ADAMTS Gene-Derived circRNA Molecules in Non-Small-Cell Lung Cancer: Expression Profiling, Clinical Correlations and Survival Analysis.

The present study examines the relationship between circular RNA (circRNA) derived from three genes of the family a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs): ADAMTS6, ADAMTS9 and ADAMTS12 and the host gene expression in non-small-cell lung cancer (NSCLC) with regard to various clinical factors. Notably, an association was identified between ADAMTS12 expression and specific circRNA molecules, as well as certain expression patterns of ADAMTS6 and its derived circRNA that were specific to histopathological subtypes. The survival analysis demonstrated that a lower ADAMTS6 expression in squamous cell carcinoma was associated with extended survival. Furthermore, the higher ADAMTS9 expression was linked to prolonged survival, while the overexpression of ADAMTS12 was correlated with a shorter survival. These findings suggest that circRNA molecules may serve as potential diagnostic or prognostic biomarkers for NSCLC, highlighting the importance of considering molecular patterns in distinct cancer subtypes.

Correlation of TIMP1-MMP2/MMP9 Gene Expression Axis Changes with Treatment Efficacy and Survival of NSCLC Patients.

In the course of lung cancer, normal cells are transformed into cancerous ones, and changes occur in the microenvironment, including the extracellular matrix (ECM), which is not only a scaffold for cells, but also a reservoir of cytokines, chemokines and growth factors. Metalloproteinases (MMPs) are among the elements that enable ECM remodeling. The publication focuses on the problem of changes in the gene expression of MMP2, MMP9 and tissue inhibitor of metalloproteinases (TIMP1) in the blood of NSCLC patients during therapy (one year after surgical resection of the tumor). The paper also analyzes differences in the expression of the studied genes in the tumor tissue, as well as data collected in publicly available databases. The results of blood tests showed no differences in the expression of the tested genes during therapy; however, changes were observed in cancerous tissue, which was characterized by higher expression of MMP2 and MMP9, compared to non-cancerous tissue, and unchanged expression of TIMP1. Nevertheless, higher expression of each of the studied genes was associated with shorter patient survival. Interestingly, it was not only the increased expression of metalloproteinase genes, but also the increased expression of the metalloproteinase inhibitor (TIMP1) that was unfavorable for patients.

Assessment of the Influence of 5-Fluorouracil on SMAD4 and TGFB1 Gene Expression, Apoptosis Induction and DNA Damage in Human Cell Lines.

PURPOSE: Suppressor of mothers against decapentaplegic homolog 4 (SMAD family member 4, SMAD4) is involved in the adenoma-carcinoma pathway, leading to the development of colon cancer. The encoded protein is a key downstream signaling mediator in the TGFß pathway. This pathway has tumor-suppressor functions, including cell-cycle arrest and apoptosis. Its activation in late-stage cancer can promote tumorigenesis, including metastasis and chemoresistance. Most colorectal cancer patients receive chemotherapy based on 5-FU as an adjuvant treatment. However, the success of therapy is hampered by multidrug resistance by neoplastic cells. In colorectal cancer, resistance to 5-FU-based therapy is influenced by SMAD4 gene expression, as patients with decreased SMAD4 gene expression probably have a higher risk of developing 5-FU-induced resistance. The mechanism leading to the development of this phenomenon is not fully understood. Therefore, the present study assesses the possible influence of 5-FU on changes in the expression of the SMAD4 and TGFB1 genes. PATIENTS AND METHODS: The effect of 5-FU on the expression of SMAD4 and TGFB1 in colorectal cancer cells derived from the CACO-2, SW480 and SW620 cell lines was evaluated using real-time PCR. The cytotoxicity of 5-FU on colon cancer cells was assessed by the MTT method, and its effect on the induction of cell apoptosis and the initiation of DNA damage using a flow cytometer. RESULTS: Significant changes in the level of SMAD4 and TGFB1 gene expression were noted in the CACO-2, SW480 and SW620 cells treated with 5-FU at various concentrations during 24 h and 48 h exposure. The use of 5-FU at a concentration of 5 µmol/L resulted in a decrease in the expression of the SMAD4 gene in all cell lines at both exposure times, while the concentration of 100 µmol/L increased the expression of the SMAD4 gene in CACO-2 cells. The level of expression of the TGFB1 gene was higher for all cells treated with 5-FU at the highest concentrations, while the exposure time was extended to 48 h. CONCLUSION: The observed in vitro changes in CACO-2 cells caused by 5-FU may be of clinical relevance when choosing the drug concentration for treating patients with colorectal cancer. It is possible that 5-FU has a stronger effect on colorectal cancer cells at the higher concentrations. Low concentrations of 5-FU may not have a therapeutic effect and may also influence drug resistance in cancer cells. Higher concentrations and prolonged exposure time may affect SMAD4 gene expression, which may increase the effectiveness of therapy.

Anticancer Properties of 3-Dietoxyphosphorylfuroquinoline-4,9-dione.

Herein, the antitumor activity of a novel synthetic analog with 5,8-quinolinedione scaffold, diethyl (2-(2-chlorophenyl)-4,9-dioxo-4,9-dihydrofuro [3,2-g]quinolin-3-yl)phosphonate (AJ-418) was investigated on two breast cancer cell lines. This analog was selected from a small library of synthetic quinolinediones on the basis of its strong antiproliferative activity against MCF-7 and MDA-MB-231 cells and 4-5-fold lower cytotoxicity towards healthy MCF-10A cells. The morphology of MCF-7 and MDA-MB-231 cancer cells treated with AJ-418 changed drastically, while non-tumorigenic MCF-10A cells remained unaffected. In MCF-7 cells, after 24 h incubation, the increased number of apoptotic cells coincided with a decrease in proliferation and cell viability. The 24 h treatment of MDA-MB-231 cells with the tested compound reduced their cell viability and proliferation rate; however, a significant pro-apoptotic effect was visible only after longer incubation times (48 h and 72 h). Then, the maximum tolerated dose (MTD) of compound AJ-418 in C3H mice after subcutaneous administration was determined to be 160 mg/kg, showing that this analog was well tolerated and can be further evaluated to assess its potential therapeutic effect in tumor-bearing mice.

Differential Expression of AP-2 Transcription Factors Family in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma-A Bioinformatics Study.

Members of the activator protein 2 (AP-2) transcription factor (TF) family are known to play a role in both physiological processes and cancer development. The family comprises five DNA-binding proteins encoded by the TFAP2A to TFAP2E genes. Numerous scientific reports describe differential expression of these TF and their genes in various types of cancer, identifying among them a potential oncogene or suppressor like TFAP2A or TFAP2C. Other reports suggest their influence on disease development and progression, as well as response to treatment. Not all members of this AP-2 family have been comprehensively studied thus far. The aim of the present article is to gather and discuss knowledge available in bioinformatics databases regarding all five members of this family and to differentiate them in relation to the two most common lung cancer subtypes: adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). In addition, to assess the difference in levels depending on a number of clinicopathological factors, the impact on patient survival and interactions with tumor-infiltrating immune cells. This article may help to identify the target for further original research that may contribute to the discovery of new diagnostic biomarkers and define the molecular differences between LUAD and LUSC, which may affect the therapy effectiveness improvement and longer survival.

Effects of the SLCO1B1 A388G single nucleotide polymorphism on the development, clinical parameters, treatment, and survival of multiple myeloma cases in a Polish population.

BACKGROUND: Multiple myeloma is one of the most common hematological malignancies worldwide. Genetic alterations may lead to the progression from monoclonal gammopathy to multiple myeloma. Additionally, the genetic background of the disease might influence therapy outcomes, including survival time. SLCO1B1, belonging to the OATPs family, is a membrane protein that mediates the uptake of a wide range of endogenous and exogenous (including drugs) compounds. METHODS AND RESULTS: In this study, the A388G single nucleotide polymorphism in the SLCO1B1 gene in Polish multiple myeloma patients was determined. This polymorphism affects the amino acid change of the protein, so it may be responsible for treatment effectiveness or risk of disease development. A388G was evaluated by the PCR-RFLP method. The presented study showed a statistically significant association between the GG genotype with longer survival of patients with multiple myeloma with Melphalan-Prednisone therapy compared to other treatment regimens (p = 0.0271). There was no statistically significant association in the frequency of genotypes (p = 0.8211) and alleles: allele A (p = 0.5442); allele G (p = 0.8020) between multiple myeloma patients and a control group. CONCLUSIONS: The A388G polymorphism does not seem to affect the increased risk of the development of multiple myeloma. However, the occurrence of the GG genotype may prolong of patients overall survival in the case of Melphalan-Prednisone therapy.

Molecular Pathogenesis of Fibrosis, Thrombosis and Surfactant Dysfunction in the Lungs of Severe COVID-19 Patients.

The global scope and scale of the SARS-CoV-2 pandemic led to huge amounts of important data from clinical observations and experimental analyses being collected, in particular, regarding the long-term impact of COVID-19 on lung tissue. Visible changes in lung tissue mainly relate to the destruction of the alveolar architecture, dense cellularity, and pulmonary fibrosis with myofibroblast proliferation and collagen deposition. These changes are the result of infection, mainly with virus variants from the first pandemic waves (Alpha to Delta). In addition, proper regulation of immune responses to pathogenic viral stimuli is critical for the control of and recovery from tissue/organ damage, including in the lungs. We can distinguish three main processes in the lungs during SARS-CoV-2 infection: damage or deficiency of the pulmonary surfactant, coagulation processes, and fibrosis. Understanding the molecular basis of these processes is extremely important in the context of elucidating all pathologies occurring after virus entry. In the present review, data on the abovementioned three biochemical processes that lead to pathological changes are gathered together and discussed. Systematization of the knowledge is necessary to explore the three key pathways in lung tissue after SARS-CoV-2 virus infection as a result of a prolonged and intense inflammatory process in the context of pulmonary fibrosis, hemostatic disorders, and disturbances in the structure and/or metabolism of the surfactant. Despite the fact that the new Omicron variant does not affect the lungs as much as the previous variants, we cannot ignore the fact that other new mutations and emerging variants will not cause serious damage to the lung tissue. In the future, this review will be helpful to stratify the risk of serious complications in patients, to improve COVID-19 treatment outcomes, and to select those who may develop complications before clinical manifestation.

Assessment of the TGFB1 gene expression and methylation status of the promoter region in patients with colorectal cancer.

The aim of this study was to evaluate the expression of the TGFB1 gene encoding the TGF-ß1 cytokine in 64 patients, and then to compare it with clinico-pathological features. The study also investigated whether the regulation of the gene expression is caused by methylation of the promoter region between - 235 and + 22 nucleotide from the start of transcription. The dependence of the relative level of the TGFB1 gene expression on the clinical advancement according to the TNM classifications was shown. Additionally, the individual grades of the T and M features of the TNM classification differed in the relative transcript levels of the TGFB1 gene. Moreover, the higher relative expression level of the studied gene was associated with a lack of vascular invasion by cancer cells and presence of lymphocytes in the neoplastic tissue. The obtained results may indicate a possible impact of the gene on the process of carcinogenesis in colorectal cancer and reduction of its expression level may be one of the factors contributing to progression of the disease.

Changes in the expression of membrane type-matrix metalloproteinases genes (MMP14, MMP15, MMP16, MMP24) during treatment and their potential impact on the survival of patients with non-small cell lung cancer (NSCLC).

The analysis concerned the comparison of the expression of membrane type matrix metalloproteinases genes in the blood and tissue of NSCLC patients during the course of the disease and comparison to the control group. Blood and neoplastic tissue taken from 45 patients diagnosed with non-small cell lung cancer was a research material. The expression level of MMP14, MMP15, MMP16 and MMP24 was evaluated by qPCR and the results were compared with controls. The expression of MMP14 and MMP24 before tumor removal surgery and 100 days after was lower than in the control group. Interestingly, one year after surgery the levels of expression of these genes were identical to those in the control group. This suggests that the expression of metalloproteinase genes changes in the course of cancer and that effective treatment results in the normalization of gene expression. Lower expression of MMP15 in the blood of patients with more advanced cancer disease was observed, confirming the suppressive nature of changes in the blood. It has also been demonstrated that higher expression of MMP14 and MMP15 in the tissue is associated with more advanced stage of disease development or more invasive nature of the lesion. There is a noticeable increase of expression level in the environment surrounding the tumor, while a lower can be observed in the blood. This may indicate that changes in the expression of metalloproteinases in cancer are much more complex than merely the tumor tissue, which may also account for the inadequacies of metalloproteinase inhibitors.

The influence of CYP2C19*2 and CYP3A5*3 variants on the development of depression and effectiveness of therapy: A preliminary study.

The most common mental illness is depression; however, its pathogenesis is not fully understood. One of the factors that may influence its development and the effectiveness of therapy are the cytochromes of the p450 complex. CYP3A5 and CYP2C19 are involved in the metabolism of drugs used in the treatment of depression. These cytochromes can also generate reactive oxygen species, which are known to participate in the pathogenesis of depression. The aim of the study was to determine the frequency of CYP3A5*3 and CYP2C19*2 variants among a group of patients with depression to identify any potential association with disease development and progression, and the effectiveness of pharmacotherapy. A group of 103 patients suffering from recurrent depressive disorder and another of 93 healthy individuals were investigated using RFLP. It was found that the CYP3A5*3 allele may have a protective role in the development of depression (p = 0.0036). Heterozygous CYP3A5*1/*3 was more common in controls than the patients (p = 0.0300). Homozygotes were associated with an earlier onset than heterozygotes (p = 0.0292). For CYP2C19, patients with at least one CYP2C19*2 allele revealed better treatment results expressed as percentage change in Hamilton Depression Rating Scale (p = 0.0239). The identification of CYP3A5 and CYP2C19 allelic variants may be useful when assessing the effectiveness of pharmacotherapy.

Importance of Altered Gene Expression of Metalloproteinases 2, 9, and 16 in Acute Myeloid Leukemia: Preliminary Study.

Acute myeloid leukemia is a group of hematological neoplasms characterized by a heterogeneous course and high mortality. The important factor in the neoplastic process is metalloproteinases, proteolytic enzymes capable of degrading various components of the extracellular matrix, which take an active part in modifying the functioning of the cell, including transformation to cancer cell. They interact with numerous signaling pathways responsible for the process of cell growth, proliferation, or apoptosis. In the present study, changes in the expression of MMP2, MMP9, and MMP16 genes between patients with AML and people without cancer were examined. The impact of cytogenetic changes in neoplastic cells on the expression level of MMP2, MMP9, and MMP16 was also assessed, as well as the impact of the altered expression on the effectiveness of the first cycle of remission-inducing therapy. To evaluate the expression of all studied genes MMP2, MMP9, and MMP16, SYBR Green-based real-time PCR method was used; the reference gene was GAPDH. For two investigated genes MMP2 and MMP16, the lower expression level was observed in patients with AML when compared to healthy people. The MMP9 gene expression level did not differ between patients with AML and healthy individuals which may indicate a different regulation of gene expression in acute myeloid leukemia. However, no correlation was observed between the genes' expression of all tested metalloproteinases and the result of cytoreductive treatment or the presence of cytogenetic changes. The obtained results show that the expression of MMP2 and MMP16 genes is reduced while the expression of MMP9 is unchanged in patients with acute myeloid leukemia. This may indicate a different regulation of the expression of these genes, and possible disruptions in gene transcription or posttranscriptional mechanisms in the MMP2 and MMP16 genes, however, do not affect the level of MMP9 expression. Obtained results in AML patients are in contrary to various types of solid tumors where increased expression is usually observed.

Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research.

BACKGROUND: Colon cancer is one of the most common types of malignant tumor worldwide. The molecular mechanism of colorectal carcinogenesis is very complex and not yet fully understood. The TGFß (transforming growth factor ß) signaling pathway plays a significant role in the development of many cancers, including colorectal cancer pathogenesis. Changes in TGFß pathway are associated with increased colorectal cancer risk, because this pathway participates in the control of important cellular processes such as cell growth, proliferation, differentiation, or apoptosis. The family of SMAD (similar to mother against decapentaplegic) proteins is closely correlated to this pathway. SMADs genes expression affects modulation of the transcription of many genes, which leads to the inhibition of cell-growth and apoptosis in colon epithelial cells. The presence of SNPs (single nucleotide polymorphisms) in SMADs genes encoding proteins involved in the control of biological processes important for the cell may play a significant role in the predisposition to the development of colorectal cancer, or in the regulation of the severity of changes related to tumor growth. Extension of data in this field may provide clinically significant conclusions influencing the implementation of personalized treatment based on specific changes characteristic of a patient with colorectal cancer. PURPOSE: The subject of this research was genotyping polymorphisms of SMAD3 (rs6494629) and SMAD4 (rs10502913, rs12968012, rs1057520801) genes in the group of patients with colorectal cancer and in the control group, and comparing the genotypic frequency distributions with clinical-pathological features within the study group and between the groups. MATERIALS AND METHODS: SNP genotyping analysis was performed on genomic DNA isolated from 84 frozen tissue sections of colorectal cancer and from 60 peripheral blood samples of patients without cancer. To evaluate the polymorphic variants of SMAD genes, the restricted fragment length of a polymorphism reaction (PCR-RFLP) was used. RESULTS: The results obtained in the study showed no significant association between the examined polymorphisms and the risk of developing colorectal cancer. CONCLUSION: More extensive studies to confirm the results obtained in this study are needed. Further studies on a larger study group divided according to the clinical stage and histological differentiation may allow finding or excluding the significance of the studied SNPs as potential markers of colorectal cancer in relation to the clinico-pathological data.

The impact of ABCB1 gene polymorphism and its expression on non-small-cell lung cancer development, progression and therapy - preliminary report.

The ABCB1 gene belongs to ATP binding cassette (ABC) transporter genes that has been previously implicated in cancer progression and drug response. This study aimed to evaluate the association between the SNP 3435 and the expression of the ABCB1 gene in lung cancer patients in the Polish population in comparison to clinicopathological parameters and treatment. 150 RNA and 47 DNA samples were isolated from 49 lung cancer cases including both tissue samples and blood taken from the same patients at three time points: diagnosis, 100 days and one year after the surgical intervention. Qualitative and real-time PCR analysis of expression were done, also genotyping by PCR-RFLP. Mutant homozygous TT and allele T are present statistically significantly more frequently in the group of patients with lung cancer. There is no difference with expression level in lung cancer tissue and blood sample taken from the same patients before surgical treatment. On the basis of blood samples analysis it was observed that the expression level of ABCB1 mRNA was growing in time. Higher levels were marked after 100 days and one year after the surgical intervention. The complementary pharmacological treatment induced higher expression levels of ABCB1. The presented data suggest an important role of ABCB1 in lung cancer, the increasing level of ABCB1 mRNA which can be connected with induction of multidrug resistance mechanism is also significant, that observation must be confirmed in further analysis.

Estimation of CYP3A4*1B single nucleotide polymorphism in patients with recurrent Major Depressive Disorder.

BACKGROUND: Major depression is the most common mental illness in the world. Failures in treatment may occur due to the presence of a subtype of depression called TRD (Treatment- Resistant Depression). CYP3A4 polymorphism (rs2740574) can increase the activity of Cytochrome P450 3A4, contributing to faster metabolism of xenobiotics and reduced response to treatment. The aim of the study was to assess the distribution of CYP3A4*1B in study and control group and to estimate the influence of particular genotypes on parameters such as: age at onset, severity of symptoms before treatment and on the effectiveness of therapy. METHODS: Total of 192 patients were enrolled in this study (102 patients suffering from recurrent Major Depression Disorder, 90 healthy blood donors). PCR Restriction Fragment Length Polymorphism method with MboII enzyme was performed. The presence of CYP3A4*1B allele was evaluated on the basis of agarose gel electrophoresis. RESULTS: There was a tendency in frequency of genotypes distribution in the study group in comparison with the control group (p = 0.050). There were no statistically significant differences in the distribution mutant allele among these two groups, but there was a tendency for mutant allele to occur more often in the study group (p = 0.050). No significant correlations were found between the specific genotype and the studied parameters: age at onset (p = 0.232), severity of the symptoms (p = 0.946), and efficacy of treatment (p = 0.882). CONCLUSION: The study suggests that CYP3A4*1B polymorphism have no influence on the predisposition to depression, the severity of depressive symptoms and the efficiency of antidepressant therapy.

Does the expression of the ACVR2A gene affect the development of colorectal cancer?

Colorectal cancer has become a serious problem, especially in highly developed countries. As reported by the World Health Organization, the number of colon cancer cases in the world in 2012 amounted to 1.36 million. It is the second most common cancer in females (614,000 cases, 9.2% of the total) and the third in males (746,000 cases, 10.0% of the total) worldwide. It is believed that TGFß pathway elements are involved in the pathogenesis of colorectal cancer. This study assessed one of these elements, the ACVR2A gene. Qualitative and quantitative analyses of the ACVR2A gene in 84 patients with colorectal cancer was performed. There was no statistically significant association between ACVR2A gene expression and age, gender, histological type, grading of tumor, vascular invasion, and presence of lymphocytes in tumor tissue. No association was observed between the ACVR2A gene expression level and the presence of metastases in regional lymph nodes and distant metastases. In this study, larger tumors (T3 and T4) were characterized by higher ACVR2A expression compared to smaller tumors (T1 and T2). This may indicate an association between ACVR2A expression and the severity of pathological changes in the tumor growth process.

The contribution of ABCG2 G34A and C421A polymorphisms to multiple myeloma susceptibility.

BACKGROUND: Breast cancer resistance protein BCRP, belonging to superfamily G of the adenosine triphosphate-binding cassette (ABC) transporters, is an efflux pump and plays a critical role in protecting cells against xenobiotics and toxic compounds including (pro)carcinogens. BCRP is expressed in many tissues, including hematopoietic stem cells. Genetic variants such as single nucleotide polymorphisms (SNPs) can change the gene expression and/or reduce their products' activity which may affect an individual's susceptibility to xenobiotics and the development of carcinoma. These changes may affect the exposure of blood cells to toxic compounds, which increases the risk of multiple myeloma. The aim of this study was to determine polymorphisms at positions G34A and C421A of the ABCG2 gene in multiple myeloma in the Polish population for the first time. MATERIALS AND METHODS: Material for the study included DNA isolated from nucleus of cells of peripheral blood of patients diagnosed with multiple myeloma (investigated group N=181) and from healthy people (control group N=97). Research into the polymorphisms was conducted using the polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The present study showed a statistically significant association between SNP C421A of the ABCG2 gene and the risk of developing multiple myeloma (P=0.0218). No statistically significant relationship was found for the other parameters analyzed, such as age, gender, or type of secreted immunoglobulin. CONCLUSION: Preliminary studies indicate that SNP C421A may become a potential predictor for the development of multiple myeloma.

Decreased MMP1 gene expression in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a heterogeneous disorder of haematopoietic stem cells or progenitor cells. Metalloproteinases (MMPs) are proteolytic enzymes whose activity is increased in different types of solid tumours. These enzymes regulate many processes associated with tumour progression. In haematological malignancy, the role of MMPs seems to be underestimated, and only metalloproteinase 2 (MMP2) and metalloproteinase 9 (MMP9) have been widely examined so far. In this work, differences in metalloproteinase 1 (MMP1) gene expression between patients with AML and healthy individuals were assessed. The relative expression level of the MMP1 gene was obtained by a real time PCR method preceded by reverse transcription. The relative level of MMP1 gene expression in patients with AML was decreased when compared to that of the control group. The role of MMP1 in AML could be different from that in solid tumours. Decreased MMP1 gene expression in AML similar to that of MMP9, shows a greater role for MMP1 in normal haematopoiesis than in the development of leukaemic cells.

Cathelicidin LL-37 Affects Surface and Intracellular Toll-Like Receptor Expression in Tissue Mast Cells.

Undoubtedly, mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, they release many proinflammatory and antimicrobial mediators, and they express pattern recognition receptors, such as TLRs. These receptors play a key role in recognition and binding molecules associated with microorganisms and molecules associated with damage. Cathelicidins exhibit direct antimicrobial activities against a broad spectrum of microbes by perturbing their cell membranes. Accumulating evidence suggests a role for these molecules in supporting cell activation. We examined the impact of human cathelicidin LL-37 on tissue mast cell TLR expression and distribution. Depending on context, we show that LL-37 stimulation resulted in minor to major effects on TLR2, TLR3, TLR4, TLR5, TLR7, and TLR9 expression. Confocal microscopy analysis showed that, upon stimulation, TLRs may translocate from the cell interior to the surface and conversely. FPR2 and EGFR inhibitors reduced the increase in expression of selected receptors. We also established that LL-37 acts as a powerful inducer of CCL3 and ROS generation. These results showed that in response to LL-37, mast cells enhance the capability to detect invading pathogens by modulation of TLR expression in what may be involved FPR2 or EGFR molecules.

In vitro effect of octenidine dihydrochloride against Trichomonas vaginalis.

Trichomoniasis is the most common non-viral sexually transmitted disease. It is associated with a wide spectrum of complications, including infertility and increased susceptibility to human immunodeficiency virus (HIV). A rising number of reports of Trichomonas vaginalis strains resistant to metronidazole has driven the search for new compounds. In the present study, the in vitro effects of the common antiseptic octenidine dihydrochloride against T. vaginalis were tested on metronidazole-resistant and -susceptible strains. Assays were performed under microaerophilic conditions in three different media containing varying concentrations of protein. It was shown that octenidine dihydrochloride is highly effective against T. vaginalis, with no difference between metronidazole-resistant and -susceptible strains. The 50% effective concentration (EC50) values ranged from 5.7 to 21.37µg/mL after 5min, from 6.48 to 10.82µg/mL after 15min and from 0.68 to 2.11µg/mL after 30min of treatment depending on the protein concentration of the test medium. Octenidine dihydrochloride, already approved in some countries for the treatment of bacterial and fungal vaginal infections, appears to be a promising alternative treatment for trichomoniasis, particularly in mixed vaginal infections or in cases caused by metronidazole-resistant strains.