of about 18%. One of the hallmarks of cancer is the extracellular matrix (ECM) remodeling, which is crucial for metastasis. This process may be regulated by miRs targeting metalloproteinases (MMPs) associated with the ECM breakdown and metastatic process or blocking the action of tissue inhibitors of metalloproteinases (TIMPs). Search for early biomarkers is essential in detecting non-small cell lung cancer (NSCLC) and distinguishing its subtypes: Adenocarcinoma (AC) from Squamous Cell Carcinoma (SCC), enabling targeted chemotherapy. Methods: MiR-17 and miR-20a targeting MMP2 and TIMP3 were selected by TCGA data analysis with further validation using miRTarBase and literature. The study group comprised 47 patients with primary NSCLC (AC and SCC subtypes). RNA was isolated from the tumor and normal-looking neighboring tissue (NLNT) free of cancer cells. MiRs from peripheral blood exosomes were extracted on admission and 5-7 days after surgery. Gene and miRs expression were assessed in qPCR using TaqMan probes. Results: The MMP2 has been expressed on a similar level in NLNT, as in cancer. While, TIMP3 expression was decreased both in cancer tissue and NLNT, with significantly lower expression in cancer. TIMP3 downregulation in NLNT and in SCC subtype correlated negatively with miR-20a . The preoperative miR-17 expression was significantly higher among patients with SCC compared to AC. Receiver operating characteristic (ROC) analysis of miR-17 as AC subtype classifier revealed 90% specificity and 48% sensitivity in optimal cut-off point with area under ROC curve (AUC): 0.71 (95%CI: 0.55-0.87). Within NSCLC subtypes: a strong negative correlation between pack-years (PY) and TIMP3 expression was observed for NLNT in the SCC group. Conclusion: The TIMP3 silencing observed in the NLNT and its negative correlation with presurgical expression of miR-20a (from serum exosomes), suggest that miRs can influence ECM remodeling at a distance from the center of the lesion. The miRs expression pattern in serum obtained before surgery significantly differs between AC and SCC subtypes. Moreover, decreased TIMP3 expression in NLNT (in SCC group) negatively correlates with the amount of tobacco smoked in a lifetime in PY., (Copyright © 2019 Czarnecka, Szmyd, Barańska, Kaszkowiak, Kordiak, Antczak, Pastuszak-Lewandoska and Brzeziańska-Lasota.)

Two suppressor genes which often undergo epigenetic silencing during the early stages of lung carcinogenesis are those encoding retinoic acid receptor-β (RARβ) and Fhit protein (FHIT). RARβ expression is regulated by miRNA-34a and miRNA-141, and FHIT expression by miRNA-143 and miRNA-217. The aim of the study was to assess how selected miRNAs regulate the expression of their targeted genes in bronchoalveolar lavage fluid (BALf), obtained from patients with SCC of the lung. It also examines the relationship between the genetic findings and the clinical and pathomorphological features of the tumor. A total of 50 BALf samples were taken: 25 from patients with SCC and 25 from healthy donors. The expression (RQ) of the selected genes was analyzed by qPCR, as well as the miRNA level, with a particular emphasis on the relationship between the expression of the genes themselves and their corresponding miRNAs; in addition, the expression of the genes and miRNAs were compared with the pathomorphological features of the tumor and the clinical features of patients. Analysis of the RQ values showed downregulation of RARß, FHIT and miRNA-34a and increased expression of miRNA-141, miRNA-143 and miRNA-217 in all BALf samples (P > 0.05). No correlation was found between the expression of the selected genes and corresponding miRNAs, history of smoking, cancer stage, age and sex of the patients. The presence of the selected genes and miRNAs in BALf material does not seem to have diagnostic potential in patients with SCC; however, the results should be verified on a larger group of patients.

Muscle strength and maximal speed are factors determining athlete's results during competition. Their association with ACTN3 gene activity has been documented. The purpose of this study was the analysis of ACTN3 gene expression during a 2 month training cycle of soccer players and its correlation with the countermovement jump (CMJ) and squat jump (SJ). The study group consisted of 22 soccer players (aged 17-18). The study material included peripheral blood lymphocytes. The relative expression (RQ) of the ACTN3 gene was analyzed by qPCR and performed before and after the two-month training cycle. Before the training cycle low expression levels of ACTN3 (median RQ = 0.95) were observed, yet after the training cycle they were elevated (median RQ = 1.98) ( p = 0.003). There was an increase in performance of both jumps: SJ (p = 0.020) and CMJ (p = 0.012) at the end of the training cycle. A simultaneous increase in the ACTN3 gene expression level and height in both jump tests was observed in 73% of athletes (p > 0.05). There were no significant relationships between the ACTN3 gene expression level and the results of the CMJ and SJ. However, explosive strength is a complex feature shaped by many different factors and it could be the reason why we did not observe correlations between these variables., (© 2019 Daria Domańska-Senderowska, Paulina Szmigielska, Aleksandra Snochowska, Zbigniew Jastrzębski, Anna Jegier, Justyna Kiszałkiewicz, Joanna Jastrzębska, Dorota Pastuszak-Lewandoska, Paweł Cięszczyk, Aleksandra Suchanecka, Michał Wilk, Michał Brzeziański, Ewa Brzeziańska-Lasota, published by Sciendo.)

CC chemokine receptor type 7 (CCR7) and its ligands has been implicated in the occurrence and progression of NSCLC. Previous studies have revealed that the diagnostic value of CCR7/CCL19 axis in lung tumorigenesis remains controversial. The present study evaluates the relationship between the mRNA expression of CCR7/CCL19 axis and selected regulatory miRNAs in NSCLC patients. It analyzes the expression level of CCR7 mRNA and its ligand in tumor tissue in relation to expression level of two miRNAs: miR let-7a and miR-335, as transcriptional regulators of study genes. Twenty-seven patients (n = 27) were enrolled. The expression of the studied genes and miRNAs was evaluated by qPCR. Tumour tissue fragments, adjacent macroscopically-unchanged lung tissue (control) and patient serum were used as biological material for study. Elevated expression of CCR7 and CCL19 mRNA was observed in patients with metastasis to lymph nodes. We noticed upregulated miR-335 expression and downregulated miR let-7a expression in patient serum with regard to AJCC tumor staging. Higher miR-335 expression and lower miR let-7a expression level was observed in patients with metastasis to lymph node. The presence of changes observed in the expression level of miR-335 and miR let-7a in the serum of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression; however, this observation requires further investigation.

Background: Loss of heterozygosity (LOH) and microsatellite instability (MSI) are frequent molecular events in thyroid tumor etiopathogenesis occurring in several chromosomal critical areas, including 3p12-25.3, 7q21-31, 10q22-24, and 15q11-13, with loci of tumor suppressor genes., Objective: We evaluated the usefulness of LOH/MSI as a diagnostic/prognostic biomarker in lesions derived from thyroid follicular cells: follicular thyroid carcinoma (FTC); follicular adenoma (FA), papillary thyroid carcinoma (PTC), and nodular goiter (NG)., Methods: We performed allelotyping (GeneMapper Software v. 4.0.) of ten microsatellite markers linked to the 1p31.2, 3p21.3, 3p24.2, 9p21.3, 11p15.5, and 16q22.1 region on DNA from 93 primary thyroid lesions then evaluated the LOH/MSI frequency and overall frequency of allelic loss (OFAL)., Results: We found regions with significantly increased frequency of LOH/MSI for specific histotypes: the 3p24.2 region for FA and 1p31.2 for FTC. LOH/MSI in 3p21.3 was significantly elevated in PTC and FTC. LOH/MSI in 3p21.3 was increased for small size tumors (T1a + T1b), tumors with no regional lymph node involvement (N0 + Nx), American Joint Committee on Cancer (AJCC) stage I tumors, and tumor diameter (Td) < 10 mm; in 1p31.2 for T2-3, N1, stage II-IV, and Td 10-30 mm; in 11p15.5 for T2-3, N1, stage II-IV, and Td > 30 mm. OFAL values were significantly higher in younger patients (< 40 years), in men, in those with T2-3 stage tumors, in those with increased Td, and in FA and FTC compared with NG and PTC., Conclusions: We confirmed the occurrence of LOH/MSI in 3p21.3 at an early stage of tumorigenesis and mapped 1p31.2 and 11p15.5 as characteristic for advanced-stage tumors. The results of our study may enable consideration of OFAL, defined as LOH/MSI coincidence in various chromosomal regions, as a tumor progression marker. OFAL values were significantly higher in follicular neoplasms (FA and FTC) than in PTC or NG; hence, increased OFAL values can be regarded as a characteristic feature of the follicular phenotype.