Oleuropein: A Potential Inhibitor for Prostate Cancer Cell Motility by Blocking Voltage-Gated Sodium Channels.

In this study, we investigated whether olive leaf and oleuropein have the potential to stop cell motility, which a metastatic cell behavior by blocking voltage-gated sodium channels (VGSCs). For this purpose, it was first prepared the aqueous extract of olive leaves (AOLE). Then it was assayed the effect on the motility of MAT-LyLu, a highly metastatic Dunning rat prostate adenocarcinoma cells of this extract. The phenolic content of AOLE was analyzed using LC-MS/MS instrument. It was observed that oleuropein was the most finding compound in AOLE. Therefore, whether oleuropein was responsible for the inhibitory effect of AOLE on the MAT-LyLu cell movement was tested. Nontoxic oleuropein concentrations and those that did not affect proliferation on MAT-LyLu cells were determined. Subsequently, it was examined the effects of oleuropein on the lateral and vertical movement of MAT-LyLu cells. To elucidate the mechanism of oleuropein affecting cell motility, whether it suppressed mRNA expression of SCN9A, which encodes the VGSC was analyzed. Accordingly, oleuropein suppressed the movement of MAT-LyLu cells by reducing SCN9A mRNA expression. In conclusion, we report the first time that oleuropein might be considered as a potential antimetastatic agent for prostate cancer due to its blocking effect on VGSC-mediated cell motility.

Novel miRNAs as potential biomarkers in stage II colon cancer: microarray analysis.

The aim of this study was to determine oncogenic and tumor-suppressing miRNA profiles associated with the development and progression of cancer using tumor tissues from patients with colorectal cancer (stage II) that did not show nodal spread or advanced metastasis to identify potential biomarkers. A microarray system (GeneChip miRNA 4.0 Array chip, Affymetrix) was used to determine the microRNA profiles of five patients with stage II colon cancer based on normal and colon tumor tissues. Of 32 identified miRNAs, an increase in three microRNAs (hsa-miR-4745-5p, hsa-miR-6126, and hsa-miR-1469) was observed in tumor tissues relative to that in control tissues. Additionally, this study demonstrated for the first time that the expression of the 8 miRNAs (hsa-miR-378i, hsa-miR-378a-3p, hsa-miR-378c, hsa-miR-378d, hsa-miR-378e, hsa-miR-378f, hsa-miR-378a-5p, and hsa-miR-378g) from miR-378 members among the differentially expressed miRNAs is reduced. The target genes of these downregulated miRNAs were determined by using DIANA miRPath v3. The effect of identified genes on colon cancer stage II was determined the biological process and biological pathway using Funrich Gene Enrichment. It was revealed that these miRNAs were affected the signaling pathways which control cell proliferation, cell-cell interaction, and apoptosis in stage II colon cancer. In patients with early stage II colon cancer, miR-378 can be used as a biomarker of colorectal cancer. Thus, miR-378 can facilitate treatment with early diagnosis.

Investigation of possible maternal and fetal factors which affect umbilical coiling index.

AIM: The aim of this study was to investigate the possible maternal and fetal factors, which affect the Umbilical Coiling Index (UCI). METHODS: This prospective, observational, analytic study was conducted using the data of 380 women with term pregnancy and newborns who presented at a University Hospital. Hemoglobin (Hb), ferritin, iron, and the total iron binding capacity (TIBC) of the maternal blood were measured, and transferrin saturation was estimated based on the ratio between serum iron and TIBC. Blood gases, ferritin, iron, and TIBC of the umbilical cord were also measured, and the transferrin saturation was calculated. The length and thickness of the umbilical cord, numbers of coilings, weight of placenta, neonatal weight were registered. The UCI was calculated dividing the total number of coils by the length of the umbilical cord (in cm). RESULTS: A positive, linear, and statistically significant relationship was found between the UCI scores and the umbilical cord blood transferrin saturation, umbilical cord thickness, and the first- and fifth-min APGAR scores (p = .044, p < .001, p = .008, p = .022, respectively). No statistically significant relationship was found between the maternal Hb values and the UCI scores (p = .472). In addition, there was no statistically significant relationship between the UCI scores and maternal ferritin, maternal transferrin saturation and umbilical cordon ferritin levels (p = .940, p = .681, and p = .975, respectively). CONCLUSIONS: A positive correlation was found between the UCI and umbilical cord transferrin saturation and between the newborn APGAR scores. However, this finding is not sufficient to explain the relationship of the umbilical cord dynamics with the newborn wellbeing and coiling.

Naringenin inhibits prostate cancer metastasis by blocking voltage-gated sodium channels.

In this study, we investigated the potential effects of naringenin on the motility of MAT-LyLu cells, which overexpress voltage-gated sodium channels and whose metastatic behaviours are associated with these channels. We first determined the concentration of naringenin that did not show toxic effects or block cell growth. Then, the effects of naringenin on cell motility in the lateral and vertical directions were tested by wound healing assays and transwell invasion assays, respectively. Finally, to determine the suppressive effects of naringenin on cell movement in both directions, the expression of the SCN9A gene, which encodes Nav1.7 voltage-gated sodium channel, was determined by real-time quantitative polymerase chain reaction. The data revealed that high concentrations of naringenin (75 µM) inhibited cell proliferation, whereas low concentrations (5 and 10 µM) decreased the movement of MAT-LyLu cells. Moreover, 10 µM naringenin displayed inhibitory effects on cell movement by reducing the expression of the SCN9A gene at the mRNA level. In conclusion, naringenin was found to have direct or indirect blocking activity on voltage-gated sodium channels encoded by the SCN9A gene.

Impact of Smoking on the Ocular Surface, Tear Function, and Tear Osmolarity.

PURPOSE: This study evaluated the effects of cigarette smoking on the ocular surface, tear function, and tear osmolarity. MATERIALS AND METHODS: A total of 50 smokers with at least 5 years of heavy smoking (defined as 1 pack/day) and 51 nonsmoking, healthy individuals were enrolled. Tear osmolarity was measured with an osmometer (TearLab™ Osmolarity System). Ocular surface examinations involved corneal fluorescein staining, measurement of the tear film breakup time (TBUT), the Schirmer 1 test, measurement of corneal sensitivity with a Cochet-Bonnet esthesiometer, and conjunctival impression cytology. Dry eye symptoms were scored using the Ocular Surface Disease Index (OSDI) questionnaire. The results were compared with those from an age and sex-matched control group. The Chi-squared and independent sample t-tests were used for statistical analyses. RESULTS: The smokers had significantly higher tear osmolarity values (305.38 ± 9.81 vs. 301.14 ± 7.04 mOsm/L; p = 0.014) and OSDI scores (34.13 ± 16.58 vs. 18.09 ± 9.61; p < 0.001) than the healthy controls. However, the TBUT, corneal sensitivity, and goblet cell density were significantly lower in smokers compared to healthy controls, but the fluorescein staining and Schirmer 1 test results were not statistically different between the smokers and controls. CONCLUSION: Smoking results in increased osmolarity of the tear film, which can damage the ocular surface and tear function.

Dynamic thiol/disulfide homeostasis in patients with age-related macular degeneration.

PURPOSE:: We evaluated dynamic thiol/disulfide homeostasis (TDH), malondialdehyde (MDA) levels, and catalase (CAT) activity in patients with age-related macular degeneration (AMD). All analyzes were conducted on plasma samples. METHODS:: Thirty-two patients with AMD and 38 age-matched healthy controls were included. Native thiol, total thiol, and disulfide levels and TDH status were determined using a novel, automated assay. MDA levels and CAT activity were determined. Percentages were compared using the chi-squared test. The Student's t-test and Mann-Whitney U-test were used to compare quantitative variables. RESULTS:: Native thiol levels were significantly lower (p=0.004) in patients with AMD (272.02 ± 52.41 µmol/l) than in healthy individuals (307.82 ± 47.18 µmol/l), whereas disulfide levels were significantly higher (p<0.001) in patients with AMD than in controls (21.64 ± 5.59 vs. 14.48 ± 5.37 µmol/L). Dynamic TDH was also significantly lower (p<0.001) in patients with AMD than in controls (13.41 ± 4.3 vs. 25.41 ± 14.52 µmol/l). No significant differences were evident in total thiol or MDA levels. Mean CAT activity was significantly higher (p=0.043) in patients with AMD compared with controls (0.035 vs. 0.018 k/ml). CONCLUSIONS:: The antioxidant/oxidant balance demonstrated by dynamic TDH is shifted to the oxidative side in patients with AMD.

Runt-Related Transcription Factor 2 (Runx2) Is Responsible for Galectin-3 Overexpression in Human Thyroid Carcinoma.

Runx2 promotes metastatic ability of cancer cells by directly activating some of the mediators regarding malignancy. Galectin-3 (Gal-3) extensively expressed in normal and transformed cells and it is responsible for many cellular processes. In this study, we aimed to investigate whether there is any relationship between runx2 transcription factor and regulation of galectin-3 expression in different human thyroid carcinoma cell lines. To show effects of runx2 transcription factor on gal-3 expression, we developed runx2 knockdown model in the thyroid carcinoma cell lines; anaplastic 8505C and 8305C and, papillary TPC-1 and follicular FTC-133 by using siRNA transfection. We analyzed the protein expressions and mRNA levels of gal-3 and MMP2/9 in the runx2-silenced cell lines using Western blotting, qPCR, and fluorescent microscopy. Our results showed that mRNA expression levels of gal-3 and MMP2/9 were downregulated in runx2-silenced cell lines. In this investigation, we revealed that regulation of gal-3 expression was strongly correlated with runx2 transcription factor in human thyroid carcinoma. Considering the contribution of human gal-3 in collaboration with MMP2/9 to the malignant characters of many cancers, regulation of their expressions through runx2 seems like one of the key regulatory mechanism for malignant potential of human thyroid carcinoma. Accordingly, runx2 transcription factor inhibitors can be a potential target in order to prevent gal-3 mediated malignancy of human thyroid carcinoma. J. Cell. Biochem. 118: 3911-3919, 2017. © 2017 Wiley Periodicals, Inc.

Correlations of maternal neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with birth weight.

OBJECTIVE: The aim of this study is to investigate the possible correlation of hemogram parameters including neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with birth weight and gestational week. MATERIALS AND METHODS: This prospective study has been conducted with 783 patients. The maternal age, parity, gestational age, type of delivery, values of complete blood count (CBC) variables and the weight of newborn were recorded. We analyzed the statistical differences between the NLR, PLR, hemoglobin (HGB), platelet distribution width (PDW), red cell distribution width (RDW), mean platelet volume (MPV), platelet, neutrophil, lymphocyte and white blood cells (WBC) in terms of the birth weight. RESULTS: There was no statistically significant difference in the NLR in terms of the birth weight (p = 0.097), whereas there was a statistically significant difference in the PLR (p < 0.001). In correlation analyses, a linear, negative, weak and statistically significant correlation was detected between NLR and PLR with the birth weight of infant and gestational week (p = 0.011 and p < 0.001, respectively). CONCLUSION: This prospective study is the first in the literature which investigates the correlation of NLR and PLR with the week of birth and birth weight of the infant. Our study suggested that the maternal NLR and PLR are negatively correlated with the week of birth and birth weight of the infant.

Unilateral hemorrhagic macular infarction associated with marijuana, alcohol and antiepileptic drug intake.

A 55-year-old male presented with a complaint of a painless and sudden loss of vision in the right eye. Fundus photography revealed loss of transparency and edema in the central macular region. Optical coherence tomography showed increased reflectivity and diffused swelling in the inner retinal layers. Fluorescein angiography revealed a large area of capillary non-perfusion with a pronounced hypofluorescent area with distinct borders. To our knowledge, this is the first report of a hemorrhagic macular infarction associated with marijuana and pregabalin misuse.

Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility.

Hedera helix L., a member of Araliaceae family, has antiproliferative, cytotoxic, antimicrobial, antifungal, antiprotozoal and anti-inflammatory effects, and is used in cosmetics. The aim of the present study was to investigate the effect of treatment with extracts of leaves and unripened fruits of H. helix on rat prostate cancer cell lines with markedly different metastatic potentials: Mat-LyLu cells (strongly metastatic) and AT-2 cells (weakly metastatic). The effects of the extracts on cell kinetics and migration were determined. Tetrodotoxin was used to block the voltage-gated sodium channels (VGSCs) associated specifically with Mat-LyLu cells. Cell proliferation was detected spectrophotometrically using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The mitotic index was determined using the Feulgen staining method. Lateral motility was quantified by wound-healing assays. The results of the present study demonstrated that cell kinetics (proliferation and mitotic activity) and motility were inhibited by ethanolic leaf extract of H. helix. The ethanolic extract of H. helix fruit suppressed Mat-LyLu cell migration, with no effect on proliferation. The opposite effects were observed in AT-2 cells; migration was not affected but proliferation was inhibited. In conclusion, the ethanolic fruit extract of H. helix may inhibit the cell migration of Mat-LyLu cells by blocking VGSCs. However, the effect of ethanolic leaf extract of H. helix treatment on the lateral motility of the cancer cells is unclear.

Idiopathic Isolated Cilioretinal Artery Occlusion Treated with Hyperbaric Oxygen Therapy.

Cilioretinal artery occlusion (CLRAO) is a rare event which has been reported in association with various systemic diseases. We report a case of idiopathic isolated CLRAO treated successfully with hyperbaric oxygen (HBO) therapy. A 26-year-old man presented with sudden, painless vision loss and an inferior hemivisual field defect in the left eye. Fundus fluorescein angiography revealed an occluded cilioretinal artery. After 2 weeks of HBO therapy, visual acuity improved from 20/200 to 20/20. The visual field defect improved.

Refractive Results Using a New Optical Biometry Device: Comparison With Ultrasound Biometry Data.

The aim of the study was to compare the measurements of optical (AL-Scan; Nidek Co., Ltd.) and ultrasonic (Echo Scan US-800; Nidek Co., Ltd.) biometry devices and to assess refractive results after cataract surgery. Eighty-one cataractous eyes of 81 patients were included in this study. Biometry was performed using the AL-Scan and an ultrasonic biometer (USB). Axial length (AL), keratometry (K) data, and intraocular lens (IOL) power calculations using the SRK/T formula were compared. Bland-Altman analysis was used to assess the extent of agreement between AL-Scan and USB data in terms of AL measurement and IOL power calculation. The K measurements of the AL-Scan were compared to autorefractor data (Canon Autorefractor RK-F1). The AL-Scan assessed the AL as longer (average difference 0.06 ± 0.18 mm; ICC = 0.987; P < 0.001) and the IOL power as greater (average difference 0.19 ± 0.66 D; ICC = 0.964; P < 0.001) than the USB. The AL-Scan also measured average K values (average difference 0.25 ± 0.25 D; ICC = 0.985; P < 0.001) greater than those given by the autorefractor. The postoperative mean absolute error was +0.30 ± 0.04 D (minimum: -0.51 D, maximum +1.04 D). The postoperative mean K value change was 0.36 ± 0.29 D (P < 0.05). The differences between measurements afforded by the AL-Scan and USB may be clinically acceptable. Keratometric changes that develop after cataract operations compromise the attainment of good refractive outcomes.

Tear function in patients with chronic renal failure undergoing hemodialysis.

OBJECTIVES: To evaluate dry eye symptoms and clinical tear film alterations in patients with chronic renal failure (CRF). MATERIALS AND METHODS: Thirty-five non-diabetic CRF patients undergoing hemodialysis, and 31 healthy individuals were enrolled. An ocular surface disease index questionnaire (OSDI) was administered, and after a complete ocular examination, Schirmer and tear break-up time (TBUT) tests were performed. RESULTS: OSDI scores were significantly higher (p<0.01) and TBUT tests were significantly lower (p=0.01) in CRF patients than in the control group. Schirmer test results were also lower in the CRF patients group, but lacked statistical significance (p=0.20). CONCLUSION: Patients with CRF should be advised to obtain an ophthalmic examination, especially for dry eye.