Iron is an essential nutrient for humans and has important functions as a cofactor for several enzymes and oxygen transporters. However, iron is potentially hazardous when present in excess amounts. In the last decade, several epidemiological reports have established an association between iron overload and risk of type 2 diabetes mellitus (T2DM). Still, the mechanism how iron overload impacts the function of pancreatic beta cells remains unclear. In this study, we utilized Gas Chromatography (GC)/Mass Spectrometry (MS) to profile and understand the metabolic changes triggered by iron content in the clonal rat (INS-1) pancreatic ?-cells. INS-1 cells were treated with 1 mM Ferric Ammonium Citrate (FAC) for 24 hrs and quenched metabolic processes. Internal standards library that allows identification of metabolite masses is generated and metabolites are extracted from samples using one-phase liquid extraction, derivation and analyzed using GC/Ms. Herein, we will focus on polar metabolites. Result and Conclusion: Alanine and lactate, which are both generated from pyruvate, were elevated in pancreatic b-cell cells treated with 1 mM of Ferric Ammonium Citrate relative to control cells. In the ?-cell, glucose metabolism leads to increased cytosolic ATP, closure of ATP-sensitive K? channels (KATPchannels), initiation of electrical activity and Ca2? dependent exocytosis of insulin-containing granules. These findings point to a clear metabolic defect in pancreatic ?-cell with iron overload.
Osteoporosis (porous bones) is a metabolic skeletal disorder clinically characterized by reduced bone mass density (BMD) and altered bone quality with microarchitectural and biomechanical abnormalities. This is a silent disease that is typically manifested by increased risk of fracture, hence leading to significant morbidity and mortality [1-4], Fractures can involve any bone; however the spine, hip, wrist and proximal humerus are the most commonly affected sites[5-7]. Traditionally, osteoporosis has been classified into Primary and Secondary types. Primary osteoporosis is usually associated with normal aging and decreased gonadal function, such as decreased levels of estrogen [8, 9], whereas secondary osteoporosis is caused by other disease process, including Vitamin D deficiency, diabetes type 2, cardiovascular disease and certain malignancies[10]. A multifactorial disease, Osteoporosis is instigated by complex interactions between genetic, metabolic and environmental factors, with a severe impact on the biomechanics of the musculoskeletal system. Environmental factors include low physical activity, smoking, alcohol, low sun exposure (decreased vitamin D production), and certain medications, such as glucocorticoids and anticonvulsants[11]. Ethnicity and race can also play a role that may influence the incidence of osteoporosis. Understanding the risk factors for osteoporosis is critical towards prevention, improved clinical management, and effective healthcare. Among the UAE female population, there is a higher rate of vitamin D deficiency and risk for osteoporotic fractures as compared to Europeans[11]. This is likely due to a combination of conservative dressing style minimizing exposure to sunlight, spending the majority of their time indoors due to the hot weather, as well as, genetic factors. To date, accurate epidemiological prevalence figures for osteoporosis in the United Arab Emirates (UAE) are not available. The UAE population above 50 years of age is estimated to be only around 7%. It is hence not surprising that the current total number of individuals with osteoporosis is relatively small. On the other hand, the prevalence of osteoporosis in the UAE is affected by the uniquely diverse population structure. The total population is around 4.9 million, with only 20% Emirati Nationals (female/male ratio of 1/1.1) and 80% expatriates (female/male ratio of 1 to 4). There is data documenting osteoporosis prevalence of approximately 2.5% at an average age of 42 years (based on screening of 1825 asymptomatic individuals). To date, there is no National Hip Fracture registry in UAE. According to the records of a major hospital in Abu Dhabi there are 2.25 osteoporotic hip fractures per 100 individuals. This report recommends that the UAE Health Authorities should consider osteoporosis and hypovitaminosis D as major health challenges and should implement management guidelines and prevention programs in collaboration with the EOS, greater access to dual energy X-ray absorptiometry (DXA) scans, as well as increased awareness/education for health care professionals and for the public [12]. Despite the emergence of studies about osteoporosis and genetic variation in VTD receptor among UAE nationals, to date none had attempted to examine the association between the two in order to provide important insight about the involvement of genetic variation in disease pathogenesis. In addition, a holistic population-specific model, which integrates main risk factors (genetic, environmental and musculoskeletal), is still lacking for females in the UAE and the GCC. This project addresses a significant health challenge in the UAE and region, Osteoporosis. We propose to focus on the association between VTD genetic and musculoskeletal variants/paramters and osteoporosis, in addition to other risk factors such as poor diet and lack of exercise in order to develop a better screening tool for specific individuals. This more effective approach might reduce health costs associated with the control and treatment of osteoporosis and or its complications including fractures, hence facilitating the development of new more relevant population-based interventions which can specifically target "high risk patients" . Research Methodology The research methodology is divided into the follwoing four phases: Phase I Recruitment of Participants and Testing for Biochemical Markers 400 participants (200 diagnosed with osteoporosis and 200 healthy age-matched controls) from Mafraq hospital orthopedic clinic will be recruited. Participants will be UAE female nationals and postmenopausal (not suffering from any other serious chronic condition like diabetes or cardiovascular disease). Biochemical markers including VTD 1, 25 (OH) D, Calcium Ca and PTH , 5 ml blood sample will be taken by a nurse from the participants after their consent. A buccal swab will be also taken for DNA extraction by the experienced phlebotomist and directly immersed into the DNA preparation solution (from kit). Swabs are used to avoid using blood samples for DNA extraction. All safety measures as per Mafraq Hospital (SEHA) will be followed during this procedure and all samples will be processed only after blood is deemed "safe to handle" as per hospital guidelines. The participants will be asked to provide some information about life style and anthropometry to collect data about factors which play a role in the predisposition to osteoporosis like diet, exercise, and smoking. The information regarding participants' biochemical test results and treatment/ medication will be recorded in an attempt to correlate all biochemical parameters which characterize osteoporosis. Phase II. Identification of Genetic Variants by Polymerase Chain Reaction (PCR) Assays DNA will be isolated from collected epithelial swabs using DNA Geno_Teck Kit. Samples will be screened for sequence variations in the VTD receptor gene by real time PCR using thermal cycler and gel electrophoresis. All DNA isolation, PCR and agarose analysis will be carried out at ZU Phase III. Bone Densitometry and Fracture Assessment using DEXA: BMD values will be measured for all subjects by the standard DEXA machine and accelerometers. Bone shock absorption will be calculated based on the Frequency Response Function (FRF). Both static and dynamic measures are then combined with BMD to assess bone quality and risk of Osteoporosis. Phase IV. Data Analysis Several bioinformatics tools will be used to identify genomic segments within VTD receptor gene. Heritability will be calculated using the SOLAR package to evaluate the influence of genetic components on phenotypic variation. Data quality control will be performed using Hardy-Weinberg equilibrium (HWE) test. Preliminary Results and Future Work This study is still in the experimental part phase. Experimental data collection at the first clinical site has been very slow which prompted the investigators to engage other hospitals. Thus far, only 67 samples were collected from Al-Mafraq hospital in Abu-Dhabi. In parallel with the data collection phase, training on the DNA extraction, PCR and DEXA were performed. Furthrmore dNA extraction and PCR analyses were performed on the 68 samples, but the number of samples is still not sufficient for complete data analysis.. Data management algorothms have also been built to facilitate the data analysis phase. Ongoing work includes changing clinical sitesleveland Clinic Abu Dhabi (CCAD) endocronology unit for better access to patients. On the other hand, once the experimental work resumes at CCAD, we anticipate fast progress as the framework has already been developed and tested.
Low Back Pain (LBP) and obesity have emerged among the very common health problems particularly in patients who are attending health care at primary levels in the United Arab Emirates. As such, the causal connection between obesity and LBP have for the past few years have piqued the interest of many researchers. There is still a wide range of controversy concerning the association between the two, in addition to the presence of conflicting observations. A significant challenge in the process of trying to ascertain the primary cause of LBP in association with obesity is the nature of the condition. This is mainly attributed to the fact that it is heterogeneous, comes in many dimensions in nature. This research proposes a clinically-driven collaborative research effort to investigate the spinal biomechanics of obesity and LBP in the UAE, a country where both obesity and LBP are more than double the global averages.
Colon cancer continues to be a major cause of cancer-related deaths in both genders. Currently, there are no defined treatments other than traditional clinical treatments which have severe side effects on health. Plants have been shown to be an excellent source of new drugs, including anticancer agents. Origanum majorana commonly known as majoram is a plant that is known to possess different therapeutic values including antioxidant and antimicrobial activities. In the present study, we investigated the anticancer effect of O. majorana oil on colon cancer (HT-29) cell line. We demonstrated that O. majorana oil inhibited the proliferation of HT-29 cell line in a time- and concentration-dependent manner. Colony formation assay illustrated that O. majorana oil reduced the ability of HT-29 to form colonies, and when established colonies were treated with O. majorana it showed that the oil was able to reduce colonies' proliferation at low concentrations while at higher concentrations the oil was able to demolish the already formed colonies. Moreover, The oil induced cell death and cell cycle arrest at G1 phase. Annexin V staining revealed an induction of apoptosis in HT-29 cells. These preliminary results make O. majorana oil a promising alternative candidate against colon cancer.
Breast cancer remains one of the most common cancers as well as one of the leading causes of worldwide cancer-related morbidity and mortality. Recently, we reported that Rhus coriaria exhibits anticancer activities by promoting cell cycle arrest and autophagic cell death of the metastatic triple negative MDA-MB-231 breast cancer cells. Here, we investigated the effect of Rhus coriaria on the migration, invasion, metastasis and tumor growth of TNBC cells. Our current study revealed that non-cytotoxic concentrations of Rhus coriaria significantly inhibited migration and invasion, blocked adhesion to fibronectin and downregulated MMP-9 and prostaglandin E2 (PgE2). Not only did Rhus coriaria decrease their adhesion to HUVECs and to lung microvascular endothelial (HMVEC-L) cells, but it also inhibited the transendothelial migration of MDA-MB-231 cells through TNF-?-activated HUVECs. Most importantly, by using chick embryo tumor growth assay, we showed that Rhus coriaria suppressed tumor growth and metastasis in vivo. Our findings demonstrate that Rhus coriaria is a promising chemopreventive and therapeutic candidate that modulate triple negative breast cancer growth and metastasis.
Plants have been shown to be an excellent source of new drugs, including anti-cancer agents. Rhus coriaria commonly known as sumac is a plant that is known to possess different therapeutic values including antioxidant and antimicrobial activities. Recently, we reported that Rhus coriaria exhibits anti-cancer activities by promoting cell cycle arrest and autophagic cell death of the metastatic triple negative MDA-MB-231 breast cancer cells. Here, we investigated the effect of Rhus coriaria on metastasis and angiogenesis of TNBC cells. We found that Rhus coriaria inhibited angiogenesis, reduced VEGF production in both MDA-MB-231 and HUVECs and downregulated the inflammatory cytokines TNF-?, IL-6 and IL-8. The underlying mechanism for Rhus coriaria effects appears to be through inhibiting NF?B, STAT3 and nitric oxide (NO) pathways. The results described in the present study identify Rhus coriaria as a promising chemopreventive and therapeutic candidate that modulate triple negative breast cancer growth and metastasis.
Subepithelial fibrosis is a difficult-to-treat feature observed in the remodeled airways of asthma patients. Novel insights into the pathogenesis of fibrosis are necessary to be able to target this irreversible structural change. Autophagy is a frequently dysregulated pathway in various fibrotic diseases. We, therefore, aimed to investigate the regulation of autophagy in bronchial fibroblasts from severe asthma patients by evaluating the expression of autophagy proteins in bronchial fibroblasts and performing bioinformatics analysis on publicly available datasets. Differential expression of LC3BII was observed in severe asthma and COPD when compared to control indicating an impairment in the autophagy pathway in severe asthma. Preliminary bioinformatics analysis revealed genes of the autophagy pathway to be differentially regulated in severe asthma when compared to control. Since current asthma medications have limited impact on subepithelial fibrosis, autophagy may present a potentially targetable pathway in order to ameliorate airway remodeling in the difficult-to-treat severe asthmatics.
It is generally believed that sequential and coordinated cascade of macrophages is essential for not only removal of damaged tissues but also their repair. The gastric mucosa comprises significant number of connective tissue cells including macrophages. It is not known whether these macrophages play a role in the activation of gastric stem cells and regeneration of gastric mucosa following injury. To analyse the effects of macrophages on gastric stem cell.To obtain macrophages from hematopoietic stem cells, whole bone marrow cells were isolated from both the femur and tibia of mice and cultured in the presence of macrophage colony stimulating factor in a non-cell culture treated petri dishes. Macrophages were treated with lipopolysaccharide (LPS) or IL-4 to induce their both pro-inflammatory and anti-inflammatory phenotypes, respectively. Condition media from these macrophage phenotypes were collected and added to cultured primary gastric stem cells for 24 hours. Then RNA was extracted from the stem cells and processed for RT-qPCR. While pro-inflammatory macrophage condition media had no effect of gastric stem cells, media obtained from cultured anti-inflammatory macrophages showed interesting effects. There was an induction of mRNA expression of genes specific for mucous (MUC6, TFF2) parietal (ATP4A) and endocrine (CHGA) cell lineages. The anti-inflammatory macrophages produce factors that play an important role in inducing gastric stem cell differentiation. Defining these factors will improve our understanding of the biology of gastric stem cells in health and disease.
Machine Learning / Data Mining techniques have proven to be a key technology in data processing and analysis in many areas. In healthcare, we can use Machine Learning / Data Mining techniques to mine the data of medical records to make better sense of it, uncover new knowledge, and generally provide better and faster health services. Diabetes is one of the diseases that has been investigated using intelligent techniques. Still, diabetes-related research continues to take place, and the use of traditional as opposed to non-traditional diabetes Type-2 risk factors in prediction tools and decision support applications instead of normal blood tests is an open research problem. The objective of the research is to find the relationships (implications) between medical tests of diabetic patients and possible diabetes complications. Also, while many researchers focused on developing models that assist in predicting diabetes with accuracy higher than the baseline standards stated in the literature, the pre-mentioned objective stated is covered in a very limited scope. There is room for deeper investigation, and the topic needs to be further examined. This study aims at localizing the problem of diabetes type-2 Metabolic Syndrome complication diagnosis to GCC nationals and especially Emirati patients, taking into consideration common medical tests e.g., HbA1c, Fasting Glucose, Random Glucose, and Insulin; and Diabetes Complications e.g., Hyperthyroidism, Hypertension, Diabetic Foot and Metabolic Syndrome.
Photo Acoustic Imaging has been recently used for several purposes, the modality has gained interest in medical applications. Photo Acoustic Tomography (PAT) is a biomedical imaging technique that depends on photo acoustic effect; which is the formation of sound waves following light absorption in a tissue sample. It is quantified by measuring the formed sound with appropriate detectors such as sensors. Compressive sensing (CS) is a new paradigm which is capable of reconstructing signals from fewer number of measurements than suggested by Nyquist rate. The objective of this paper is to show how to apply the CS framework to form a full view PAT image with less number of sensors. In this paper, numerical simulations are done to reconstruct PA image using CS framework. A comparison is done in terms of speed and quality between three different CS algorithms which are Alternating Direction Method of Multipliers, l_1-MAGIC and CVX toolbox.
