Chlorogenic acid attenuates cisplatin-induced ovarian injury in rats.

The aim of this study was to determine the possible therapeutic effect of chlorogenic acid (CGA) on cisplatin (CDDP)-induced ovarian damage in rats. Rats were first exposed to CDDP (5 mg/kg) and then treated CGA (1.5 and 3 mg/kg) for three days. Oxidative stress (OS), inflammation and apoptosis markers were determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically. The levels of OS, inflammation and apoptosis biomarkers increased by CDDP administration (p < 0.05). Treatments with CGA significantly alleviated these markers dose-dependently (p < 0.05). These data reveal that CGA may exert an ovoprotective effect by reducing pro-inflammatory mediators and enhancing antioxidant status in ovarian tissue.

Ethyl pyruvate attenuates cisplatin-induced ovarian injury in rats via activating Nrf2 pathway.

Although cisplatin (CDDP) is an antineoplastic drug widely used for the treatment of various tumors, its toxicity on the reproductive system is a concern for patients. Ethyl pyruvate (EP) possesses potent antioxidant and anti-inflammatory activities. The objective of this study was to evaluate the therapeutic potential of EP on CDDP-mediated ovotoxicity for the first time. Rats were exposed to CDDP (5 mg/kg) and then treated with two doses of EP (20 and 40 mg/kg) for 3 days. Serum fertility hormone markers were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were also determined. In addition, how CDDP affects the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway and the effect of EP on this situation were also addressed. EP improved CDDP-induced histopathological findings and restored decreasing levels of fertility hormones. EP treatment also reduced the levels of CDDP-mediated OS, inflammation, ERS and apoptosis. In addition, EP attenuated CDDP-induced suppression in the levels of Nrf2 and its target genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase-1, superoxide dismutase and glutathione peroxidase. Histological and biochemical results showed that EP can have therapeutic effects against CDDP-induced ovotoxicity with antioxidant, anti-inflammatory and Nrf2 activator activities.

The therapeutic effect of silibinin against 5-fluorouracil-induced ovarian toxicity in rats.

5-Fluorouracil (5-FU) is a fluoropyrimidine group antineoplastic drug with antimetabolite properties and ovotoxicity is one of the most important side effects. Silibinin (SLB) is a natural compound that is used worldwide and stands out with its antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the therapeutic effect of SLB in 5-FU-induced ovototoxicity using biochemical and histological analysis. This study was carried out in five main groups containing six rats in each group: control, SLB (5 mg/kg), 5-FU (100 mg/kg), 5-FU + SLB (2.5 mg/kg), and 5-FU + SLB (5 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and caspase-3 were determined using spectrophotometric methods. Hematoxylin and eosin staining method was employed for histopathological examination. MDA, TOS, 8-OHdG, TNF-α, MPO, and caspase-3 levels in 5-FU group were significantly increased compared with the control group, while the levels of TAS, SOD, and CAT were decreased (p < 0.05). SLB treatments statistically significantly restored this damage in a dose-dependent manner (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration, and leukocyte infiltration were significantly higher in the 5-FU group compared with the control group, SLB treatments also statistically significantly restored these damages (p < 0.05). In conclusion, SLB has a therapeutic effect on the ovarian damage induced by 5-FU via decreasing the levels of oxidative stress, inflammation, and apoptosis. It may be helpful to consider the usefulness of SLB as an adjuvant therapy to counteract the side effects of chemotherapy.

Ameliorative effect of gallic acid on cisplatin-induced ovarian toxicity in rats.

The aim of the present study was to evaluate the protective effect of gallic acid (GA) against cisplatin (CDDP)-induced ovarian toxicity, for the first time. The ovarian damage was generated with CDDP (5 mg/kg) intraperitoneally (i.p.) administration in rats. GA (2.5 and 5 mg/kg) were administered i.p. for 3 consecutive days. The study was carried out in 5 main groups containing 6 rats in each group: control, GA (5 mg/kg), CDDP, CDDP + GA (2.5 mg/kg) and CDDP + GA (5 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3 and tumor necrosis factor-alpha (TNF-α) were determined. Hematoxylin and eosin staining method was employed for the histopathological examination. In the CDDP group, it is determined that statistically significant decreasing in the levels of TAS and CAT, and increasing in the levels of MDA, TOS, OSI, 8-OHdG, caspase-3 and TNF-α (p < 0.05) compared with control group. GA administrations statistically significantly restored this damage (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration and leukocyte infiltration were significantly higher in the CDDP group than in the control group, GA administrations statistically significantly restored these damages (p < 0.05). In conclusion, this study showed that GA prevented CDDP-induced ovarian damage with its antioxidant, anti-apoptotic and anti-inflammatory activities. More comprehensive studies are needed to see the underlying mechanisms.

The ameliorative effect of Primula vulgaris on cisplatin-induced nephrotoxicity in rats and quantification of its phenolic components using LC-ESI-MS/MS.

Cisplatin (CDDP) is an important chemotherapeutic agent, accumulation of which in kidney tissue causes nephrotoxicity and renal failure. The aim of this study was to evaluate, for the first time in the literature, the protective effect of dimethyl sulfoxide (DMSO) extract of Primula vulgaris leaf (PVE) against CDDP-induced nephrotoxicity in rats. The PVE content was characterized using liquid chromatography-mass spectrometry. Nephrotoxicity was induced with a single dose of CDDP (7.5 mg/kg). Thirty female Wistar-Albino rats were divided into five groups (control, DMSO, CDDP (7.5 mg/kg), CDDP + PVE (25 mg/kg), and CDDP + PVE (50 mg/kg)). Biochemical and histopathological analyses were then performed. Rutin, gallic acid, p-coumaric acid and protocatechuic acid were identified as major components of PVE. Total antioxidant status and glutathione (GSH) values increased significantly in the serum samples from the treatment group compared to the CDDP group, while blood urea nitrogen, creatinine, oxidative stress index, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total oxidant status, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) values decreased significantly. GSH levels increased significantly in the treatment group compared to the CDDP group, while TNF-α, caspase-3, 8-OHdG, MDA levels and damage scores decreased significantly. In conclusion, PVE exhibited strong protective effects through its anti-apoptotic, antioxidant, and anti-inflammatory activities against nephrotoxicity and oxidative damage caused by CDDP in rats.

An Investigation of the Antiproliferative Effect of Rhododendron luteum Extract on Cervical Cancer (HeLa) Cells via Nrf2 Signaling Pathway.

The aim of the present study was to investigate the role of Rhododendron luteum extract (RLE) in the induction of Nrf2­related oxidative stress and endoplasmic reticulum (ER) stress in human cervical cancer (HeLa) cells. The antiproliferative effect of RLE on HeLa and fibroblast cells was determined using the MTT assay. The effects of RLE on the cell cycle, apoptosis, and production of reactive oxygen species (ROS) in HeLa cells were evaluated using fluorescent probes. The mRNA expression levels of Nrf2 [and its targets glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD)], and C/EBP homologous protein (CHOP, an ER stress marker were determined using reverse transcription­quantitative polymerase chain reaction (RT-PCR). The results demonstrated that RLE exhibited a selective cytotoxic effect (2.9-fold) on HeLa cells compared to fibroblast cells. RLE arrested the cell cycle at the S phase, and induced apoptosis, ER stress, and ROS formation. In addition, RLE significantly suppressed the expression levels of Nrf2, GCLC and G6PD (0.65, 0.69, and 0.54-fold, respectively) and increased the expression of CHOP (4.48-fold) in HeLa cells at 72 h of treatment (p < 0.05). These results show that the antiproliferative effect of RLE occurs through the Nrf2 and ER stress pathways, and the results should now be supported by further in vivo studies.

p-Coumaric acid alleviates cisplatin-induced ovarian toxicity in rats.

OBJECTIVE: The therapeutic value of cisplatin (CDDP) as an anticancer drug is limited by its ovo-otoxicity. The effect of natural phenolic acids in the prevention of many diseases related to oxidative stress has been reported. Here, the ability of p-coumaric (pCA) acid, a member of phenolic acids, to protect rat ovary tissue against CDDP-induced oxidative stress was investigated. METHODS: The study was carried out in five main groups containing six rats in each group: control, pCA (4 mg/kg), CDDP, CDDP plus pCA (2 mg/kg), and CDDP plus pCA (4 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and tumor necrosis factor-alpha (TNF-α) were determined. Hematoxylin and eosin staining method was employed for the histopathological examination. RESULTS: In the CDDP group, it is determined that statistically significant decreasing in the levels of TAS and CAT, and increasing in the levels of MDA, TOS, OSI, 8-OHdG, caspase-3, and TNF-α compared with control group (p < 0.05). pCA administration statistically significantly restored this damage in a dose-dependent manner (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration, and leukocyte infiltration were significantly higher in the CDDP group than in the control group, pCA administrations statistically significantly restored these damages (p < 0.05). CONCLUSIONS: The data presented here indicate that pCA protects ovarian tissues of rats against CDDP-induced oxidative stress, inflammation, and apoptosis. It may be worthy to consider the usefulness of pCA as adjuvant therapy in cancer management.

Suppression of cisplatin-induced ovarian injury in rats by chrysin: an experimental study.

The aim of this study was to investigate the potential therapeutic efficacy of chrysin (CHS) against ovotoxicity caused by intraperitoneal administration of cisplatin (CDDP) in rats. In this experimental study, 24 female rats were randomly divided into four groups: control, CHS (2 mg/kg), CDDP (5 mg/kg) and CDDP (5 mg/kg) + CHS (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), interleukin-6 (IL-6) and myeloperoxidase (MPO) were determined in the ovarian tissues using spectrophotometric methods. In addition, the ovarian samples were evaluated histopathologically by hematoxylin&eosin staining. The results revealed that the levels of MDA, TOS, IL-6 and MPO significantly increased by CDDP administration compared with control group (p < 0.05). Also, it was found that CDDP significantly decreased TAS and SOD levels (p < 0.05). CHS ameliorated CDDP-induced the increased levels of MDA, TOS, IL-6, MPO and increased the levels of TAS and SOD significantly (p < 0.05). Histological findings also supported the therapeutic effect of CHS against CDDP-induced ovarian damage parameters. In conclusion, our results showed that CHS exhibits a therapeutic effect against CDDP-induced ovotoxicity and therefore the use of CHS after chemotherapy may improve the side effets of CDDP. IMPACT STATEMENTWhat is already known about this subject? Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited due to dose-related tissue toxicity. Chrysin (CHS), a natural flavone, exhibits various beneficial activities, including antioxidant, anti-inflammatory and anticancer. There are increasing evidences in the literature that CHS reduces the toxicity of various chemotherapeutic agents, such as CDDP, doxorubicin and cyclophosphamide, in colon, kidney and liver tissues through its antioxidant and anti-inflammatory potential.What do the results of this study add? This study demonstrated that CHS can abolish CDDP-induced in vivo ovarian injury by decreasing MDA, TOS, IL-6 and MPO levels and increasing SOD and TAS levels through its antioxidant and anti-inflammatory potential.What are the implications of these findings for clinical practice and/or further research? This study revealed the therapeutic potential of CHS against CDDP-induced acute ovotoxicity, for the first time. Further pre-clinical studies are necessary to prove the beneficial effect of CHS on the prevention of CDDP-induced ovarian toxicity.

Plasma and Erytrocyte Oxidative Stress Markers in Children with Frequent Breath-Holding Spells.

BACKGROUND: Breath-holding spells (BHS) are common non-paroxysmal events with unknown pathophysiology. BHS have been associated not only with iron deficiency anemia (IDA) but also with oxidant/antioxidant imbalance and erythrocyte injury induced by hypoxia. The present study was designed to investigate the contribution of IDA in BHS and the oxidant/antioxidant balance in children with or without IDA in BHS and compare them with healthy controls.Additionally, the study also aimed to examine the effect of the frequency of BHS attacks (mild or severe) on the oxidant/antioxidant balance and to determine the best predictive oxidant and antioxidant markers. MATERIALS AND METHODS: The study included 66 children with BHS aged 6-48 months who had been followed up for a minimum period of one year between 2014 and 2018. A control group of 30 age- and gender-matched healthy children was included in the study. The patient group was divided into 2 groups (IDA and non-IDA) and these groups were compared between each other and also with the control group. The IDA group was divided into subgroups based on the frequency of BHS attacks. Blood samples were obtained within a maximum period of 24 h following the spell. Levels of protein carbonyl, nitrite, nitrate, TOS, TAS, OSI, MDA, enzyme activities of GPx, CAT,enzyme activities of erythrocyte SOD, CAT, and GPx, and the level of MDA were measured. RESULTS: In patients with IDA, the oxidant levels increased while the antioxidant enzyme activities decreased. In all patients, the levels of MDA, carbonyl, TOS, OSI increased and the levels of TAS, activities SOD, and CAT decreased, whereas the enzyme activities of erythrocyte SOD, CAT, GPx decreased significantly compared to those of control group. Increased of erythrocyte MDA levels had 10.32, decreased enzyme activities of erythrocyte SOD levels had a 10.25, and decreased enzyme activities of erythrocyte CAT had a 5.33 times greater risk for spell. CONCLUSION: The results indicated that the oxidant/antioxidant balance in children with BHS was impaired in favor of oxidants at both levels, regardless of the presence of IDA and the increased frequency of BHS attacks per day. Moreover, the presence of IDA was found to be associated with increased oxidative stress in children with BHS, particularly at the erythrocyte level. Erythrocyte level; among the erythrocyte MDA oxidant parameters, erythrocyte SOD and antioxidant parameters, they are the biomarkers that show the best probability of having a BHS attack and an increase in the frequency of apnea attacks.

Serum ischemia-modified albumin level returns to its premenopausal level with 1-year hormone therapy in healthy menopausal women.

INTRODUCTION: To assess the effect of hormone therapy (HT) on serum ischemia modified albumin (IMA) levels in healthy menopausal women. MATERIAL AND METHODS: Thirty surgical menopausal women who were admitted to our menopausal polyclinic during a 1-year period and diagnosed with menopause and planned to have HT for menopausal symptoms were enrolled in this prospective study. The serum IMA levels were recorded before and after (3 months, 6 months, 12 months later) hormone treatment (2 mg estradiol hemihydrate). RESULTS: The mean age of women was 47.60 ± 2.34 years. The mean serum IMA levels were 0.610 ± 0.096 absorbance units (ABSU) at the beginning and 0.484 ± 0.080 ABSU after 3 months of hormone therapy. Following 6 months of hormone therapy, serum IMA level was 0.546 ± 0.075, and reached 0.580 ± 0.089 ABSU following 12 months of therapy. CONCLUSIONS: These findings suggest that HT may not block the menopause induced ischemia process. Although HT had a positive effect on serum IMA levels following 3 months' use, serum IMA levels returned to baseline levels after 12 months' use. Based on this study's findings, long-term use of HT may not have a positive effect on cardiovascular disease protection.

Rosa canina Extract has Antiproliferative and Proapoptotic Effects on Human Lung and Prostate Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Rosa species, there has been only limited research into the cytotoxic effect of Rosa canina. The purpose of this research was to evaluate the antioxidant properties, phenolic characterization, and cytotoxic effects of R. canina on human lung (A549) and prostate (PC-3) cancer cells and the possible mechanisms involved. The antioxidant properties and phenolic characterization of the extract were determined using spectrophotometric methods and RP-HPLC, respectively. The cytotoxic activity of the extract was determined using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis, the cell cycle, mitochondrial membrane potential (MMP), and caspase activity using fluorometric and luminometric methods. The TPC value of the extract was 58.97 ± 2.22 mg gallic acid equivalents per gram sample, and ascorbic acid and p-coumaric acid were detected as major phenolics in the extract. R. canina extract exhibited a selective cytotoxic effect on A549 and PC-3 cells compared to normal fibroblast cells. The extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP and increased caspase activity in these cells. Phytomedical applications of R. canina may represent promising approaches in the treatment of cancer.

Dorycnium pentaphyllum Extract Has Antiproliferative Effect on Human Cervix and Colon Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Fabaceae species, limited researches have been conducted on the cytotoxic effect of Dorycnium pentaphyllum. The aim of this study was to evaluate the phenolic characterization and the cytotoxic effect of D. pentaphyllum on human cervix (HeLa) and colon (WiDr) cancer cells and the possible mechanisms involved. Total phenolic content (TPC) and phenolic characterization of the extract were investigated using the Folin-Cioceltau method and RP-HPLC, respectively. The cytotoxic effect of the extract was evaluated using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 141.2 ± 0.8 mg gallic acid equivalent per g sample, and quercetin was detected as major phenolics. D. pentaphyllum extract exhibited a selective cytotoxic effect on HeLa and WiDr cells compared to normal fibroblast and colon cells, respectively. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in these cells. Further studies may be useful in developing a natural product based new generation pharmacological agent.

Berberine inhibits the ischemia-reperfusion induced testicular injury through decreasing oxidative stress.

PURPOSE: The aim of this study was to investigate the effect of berberine (BBR) on oxidative stress in an experimental testicular I/R injury model. METHODS: Eighteen rats were divided into three groups: control group, torsion-detorsion (T/D) group, and BBR + T/D group. In the pre-treatment of the BBR group, 200 mg/kg BBR was given intraperitoneally 30 min before detorsion. Tissue malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS) levels were determined using colorimetric methods. Histological evaluation of the tissue samples was evaluated using hematoxylin-eosin staining. RESULTS: In T/D group, tissue MDA, TOS, and oxidative stress index levels were higher than control group. These increases were significantly reversed with BBR pre-treatment. Although Johnsen scores were lower in T/D group than the control group, BBR pre-treatment recovered the Johnsen scores. CONCLUSION: These results suggest that BBR can inhibit I/R-induced testicular injury by suppressing oxidative stress. Further studies may prove that BBR is a useful agent as an adjunctive treatment in surgical repair in human cases.

Dimethyl Sulfoxide Extract of Dianthus carmelitarum Induces S Phase Arrest and Apoptosis in Human Colon Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Dianthus species, there has been only limited research into the cytotoxic effect of Dianthus carmelitarum. The purpose of this research was to evaluate the phenolic characterization and the cytotoxic effect of D. carmelitarum on human colon cancer (WiDr) cells and the possible mechanisms involved. Total polyphenolic contents (TPC) and phenolic characterization of the extract were evaluated using the Folin-Cioceltau method and reversed-phase high performance liquid chromatography (RP-HPLC), respectively. The cytotoxic activity of the extract was determined using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 784.8 ± 40.3 mg gallic acid equivalent per 100 g sample, and sinapic acid and benzoic acid were detected as major phenolics in the extract. D. carmelitarum extract exhibited a selective cytotoxic effect (3.6-fold) on WiDr cells compared to normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. Phytomedical and nutraceutical applications of D. carmelitarum may represent promising approaches in the treatment of cancer.

The value of endoplasmic reticulum stress markers (GRP78 and CHOP) in the diagnosis of acute mesenteric ischemia.

AIM: To evaluate levels of the endoplasmic reticulum (ER) stress markers GRP78 and CHOP in acute mesenteric ischemia (AMI) and to examine relations with degrees of AMI-related intestinal injury. MATERIALS AND METHODS: Twenty-four rats were divided into four groups. Group I and Group III represented the control groups, from which blood and tissue specimens were collected 2 and 6 h after laparotomy without superior mesenteric artery (SMA) ligation. Group II and Group IV constituted the ischemia groups, from which blood and tissue specimens were collected 2 and 6 h after SMA ligation. The ER stress markers GRP78 and CHOP, total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) were investigated in each group. Ileum specimens were assessed in terms of ischemic injury, and appropriate comparisons were performed. RESULTS: Significantly higher GRP78, CHOP, TOS, and TAS values were determined in the ischemia groups (groups II and IV) compared to the control groups (groups I and III). This elevation was greater in the 6 h ischemia group, the group exposed to the greatest ischemic injury (Group IV). Significant and powerful correlation was present between histopathological damage and levels of the ER stress markers and oxidative markers. CONCLUSION: According to our results, ER stress markers (GRP78 and CHOP) increase significantly following ischemic injury. This elevation has the potential to be used diagnostically and also in prognostic terms due to the powerful correlation it exhibits with AMI-related ischemic injury.

Biotin deficiency in hyperemesis gravidarum.

The aim of this study was to determine the serum biotin levels in patients with hyperemesis gravidarum (HG). Ninety pregnant women with HG (mild (n = 30), moderate (n = 30) and severe (n = 30)), and 80 pregnant women without HG were included for this study. In both groups, serum biotin levels were measured. There were no statistically significant differences in demographic and clinical characteristics between the HG groups and the control group except for PUQE scores. Serum biotin levels in all hyperemesis gravidarum groups were statistically significantly lower than control group. Negative statistically significant correlation between hyperemesis gravidarum severity and serum biotin levels was noted. This is the first study that shows low serum biotin levels in women with hyperemesis gravidarum. Impact statement What is already known on this subject? Almost 80% of pregnant women have nausea and vomiting. If nausea and vomiting became severe and the symptoms combined with weight loss and ketonuria; the diagnosis should be hyperemesis gravidarum (HG). The etiopathogenetic factors of this unwanted condition have not been exactly known. Biotin is an essential water-soluble vitamin. Biotin catabolism increases in pregnancy. Marginal biotin deficiency occurs in approximately 50% of the gestations despite the "normal" biotin intake on the diet. What do the results of this study add? Current study results elucidated that serum biotin levels were lower in HG cases compared to non HG cases. This study is the first study that reports the association between low serum level of biotin and HG. What are the implications of these findings for clinical practice and/or further research? Further research is needed to show the importance of biotin supplementation in women with hyperemesis gravidarum.

Is ovarian volume a good predictor to determine metabolic syndrome development in polycystic ovary patients.

The aim of this study was to investigate the findings of ultrasound that could predict the metabolic syndrome (MetS) which may develop in polycystic ovary syndrome (PCOS) patients. A total of 96 consecutive PCOS patients, who were scheduled for any gynaecologic examination from January 2015 to January 2016 and who were eligible for the study, were prospectively enrolled in it. About 15.6% of PCOS patients were diagnosed with MetS. The mean age of the MetS patients and the non-MetS patients were 25.8 and 23.3, respectively (p = .056). The mean ovary volume was calculated as being 11.7 mL in the MetS patients and as 9.6 mL in the non-MetS patients (p = .027). The Doppler and the other ultrasound findings were compared between the groups and no significant difference was observed. When a receiver operator characteristic curve analysis was conducted for the ovarian volume to predict MetS, the area under curve was 0.67 (95% CI, 0.52-0.81). The optimum cut-off point for OV was determined at 9.2 mL, with the sensitivity and specificity of 80.0% and 50.6%, respectively. The risk of developing MetS appears to be higher in PCOS patients with higher OV values. Impact statement What is already known on this subject? Metabolic syndrome is not rare in PCOS patients. There are several studies to specify a predictor for MetS development in PCOS. Most are biochemical predictors, such as hyperandrogenemia, a visceral adiposity index, lipid accumulation product, adiponectin index and a leptin-to-adiponectin ratio. What do the results of this study add? The ultrasound markers to predict the insulin resistance at PCOS is already used, but are new for predicting MetS. What are the implications of these findings for clinical practice and/or further research? Ultrasound is an available tool in most clinics and predicting MetS is important for the future health problems of PCOS patients.

The Diagnostic Value of FNDC5/Irisin in Renal Cell Cancer.

PURPOSES: The aim of this study was to determine the diagnostic significance of fibronectin type III domain containing protein 5 (FNDC5)/Irisin levels in the sera of patients with renal cell cancer. MATERIALS AND METHODS: In the study, 48 individuals were evaluated. The patient group included 23 subjects diagnosed with renal tumor, and the control group of 25 healthy individuals. Patients diagnosed with renal tumor received surgical treatment consisting of radical or partial nephrectomy. Blood specimens were collected and serum FNDC5/ Irisin and carcinoembryonic antigen (CEA) levels were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: FNDC5/irisin and CEA levels in renal cancer patients were significantly higher compared with the control group (p=0.0001, p=0.009, respectively). Also, FNDC5 levels was more sensitive and specific than CEA levels. The best cut-off points for FNDC5/ irisin were >105pg/mL and CEA were >2.67ng/mL for renal cancer. CONCLUSIONS: FNDC5/Irisin may be used as a diagnostic biomarker for renal cancer.

A Comparison of the Effects of Grayanotoxin-Containing Honey (Mad Honey), Normal Honey, and Propolis on Fracture Healing.

OBJECTIVES: Delayed healing and non-union of fractures have a significant effect upon patient morbidity. Studies have therefore largely concentrated on accelerating fracture healing. This study was intended to compare the effect of "mad honey" and propolis on fracture healing using radiological and histopathological analysis. SUBJECTS AND METHODS: Femur fracture was surgically performed on 48 rats, followed by fixation. Animals were then divided into 8 groups: 2 control groups (15- and 30-day) and 6 treatment groups (15- and 30-day normal honey, 15- and 30-day "mad honey," and 15- and 30-day propolis). Rats were sacrificed at the end of these periods, and radiological and histological examinations were performed. RESULTS: Radiological healing in the propolis group after 15-day therapy was statistically better than in the control (p = 0.004) and normal honey (p = 0.006) groups. After 30-day therapy, healing in the propolis group (p = 0.005) and grayanotoxin-containing "mad honey" group (p = 0.007) were significantly better than in the control group. Histologically, there was a statistically significant difference between the 15-day propolis group and the other groups (control, honey, mad honey: p = 0.003, p = 0.003, and p = 0.002, respectively). We also found a statistically significant difference when the 30-day propolis group (p = 0.005) and "mad honey" group (p = 0.007) were compared to the control group. CONCLUSIONS: This study shows that grayanotoxin-containing "mad honey" and propolis can accelerate fracture healing.

Serum carbonic anhydrase I and II autoantibodies in patients with chronic lymphocytic leukaemia.

Cancer is the second most important cause of mortality, and millions of people either have or have had the disease. Leukaemia is one of the most common forms of cancer. Autoantibodies that have developed against the organism's self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA) autoantibodies have been determined in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been fully explained. The purpose of this study was to determine CA I and II autoantibodies in subjects with chronic lymphocytic leukaemia (CLL) and to provide a novel perspective regarding the autoimmune basis of the disease. Autoantibody levels were investigated using enzyme-linked immunosorbent assay (ELISA) in serum samples from 37 patients with CLL and 37 healthy peers. Anti-CA I titres in the CLL group were significantly higher compared with the control group (p = 0.0001). However, there was no significant difference between CLL and control groups in terms of anti-CA II titres (p = 0.278). The prevalences of CA I and II autoantibodies in patients with CLL in this study were 27% and 24.3%, respectively. Our results suggest that these autoantibodies may be involved in the pathogenesis of CLL. More extensive studies are now needed to reveal the entire mechanism.