Curcumin induces DNA damage by mediating homologous recombination mechanism in triple negative breast cancer

Curcumin has a therapeutic potential activity through modulation of different signaling pathways in various types of cancer. However, the relationship between the efficacy of curcumin and the homologous recombination (HR) mechanism which plays important roles in the repair of double strand DNA (dsDNA) breaks remains uncertain. Herein, we explored curcumin-dependent dsDNA breaks and the association of curcumin with HR mechanism in triple negative breast cancer (TNBC). The cytotoxic and therapeutic activity of curcumin on HCC1937 (BRCA1 mutant), MDA-MB-231 (BRCA1 wild type) TNBC and HUVEC control cell lines were assessed. Then, the expression level and subcellular localization of H2AX, PARP1, BRCA1 and RAD51 were detected by RT-PCR and immunofluorescence analysis. Furthermore, ultrastructural changes of cell death were observed by TEM. Our findings for the first time demonstrated that curcumin?s therapeutic activity was more pronounced in HCC1937 cells through the suppression of HR mechanism and the induction of dsDNA breaks. Consequently, curcumin based therapy could benefit in patients with TNBC particularly especially in women with a BRCA1 mutation

Etanercept protects ovarian reserve against ischemia/reperfusion injury in a rat model

Introduction: Etanercept has been widely used in autoimmune diseases for blocking tumor necrosis factor alpha (TNF-alpha), which is an inflammatory cytokine. The anti-apoptotic and anti-inflammatory effects of etanercept against ischemia/reperfusion (I/R) injury have been shown for several tissues in rat studies, but to the best of our knowledge, there are no reports on its protective effects following similar injury in ovarian tissue. The aim of this study was to investigate whether etanercept has beneficial effects on ovarian I/R injury, as well as on ovarian reserve. Material and methods: Twenty-four rats were randomly divided into four groups (n = 6/group): sham (laparotomy only); sham + etanercept; I/R; and I/R + etanercept. Ischemia was induced for 3 h by twisting the ovary, and 24 h after detorsion the ovarian tissues were collected to evaluate histopathologic changes, glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) concentrations for oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, caspase-3 activity for apoptosis and ovarian follicle counts. To measure anti-Mullerian hormone (AMH), serum samples were drawn before and after surgery. Results: Tissue GSH and SOD levels were significantly higher, while MDA and MPO levels were significantly lower in the I/R + etanercept group than in the I/R group (p < 0.05, p < 0.01, respectively). Tissue 8-OHdG and caspase-3 activity were significantly lower in the I/R+etanercept group than in the I/R group (p < 0.05, p < 0.01, respectively). Preoperative and postoperative AMH levels were compared and there was a significant reduction in the I/R and I/R + etanercept groups (p < 0.001, p < 0.001). The reduction of AMH in the I/R + etanercept group was significantly lower than in the I/R group. The primordial, preantral and small antral follicle numbers were also significantly higher in the I/R + etanercept group compared to the I/R group (p < 0.001, p < 0.001, p < 0.005, respectively). Conclusions: Etanercept attenuated inflammation and related oxidative stress and also helped to preserve ovarian reserve following ovarian I/R damage

Differentiation of hematopoietic stem cells isolated from peripheral blood to megakaryocyte

Objective: Thrombocytopenia remains a serious problem in patients treated with high-dose chemotherapy and bone marrow transplantation. In recent years, infusion of ex vivo expanded megakaryocytes (Mk) progenitors into patients has been proposed as a strategy for shortening the time of platelet engraftment. The development of in vitro culture methods to obtain sufficient numbers of Mks from haematopoietic stem cells (HSC) is an important target in basic and clinical research projects. The aim of this study was to develop a two-step ex vivo expansion culture system of Mk progenitors from peripheral blood stem cells (PBSC). Methods: PBSC were harvested from three healthy adult donors. CD34+ cells were isolated and cultured in serum free media supplemented with thrombopoietin (TPO) (50 ng/ml), Interleukin 3 (IL-3) (20 ng/ml) and Interleukin 6 (IL-6) (20 ng/ml) for 12 days followed by an incubation with IL-6 (20 ng/ml) and TPO (50 ng/ml) for another 9 days. The differentiation of Mks was monitored by flow cytometry (% of CD34+/41+ cells). The morphology of the cells was studied by light, electron and fluorescence microscopy. Results: Morphological analysis of cells generated after 7 days of culture showed typical aspects of developing Mks. The percentage of CD41+ cells was higher than 70 on day 21. Conclusion: The results obtained in this study demonstrated that this two-step culture system is an effective method to obtain high rates of megakaryocytes. It is obvious that this promising method needs further development for clinical applications

Nasal septal turbinate: Cadaveric study

Background: Despite the importance of its location, the functional behavior of the nasal septal turbinate (NST) is still not completely understood. Basic histological knowledge is still lacking. The aim of this study was to describe the histological features of the NST and to compare its morphometric features to those of the adjacent nasal septum and the inferior and middle turbinates. Methods: The study included 50 fresh cadavers. Excisional biopsy specimens of the NST with adjacent posterior septum were collected. In addition, mucosal and submucosal biopsy specimens were taken of the inferior and middle turbinates. Morphometric analysis was performed on five different tissue types: glandular elements, connective tissue stroma, arterial structures, and capillary or venous sinusoids. Results: The mean proportion of venous sinusoids was statistically lower in the nasal septum and NST than in the inferior and middle turbinate. The mean proportion of glandular tissues was higher in the NST than in other regions of the nasal cavity. The mean proportion of arterial tissue was lower in the nasal septum and the NST. Significantly fewer capillary elements were found in the inferior and middle turbinates than in the nasal septum and NST. The mean proportion of connective tissues was lower in the NST than in other regions of the nasal cavity. Conclusion: The similar histopathological cell distribution in the middle and inferior turbinate supported a function as an erectile organ, but the findings for the NST pointed to different functional properties of this region

Effect of perinatal biotin deficiency on auditory pathway of the Wistar-Albino rats

Aim: Severe biotin deficiency associated with biotinidase enzyme deficiency in newborns is seen as severe neurological problems and hearing loss. However, the effect on the infant of deficiencies in the maternal diet during pregnancy are not clear. Material and methods: The study included 16 female Wistar albino rats and 4 male Wistar albino rats, that were mated and then the females were separated into 4 groups. At 40 days after the birth, 3 pups were selected from each group, and these 12 pups were evaluated with DPOAE and ABR electrophysiologically and the cochlea was examined ultrastructurally with electron microscopy. Results: In the DPOAE evaluation, At 8000 and 11,000 Hz, the signal-noise ratios in the B-N and B-B groups were statistically significantly higher (p < .05). In ABR, lengthening of the latency periods was determined in all the waves at both 8 and 16 kHz in the B-B group. When the IPL periods were examined, lengthening in IPL 1-5 was statistically significant in the B-B group only at 8 kHz. Conclusions: Biotin can be said to have an effect on hearing pathways. However, specifically where on the hearing pathways that biotin is involved has not been clarified

Association of Conductive Hearing Loss with the Structural Changes in the Organ of Corti

Objective: The aim of the study was to evaluate the association of conductive hearing loss (CHL) with the structural changes in the organ of Corti. Methods: Twenty ears of 10 healthy adult Wistar albino rats were included in the study. The right ears (n = 10) of the animals served as controls (group 1), and no surgical intervention was performed in these ears. A tympanic membrane perforation without annulus removal was performed under operative microscope on the left ears (n = 5) in 5 of 10 animals (group 2). A tympanic membrane perforation with annulus removal was performed under operative microscope on the left ears (n = 5) of the remaining 5 animals (group 3). Auditory brainstem response testing was performed in the animals before the interventions. After 3 months, the animals were sacrificed, their temporal bones were removed, and inner ears were investigated using scanning electron microscopy (SEM). The organ of Corti was evaluated from the cochlear base to apex in the modiolar axis, and the parameters were scored semiquantitatively. Results: In group 1, the pre- and post-intervention hearing thresholds were similar (p > 0.05). In group 2, a hearing decrease of at least 5 dB was encountered in all test frequencies (p > 0.05). In group 3, at the frequency range of 2-32 kHz, there was a significant hearing loss after 3 months (p < 0.01). After 3 months, the hearing thresholds in group 2 and 3 were higher than group 1 (p < 0.01). The hearing threshold in group 3 was higher than group 2 (p < 0.01). On SEM evaluation, the general cell morphology and stereocilia of the outer hair cells were preserved in all segments of the cochlea in group 1 with a mean SEM score of 0.2. There was segmental degeneration in the general cell morphology and outer hair cells in group 2 with a mean SEM score of 2.2. There was widespread degeneration in the general cell morphology and outer hair cells in group 3 with a mean SEM score of 3.2. The SEM scores of group 2 and 3 were significantly higher than group 1 (p < 0.05). The SEM scores of group 3 were significantly higher than group 2 (p < 0.05). Conclusion: CHL may be associated with an inner ear damage. The severity of damage appears to be associated with severity and duration of CHL. Early correction of CHL is advocated in order to reverse or prevent progression of the inner ear damage, which will enhance the success rates of hearing restoration surgeries. Subjective differences and compliance of the hearing aid users may be due to the impact of CHL on inner ear structures

The effect of topical and systemic tranexamic acid on fracture healing in rats

Objective: The aim of the present study was to determine the effect of topical and systemic tranexamic acid (TXA) on fracture healing in a rat surgical model. Methods: We created standard, right-sided, open, diaphyseal femoral fractures with intramedullary Kirschner wire fixation in 48 male rats and divided them into three groups: a topical TXA (10 mg/kg) group, a systemic TXA (10 mg/kg) group, and a control group. Fracture healing was evaluated radiographically and histologically after early (week 2) and late (week 4) postoperative sacrifice. Results: The radiological scores differed significantly among the all groups (p-0.001), as did the week 2 and 4 scores (p=0.003 and p=0.010, respectively). Radiologically, the topical TXA group exhibited better bone healing at both 2 (p=0.001) and 4 (p=0.007) weeks than the control group, and the systemic group showed better healing at both 2 (p=0.027) and 4 (p=0.023) weeks than the control TXA group. Moreover, bone healing was better in the group treated with topical rather than systemic TXA on radiological examinations performed at 2 (p=0.001) and 4 (p=0.007) weeks postoperatively (p=0.001 and p=0.007, respectively). Histologically, the groups differed significantly (p=0.001). The histological scores differed significantly among the all groups (p=0.001). At 2 weeks, the topical TXA group exhibited significantly better bone healing than the control group (p=0.001). Conclusion: Our results suggested that topical application of TXA in fracture patients may accelerate healing, whereas systemic administration may adversely affect healing

Effects of Tumescent Solution on Fat Survival

Autologous fat transfer is a commonly used procedure in plastic surgery practice. The long-term survival rate of fat grafts is the most important issue for satisfactory results. The presented study includes the effects of different tumescent solutions on long-term fat graft survival. A total of 24 rats were divided into four groups: sham, lidocaine, adrenaline, and lidocaine + adrenaline groups. In all groups except the sham group, right inguinal fat pad was harvested 10 minutes after injecting 5 cc of the appropriate tumescent solution. The fat pad was trimmed and reimplanted to the interscapular area. After 3 months, fat pad was reharvested and sent for histopathologic evaluation. The harvested fat grafts were weighted in both surgical sessions. A significant difference was observed in comparison of fat grafts weights between the initial operation and the postoperative third month (p = 0.002). By intergroup comparisons, a significant difference was observed between sham and adrenaline groups (p = 0.002) and between sham and lidocaine + adrenaline groups (p = 0.007). No statistical difference was observed by the comparison of TUNNEL results (p = 0.663). The histopathologic evaluation of the specimens revealed similar results between groups. The injection of tumescent solutions containing only lidocaine before fat harvesting yields similar long-term fat graft survival rates in comparison to the conduction of surgical procedure without injecting any tumescent fluid. However, the injection of solutions containing adrenaline with or without lidocaine may decrease the long-term survival rates of fat autografts