The Effects of Frondoside A in Acute Leukemia

Among hematological malignancies, acute leukemia is the major cause of mortality. Despite improvement of survival with current chemotherapies, some patients still diefrom the disease or the treatment side effects. Thus, new therapeutic agents are needed. Anti-cancer drugs derived from natural products are of interest. Frondoside A is a triterpenoid glycoside form the sea cucumber, Cucumaria frondosa that has shown potent antitumor effects in various cancers. Previous studies in acute leukemia are limited. The current study investigated the effects of frondoside a in acute leukemia cell lines alone and in combination with drugs currently used for this malignancy. This study is the first to attempt comparing the efficacy of this compound to available conventional drugs. The acute leukemia cell lines used were CCRF-CEM, HL-60 and THP-1. Cells were cultured and treated with different concentrations of frondoside A, vincristine sulphate, asparaginase and prednisolone each compound alone and in combination with frondoside A. Experiments were conducted with treatment incubation periods of 24, 48 and 72h. The inhibitory concentration 50 (IC50) for each compound at each time point was determined for the three cell lines using the CellTiter-Glo luminescence assay. Induction of apoptosis was examined using Annexin V test and expression of apoptosis-related genes (low-density expression array) was investigated in two acute leukemia cell lines. The expression of protein products of selected genes was also investigated. The effect of frondoside A combined with NFκB pathway inhibitor, andrographolide in acute leukemia cell lines was also examined. CCRF-CEM cells were very sensitive to frondoside a treatment while HL-60 and THP-1 were less sensitive. Frondoside A markedly enhanced the anticancer effects of all of the conventional drugs in all cell lines. Synergistic effects were seen in some of the combination concentrations. Induction of apoptosis was confirmed morphologically and by Annexin V in CCRF-CEM and THP-1 treated cells. Analysis of the effect of frondoside a on expression of apoptosis-related genes showed marked changes in multiple pro- and anti-apoptotic genes. Expression of some genes coding for both pro-apoptosis and anti-apoptosis proteins were increased, suggesting that a survival pathway was also activated in the frondoside A-treated cells. Frondoside A treatment increased the gene expression of multiple members of both the intrinsic and extrinsic as well as the executioner pathways. The compound also up regulated the genes encoding multiple death receptors and death effect or domains. In THP-1 cells, frondoside a treatment resulted in the increased expression of the tumor suppressor protein p21 and it decreased the expression of the mutated p53 protein in CCRF-CEM cells. Frondoside A treatment also markedly up regulated multiple genes in the NFκB pathway with changes being more marked in the THP-1 cell line, which is more resistant to the effects of frondoside A. Combining andrographolide IC50 concentration with frondoside A in the treatment of acute leukemia cell line resulted in marked enhancement of frondoside A anti-leukemia effect. Frondoside A has marked anti-leukemia effects. It decreased the viability of acute leukemia blasts and induces apoptosis. The apoptosis appeared to be due to the activation of both extrinsic and intrinsic pathways. Resistance to frondoside A can be due to the activation of the NFκB survival pathway in the treated cells and combining the treatment with NFκB pathway inhibitors results in dramatic enhancement of the anti-leukemic effect of frondoside A. Frondoside A affected different genes and pathways in leukemia blast cells and inhibiting malignant cells by targeting multiple pathways might be more beneficial in the treatment strategy. It potentiates the anticancer effects of all three drugs currently used to treat acute leukemias and it may be a valuable addition to the therapeutic options in these deadly diseases especially in high-risk patients by sparing the side effects of high dose therapy and bone marrow transplantation

Association of Vitamin D receptor gene BsmI polymorphism with type 2 diabetes mellitus in Pakistani population

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with strong genetic components. The reported association of vitamin D receptor (VDR) gene polymorphisms varies among ethnic groups.Objectives: The present study was conducted to determine association of vitamin D receptor gene BsmI (rs1544410 A>G) polymorphism with type 2 diabetes mellitus in Pakistani population.Methods: Blood samples were collected from 150 T2DM patients and 100 non-diabetic engaged by convenient sampling method. After collection of demographic data, assessment of fasting glucose (FG), vitamin D, HbA1c, renal function tests, liver function tests and lipid profile was done. Candidate gene polymorphism was analyzed by DNA amplification with polymerase chain reaction and endonuclease digestion.Results: Biochemical parameters were significantly different among case and control groups. Associations of BsmI genotype with T2DM, related complications and biochemical variables were not significant.Conclusion: The current study did not provide evidence for the association of VDR gene BsmI polymorphism with T2DM in Pakistani population.Keywords: Vitamin D receptor gene; single nucleotide polymorphism; type 2 diabetes mellitus

Medical images protection and authentication using hybrid DWT-DCT and SHA256-MD5 hash functions

© 2017 IEEE. This paper deals with a blind digital watermarking technique for the ownership protection and content authentication of X-ray and MRI medical images. Extreme care is required before embedding watermarking information in medical images, to protect the image quality to avoid the wrong diagnosis. The proposed watermarking technique contains a robust watermark for the ownership protection and fragile watermarks for the content authentication. In the watermarking technique, the medical image is divided into regions and the watermark information is embedded in both the transform domain and the spatial domain. The proposed watermarking technique was successfully tested on a variety of X-ray and MRI medical images and offered high peak signal to noise ratios, similarity structure index measure values and wavelet domain signal to noise rations

Inhibition of protein glycation and advanced glycation end products by ascorbic acid

Advanced glycation end products (AGEs) formation is increased in diabetes mellitus, leading to microvascular and macrovascular complications. Recently, much attention has been focused on natural and synthetic inhibitors to delay the onset or progression of diabetes and its comorbidities. Ascorbic acid (AA) can react with proteins, including hemoglobin and possibly interfere with protein glycation process. An in vitro glycation model containing plasma from type 2 diabetic and non-diabetic healthy volunteers together with glucose as glycating agent was used to study antiglycation activity of AA. Samples with different concentrations of glucose and AA were incubated for five weeks at 37°C. Nonenzymatic glycation (NEG) was quantitated by thiobarbituric acid calorimetry and AGEs were measured by enzyme linked immuno-sorbent assay (ELISA). The NEG and AGEs levels were reduced by AA. Increasing the AA concentrations greatly diminished protein glycations, indicating dose-dependent effects of AA. Plasma NEG and AGEs were decreased with an average of 20 to 26% (p < 0.05) and 26 to 28% (p < 0.05). A significant correlation was found between the glycation inhibition and the inhibition of AGE formation (p < 0.05). The antiglycation role of AA is evident in the present study and it also indicates the possibility of inexpensive, relatively non-toxic vitamin therapy for the prevention and treatment of diabetic complications. It is plausible that AGEs inhibition by AA may also form the basis for future intervention strategies in both diabetic and non-diabetic individuals.Keywords: Diabetes mellitus, glycation, advanced glycation end products, hyperglycemia, ascorbic aci

Determination of in vitro antidiabetic effects of Zingiber officinale Roscoe

Aqueous extracts of Zingiber officinale rhizomes were studied to evaluate their antidiabetic effects on protein glycation and on the diffusion of glucose in vitro in the present study. Zingiber officinale rhizome aqueous extract were examined at concentrations of 5, 10, 20 and 40 g/L. The antidiabetic effects were found to be dose-dependent. Antidiabetic potential of Zingiber officinale was mainly through inhibition of the glucose diffusion and to a limited extent by reducing the glycation. However, further studies are needed to determine in vitro effects of therapeutic potential by restraining postprandial glucose absorptions and plasma protein glycations in diabetic subjects.Extratos aquosos de rizomas Zingiber officinale foram estudados para avaliar os seus efeitos antidiabéticos em glicação de proteínas e sobre a difusão de glicose in vitro, no presente estudo. Extratos aquosos de Zingiber officinale foram examinados nas concentrações de 5, 10, 20 e 40 g extrato de planta/L. Os efeitos antidiabéticos observados eram dependentes da dose. O potencial antidiabético de Zingiber officinale se verificou, principalmente, através da inibição da difusão de glicose e, em menor extensão, através da redução da glicação. Estudos adicionais são necessários para elucidar se efeitos in vitro representam potencial terapêutico, restringindo a absorção de glicose pós-prandial e a glicação de proteínas plasmáticas em indivíduos diabéticos

Association of Vitamin D receptor gene BsmI polymorphism with type 2 diabetes mellitus in Pakistani population

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with strong genetic components. The reported association of vitamin D receptor (VDR) gene polymorphisms varies among ethnic groups. Objectives: The present study was conducted to determine association of vitamin D receptor gene BsmI (rs1544410 A>G) polymorphism with type 2 diabetes mellitus in Pakistani population. Methods: Blood samples were collected from 150 T2DM patients and 100 non-diabetic engaged by convenient sampling method. After collection of demographic data, assessment of fasting glucose (FG), vitamin D, HbA1c, renal function tests, liver function tests and lipid profile was done. Candidate gene polymorphism was analyzed by DNA amplification with polymerase chain reaction and endonuclease digestion. Results: Biochemical parameters were significantly different among case and control groups. Associations of BsmI genotype with T2DM, related complications and biochemical variables were not significant. Conclusion: The current study did not provide evidence for the association of VDR gene BsmI polymorphism with T2DM in Pakistani population. DOI: https://dx.doi.org/10.4314/ahs.v19i2.41 Cite as: Fatma H, Abdul SN. Association of vitamin D receptor gene BsmI polymorphism with type 2 diabetes mellitus in Pakistani population.Afri Health Sci.2019;19(2): 2164-2171. https://dx.doi.org/10.4314/ahs.v19i2.4

Random forest models for motorcycle accident prediction using naturalistic driving based big data

Motorcycle accident studies usually rely upon data collected from road accidents collected through questionnaire surveys/police reports including characteristics of motorcycle riders and contextual data such as road environment. The present study utilizes big data, in the form of vehicle trajectory patterns collected through GPS, coupled with self-reported road accident information along with motorcycle rider characteristics to predict the likelihood of involvement of a motorcyclist in an accident. Random Forest-based machine learning algorithm is employed by taking inputs based on a variety of features derived from trajectory data. These features are mobility-based features, acceleration event-based features, aggressive overtaking event-based features and motorcyclists socio-economic features. Additionally, the relative importance of features is also determined which shows that aggressive overtaking event-based features have more impact on motorcycle accidents as compared to other categories of features. The developed model is useful in identifying risky motorcyclists and implementing safety measures focused towards them

Adapting Medical Museums: Technology, Education, and Research

In Malaysia, medical museums are transforming, extending their reach beyond conventional medical student training to encompass public education and health awareness. This modernisation incorporates cutting-edge technologies such as 3D printing, QR codes, augmented reality, diversified exhibitions, and hands-on learning experiences. The overarching goal is to captivate a broader audience while advancing medical research and public health education. To achieve this, strategies like interactive exhibits and multi-sector collaborations are employed. This study explores the role of medical museums and the impact of technological innovations on visitor experience and engagement

The Effect of Gender, Experience, and Training on Teachers’ Written Corrective Feedback Practices

This study investigated whether EFL Post-Basic education teachers’ perceptions toward teachers’ practice of written corrective feedback (WCF) varied according to three contextual variables gender, teaching experience, and in-service training on WCF. It also attempted to investigate the challenges teachers encounter when providing WCF. The quantitative data was collected from 156 EFL teachers who were teaching Post-Basic education grades (11-12). The participants were randomly selected from three governorates in Oman: Muscat, Al Batinah South, and Sharqia North. The study showed that the only variable that had an effect on teachers’ perceptions was the number of training workshops/courses received on WCF. It also revealed that teachers perceived the challenge of focusing on all types of errors (content, organisation, and language) simultaneously as the most common difficulty they were experiencing. Some suggested recommendations of the study for the Ministry of Education, EFL teachers, and further studies were finally provided

Smart Dynamic Traffic Monitoring and Enforcement System

Enforcement of traffic rules and regulations involves a wide range of complex tasks, many of which demand the use of modern technologies. variable speed limits (VSL) control is to change the current speed limit according to the current traffic situation based on the observed traffic conditions. The aim of this study is to provide a simulation-based methodological framework to evaluate (VSL) as an effective Intelligent Transportation System (ITS) enforcement system. The focus of the study is on measuring the effectiveness of the dynamic traffic control strategy on traffic performance and safety considering various performance indicators such as total travel time, average delay, and average number of stops. United Arab Emirates (UAE) was selected as a case study to evaluate the effectiveness of this strategy. A micro simulation software package VISSIM with add-on module VisVAP is used to evaluate the impacts of VSL. It has been observed that VSL control strategy reduced the average delay time per vehicle to around 7%, travel time by 3.2%, and number of stops by 48.5%. Dynamic traffic control strategies also alleviated congestion by increasing the capacity of the bottleneck section and improving safety. Results of this study would act as a guidance for engineers and decision makers to new traffic control system implementation