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.

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.

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.

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.

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.

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.

Exogenous ATP administration prevents ischemia/reperfusion-induced oxidative stress and tissue injury by modulation of hypoxanthine metabolic pathway in rat ovary / Administração exógena de ATP impede isquemia/induzidas por reperfusão de estresse oxidativo de tecidos e lesões pela modulação da hipoxantina via metabólica em ovários de ratos

In this study, xanthine oxidase (XO), malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels in the ovarian tissues of rats during the development of ischemia and postischemia-induced reperfusion were investigated, and the effect of ATP on ischemia-reperfusion (I/R) damage was biochemically and histopathologically examined. The results of the biochemical analyses demonstrated that ATP significantly reduced the level of XO and MDA and increased the amount of GSH in both ischemia and I/R-applied ovarian tissue at the doses administered. Furthermore, ATP significantly suppressed the increase in MPO activity that occurred following the application of post ischemia reperfusion in the ovarian tissue. The biochemical results obtained in the present study coincide with the histological findings. The severity of the pathological findings, such as dilatation, congestion, haemorrhage, oedema and polymorphonuclear nuclear leukocytes (PMNLs), increased in parallel with the increase observed in the products of XO metabolism. In conclusion, exogenously applied ATP prevented I/R damage by reducing the formation of XO in ischemic ovarian tissue.

Neste estudo, a xantina oxidase (XO), o malondialdeído (MDA), mieloperoxidase ( MPO ) e glutationa ( GSH) nos tecidos do ovário de ratos, durante o desenvolvimento de isquemia e reperfusão induzida por pós-isquemia foi investigada, e o efeito de ATP em isquemia e reperfusão (I/R). O dano foi verificado por provas bioquímicas e por histopatologia. Os resultados das análises bioquímicas mostraram que o ATP reduziu significativamente o nível de XO e MDA e aumentou a quantidade de GSH em ambas as isquemia e no tecido do ovário de I / R - aplicado nas doses administradas. Além disso, o ATP suprimiu significativamente o aumento na atividade de MPO que ocorreu na sequência da aplicação de pós-isquemia reperfusão no tecido ovariano. Os resultados bioquímicos obtidos no presente estudo coincidem com os achados histológicos. A gravidade dos achados patológicos, como a dilatação, congestão, hemorragia, edema e polimorfonucleares leucócitos nucleares (PMNLs), aumentou em paralelo com o aumento observado nos produtos do metabolismo XO. Em conclusão, aplicando exogenamente ATP impedido de I/R, houve danos pela redução da formação de tecido de ovário de XO na isquemia.

Benefits of the antioxidant and anti-inflammatory activity of etoricoxib in the prevention of ovarian ischemia/reperfusion injury induced experimentally in rats.

AIM: This study is a biochemical investigation of the effect of etoricoxib, a selective cyclooxygenase (COX)-2 inhibitor, on ischemia/reperfusion (I/R) injury experimentally induced in rat ovaries. METHODS: Experimental animals were divided into four groups: (i) ovarian ischemia/reperfusion (IRG); (ii) 30 mg/kg etoricoxib + ovarian ischemia/reperfusion (EIRG-30); (iii) 60 mg/kg etoricoxib + ovarian ischemia/reperfusion (EIRG-60); and (iv) a sham operation (SG) control group. RESULTS: The results showed levels of malondialdehyde in the IRG, EIRG-30, EIRG-60 and SG group ovarian tissue of 20.2 ± 3.4, 11.2 ± 3.2, 5.5 ± 1.9 and 3.8 ± 1.5 µmol/g protein, respectively. Myeloperoxidase activity for these groups was 24.2 ± 6.7, 13 ± 2.4, 4 ± 1.8 and 3.5 ± 1.9 U/g protein, and total glutathione levels were 1.6 ± 0.8, 4.5 ± 1.9, 6.5 ± 1.9 and 7.5 ± 2.4 nmol/g protein, respectively. COX-1 activity in IRG, EIRG-30, EIRG-60 and SG group rat ovarian tissue was 5.0 ± 2.8, 12.2 ± 2.4, 16.7 ± 2.8 and 17.5 ± 4.7 U/mg protein, and COX-2 activity was 18.3 ± 2.7, 3.5 ± 1, 1.8 ± 0.7 and 0.7 ± 0.3 U/mg protein, respectively. CONCLUSION: Etoricoxib prevented oxidative damage induced with I/R in rat ovarian tissue. This property of etoricoxib suggests that it can be clinically beneficial in the prevention of damage that may arise with reperfusion by detorsion for the protection of the ovaries against torsion.

The effect of mirtazapine on cisplatin-induced oxidative damage and infertility in rat ovaries.

Cisplatin causes infertility due to ovarian toxicity. The toxicity mechanism is unknown, but evidence suggests oxidative stress. In this study, the effect of mirtazapine on cisplatin-induced infertility and oxidative stress in rats was investigated. 64 female rats were divided into 4 groups of 16. Except for the controls that received physiologic saline only, all were administered with cisplatin (5 mg/kg i.p.) and mirtazapine (15 mg/kg p.o.) or mirtazapine (30 mg/kg p.o.) for 10 days. After this period, six rats from each group were randomly selected, and malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), total gluthatione (tGSH), gluthatione peroxidase (GPx), superoxide dismutase (SOD), and 8-hydroxy-2 deoxyguanine (8-OH Gua) levels were measured in their ovarian tissues. Reproductive functions of the remaining rats were examined for 6 months. The MDA, MPO, NO groups and 8-OH Gua levels were higher in the cisplatin-treated groups than the controls, which was not observed in the mirtazapine and cisplatin groups. GSH, GPx, and SOD levels were reduced by cisplatin, which was prevented by mirtazapine. Cisplatin caused infertility by 70%. The infertility rates were, respectively, 40% and 10% for the 15 and 30 mg/kg mirtazapine administered groups. In conclusion, oxidative stress induced by cisplatin in the rat ovary tissue causes infertility in the female rats. Mirtazapine reverses this in a dose-dependent manner.