Antiproliferative, antimigratory, and apoptotic effects of diffractaic and vulpinic acids as thioredoxin reductase 1 inhibitors on cervical cancer.

Cervical cancer is among the most frequently observed cancer types in females. New therapeutic targets are needed because of the side impacts of existing cancer drugs and the inadequacy of treatment methods. Thioredoxin reductase 1 (TrxR1) is often overexpressed in many cancer cells, and targeting TrxR1 has become an attractive target for cancer therapy. This study investigated the anticancer impacts of diffractaic and vulpinic acids, lichen secondary metabolites, on the cervical cancer HeLa cell line. XTT findings demonstrated showed that diffractaic and vulpinic acids suppressed the proliferation of HeLa cells in a dose- and time-dependent manner and IC50 values were 22.52 µg/ml and 66.53 µg/ml at 48 h, respectively. Each of these lichen metabolites significantly suppressed migration. Diffractaic acid showed an increase in both the BAX/BCL2 ratio by qPCR analysis and the apoptotic cell population via flow cytometry analysis on HeLa cells. Concerning vulpinic acid, although it decreased the BAX/BCL2 ratio in this cells, it increased apoptotic cells according to the flow cytometry analysis results. Diffractaic and vulpinic acids significantly suppressed TrxR1 enzyme activity rather than the gene and protein expression levels in HeLa cells. This research demonstrated for the first time, that targeting TrxR1 with diffractaic and vulpinic acids was an effective therapeutic strategy for treating cervical cancer.

Toxicity of Glycyl-l-Prolyl-l-Glutamate Pseudotripeptides: Cytotoxic, Oxidative, Genotoxic, and Embryotoxic Perspectives.

The tripeptide H-Gly-Pro-Glu-OH (GPE) and its analogs began to take much interest from scientists for developing effective novel molecules in the treatment of several disorders including Alzheimer's disease, Parkinson's disease, and stroke. The peptidomimetics of GPEs exerted significant biological properties involving anti-inflammatory, antiapoptotic, and anticancer properties. The assessments of their hematological toxicity potentials are critically required for their possible usage in further preclinical and clinical trials against a wide range of pathological conditions. However, there is so limited information on the safety profiling of GPE and its analogs on human blood tissue from cytotoxic, oxidative, and genotoxic perspectives. And, their embryotoxicity potentials were not investigated yet. Therefore, in this study, measurements of mitochondrial viability (using MTT assay) and lactate dehydrogenase (LDH) release as well as total antioxidant capacity (TAC) assays were performed on cultured human whole blood cells after treatment with GPE and its three novel peptidomimetics for 72 h. Sister chromatid exchange (SCE), micronucleus (MN), and 8-oxo-2-deoxyguanosine (8-OH-dG) assays were performed for determining the genotoxic damage potentials. In addition, the nuclear division index (NDI) was figured out for revealing their cytostatic potentials. Embryotoxicity assessments were performed on cultured human pluripotent NT2 embryonal carcinoma cells by MTT and LDH assays. The present results from cytotoxicity, oxidative, genotoxicity, and embryotoxicity testing clearly propounded that GPEs had good biosafety profiles and were trouble-free from the toxicological point of view. Noncytotoxic, antioxidative, nongenotoxic, noncytostatic, and nonembryotoxic features of GPE analogs are worthwhile exploring further and may exert high potentials for improving the development of novel disease-modifying agents.

May endocan be a new biomarker in the diagnosis of endometriosis?

AIM: As known, inflammatory substances are considered to have a role in the onset and progression of endometriosis. In this study, we aimed to find a biomarker that can be used in the diagnosis of endometriosis by investigating the serum levels of endocan, which is a substance that we know to have an important role in angiogenesis and inflammation, in patients with endometriosis. STUDY DESIGN: 45 patients between the ages of 18-40 with the diagnosis of stage 3-4 endometriosis and whose postoperative histopathological tissue diagnoses were endometriosis were included in the study as study group. As the control group, a total of 45 healthy women between the ages of 18-40 were included in the study. The two groups were statistically compared. RESULTS: There was no statistically significant difference between the two groups in terms of age, BMI, LH, E2, and mean Hb values. It was observed in the examination of the endocan levels that the mean values in the study (endometriosis, patient group) group were statistically and significantly higher compared to the control (healthy) group (p:0.000). Also, mean FSH and Ca125 levels were determined to be statistically and significantly higher in the endometriosis group (p:0.042 and p:0.000). CONCLUSION: In this study, we found a statistically significant correlation between the levels of serum endocan and endometriosis. As the results, endocan can be used as a new biomarker to diagnose patients with endometriosis or in their follow up period. Much more comprehensive future studies are needed on this subject.

Lipoic Acid Conjugated Boron Hybrids Enhance Wound Healing and Antimicrobial Processes.

Complications of chronic non-healing wounds led to the emergence of nanotechnology-based therapies to enhance healing, facilitate tissue repair, and prevent wound-related complications like infections. Here, we design alpha lipoic acid (ALA) conjugated hexagonal boron nitride (hBN) and boron carbide (B4C) nanoparticles (NPs) to enhance wound healing in human dermal fibroblast (HDFa) cell culture and characterize its antimicrobial properties against Staphylococcus aureus (S. aureus, gram positive) and Escherichia coli (E. coli, gram negative) bacterial strains. ALA molecules are integrated onto hBN and C4B NPs through esterification procedure, and molecular characterizations are performed by using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and UV-vis spectroscopy. Wound healing and antimicrobial properties are investigated via the use of cell viability assays, scratch test, oxidative stress, and antimicrobial activity assays. Based on our analysis, we observe that ALA-conjugated hBN NPs have the highest wound-healing feature and antimicrobial activity compared to ALA-B4C. On the other hand, hBN, ALA-B4C, and ALA compounds showed promising regenerative and antimicrobial properties. Also, we find that ALA conjugation enhances wound healing and antimicrobial potency of hBN and B4C NPs. We conclude that the ALA-hBN conjugate is a potential candidate to stimulate regeneration process for injuries.

Management of patients with urinary tract endometriosis by gynecologists

Objective: The aim was to report the postoperative outcomes of urinary tract endometriosis (UTE), which is a form of deep, infiltrative endometriosis, and to contribute to the literature by presenting our experience. Material and Methods: In the present study, patients who underwent surgery for endometriosis at our clinic between 2005 and 2019 and had a final pathological diagnosis of UTE were examined in detail. Patient information was retrospectively retrieved from the medical records. Data obtained pre-, peri-, and postoperatively were analyzed. Results: Mean age of the 70 patients included, according to the study criteria, was 32.73±7.09 years. Ureteral involvement alone was observed in 49% (n=34) of the patients, bladder involvement alone was observed in 24% (n=17) of the patients, and both bladder and ureteral involvement were observed in 27% (n=19) of the patients. Microscopic hematuria was detected in 16% (n=11) of the patients, whereas preoperative urinary tract findings, such as recurrent urinary tract infections, were detected in 19% patients (n=13). Of the patients, 56% (n=39) were identified with dyspareunia, 56% (n=39) with dysmenorrhea, and 30% (n=21) with pelvic pain. Visual analog scale score was significantly lower after the procedure (p<0.0001). Conclusion: Although postoperative results were typically considered positive, surgical method performed in deep infiltrative endometriosis should aim to preserve fertility, improve quality of life, and reduce the complication rate to a minimum.

Effect of diazepam, sertraline and melatonin on the stress-induced reproductive disorders and intrauterine growth restriction in female rats.

OBJECTIVE: Psychological stress is an important factor triggering depression and anxiety. Infertility is known to cause stress; however, it is not clearly known whether stress causes infertility as well. In addition, there are different opinions accounting for the relation of stress-induced oxidative stress to infertility and intrauterine growth restriction. The aim of the study is to examine the effect of sertraline, diazepam and melatonin on the infertility, intrauterine growth restriction and oxidative stress that can be caused by forced immobilization stress management (FISM) in female rats. MATERIALS AND METHODS: Wistar rats were grouped as healthy rats (HG) applied distilled water, stress treated control group (SC), and 20 mg/kg sertraline + stress (SS), 2 mg/kg diazepam + stress (DS) and 10 mg/kg melatonin + stress (MS) treated rats. The medicines were administered orally once a day for 30 days. At the end of this period, oxidant/antioxidant parameters were measured through the blood samples collected from the tail veins of all rats. Then the rats were kept in a suitable environment for 2 months for breeding. RESULTS: FISM caused oxidative stress in blood serum of animals, infertility and intrauterine growth restriction (decrease in birth weight of the baby). Best medicines to suppress FISM-related oxidative stress are melatonin > diazepam > sertraline respectively, while sertraline > diazepam > melatonin were most successful in terms of preventing infertility. The best medicines preventing the FISM-caused intrauterine growth restriction were found to be melatonin > diazepam > sertraline, respectively. CONCLUSION: FISM causes oxidative stress in animals. Oxidative stress is understood to affect the intrauterine growth negatively although it is not a major component in the pathogenesis of infertility. While melatonin is only effective in preventing the oxidative stress-related intrauterine growth restriction, antidepressants and anxiolytic treatment were found to be helpful in preventing both infertility and intrauterine growth restriction.

Comparison of two natural tissue repair-based surgical techniques; sacrospinous fixation and uterosacral ligament suspension for pelvic organ prolapse treatment.

INTRODUCTION AND PURPOSE: The present study aims to compare the effectiveness and perioperative results of the natural tissue repair-based treatments sacrospinous fixation (SSF) and uterosacral ligament suspension (USLS) based on the preoperative Pelvic Organ Prolapse Quantification system (POP-Q). MATERIALS AND METHODS: Medical records of patients with stage ≥2 uterine prolapse between January 2011 and December 2016 were retrospectively examined. Preoperative POP-Q stages, demographic characteristics, perioperative results, and recurrence ratios in mid-term follow-up for patients were compared. RESULTS: Overall, 235 patients were determined according to our study's inclusion criteria. A total of 155 patients underwent vaginal hysterectomy and USLS (VH/USLS), whereas 80 patients underwent vaginal hysterectomy and SSF (VH/SSF). There were no significant differences between groups in terms of body mass index (BMI), age, and parity as well as cardiovascular disease and diabetes mellitus. There was no significant difference in terms of anatomical success and clinical success rates in the postoperative follow-up period between both groups. (p = 0.588 and 0.692, respectively). However, the assessment of results based on preoperative stages of patients revealed that recurrence and anatomical failure were higher in the stage 4 group (p < 0.001). CONCLUSION: Our findings indicate that the main determinant factor in evaluating recurrence rates is preoperative POP-Q staging of the patient. Recurrence rates significantly increase with disease stage. Consistent with studies that do not report a clear superiority for USLS or SSF, we observed no significant differences between both procedures in terms of recurrence. The effectiveness of these procedures is similar. We believe that prospective, long-term follow-up studies with larger populations are required to accurately identify preoperative risk factors and compare them with mesh techniques.

Fetal renal blood flow velocimetry and cerebro-placental ratio in patients with isolated oligohydramnios.

OBJECTIVE: It's proposed that oligohydramnios is caused by decreased renal perfusion due to redistribution of fetal blood at fetal growth restriction. Isolated oligohydramnios refers to the presence of oligohydramnios without fetal structural and chromosomal abnormalities, without fetal growth restriction, without intrauterine infection, and in the absence of known maternal disease. It's unknown whether the redistribution or decreased renal perfusion cause isolated oligohydramnios. The aim of the study was to evaluate fetal renal artery Doppler blood velocimetry and cerebro-placental ratio (CPR) among women with isolated oligohydramnios between 25-40 weeks of gestational age. STUDY DESIGN: The middle cerebral artery, umbilical artery and, renal artery pulsatility index (PI) values were measured in 45 fetuses with isolated oligohydramnios and 65 fetuses with normal amniotic fluid. Oligohydramnios was defined as deepest vertical amniotic fluid being measured lower than 1cm. The CPR (middle cerebral artery PI/umbilical artery PI) and renal artery PI values were expressed as multiples of the normal median (MoM) and were compared between the two groups. RESULTS: There was no difference in MoM of CPR PI (p=0.167) and MoM of renal artery PI values (right p=0.253, left p=0.353) between the groups. CONCLUSION: The renal artery Doppler velocimetry and CPR were not significantly different in the women with isolated oligohydramnios, compared to the women with normal amniotic fluid.

Use of vacuum-assisted closure in massive puerperal genital hematoma.

Puerperal genital hematomas are rare but life-threatening complications of obstetric emergencies. A pregnant patient (39 weeks) underwent a mediolateral episiotomy during a vaginal delivery. An afterbirth hematoma (approximately 20 cm in diameter) was evacuated, but the use of a vacuum-assisted wound closure system was applied after the sutures opened on the 7th postoperative day. On the 10th day of the vacuum-assisted closure (VAC) application, the wound was completely closed. VAC is an alternative treatment modality that can drain an infection and increase the proportion of granulation tissue in humid and irregular surfaces such as the perineum.

Congenital Ewing's Sarcoma, a Rare and Difficult Diagnosis: A Case Report.

We have interestedly read the article written by Thalia Wong BS in July 2015, which is about Pediatric Blood Cancer, including clinical findings and results of infants <1 year of age with Ewing sarcoma. We report a case with congenital Ewing's sarcoma that easily interfered with rabdomyosarcoma in a pregnant woman. A 32-year-old multigravida with a big neck mass at 35 weeks was referred to our clinic. The final diagnosis of extraskeletal Ewing's sarcoma was made. Hepatic metastasis was detected and treatment by chemotherapy was initiated. Ewing's sarcoma is usually noted among adolescents or young adults and more rarely than among newborns. This case is important because of its rarity.

Spontaneous Ovarian Hyperstimulation Syndrome with FSH Receptor Gene Mutation: Two Rare Case Reports.

Development of ovarian hyperstimulation syndrome (OHSS) is very rare in a spontaneous ovulatory cycle and it is usually seen during pregnancy. In the etiology of OHSS, higher hCG (molar pregnancies or multiple pregnancies) and thyroid-stimulating hormone (TSH) levels have been accused. In recent years, some follicle-stimulating hormone (FSH) receptor (FSHR) gene mutations have been described in patients with OHSS in the first trimester with normal hCG levels. Herein, we report two cases of FSHR gene mutation during the investigation of the etiology of spontaneous OHSS. Although OHSS is typically associated with ovulation induction, it should be kept in mind that this condition may also develop in spontaneous pregnancies.

Amniotic fluid NF-kB concentration in pregnant women with a high risk of prenatal screening test results.

OBJECTIVES: Nuclear factor-kappa beta (NF-kB) can potentially be related to certain fetal chromosomal abnormalities. This study aimed to determine whether the concentration of NF-kB changes in the amniotic fluid (AF) of pregnant women who have a high risk of fetal down syndrome (DS) results in prenatal screening and diagnosis testing. MATERIAL AND METHODS: 108 patients with an abnormal first trimester combined screening test (FTCST) were subjected to amniocentesis and fetal karyotype analysis between 16 and 20 weeks of gestation. Amniocentesis material obtained from 86 patients conformed with our research criteria and only this was included in the study. Among the 86 amniocentesis results, there were 12 patients with confirmed DS. The karyotypes of the remaining patients were normal. Therefore the total study group was divided into two groups: patients with DS fetal karyotype (Group 1, n = 12) and patients with normal fetal karyotype (Group 2, n = 74). We used the ELISA method to assess the concentration of NF-kB and high sensitivity C-reactive protein (hsCRP) in each sample of AF. RESULTS: We observed significantly lower NF-kB concentrations in the AF of the women in Group 1 compared with the women in Group 2. Patients in Group 1 also had a higher concentration of hsCRP in their AF when compared with patients in Group 2. The FTCST results for patients in Group 1 showed a significantly higher risk than for those of Group 2. There were no statistically significant correlations detected when comparing the amniotic fluid nuclear factor-kappa beta (AF-NF-kB) levels with other clinical and laboratory parameters. CONCLUSIONS: AF-NF-kB may play a role in the pathogenesis of fetal down syndrome.

Does endocan level increase in women with polycystic ovary syndrome? A case - control study.

OBJECTIVES: To evaluate endocan levels of patients with polycystic ovary syndrome (PCOS) in comparison to healthy women. MATERIAL AND METHODS: A cross-sectional case-control study on 88 patients with PCOS (mean age, 22.06 ± 4.24 years; body mass index [BMI], 23.9 ± 4.74 kg/m2) and 87 age- and BMI-matched healthy women (mean age, 23.71 ± 4.42 years; BMI, 22.15 ± 3.03 kg/m2). RESULTS: Serum endocan level was significantly higher in PCOS group than control group (540.9 ± 280.3 pg/mL vs. 355.5 ± 233.5 pg/mL, respectively; p < 0.001). The presence of polycystic ovary finding on ultrasonography or oligomenorhea did not produce significant effect on serum endocan levels (p > 0.05). In PCOS group, endocan level was negatively correlated with BMI and C-reactive protein level, and positively correlated with high density lipoprotein level (p < 0.05). CONCLUSIONS: Blood endocan level is increased in PCOS. Further studies are needed to evaluate the clinical value of blood endocan level as a marker for the risk of cardiovascular and metabolic diseases in patients with PCOS.

Low transcriptional activity of PON2 in recurrent abortion: A novel therapeutic agent?

OBJECTIVE: Oxidative stress has been reported to be associated with various pregnancy complications and to play key roles in many of them. An inadequate level of antioxidant defense may eventually lead to an early pregnancy loss. There is a lack of information about the roles of the PON2 and PON3 enzymes in the etiology of the cases of unexplained recurrent abortus. The aim of our study is to determine and present the data regarding the roles of these enzymes for the first time. MATERIALS AND METHODS: We measured the transcriptional levels of the PON2 and PON3 enzymes in the curettage materials obtained from the patients with unexplained recurrent abortus (n=25) and compared the results with those measured in the abortus materials from healthy pregnant women (n=50) who had undergone a voluntary abortion. The transcriptional activities of PON2 and PON3 enzymes were measured through quantification of their respective mRNAs by RT-qPCR assay. For each gene, 2-ΔCt replication values of the control and the patient groups were compared using the Student's t-test, and the p values were calculated thereafter. Fold-changes in the enzyme transcription levels were interpreted as up- or down-regulation. RESULTS: PON2 mRNA expressions were found to be highly decreased in the patient group (p=0.000002). PON3 transcription, when compared to the healthy pregnant women, was found to be down-regulated in the patient group; however, the difference was not statistically significant (p=0.69). CONCLUSIONS: In this study, we evaluated the expressional regulation of the PON2 and PON3 enzymes in unexplained recurrent abortus. Our results demonstrate for the first time that the expressions of PON2 and PON3 are down-regulated in the abortion specimens of the patients with recurrent miscarriage. Although both enzymes had low expression levels, the decrease in the transcriptional activity of PON2 revealed a high statistical significance. According to these results, it is rational to speculate that PON2 may be a novel therapeutic agent in the management of the cases with unexplained recurrent abortion.

The effect of rutin on ovarian ischemia-reperfusion injury in a rat model.

The effect of rutin on ovarian ischemia-reperfusion (I/R) injury was investigated in this experimental study. Eighteen Wistar albino female rats were divided into three groups as follows: I/R group (IRG; n = 6), 50 mg/kg rutin + I/R group (RG; n = 6), and a healthy control group scheduled for a sham operation (SG; n = 6). 2 h of ischemia and following 2 h of reperfusion were created in the IRG and RG by using a torsion model involving atraumatic vascular clips. Rutin, a flavonoid glycoside, was injected intraperitoneally at the dose of 50 mg/kg to RG group 1 h before reperfusion. Then, rats were euthanized and their ovaries were removed for biochemical and histopathological examination and also assessment of the gene expressions. IRG group had a significant increase in malondialdehyde (MDA) levels, in the expressions of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), and also in the activity of cyclooxygenase 2 (COX-2) unlike the significant decrease in total glutathione (tGSH) levels and the activity of COX-1 when compared to the SG group. However, rutin significantly decreased MDA levels, the expressions of TNF-α and IL-1ß, and also the activity of COX-2 while it increased significantly tGSH levels and the activity of COX-1 in the RG group in comparison with the IRG group. Rutin ameliorated the I/R-induced ovarian injury in rats via its possible antioxidative and anti-inflammatory effects.

Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies.

OBJECTIVE: Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. METHODS: We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. RESULTS: Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non-treated group. CONCLUSIONS: These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women.

Does antenatal betamethasone have negative effects on fetal activities and hemodynamics in cases of preeclampsia without severe features? A prospective, placebo-controlled, randomized study.

AIM: To evaluate whether antenatal betamethasone affects the fetal biophysical profile (BPP) and Doppler indices of umbilical and middle cerebral arteries (MCAs) in cases of preeclampsia without severe features. MATERIALS AND METHODS: Forty singleton preeclamptic pregnancies without severe features at gestational ages of 28-34 weeks were randomly divided into two groups of 20 patients: betamethasone and control groups. Patients in the betamethasone group were administered two consecutive doses of 12 mg betamethasone intramuscularly, 24 h apart, and patients in the control group were administered the same volume of saline as a placebo. All participants were evaluated before (0 h) and at hours 24, 48, and 72 of betamethasone/placebo administration using BPP scoring and umbilical and MCA Doppler examinations. RESULTS: Total BPP scores were significantly lower in the betamethasone group across the three time points during the follow-up period (p < 0.001). None of the Doppler indices differed significantly between the groups (p > 0.05). CONCLUSION: Antenatal betamethasone negatively affects fetal BPP score parameters, including the non-stress test, fetal body and breathing movements, without affecting vascular indices of umbilical arteries and MCAs. Clinician awareness of this transient drug-induced effect might be valuable for preventing iatrogenic preterm delivery for fetuses in preeclamptic pregnancies without severe features.

Effect of Cervical Lidocaine Gel for Pain Relief in Pipelle Endometrial Sampling.

OBJECTIVE: To evaluate the efficacy of cervical lidocaine gel in reducing patient discomfort during Pipelle endometrial sampling. MATERIALS AND METHODS: From September 2012 to January 2013, 137 patients were evaluated with Pipelle endometrial biopsy. For group 1 (77 women), 2% lidocaine gel was applied to the cervical canal 3 min before endometrial sampling. For group 2 (60 women), a placebo gel was applied. The pain experienced by the patients during biopsy was evaluated using a 100 mm visual analog scale. RESULTS: The pain score was significantly lower during suction curettage (T3) in the group 1 than in the group 2. There was no significant difference between the groups in terms of pain score in other stages of the procedure (2.6±1.3 and 4.5±1.4; p=0.03). CONCLUSION: Cervical 2% lidocaine gel is simple and effective for decreasing pain associated with Pipelle endometrial biopsy.