Total Antioxidant Potential, Total Phenolic Profile and Cytotoxic Activity Against Brain Cancer: Melocan and Galdirik§.

Research background: Brain cancer is known to be one of the most difficult types of cancer to cure. It has a serious impact on the lives of diagnosed people due to the insufficient treatment options and their side effects. The search for new alternative treatments is therefore ongoing. Melocan (Smilax excelsa L.) and galdirik (Trachystemon orientalis) are of great importance in both traditional culinary culture and traditional medicine around the Black Sea; however, the knowledge about their antioxidant and cytotoxic effects remains fairly limited. Experimental approach: The aim of this study is to determine the antioxidant and cytotoxic activity of Smilax excelsa and Trachystemon orientalis on the C6 glioblastoma cell line. The plants of Smilax excelsa and Trachystemon orientalis were dried and extracted and then their total phenolic content (TPC) and phenolic profiles were studied. In addition, their total antioxidant status (TAS) and total oxidant status (TOS) were determined using an assay kit. We also analysed the total antioxidant activity (TAA) using the DPPH radical scavenging assay and the cytotoxic effect on the glioma cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Results and conclusions: According to the results, the water extracts of Smilax excelsa and Trachystemon orientalis had higher TPC (expressed in gallic acid equivalents on dry mass basis: 1158.17 and 262 mg/100 g, respectively) than the ethanol extracts. TAA expressed in Trolox equivalents on dry mass basis was 192.86 and 131.92 mg/100 g for Smilax excelsa and Trachystemon orientalis, respectively. The MTT assay showed that Trachystemon orientalis had a greater cytotoxic effect. In conclusion, the findings of the current study are promising for the development of new drugs. Novelty and scientific contribution: This is the first study that aims to evaluate the potential cytotoxic activity of two local Turkish plants, Smilax excelsa and Trachystemon orientalis, against C6 glioblastoma cells. The results confirm that both plants could be used as good therapeutic agents for the treatment of cancer in the future.

Biochemical and histopathologic assessment of effects of acitretin on epiphyseal growth plate in rats.

INTRODUCTION: Acitretin is a commonly used retinoid in dermatology. Although there are generally known side effects, the effects on the epiphyseal plaque and bone metabolism are not clear in the literature. AIM: To histopathologically investigate the effects on the epiphyseal plate and assess variations in bone metabolism caused by acitretin. MATERIAL AND METHODS: Three groups were formed with 10 rats in each group. The 1st group (n = 10, 5 male, 5 female) were administered 10 mg/kg/day oral acitretin solution and the 2nd group (n = 10, 5 male, 5 female) were administered 3 mg/kg/day oral acitretin solution. The control group were given normal standard feed and water. Rats were sacrificed at the end of 4 weeks. The proximal tibias were excised and histopathologically and immunohistochemically assessed. Biochemical assessment was also carried out. RESULTS: Staining with haematoxylin-eosin found reductions in the epiphyseal plate in the 1st and 2nd group compared to the control group, though this situation was not statistically significant. Immunohistochemical studies did not encounter Type II collagen in the epiphyseal bone, proliferative zone and hypertrophic zone in the control group, low dose acitretin solution group and high dose acitretin solution group. Type II collagen was not observed in osteoids and osteoblasts. Type I collagen was not observed in the hypertrophic zone and proliferative zone of any group. CONCLUSIONS: Our data show that though acitretin caused degeneration of the epiphyseal plate, it did not cause clear thinning and we identified no significant variations in bone metabolism markers.

Expression of Laminin Receptor 1 in Normal, Hyperplastic, and Malignant Endometrium.

Laminin receptor 1 may have a role in the progression from endometrial hyperplasia with or without atypia to endometrial cancer. Therefore, we aimed to investigate the pattern, percentage, and intensity of laminin receptor 1 expression in normal, hyperplastic, and neoplastic endometrium. Paraffin blocks of 131 specimens with the diagnoses of normal endometrium (n=25), endometrial hyperplasia with atypia (n=21) or without atypia (n=55), and endometrial cancer (n=30) were immunostained with laminin receptor 1 antibody, and its expression percentage, pattern, and intensity in the epithelial cytoplasm, basement membrane, and endometrial stroma of these tissues were assessed. When compared with hyperplasia with or without atypia and endometrial cancer, the percentage of nonstaining with laminin receptor 1 in the epithelial basement membrane was higher (96%), and the percentage of <50% staining with laminin receptor 1 was lower (4%) in the normal endometrium (P=0.001). While a progressive increment in staining percentage and density of epithelial cytoplasm and basement membrane was noted through an orderly progression from normal endometrium to endometrial hyperplasia without atypia, endometrial hyperplasia with atypia, and cancer of endometrium (P<0.001), such a relationship was not found for the staining percentage and density of endometrial stroma (P>0.05). Disease progression-related gradual increment in laminin receptor 1 expression in the epithelial basement membranes of hyperplastic endometrium with or without atypia and cancer of endometrium reveals that it may play a substantial role in the transition from premalignant to the malignant state of endometrial lesions.

Ezrin Inhibition Up-regulates Stress Response Gene Expression.

Ezrin is a member of the ERM (ezrin/radixin/moesin) family of proteins that links cortical cytoskeleton to the plasma membrane. High expression of ezrin correlates with poor prognosis and metastasis in osteosarcoma. In this study, to uncover specific cellular responses evoked by ezrin inhibition that can be used as a specific pharmacodynamic marker(s), we profiled global gene expression in osteosarcoma cells after treatment with small molecule ezrin inhibitors, NSC305787 and NSC668394. We identified and validated several up-regulated integrated stress response genes including PTGS2, ATF3, DDIT3, DDIT4, TRIB3, and ATF4 as novel ezrin-regulated transcripts. Analysis of transcriptional response in skin and peripheral blood mononuclear cells from NSC305787-treated mice compared with a control group revealed that, among those genes, the stress gene DDIT4/REDD1 may be used as a surrogate pharmacodynamic marker of ezrin inhibitor compound activity. In addition, we validated the anti-metastatic effects of NSC305787 in reducing the incidence of lung metastasis in a genetically engineered mouse model of osteosarcoma and evaluated the pharmacokinetics of NSC305787 and NSC668394 in mice. In conclusion, our findings suggest that cytoplasmic ezrin, previously considered a dormant and inactive protein, has important functions in regulating gene expression that may result in down-regulation of stress response genes.

Investigation of role of vascular endothelial growth factor, Annexin A5 and Apelin by immunohistochemistry method in placenta of preeclampsia patients.

Preeclampsia is a disease characterized by hypertension and proteinuria occurred after 20 weeks of gestation. Preeclampsia is a major cause of maternal and fetal morbidity and mortality.  The pathophysiological mechanism of preeclampsia is not known exactly yet. Preeclampsia endothelial cell dysfunction, associated with inadequate trophoblastic invasion is characterized by abnormal placentation. Vascular endothelial growth factor (VEGF) according to is an angiogenic cytokine, Annexin A5 is among endogenous peptides are both expressed from placental trophoblasts and Apelin is a multifunctional peptide and expressed by placental trophoblasts and endothelial cells. It was aimed to investigate roles of these parameters occurring in preeclampsia and to compare immunoreactivity of them in normal and preeclamptic placenta. In this study, placentas were collected from 20 normotensive pregnant women as controls, 16 mild-preeclamptic pregnant women, and 16 severe preeclamptic women. VEGF, Annexin A5 and Apelin were examined in samples of placenta tissues by streptavidin-biotin-peroxidase complex immunohistochemical methods. Immunoreactivity scores (IRS) were obtained for each parameter.  VEGF and Apelin IRS were increased significantly in preeclamptic groups compared with control group (p <0.026, p<0.002 respectively). But Annexin A5 IRS was decreased significantly in preeclamptic groups compared with control group (p<0.04). In correlation with the intensity of disease, increase in VEGF and Apelin, and decrease in Annexin A5 supports roles of hemo-dynamic alterations in fetoplacental circulation and structural alterations in uteroplacental bed occurring in preeclampsia.

Investigating the Effect of Korean Red Ginseng on the Viability of Random-Pattern Skin Flaps in Rats.

OBJECTIVE: This experimental study investigated the efficacy of Korean Red Ginseng (KRG) extract in reducing the partial losses of random flaps. METHOD: Forty Wistar Albino rats were randomly distributed into 4 groups as (A) control group, (B) stress group, (C) oral KRG group, and (D) intraperitoneal KRG group. The modified McFarlane flap of 9 × 3 cm with a caudal pedicle was harvested from the back of the rats in all the groups. Korean Red Ginseng was administered to groups C and D at standard doses for 10 days. After 10 days, the flaps were removed in all groups and were examined macroscopically, histopathologically, histochemically, and biochemically. The results were statistically analyzed and compared among the groups. RESULTS: The flap necrosis rates were significantly lower in groups C and D compared with groups A and B (P < 0.05). The vascular density, antioxidant activity, and hypoxia-inducible factor-1α levels were significantly higher in the groups C and D compared with the groups A and B (P < 0.05). Although vascular density, hypoxia-inducible factor-1α, and catalase levels were negatively correlated with the flap necrosis rates, there was a significantly positive correlation between malondialdehyde and necrosis rates. CONCLUSIONS: Korean Red Ginseng increases the viability of random pattern skin flaps, resulting in reduced rates of distal necrosis. Korean Red Ginseng has antioxidant activity and increases neovascularization.

Tonsillar solitary fibrous tumour: A interesting rare case.

A solitary fibrous tumour (SFT) is a rare mesenchymal tumour that frequently originates in the mesothelium-covered surfaces, such as the pleura and peritoneum. It may develop in various body parts, including the head and neck. These tumours may arise in several different patterns, which results in difficulties in diagnosing them. This case is a solitary tumour developing from the palatine tonsil in a 17-year-old male patient; it is the second case in the literature. The tumour has the histopathological characteristics of a patternless pattern, a slight pleomorphism, and a composition of hypercellular and hypocellular sites. Immunohistochemically, the tumour cells showed a strong positive staining with CD34, Bcl-2, and vimentin. No recurrence developed in the patient's approximately 18-month-long follow-up period.

The Effect of the Active Ingredient Thymoquinone on Flap Viability in Random Pattern Flaps in Rats.

Thymoquinone (TQ) is a plant extract that has been shown to have antioxidant, anti-inflammatory, angiogenic, antimicrobial, and anticarcinogenic effects. The aim of this study is to research how the use of TQ affects flap viability. 42 rats were placed into 6 groups, with 7 rats in each. A 3 × 10 cm McFarlane flap model was used on the test animals. The sham group had used neither surgical nor TQ treatment. The control group had surgery but no treatment afterwards. The preoperative TQ group was given oral doses of 2 mg/kg. TQ for 10 days preoperatively with no treatment after the surgical procedure. The postoperative TQ group received oral doses of 2 mg/kg TQ for 10 days after the surgical process. The preoperative + postoperative (pre + postoperative) TQ group was given oral doses of 2 mg/kg TQ for 10 days both preoperatively and postoperatively. Finally, the dimethylsulfoxide group received 10 mg/kg dimethylsulfoxide (DMSO) for 10 days both preoperatively and postoperatively. Ten days after surgery the findings were evaluated. The average rates of necrosis were found to be 29.7 % in the control group, 19.18 % in the preoperative TQ group, 13.05 % in the postoperative TQ group, 8.42 % in the pre + postoperative TQ group, and 29.03 % in the DMSO group. The experimental groups had better area measurement, histopathological, and electron microscopic results than the control group (All; p < 0.05). We believe that, because of its antioxidant, anti-inflammatory, and angiogenic properties, thymoquinone is an agent that can prevent ischemia-reperfusion damage and, therefore, prevent necrosis.

Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model.

This study aimed to investigate the possible protective effect of paricalcitol on experimental amikacin-induced nephrotoxicity model in rats. Wistar albino rats (n = 32) were allocated into four equal groups of eight each, the control (Group C), paricalcitol (Group P), amikacin-induced nephrotoxicity (Group A), and paricalcitol-treated amikacin-induced nephrotoxicity (Group A + P) groups. Paricalcitol was given intra-peritoneally at a dose of 0.4 µg/kg/d for 5 consecutive days prior to induction of amikacin-induced nephrotoxicity. Intra-peritoneal amikacin (1.2 g/kg) was used to induce nephrotoxicity at day 4. Renal function parameters, oxidative stress biomarkers, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio), kidney histology, and vascular endothelial growth factor (VEGF) immunoexpression were determined. Group A + P had lower mean fractional sodium excretion (p < 0.001) as well as higher creatinine clearance (p = 0.026) than the amikacin group (Group A). Renal tissue malondialdehyde levels (p = 0.035) and serum 8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) (p < 0.001) were significantly lower; superoxide dismutase (p = 0.024) and glutathione peroxidase (p = 0.007) activities of renal tissue were significantly higher in group A + P than in group A. The mean scores of tubular necrosis (p = 0.024), proteinaceous casts (p = 0.038), medullary congestion (p = 0.035), and VEGF immunoexpression (p = 0.018) were also lower in group A + P when compared with group A. This study demonstrates the protective effect of paricalcitol in the prevention of amikacin-induced nephrotoxicity in an experimental model. Furthermore, it is the first study to demonstrate that paricalcitol improves oxidative DNA damage in an experimental acute kidney injury model.

Chemotherapy-induced acral erythema with involvement of the face and neck: A case report.

Chemotherapy-induced acral erythema (CIAE) is a cutaneous response to diverse chemotherapeutic drug administration. These drugs cause symmetrical and painful erythema of palmoplantar surfaces. Bulla formation, desquamation, and subsequent reepithelialization may occur. Commonly, the lesions slowly resolve over 7-15 days, through desquamation, followed by regeneration of the skin. Here, we described a case of CIAE, with involvement of face and neck in a patient treated for breast cancer using a number of chemotherapeutic agents. Face involvement in CIAE has not been previously reported in the literature.