Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Cancer stem cells, their microenvironment and anoikis

Tumors are composed of a variety of cancer cells, all of which contribute to tumor heterogeneity. Among these populations of cells, cancer stem cells (CSCs) have an important role in the initiation and progression of cancer. CSCs are maintained extrinsically within the tumor microenvironment, which contains both cellular and physical factors. As a barrier to metastases, cells normally undergo apoptosis (cell death process) after they lose contact with their extracellular matrix or neighboring cells. This cell death process has been termed “anoikis.” The tumor cells that acquire malignant potential develop mechanisms to resist anoikis. The tumor microenvironment has been acknowledged to contribute to anoikis resistance of bystander cancer cells via modulation of the matrix stiffness, enhancement of oxidative stress, production of pro-survival soluble factors, trigger of epithelial-mesenchymal transition (EMT), and self-renewal ability, thus leading to metabolic deregulations of cancer cells. In this article, we review the significance of perivascular cells, extracellular matrix, tumor stiffness, and hypoxia in the regulation of CSC plasticity and anoikis resistance. With a better understanding of the CSC interaction with its niche and anoikis resistance, it is possible to identify potential therapeutic targets for the development of more effective treatments against cancer

The rhythmicity of life: A review of the circadian clocks

Physiology of the mammalian body has been adapted to diurnal cycles of around 24 h, an evolutionary situation that affects a wide spectrum of biological events including sleep-to-wake transitions, feeding/fasting, body temperature, and hormonal regulations. The patterns of the diurnal cycle occur due to rhythmic oscillations that arise from the suprachiasmatic nucleus of hypothalamus, which also can be defined as the pacemaker of the system. The clock can be defined as a molecular machinery driven by the core clock genes that encode clock proteins in a rhythmic oscillatory fashion maintained by the light/dark cycles of the environment. Although the well-established knowledge refers to the function of the circadian rhythm as maintenance of the normal physiology, growing evidence shows that disruptions in the system usually caused by genetic and/or epigenetic misregulations may have a direct effect to lead major pathological conditions, such as carcinogenesis. This review outlines the main molecular aspects of circadian physiology, and reveals the reasons for and results of the circadian disruptions at different levels. In spite of the fact that more proof is needed for a direct correlation between circadian disruptions and oncogenesis and other pathological events, data obtained from current research supports the role of circadian rhythms in malfunctioning of the normal cellular metabolism

The relationship of seminal leptin levels with semen parameters and dna fragmentation

Amaç: Bu çalışmamızda insan semen leptin düzeylerini ve semen parametreleri ile ilişkisinin incelenmesi amaçlanmıştır. Materyal ve Metod: YNormal ve oligoastenoteratospermik 30 hastalık gruplar oluşturuldu. Hastaların semen örneklerinde leptin ve DNA fragmantasyon düzeyleri incelendi, ayrıca sperm sayısını ve motilite oranlarını içeren semen parametreleri de- ğerlendirildi. Bulgular: İnfertil hastalarda sperm sayısı ve motilite oranları normal gruba göre anlamlı olarak azalmıştır: 6,40±4,29 (x106/ mL), % 38,63±14,92 (p<0,0001). DNA fragmantasyon oranları normal grupta % 21,00±8,23 olarak gözlenirken infertil erkeklerde % 38,43±14,23 oranıyla anlamlı olarak yüksek bulunmuş, semen leptin oraları ise normal grupta 347,58±111,13 ng/mL olarak gözlenirken, infertil grupta 267,63±56,36 ng/mL düzeyi ile anlamlı olarak azaldığı gözlenmiştir. İnfertil gruplar kendi içinde incelendiği zaman ise semen leptin düzeyi ile yaş, volüm, sperm sayısı ve motilitesi arasında istatistiksel olarak anlamlı olacak bir ilişki saptanmamıştır. Sonuç: Çalışmamızda, oligoastenoteratozoospermik erkek infertilitesinde serum leptin seviyelerinin azalmış olduğunu, ama sperm motilitesi ile anlamlı bir ilikinin bulunmadı gözlemlenmiştir. Leptinin semende tanısal bir kriter olarak kullanılabilmesi için daha geni kapsamlı çalışmaların yapılması gerektiği düşünülmektedir.Objective: The objective of this study is to investigate the relationship between human seminal leptin levels and semen parameters.Material and Methods: Study groups include 30 males with oligoasthenoteratozoospermia and 30 males who have normal semen parameters. Leptin and DNA fragmentation levels were investigated in both groups, along with a variety of semen parameters including sperm count and motility.Results: In comparison with the normal males, sperm count and motility have decreased significantly in infertile patients: 6,40&plusmn;4,29(x106/mL), %, 38,63&plusmn;14,92 (p&lt;0,0001). DNA fragmentation levels were found as 21,00&plusmn;8,23 % and 38,43&plusmn;14,23 %, in normal and patient groups respectively. Seminal leptin levels were 347,58&plusmn;111,13 ng/mL in the normal group, while there was a significant decrease to 267,63&plusmn;56,36 ng/mL in the infertile group. Among infertile patient groups, no significant difference was observed regarding the relationship between seminal leptin levels and age, volume, sperm count and motility.Conclusion: In our study it was demonstrated that, serum leptin levels decrease in oligoasthenoteratozoospermic infertile males, while there is not a significant relation with the motility of sperm. In order to use seminal leptin levels as a diagnostic tool more extensive studies are needed

Microrna analysis of human decidua mesenchymal stromal cells from preeclampsia patients

Introduction: In preeclampsia (PE), human decidua mesenchymal stromal cells (hDMSCs) are exposed toabnormally high levels of oxidative stress and inflammatory factors circulating in the maternal blood. MicroRNAs(miRNAs) have been shown to have a significant impact on the differentiation, maturation and function ofmesenchymal stromal cells (MSCs). Our aim in the present study is firstly to investigate differentially expressedmiRNA levels to be used as a biomarker in the early detection of PE and secondly to investigate whether thosedifferentially expressed miRNAs in hDMSCs have an effect on the pathogenesis of PE.Methods: This study covers miRNA expression analysis of hDMSCs from 7 PE patient and 7 healthy pregnantwomen and is a preliminary study to investigate putative biomarkers. After cell culture and cell sorting, totalRNA including miRNAs were isolated from hDMSCs. Let-7b-3p, let-7f-1-3p, miR-191–3p, miR-550a-5p, miR-33b-3p and miR-425–3p were used for miRNA analysis and U6 snRNA was used for normalization of the samples.MiRNA analysis was performed by droplet digital polymerase chain reaction (ddPCR) method and obtainedresults were evaluated statistically.Results: As a result of the analysis, it was observed that the levels of hsa-miR-33b-3p significantly (AUC: 0.93, p =0.04, fold change: 4.5) increased in hDMSC of PE patients compared to healthy controls. However, let-7b-3p, let-7f-1-3p, miR-191–3p, miR-550a-5p, and miR-425–3p were not considered as significant because they did notmeet the p &lt; 0,05 requirement.Discussion: Within the scope of the study, it is predicted that miR-33b-3p (p = 0.004, AUC = 0.93) can be used asa biomarker in detecting PE

Antioxidant activity of CAPE (Caffeic Acid Phenethyl Ester) in vitro can protect human sperm deoxyribonucleic acid from oxidative damage

Purpose: Sperm processing (e.g., centrifugation) used in preparation for assisted reproduction can result in excessive generation of reactive oxygen species (ROS) and potential sperm damage. The use of antioxidants during sperm processing has been shown to prevent iatrogenic sperm damage, including DNA damage. In this study, we evaluated the effect of caffeic acid phenethyl ester (CAPE) on oxidative stress mediated sperm dysfunction and DNA damage. Methods: Semen samples were obtained to liquefy at room temperature. After centrifugation and washing protocols, spermatozoa were incubated in a single step supplemented medium with either of 10, 50 or 100 µmol/L CAPE for 2 hours at 36 °C. After incubation period, MDA levels of seminal plasma were measured. The fragmentation in sperm DNA was detected by light microscopy via use of an aniline blue assay, while ultrastructural morphology was analyzed by transmission electron microscopy. Results: Significant increase has been observed in percent chromatin condensation (assessed by aniline blue staining) and Malondialdehyde (Mmol/L) in oligoasthenoteratozoospermia group before the centrifugation (0.57 ± 0.15). Incubation of samples with 100 µmol/L CAPE after centrifugation resulted in a significantly lower percent chromatin condensation compared to samples incubated without CAPE (0.42 ± 0.12) (P <0.0033). Incubation of all samples with CAPE (10 µmol/L, 50 µmol/L, 100 µmol/L.) after centrifugation resulted in a significantly lower percentage of Malondialdehyde levels. Conclusions: The data suggests that preincubation of spermatozoa with the antioxidant CAPE offers protection against oxidative DNA damage in vitro.The Ministry of Economic Affairs and Employmen

Wound healing effects of methanol extract of Laurocerasus officinalis roem

WOS: 000469009000004PubMed ID: 30409033Laurocerasus officinalis Roem. (syn: Prunus laurocerasus L.) is a member of Rosaceae family. We investigated the antimicrobial and antioxidant activity of L. officinalis Roem in wound healing both in vivo and in vitro using an excisional wound model model in mice. We used four groups of eight mice as follows: untreated (control), empty gel, extract +gel (L. officinalis +gel), and Madecassol (R) groups. All treatments were applied topically once daily. The scar area, percentage wound closure and epithelization time were measured. L. officinalis promoted wound healing and increased granulation tissue, epidermal regeneration and angiogenesis. L. officinalis extract, which is known for its antioxidant and antimicrobial activities, may be useful for promoting wound healing

Additional file 5: Figure S2. of DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease

Validation of the bisulfite modification and pyrosequencing assays for relevant loci in HDAC4, HOXA2 and PPP1R18 genes. Plots comparing 0, 25, 50, 75 and 100 % of methylated DNA with obtained methylation results are shown; only assays with an acceptable performance (r 2 values over 0.95) were used in this study. (TIF 149 kb

Additional file 2: Table S1. of DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease

Summary of differentially methylated regions. (DOCX 16 kb

Additional file 7: Table S4. of DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease

Demographic, clinical and laboratory characteristics of the non-progressors and progressors in serial biopsies. (DOCX 18 kb