Proapoptotic and antimetastatic properties of supercritical CO2 extract of Nigella sativa Linn. Against breast cancer cells

Nigella sativa, commonly referred as black cumin, is a popular spice that has been used since the ancient Egyptians. It has traditionally been used for treatment of various human ailments ranging from fever to intestinal disturbances to cancer. This study investigated the apoptotic, antimetastatic, and anticancer activities of supercritical carbon dioxide (SC-CO) extracts of the seeds of N. sativa Linn. against estrogen-dependent human breast cancer cells (MCF-7). Twelve extracts were prepared from N. sativa seeds using the SC-CO extraction method by varying pressure and temperature. Extracts were analyzed using FTIR and UV-Vis spectrometry. Cytotoxicity of the extracts was evaluated on various human cancer and normal cell lines. Of the 12 extracts, 1 extract (A3) that was prepared at 60 C and 2500 psi (∼17.24 MPa) showed selective antiproliferative activity against MCF-7 cells with an IC of 53.34±2.15 μg/mL. Induction of apoptosis was confirmed by evaluating caspases activities and observing the cells under a scanning electron microscope. In vitro antimetastatic properties of A3 were investigated by colony formation, cell migration, and cell invasion assays. The elevated levels of caspases in A3 treated MCF-7 cells suggest that A3 is proapoptotic. Further nuclear condensation and fragmentation studies confirmed that A3 induces cytotoxicity through the apoptosis pathway. A3 also demonstrated remarkable inhibition in migration and invasion assays of MCF-7 cells at subcytotoxic concentrations. Thus, this study highlights the therapeutic potentials of SC-CO extract of N. sativa in targeting breast cancer

Magnetism and Piezoelectricity in Stable Transition Metal Silicate Monolayers

Two-dimensional van der Waals (2D vdW) materials that display ferromagnetism and piezoelectricity have received increased attention. Despite numerous 2D materials have so far been reported as ferromagnetic, developing an air stable and transferable vdW material that is multiferroic has been challenging. To address this problem, we report our work on layered transition metal silicates that are derivatives of kaolinites and lizardites with transition metal substituting on Al$^{3+}$ and Mg$^{2+}$ sites using ab-initio calculations. Using Density Functional Theory (DFT), we show that these compounds are stable under varying O$_2$ partial pressure and can be synthesized using a surface assisted method. We show that these materials have finite out-of-plane piezoelectric response thanks to the lack of inversion symmetry and also they can be tailored to be ferrimagnetic with a non-zero net moment

Antiangiogenic Effect of Ficus deltoidea Jack Standardised Leaf Extracts

Purpose: To standardise the methanol and aqueous extracts of Ficus deltoidea leaf by developing a reverse phase high performance liquid chromatography (RP-HPLC) for determination of the ursolic acid content and to investigate their antiangiogenic activity.Methods: To prepare the water extract (FD-A), the powder of the plant was extracted with water under reflux for 24 h at 50 ˚C. The methanol extract (FD-M) was prepared using Soxhlet extractor for 24 h at 50 ˚C. The extracts were standardised for ursolic acid content by reverse phase high performance liquid chromatography (RP-HPLC), as well as by total phenolic and flavonoid contents. Antiangiogenic activity was studied using ex vivo rat aortic rings and in vivo chick chorioallantoic membrane angiogenesis models. The anti-proliferative effect of the extracts against normal human endothelial cells and two cancer cell lines was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.Results: In rat aortic rings, methanol and water extracts inhibited the outgrowth of microvessels with IC50 values of 48.2 ± 1.1 and 62.7 ± 1.4 μg ml-1, respectively. Methanol and water extracts at doses of 100 μg disc-1 also inhibited vascularisation of chick embryo chorioallantoic membrane with inhibition values of of 62.0 ± 6.3 and 43.3 ± 4.8 %, respectively. In addition, both extracts showed potent cytotoxicity against breast and colon cancer cells while demonstrating non-cytotoxic activity against normal endothelial cells. Furthermore, the two extracts showed relatively high concentration of ursolic acid, total phenolics and flavonoids associated with potent antiangiogenic activity.Conclusion: The inhibition of angiogenesis by F. deltoidea extracts may be attributed to the relatively high ursolic acid content as well as the presence of antioxidant compounds of phenolics and flavonoids in the extracts.Keywords: Ficus deltoidea, Antiangiogenesis, Ursolic acid, Cytotoxicity, Antioxidan

The effect of a proposed training program for the foundation course on basic skills and Body Composition among members of karate clubs in the Governorate of Jenin - Palestine

The study aimed to identify the effect of a proposed training program for the foundation course of the basic skills and body composition of the members of karate clubs in the governorate of Jenin – Palestine. The researchers used the experimental approach due to its suitability to the nature and objectives of the study. To achieve this, the study was conducted on a carefully chosen sample of karate clubs (the Talented Academy of Physical Fitness and self Defense, Arrabah Karate Club and Zababdeh Karate Club). The sample consisted of 50 members, 10 of those members were of exploratory sample, and the rest 40 members were considered as a basic sample that had been divided randomly into two groups. 20 members of experimental group and 20 members of control group. The researchers used Tanita DC-360 P to measure body components and in addition to a set of tests that measure basic skills. The training program was applied for a period of (10) weeks with (3) training sessions per week. Each training session took (60) minutes. In addition, the statistical packages program was used to analyze the data. The results showed that there were differences among the members of the experimental group between the pre and post measurements of body composition and basic skills. The results also indicated that there were no statistically significant differences between the members of the experimental and control groups in the post-measurement of body composition, while the results showed that there were statistically significant differences in the post-measurement of basic skills in karate, which came in favor of the members of the experimental group. The researchers recommended to the need to take account of the training program proposed by the coaches of karate clubs (kata) in the West Bank, especially in the training phase for basic karate skills

Ternary complex modeling, induced fit docking and molecular dynamics simulations as a successful approach for the design of VHL-mediated PROTACs targeting the kinase FLT3

Proteolysis targeting chimeras (PROTACs) have proven to be a novel approach for the degradation of disease-causing proteins in drug discovery. One of the E3 ligases for which efficient PROTACs have been described is the Von Hippel-Lindau factor (VHL). However, the development of PROTACs has so far often relied on a minimum of computational tools, so that it is mostly based on a trial-and-error process. Therefore, there is a great need for resource- and time-efficient structure-based or computational approaches to streamline PROTAC design. In this study, we present a combined computational approach that integrates static ternary complex formation, induced-fit docking, and molecular dynamics (MD) simulations. Our methodology was tested using four experimentally derived ternary complex structures of VHL PROTACs, reported for BRD4, SMARCA2, FAK, and WEE1. In addition, we applied the validated approach to model a recently in-house developed FLT3-targeted PROTAC (MA49). The results show that static ternary models generated with a protein–protein docking method implemented in the software MOE have a high predictive power for reproducing the experimental 3D structures. The induced-fit docking of different active PROTACs to their respective models showed the reliability of this model for the development of new VHL-mediated degraders. In particular, the induced-fit docking was sensitive to structural changes in the PROTACs, as evidenced by the failed binding modes of the PROTAC negative controls. Furthermore, MD simulations confirmed the stability of the generated complexes and emphasized the importance of dynamic studies for understanding the relationship between PROTAC structure and function

Density functional theory study on the catalytic dehydrogenation of methane on MoO3 (010) surface

Methane conversion offers hydrocarbon building blocks of high market value, which are easier to transport than natural gas. Under non-oxidative conditions, the process can also produce clean hydrogen fuel. In this study, we explored the catalytic dehydrogenation of methane on molybdenum oxide (MoO3) surface. Periodic density functional theory calculations were performed to study the adsorption of CH4 on two different supercells of the MoO3 (010) surface. It was found that CH4 adsorption was more favorable on a smooth surface constructed of Mo and O network, rather than a surface made with dangling O atoms as thought before. A reaction mechanism for hydrogen formation was then proposed. The first energy barrier for the H-abstraction step was calculated to be 66.4 kJ/mol, which is lower than previously reported values obtained for simple MoxOy clusters. The reactions were discussed using the two-state reactivity approach, where different electronic states can play a role in the H-abstraction step. The mechanism also showed the formation of methyl radicals and ethylene, in addition to molecular hydrogen.This research is funded by Qatar University’s grant number QUCG-CAS-21221

Enhancing the performance of pyridyl carboxamide-N,N-dimethyl amino chalcone (PCC) as a dye sensitizer for dye-sensitized solar cells (DSSCs) through the incorporation of electron donor moieties

This study has focused on enhancing the performance of pyridyl carboxamide-N,N-dimethyl amino chalcone (PCC) as a sensitizer for dye-sensitized solar cells (DSSCs) by strategically incorporating electron donor moieties identified in a literature review. Our reviewing the previous reports highlights the pivotal role of electron donors in optimizing light harvesting, electron injection, and overall power conversion efficiency in organic dye sensitizers, particularly those following a donor-bridge-acceptor (D-π-A) architecture. The selected donor moieties, including dithieno[3,2-b:2′,3′-d]thiophene (DTT), benzodithiophene (BDT), triphenylamine (TPA), carbazole (CBZ), and triazatruxene (TAZ), are systematically introduced into the molecular structure of PCC (abbreviated as PCC-DTT, PCC-BDT, PCC-TPA, PCC-CBZ, and PCC-TAZ, respectively). The performance of these modified compounds is rigorously evaluated using density functional theory (DFT) methods. Validation results revealed that the most reliable method for PCC derivative characterization involved the combination of the functional B3PW91 with a 6-31G(d) basis set. The results indicate that the incorporation of certain donor moieties, particularly BDT, significantly enhances the electronic and optical properties of PCC, including lower HOMO energy levels, a narrow energy gap (Egap), enhanced absorption intensity, and a redshift in absorption peaks. Evaluation of photovoltaic properties including electron injection (ΔGinj), and open circuit voltage (Voc), indicated facilitating spontaneous electron injection from the dyes to the TiO2 conduction band. Notably, PCC-TAZ demonstrated the lowest electron regeneration (ΔGreg), suggesting a notable potential for efficient electron regeneration

Influence of Thermomechanical Treatment on the Mechanical Behavior of Protaper Gold versus Protaper Universal (A Finite Element Study)

AIM: To compare and evaluate the influence of thermomechanical treatment of Protaper Gold file versus Protaper Universal file during testing of bending and torsion using ï¬nite-element analysis. METHODS: Two nickel-titanium NiTi rotary ï¬les (ProTaper Gold and ProTaper Universal) were used in this study. The files were imaged using stereomicroscope to produce 3D models. The behaviour of the instrument during bending and torsion was numerically analysed in CAD/CAM software package. RESULTS: Under bending, ProTaper, Gold showed higher flexibility and flexural resistance than ProTaper Universal. The highest stress was related at the cutting edge of both files. While during testing of torsion, the maximum amount of stresses was related to the base of the flutes in both files. ProTaper Gold showed higher torsional resistance than the ProTaper Universal file. CONCLUSION: Thermomechanical treatment improved the mechanical response (bending and torsional resistance) of NiTi files

TriNetX and Real-World Evidence: A Critical Review of Its Strengths, Limitations, and Bias Considerations in Clinical Research

Introduction: The increasing utilization of real-world data platforms in medical research necessitates a comprehensive understanding of their methodological strengths and limitations. TriNetX has emerged as a significant platform for exploring large healthcare datasets. This review aims to critically evaluate the methodological framework and limitations of TriNetX, assess the impact of electronic health record coding accuracy on data reliability, and analyze the platform\u27s capacity for generating generalizable real-world evidence in clinical research. Methods: We conducted a comprehensive review examining TriNetX\u27s data architecture, quality metrics, and research applications, focusing on data integrity, platform architecture, and the external validity of research findings. Results: The analysis reveals significant methodological considerations. TriNetX\u27s reliance on retrospective data introduces biases such as selection bias and confounding variables. The coding accuracy of electronic health records, which have not been independently validated, is a critical determinant of data reliability. The demographic representation is limited, affecting the generalizability of results. Discussion: Despite its extensive use, TriNetX\u27s effective utilization requires careful consideration of its inherent limitations. The platform\u27s data, predominantly from insured populations in academic and acute care settings, may not fully represent broader demographic groups. Addressing these methodological constraints is crucial for enhancing the reliability and applicability of research findings derived from TriNetX. Conclusions: TriNetX is a valuable resource for healthcare research. However, its limitations must be acknowledged, and future research should focus on standardizing data collection and enhancing data validation processes to mitigate platform-specific biases and improve the quality and applicability of the findings

Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

Background: Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.Results: Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay. KA was found to be non-cytotoxic against HUVECs with IC40.97 ± 0.37 μg/ml. KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.Conclusions: The non-cytotoxic compound, KA, may be a potent antiangiogenic agent; its activity may be attributed to inhibition of endothelial cells migration and differentiation as well VEGF suppression