Bone metastasis in breast cancer: The story of RANK-Ligand

AbstractThe primary cellular mechanism responsible for osteolytic bone metastases is osteoclastic activation. Preclinical models have shown that breast cancer cells can produce parathyroid hormone-related protein (PTHrP), and other osteolytic molecules, which stimulate excessive osteoclastic bone resorption and establishment of osteolytic lesions. It has been shown that PTHrP by itself cannot directly induce osteoclastic activation, but it mediates its effect through the transactivation of RANK-ligand (RANKL) gene on stromal and osteoblastic cells. Accordingly RANKL up-regulation has been considered as a prerequisite in virtually all conditions of cancer induced bone destruction. Hence, therapeutic targeting of RANKL seems to be a rational approach to treat or even to prevent the process of bone metastases.In this review, we will focus on the unique patho-physiological aspects related to the evolution of bone metastases in breast cancer, emphasizing the pivotal role of RANKL and some other key molecules in osteoclastic bone resorption. We will discuss the therapeutic interventions using bisphosphonates and RANKL inhibitors in patients with bone metastases and the outcome of this novel approach

Garay’s Condition of Deformed Cylindrical and Translation Surfaces in E3

The motivation of the present work is to develop the finiteness property in our work [1, 2, 3, 4] by using Garay’s condition [5]. The mean curvature flow and the finiteness property of the cylindrical surfaces in E3 are investigated. Additionally, the linear deformation of such surfaces is studied. Finally, the translation surfaces are discussed

An Investigation of Biodiesel Production from Wastes of Seafood Restaurants

This work illustrates a comparative study on the applicability of the basic heterogeneous calcium oxide catalyst prepared from waste mollusks and crabs shells (MS and CS, resp.) in the transesterification of waste cooking oil collected from seafood restaurants with methanol for production of biodiesel. Response surface methodology RSM based on D-optimal deign of experiments was employed to study the significance and interactive effect of methanol to oil M : O molar ratio, catalyst concentration, reaction time, and mixing rate on biodiesel yield. Second-order quadratic model equations were obtained describing the interrelationships between dependent and independent variables to maximize the response variable (biodiesel yield) and the validity of the predicted models were confirmed. The activity of the produced green catalysts was better than that of chemical CaO and immobilized enzyme Novozym 435. Fuel properties of the produced biodiesel were measured and compared with those of Egyptian petro-diesel and international biodiesel standards. The biodiesel produced using MS-CaO recorded higher quality than that produced using CS-CaO. The overall biodiesel characteristics were acceptable, encouraging application of CaO prepared from waste MS and CS for production of biodiesel as an efficient, environmentally friendly, sustainable, and low cost heterogeneous catalyst

Renoprotective effect of red grape (Vitis vinifera L.) juice and dark raisins against hypercholesterolaemia-induced tubular renal affection in albino rats

Background: Red grape juice (RGJ) and dark raisins (DR) are rich in polyphenols and antioxidants. This study aimed to assess the efficacy of RGJ and DR in protec- ting the renal tubules against hypercholesteraemic-induced pathological changes.  Materials and methods: Forty albino rats divided into four groups (n = 10) were utilised in this study. They included the control, high cholesterol diet (HCD)-fed, HCD+RGJ-fed, and HCD+DR-fed groups. Body weight gain, food and water in- take, blood and insulin levels, lipid profile and kidney functions were assessed at the start of the experiment and after 12 weeks. The right kidney was dissected out and processed for both light and electron microscopic examination. Desmin and cytokeratin antibodies were utilised as histologic markers to assess the integrity of the proximal (PTs) and distal tubules (DTs) of the kidney.  Results: Administration of HCD resulted in hypercholesterolaemia in rats as evi- denced by the lipid profile. The PTs of hypercholesteraemic rats appeared dilated with hyaline casts and mitochondria in most of the tubular cells were affected. Immunohistochemical assessment revealed affection of both PTs and DTs. Both RGJ and DR, when administered along with the HCD for 12 weeks, improved the lipid profile, kidney functions as well as the histologic and cellular changes-induced by hypercholesterolaemia in the rats. The effect of raisins was superior to RGJ which might be due to its high contents of fibres and proteins.  Conclusions: This study highlighted the importance of supplementation of red grape and raisins in protection against the harmful effects induced by deposition of fat on the renal tubules’ structure and function.

MaaSim: A Liveability Simulation for Improving the Quality of Life in Cities

Urbanism is no longer planned on paper thanks to powerful models and 3D simulation platforms. However, current work is not open to the public and lacks an optimisation agent that could help in decision making. This paper describes the creation of an open-source simulation based on an existing Dutch liveability score with a built-in AI module. Features are selected using feature engineering and Random Forests. Then, a modified scoring function is built based on the former liveability classes. The score is predicted using Random Forest for regression and achieved a recall of 0.83 with 10-fold cross-validation. Afterwards, Exploratory Factor Analysis is applied to select the actions present in the model. The resulting indicators are divided into 5 groups, and 12 actions are generated. The performance of four optimisation algorithms is compared, namely NSGA-II, PAES, SPEA2 and eps-MOEA, on three established criteria of quality: cardinality, the spread of the solutions, spacing, and the resulting score and number of turns. Although all four algorithms show different strengths, eps-MOEA is selected to be the most suitable for this problem. Ultimately, the simulation incorporates the model and the selected AI module in a GUI written in the Kivy framework for Python. Tests performed on users show positive responses and encourage further initiatives towards joining technology and public applications.Comment: 16 page

High Performance Liquid Chromatographic Assay for the Simultaneous Determination of Posaconazole and Vincristine in Rat Plasma

Purpose. Developing a validated HPLC-DAD method for simultaneous determination of posaconazole (PSZ) and vincristine (VCR) in rat plasma. Methods. PSZ, VCR, and itraconazole (ITZ) were extracted from 200 μL plasma using diethyl ether in the presence of 0.1 M sodium hydroxide solution. The organic layer was evaporated in vacuo and dried residue was reconstituted and injected through HC-C18 (4.6 × 250 mm, 5 μm) column. In the mobile phase, acetonitrile and 0.015 M potassium dihydrogen orthophosphate (30 : 70 to 80 : 20, linear gradient over 7 minutes) pumped at 1.5 mL/min. VCR and PSZ were measured at 220 and 262 nm, respectively. Two Sprague Dawley rats were orally dosed PSZ followed by iv dosing of VCR and serial blood sampling was performed. Results. VCR, PSZ, and ITZ were successfully separated within 11 min. Calibration curves were linear over the range of 50–5000 ng/mL for both drugs. The CV% and % error of the mean were ≤18% and limit of quantitation was 50 ng/mL for both drugs. Rat plasma concentrations of PSZ and VCR were simultaneously measured up to 72 h and their calculated pharmacokinetics parameters were comparable to the literature. Conclusion. The assay was validated as per ICH guidelines and is appropriate for pharmacokinetics drug-drug interaction studies

Stellar parameters of Be stars observed with X-shooter

Aims. The X-shooter archive of several thousand telluric star spectra was skimmed for Be and Be-shell stars to derive the stellar fundamental parameters and statistical properties, in particular for the less investigated late type Be stars, and the extension of the Be phenomenon into early A stars. Methods. An adapted version of the BCD method is used, utilizing the Balmer discontinuity parameters to determine effective temperature and surface gravity. This method is optimally suited for late B stars. The projected rotational velocity was obtained by profile fitting to the Mg ii lines of the targets, and the spectra were inspected visually for the presence of peculiar features such as the infrared Ca ii triplet or the presence of a double Balmer discontinuity. The Balmer line equivalent widths were measured, but due to uncertainties in determining the photospheric contribution are useful only in a subsample of Be stars for determining the pure emission contribution. Results. A total of 78 Be stars, mostly late type ones, were identified in the X-shooter telluric standard star archive, out of which 48 had not been reported before. The general trend of late type Be stars having more tenuous disks and being less variable than early type ones is confirmed. The relatively large number (48) of relatively bright (V > 8.5) additional Be stars casts some doubt on the statistics of late type Be stars; they are more common than currently thought: The Be/B star fraction may not strongly depend on spectral subtype.Comment: Accepted for publication in A&