Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gammasecretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, delta-like ligand 4 (DLL4), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors ((GSIs)) and DLL4 monoclonal antibody (mAb) may produce synergistic benefits. Further, the (GSIs) (DAPT, LY-411575, RO4929097, MK0752, etc. ) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss solid lipid nanoparticles (SLNs) based drug delivery systems containing (GSIs) and surface modified with DR-5 and DLL4 monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of (GSIs). Further, DLL4 mAb and (GSIs) are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.

Background: Gunshot injuries ((GSIs)), a serious public health problem, can affect the pediatric age group and adults. Objectives: This study aimed to describe the injuries that occurred in children aged 0-16 years who were brought to the emergency department (ED) of Şehitkamil State hospital in Gaziantep, Turkey, due to (GSIs). Methods: This descriptive-retrospective study was conducted in the ED of the child trauma center of Gaziantep. This study retrospectively reviewed the records of children aged 0 - 16 years admitted to the ED with (GSIs) from 01/01/2014 to 30/09/2020. Results: A total of 66 GSI cases were included in the study. The most common injury was in the abdominal region. Internal organ/vessel/bone injuries were detected in 59.1% of the cases (n = 39). Surgical treatment was applied to 60.6% of the cases (n = 40) within 7 days. The mortality rate was 12.1% (n = 8). The length of stay in the trauma unit was 4.34 ± 4.33 days. Conclusion: Most injuries are detected in the abdomen. GSI was more common in boys. The prognosis is worse in those with internal organ/vascular/bone injuries. These patients have higher mortality, longer hospital stay, and a higher rate of surgical operation.

Background: Vitamin D affects the pancreatic beta cell function and in vitro studies have shown that vitamin D may influence insulin secretion, apoptosis, and gene regulation. However, the outcomes have differed and there has been uncertainty regarding the effect of different vitamin D metabolites on insulin secretion. Objectives: We hypothesized that vitamin D could increase insulin secretion in insulin producing beta cells and investigated the effect of 25(OH) vitamin D and 1, 25(OH)2 vitamin D on insulin secretion. Methods: The study was conducted in INS1E cells, an established insulinoma cell line from rat. The cells were divided into three groups; a control group, a group with 1, 25(OH)2 vitamin D enriched medium (10 nM), and a group with 25(OH) vitamin D (10 nM) supplemented medium. After 72 hours of treatment, the cells underwent glucose stimulation at different concentrations (0, 5, 11, and 22 mM) for 60 minutes. Results: INS1E cells treated with 1, 25(OH)2 vitamin D showed a trend towards increased insulin secretion at all glucose concentrations compared to control cells and at 22mMglucose, the difference was significant (18. 40 +/-1. 97 vs 12. 90 +/-2. 22 nmol/L, P < 0. 05). However, pretreatment with 25(OH) vitamin D did not show any significant increase in insulin secretion compared to cells without vitamin D treatment. There was no difference in insulin secretion in cells not stimulated with glucose. Conclusions: Treatment with 1, 25(OH)2 vitamin D combined with high levels of glucose increased insulin secretion in INS1E cells, whereas 25(OH) vitamin D had no effect. This suggests that glucose stimulated insulin secretion in INS1E beta cells appears to be related to the type of vitamin D metabolite treatment.

Background: Glucokinase serves as a glucose sensor in pancreatic β-cells and plays a key role in glucose homeostasis and glucose-stimulated insulin secretion ((GSIs)). In the present study we examined the effect of glucosamine, a glucokinase inhibitor, on the pancreatic glucokinase and hexokinase activities and on insulin secretion from freshly rat pancreatic islets of Langerhans. Insulin concentration was measured by rat insulin ELISA kit. Methods: The pancreatic islets from normal and type 2 diabetic (nSTZ) rats were isolated by collagenase digestion method. Glucose phosphorylation was quantitated by measuring the rate of glucose-6-phosphate formation in the fluorometric assay. Insulin secretion from hand-picked islets was evaluated in static incubation system. Insulin concentration was measured by rat insulin ELISA kit. Results: Our findings demonstrate that glucosamine in a dose dependent manner, reduced glucokinase activity in islet extract, but had no effect on hexokinase activity. The glucose-stimulated insulin secretion was inhibited by glucosamine but it had no effect on the basal insulin secretion. In diabetic rats glucokinase was decreased while the basal insulin secretion and the activity of hexokinase were higher than normals. Conclusion: Based on results obtained from the present study, the assumption could be made that the decrease in the activity of glucokinase of pancreatic islets could be related to the impaired glucose stimulated insulin secretion. The increase in basal insulin secretion of diabetic rats may be due to an increase in pancreatic hexokinase activity.

Where closely jointed rock masses are encountered in slopes, failure can occur both through the rock mass, as a result of combination of macro and micro jointing, and also through rock substance. Determination of the strength of these rock masses is quite difficult since the size of representative specimens of them is too large for laboratory testing. This difficulty can be overcome by using a non-linear rock mass failure criterion or by back analysis of such slopes. In this paper, a new procedure, and accompanying computer program, is presented for estimation of shear strength parameters, mobilized in slopes cut, in closely jointed rock masses, which obey a non-linear failure criterion, rather than a linear one. In this procedure, the necessary constants to calculate normal stress are dependent to shear strength parameters of the failed rock masses. These parameters can be determined, using a main cross section across the failed slope, without the need for exact value of Geological Strength Index (GSI). In this respect, trials are made with different GSIm and (GSIs) values, corresponding to various possible combinations of the constant m and s, satisfying the limit equilibrium condition, used in the Hoek & Brown’s failure criterion. The proposed procedure provides a quick check for the GSI obtained from the site investigations. The proposed procedure is used in conjunction with the Morgenstern-Price method of slope analysis, for circular or noncircular slip surfaces. The method outlined in this paper has been satisfactorily applied to Duna landslide, in the right bank of upper dam of Siah Bishe pump-storage, north of Iran.

Objective(s): Type 1 diabetes mellitus is a common autoimmune and multifactorial disorder. Researchers have been interested in making a favorable islet-like tissue model for the treatment of diabetes. The main objective of this study was to determine the effects of the spleen extracellular matrix (S-ECM) on the function of the MIN6 cell line (a β,-cell model). Materials and Methods: In this experimental research, Wistar rat spleens were decellularized by sodium dodecyl sulfate (SDS) and Triton X-100. S-ECM was characterized by histological assessments, scanning electron microscopy, determination of residua DNA, and examination of the mechanical tensile property. Then, MIN6 cells were seeded on S-ECM scaffold. Glucose-stimulated insulin secretion and mRNA expression of insulin-related genes were examined to confirm the function of the cells. Results: The main components of S-ECM such as collagen and glycosaminoglycan remained after decellularization. Furthermore, very low residual DNA and appropriate mechanical behavior of S-ECM provided an ideal extracellular microenvironment for the MIN6 cells. (GSIs) results showed that the seeded cells in S-ECM secreted more insulin than the traditional two-dimensional (2D) culture. The expression of specific insulin-related genes such as PDX-1, insulin, Maf-A, and Glut-2 in the recellularized scaffold was more significant than in the 2D traditional cultured cells. Also, MTT assay results showed that S-ECM were no cytotoxic effects on the MIN6 cells. Conclusion: These results collectively have evidenced that S-ECM is a suitable scaffold for stabilizing artificial pancreatic islands.

In this study, the effects of different light regimes on the reproductive activity of a typical Indo- Pacific coral reef rabbitfish, Siganus sutor, were evaluated. Forty- five adult fish were exposed to nine different photoperiod (8L: 16D, 12L: 12D, 16L: 8D) and light intensity (1000, 2000, 3000 lux) combinations with three replicates and five other fishes reared under indoor light condition (Control).Gonadosomatic Index (GSI) and Hepatosomatic Index (HSI) were calculated after 60 days and compared among different experimental regimes in males and females. In the control group, GSI and HSI mean values were 4.67 and 3.24%, respectively, for females and 10.05 and 2.10%, respectively, for males, and these fish showed differences in comparison with the exposed fish. Females kept under 1000 and 2000 lux light intensities had a higher GSI mean value (9.26 and 10.39%, respectively) and also lower average HSI (2.10 and 2.31%, respectively) in 16L: 8D treatment. A similar result was also obtained for males, whereas the 3000 lux light intensity, 8L: 16D day length combination led to more gonadal development ((GSIs) of 16.41% in females and 12.03% in males). A comparison of results among different photoperiods also confirmed that maturation was induced better in fish maintained under 16L: 8D in both sexes. This investigation revealed the visible role of both photoperiod and light intensity on inducing maturity in the whitespotted rabbitfish, S. sutor. Thus, rearing of adults exposed to an artificial light regime, including 16L: 8D and 2000 lux light intensity, promotes more gonadal development than that occurring in the wild.