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Fulltext Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics

Jan R, Chaudhry GE

Adv Pharm Bull, 2019 Jun;9(2):205-218.
PMID: 31380246 DOI: 10.15171/apb.2019.024

Various physiological processes involve appropriate tissue developmental process and homeostasis - the pathogenesis of several diseases connected with deregulatory apoptosis process. Apoptosis plays a crucial role in maintaining a balance between cell death and division, evasion of apoptosis results in the uncontrolled multiplication of cells leading to different diseases such as cancer. Currently, the development of apoptosis targeting anticancer drugs has gained much interest since cell death induced by apoptosis causes minimal inflammation. The understanding of complexities of apoptosis mechanism and how apoptosis is evolved by tumor cells to oppose cell death has focused research into the new strategies designed to induce apoptosis in cancer cells. This review focused on the underlying mechanism of apoptosis and the dysregulation of apoptosis modulators involved in the extrinsic and intrinsic apoptotic pathway, which include death receptors (DRs) proteins, cellular FLICE inhibitory proteins (c-FLIP), anti-apoptotic Bcl-2 proteins, inhibitors of apoptosis proteins (IAPs), tumor suppressor (p53) in cancer cells along with various current clinical approaches aimed to selectively induce apoptosis in cancer cells.
Fulltext Vitex rotundifolia fractions induce apoptosis in human breast cancer cell line, MCF-7, via extrinsic and intrinsic pathways

Chaudhry GE, Jan R, Mohamad H, Tengku Muhammad TS

Res Pharm Sci, 2019 Jun;14(3):273-285.
PMID: 31160905 DOI: 10.4103/1735-5362.258496

Breast cancer is amongst frequently diagnosed cancer type throughout the world. Due to reduced efficacy of current chemotherapeutics, several natural products have been screened for better alternatives. The cytotoxic activity of fractions prepared from leaves extract of Vitex rotundifolia (V. rotundifolia) on human breast cancer cell line, MCF-7 was studied. The fractions F1, F2, F3, and F5 of V. rotundifolia produced concentration-dependent cytotoxic effects on MCF-7 cell line. The relative potential of cytotoxicity of the fractions on MCF-7 cell line was found to be F3 > F2 > F5 > F1. The active fractions induce apoptosis in MCF-7 cell line determined by annexin V base assay. The phosphatidylserine externalization and the presence of DNA fragmentation in treated cells confirms the early and late apoptosis in treated cells. The V. rotundifolia fractions induced apoptosis by both pathways; extrinsic pathways via activation of caspase-8 and intrinsic pathways through enhanced bax/bcl-2 ratio and activation of caspase-3/7 and caspase-9 proapoptotic proteins. Furthermore, chemical profiling indicates various phenolic, flavonoids, and terpenoids compounds in the active fractions. Thus, V. rotundifolia might be a suitable candidate to investigate further and develop molecular targeted cancer therapeutics by understanding the fundamental mechanisms involved in the regulation of cell death in cancer cells.
Solutions of a three-dimensional multi-term fractional anomalous solute transport model for contamination in groundwater

Ahmad I, Ali I, Jan R, Idris SA, Mousa M

PLoS One, 2023;18(12):e0294348.
PMID: 38064451 DOI: 10.1371/journal.pone.0294348

The study presents a meshless computational approach for simulating the three-dimensional multi-term time-fractional mobile-immobile diffusion equation in the Caputo sense. The methodology combines a stable Crank-Nicolson time-integration scheme with the definition of the Caputo derivative to discretize the problem in the temporal direction. The spatial function derivative is approximated using the inverse multiquadric radial basis function. The solution is approximated on a set of scattered or uniform nodes, resulting in a sparse and well-conditioned coefficient matrix. The study highlights the advantages of meshless method, particularly their simplicity of implementation in higher dimensions. To validate the accuracy and efficacy of the proposed method, we performed numerical simulations and compared them with analytical solutions for various test problems. These simulations were carried out on computational domains of both rectangular and non-rectangular shapes. The research highlights the potential of meshless techniques in solving complex diffusion problems and its successful applications in groundwater contamination and other relevant fields.
Author Correction: Exploring the dynamics of HIV and CD4+ T-cells with non-integer derivatives involving nonsingular and nonlocal kernel

Shutaywi M, Shah Z, Vrinceanu N, Jan R, Deebani W

Sci Rep, 2024 Nov 12;14(1):27746.
PMID: 39533020 DOI: 10.1038/s41598-024-79313-2
Fulltext Vitex Rotundifolia Fractions Induced Apoptosis in Human Breast Cancer T-47D Cell Line via Activation of Extrinsic and Intrinsic Pathway

Chaudhry GE, Jan R, Naveed Zafar M, Mohammad H, Muhammad TST

Asian Pac J Cancer Prev, 2019 Dec 01;20(12):3555-3562.
PMID: 31870094 DOI: 10.31557/APJCP.2019.20.12.3555

OBJECTIVE: Breast cancer is the most frequently diagnosed cancer worldwide. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the extract and fractions of Vitex rotundifolia (leaves) in breast cancer cell line, T-47D.
METHODS: The cytotoxicity activity was measured using MTS assay. The mode of cell death was analysed by early (phosphatidylserine externalization) and late apoptosis (DNA fragmentation). The caspases 8, 9, 3/7 and apoptotic proteins bax, bcl-2 study were done by western blot and ELISA method.
RESULTS: The methanol extract was found to inhibit 50% growth of T-47D cells at the concentration of 79.43µg/ml respectively after 72hr. From seven fractions, fraction F1, F2 and F3 produced cytotoxicity effects in T-47D cell line with IC50 (72hr) < 30µg/ml. The results obtained by Annexin V/PI apoptosis detection assay and TUNEL assay suggest that active fractions of Vitex rotundifolia induced early and late apoptosis (DNA fragmentation) in T-47D cell line. Moreover, western blot analysis and Caspase GloTM luminescent assay demonstrated that fractions F2 and F3 triggered apoptotic cell death via activation of caspases -8, -9 and -3/7 and up-regulation of Bax and down-regulation of Bcl-2 protein. Furthermore, chemical profiling confirms the presence of potential metabolites (vitexicarpin) in fractions of Vitex rotundifolia.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in fractions of Vitex rotundifolia as future cancer therapeutic agent for the treatment of breast cancer.
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Fulltext Analysis of the dynamics of a vector-borne infection with the effect of imperfect vaccination from a fractional perspective

Tang TQ, Jan R, Khurshaid A, Shah Z, Vrinceanu N, Racheriu M

Sci Rep, 2023 Sep 01;13(1):14398.
PMID: 37658134 DOI: 10.1038/s41598-023-41440-7

The burden of vector-borne infections is significant, particularly in low- and middle-income countries where vector populations are high and healthcare infrastructure may be inadequate. Further, studies are required to investigate the key factors of vector-borne infections to provide effective control measure. This study focuses on formulating a mathematical framework to characterize the spread of chikungunya infection in the presence of vaccines and treatments. The research is primarily dedicated to descriptive study and comprehension of dynamic behaviour of chikungunya dynamics. We use Banach's and Schaefer's fixed point theorems to investigate the existence and uniqueness of the suggested chikungunya framework resolution. Additionally, we confirm the Ulam-Hyers stability of the chikungunya system. To assess the impact of various parameters on the dynamics of chikungunya, we examine solution pathways using the Laplace-Adomian method of disintegration. Specifically, to visualise the impacts of fractional order, vaccination, bite rate and treatment computer algorithms are employed on the infection level of chikungunya. Our research identified the framework's essential input settings for managing chikungunya infection. Notably, the intensity of chikungunya infection can be reduced by lowering mosquito bite rates in the affected area. On the other hand, vaccination, memory index or fractional order, and treatment could be used as efficient controlling variables.
Fulltext Analytical study on couple stress flow of GO-EG and GO-W nanofluid over an extending cylinder along with variable viscosity

Rehman A, Khun MC, Salleh Z, Khan W, Albely MS, Jan R, et al.

Heliyon, 2023 Dec;9(12):e22491.
PMID: 38076163 DOI: 10.1016/j.heliyon.2023.e22491

The main goal of this research is to present the concept of enhancing heat transfer within emerging technology. To achieve this, tiny metal and nonmetal particles ranging from 1 to 100 nm in size are introduced into base liquids. These nanoscale particles are utilized to improve the thermal performance of the liquids, leading to what are termed nanofluids. The utilization of these fluids and the examination of the flow of thin films have valuable implications across various sectors such as engineering, technology, and industries. This research focuses on analyzing the convective flow behavior of nanofluids, specifically, graphene oxide-ethylene glycol (GO-EG) and graphene oxide-water (GO-W) on a moving surface. The study investigates the impacts of magnetic fields and varying viscosity. By making use of the thermophysical characteristics of the base fluid and the nanofluid, as well as implementing a similarity transformation within the fundamental equations that govern energy and momentum, we formulate a 5th order nonlinear ordinary differential equation (NODE) to describe the velocity profile. This is combined with a second-order NODE that describes the distribution of temperature. To solve this derived NODE, we employ a method known as the Homotopy Analysis Method (HAM) for analytical solution. The impact of the relevant factors, Prandtl number, including magnetic field parameter, thickness of the liquid, couple stress parameter, temperature distribution, dynamic viscosity, and Eckert number, on the skin friction, velocity profile, and Nusselt's number are interrogated through graphical representation. The velocity field exhibits a decline as the couple stress parameter, magnetic field parameter, liquid thickness, and dynamic viscosity experience an increase. Conversely, the temperature field displays a rise as the Eckert number and dynamic viscosity experience an increase. To ensure the convergence of the issue, dual solutions of the problem are employed, and this is verified through the utilization graphs and tables. Due to the considerable challenge encountered in heat transfer applications for cooling diverse equipment and devices across industries like automotive, microelectronics, defense, and manufacturing, there is a strong expectation that this theoretical methodology could make a favorable contribution towards enhancing heat transfer efficiency. This improvement is sought to meet the requirements of the manufacturing and engineering sectors.
A fractional perspective on the transmission dynamics of a parasitic infection, considering the impact of both strong and weak immunity

Tang TQ, Jan R, Shah Z, Vrinceanu N, Tanasescu C, Jan A

PLoS One, 2024;19(4):e0297967.
PMID: 38656969 DOI: 10.1371/journal.pone.0297967

Infectious disease cryptosporidiosis is caused by the cryptosporidium parasite, a type of parasitic organism. It is spread through the ingestion of contaminated water, food, or fecal matter from infected animals or humans. The control becomes difficult because the parasite may remain in the environment for a long period. In this work, we constructed an epidemic model for the infection of cryptosporidiosis in a fractional framework with strong and weak immunity concepts. In our analysis, we utilize the well-known next-generation matrix technique to evaluate the reproduction number of the recommended model, indicated by [Formula: see text]. As [Formula: see text], our results show that the disease-free steady-state is locally asymptotically stable; in other cases, it becomes unstable. Our emphasis is on the dynamical behavior and the qualitative analysis of cryptosporidiosis. Moreover, the fixed point theorem of Schaefer and Banach has been utilized to investigate the existence and uniqueness of the solution. We identify suitable conditions for the Ulam-Hyers stability of the proposed model of the parasitic infection. The impact of the determinants on the sickness caused by cryptosporidiosis is highlighted by the examination of the solution pathways using a novel numerical technique. Numerical investigation is conducted on the solution pathways of the system while varying various input factors. Policymakers and health officials are informed of the crucial factors pertaining to the infection system to aid in its control.
Fulltext Fractional view analysis of sexual transmitted human papilloma virus infection for public health

Bahi MC, Bahramand S, Jan R, Boulaaras S, Ahmad H, Guefaifia R

Sci Rep, 2024 Feb 06;14(1):3048.
PMID: 38321259 DOI: 10.1038/s41598-024-53696-8

The infection of human papilloma virus (HPV) poses a global public health challenge, particularly in regions with limited access to health care and preventive measures, contributing to health disparities and increased disease burden. In this research work, we present a new model to explore the transmission dynamics of HPV infection, incorporating the impact of vaccination through the Atangana-Baleanu derivative. We establish the positivity and uniqueness of the solution for the proposed model HPV infection. The threshold parameter is determined through the next-generation matrix method, symbolized by [Formula: see text]. Moreover, we investigate the local asymptotic stability of the infection-free steady-state of the system. The existence of the solutions of the recommended model is determined through fixed-point theory. A numerical scheme is presented to visualize the dynamical behavior of the system with variation of input factors. We have shown the impact of input parameters on the dynamics of the system through numerical simulations. The findings of our investigation delineated the principal parameters exerting significant influence for the control and prevention of HPV infection.
Fulltext #EEGManyLabs: Investigating the replicability of influential EEG experiments

Pavlov YG, Adamian N, Appelhoff S, Arvaneh M, Benwell CSY, Beste C, et al.

Cortex, 2021 11;144:213-229.
PMID: 33965167 DOI: 10.1016/j.cortex.2021.03.013

There is growing awareness across the neuroscience community that the replicability of findings about the relationship between brain activity and cognitive phenomena can be improved by conducting studies with high statistical power that adhere to well-defined and standardised analysis pipelines. Inspired by recent efforts from the psychological sciences, and with the desire to examine some of the foundational findings using electroencephalography (EEG), we have launched #EEGManyLabs, a large-scale international collaborative replication effort. Since its discovery in the early 20th century, EEG has had a profound influence on our understanding of human cognition, but there is limited evidence on the replicability of some of the most highly cited discoveries. After a systematic search and selection process, we have identified 27 of the most influential and continually cited studies in the field. We plan to directly test the replicability of key findings from 20 of these studies in teams of at least three independent laboratories. The design and protocol of each replication effort will be submitted as a Registered Report and peer-reviewed prior to data collection. Prediction markets, open to all EEG researchers, will be used as a forecasting tool to examine which findings the community expects to replicate. This project will update our confidence in some of the most influential EEG findings and generate a large open access database that can be used to inform future research practices. Finally, through this international effort, we hope to create a cultural shift towards inclusive, high-powered multi-laboratory collaborations.