Biomaterials for the extracellular control of mesenchymal stem cell pro-angiogenic potential

With the prevalence of ischemic heart disease, cell based treatments have emerged as promising therapeutic options to promote angiogenesis. The use of adult mesenchymal stem cells (MSCs), particularly, is an area of active investigation. However, clinical efficacy has proved variable, likely on account of ill-defined cell delivery formulations and the inherent complexity of cellular secretion. The versatility of MSCs and their responsiveness to the environment make them very malleable to changes in the microenvironment. The use of well-defined biomaterials enables studying the influence of extracellular matrix properties on MSCs, which in turn gives criteria for the design of optimal biomaterials for therapeutic efficacy. After a short introduction we explore using model polyacrylamide hydrogel systems in Chapter 2 to study the effects of matrix elasticity and composition on MSC pro-angiogenic potential, showing elasticity can play a large role – dependent on matrix composition. In Chapter 3 we use micropatterning to reveal how changing cell shape (modulating cellular cytoskeleton, focal adhesions and contractility) can modulate not only the pro-angiogenic potential of MSCs but their phenotype and epigenetic state. We develop a biocompatible PEG-based hydrogel system in Chapter 4 and we show that this system can be used to spatially guide angiogenesis. Finally, in Chapter 5, we demonstrate a magnetoactive hydrogel system where mechanical properties can be modulated in vitro in order to study the effects of temporal changes in matrix properties, such as those that occur during infarction. Overall, we believe the work presented here demonstrates the importance and utility of extracellular properties in modulating stem cell behavior, especially in the context of cell-based therapies, and should aid in the development of biomaterials for the treatment of ischemic cardiovascular disease

AndroShield:automated Android applications vulnerability detection, a hybrid static and dynamic analysis approach

The security of mobile applications has become a major research field which is associated with a lot of challenges. The high rate of developing mobile applications has resulted in less secure applications. This is due to what is called the “rush to release” as defined by Ponemon Institute. Security testing—which is considered one of the main phases of the development life cycle—is either not performed or given minimal time; hence, there is a need for security testing automation. One of the techniques used is Automated Vulnerability Detection. Vulnerability detection is one of the security tests that aims at pinpointing potential security leaks. Fixing those leaks results in protecting smart-phones and tablet mobile device users against attacks. This paper focuses on building a hybrid approach of static and dynamic analysis for detecting the vulnerabilities of Android applications. This approach is capsuled in a usable platform (web application) to make it easy to use for both public users and professional developers. Static analysis, on one hand, performs code analysis. It does not require running the application to detect vulnerabilities. Dynamic analysis, on the other hand, detects the vulnerabilities that are dependent on the run-time behaviour of the application and cannot be detected using static analysis. The model is evaluated against different applications with different security vulnerabilities. Compared with other detection platforms, our model detects information leaks as well as insecure network requests alongside other commonly detected flaws that harm users’ privacy. The code is available through a GitHub repository for public contribution

Foliar application of chitosan zinc oxide nanoparticles on wheat productivity and water use efficiency under deficit irrigation water

The effectiveness of chitosan zinc oxide nanoparticles (CS-ZnO-NPs) on growth and yield of wheat (Triticum aestivum L., Sakha-93), zinc content and water use efficiency (WUE) under water stress were investigated. A pot experiment was conducted in a completely randomized design by foliar application of CS-ZnO-NPs. Wheat plants were sprayed four times at 15, 30, 45 and 60 days after sowing. The treatments were: control (treated with distilled water), 50, 100 and 150 ppm of CS-ZnO-NPs under 100, 80 and 60% of field capacity. Water shortage has a negative effect on growth parameters and productivity of wheat plants. While the foliar application of 150 ppm CS-ZnO-NPs significantly increased (P≤0.05) NPK content, growth parameters which in turn led to increase the productivity. The highest values of wheat yield were: 4990.55, 4453.50 and 4350.50 kg/ha under 100 80 and 60% of irrigation water, respectively at 150 ppm CS-ZnO-NPs. The highest values of N, P and K content in wheat grain were 1.95, 0.43 and 1.66, respectively at 100% FC under150 ppm CS-ZnO-NPs compared to control. Zn content in wheat grain significantly increased (P≤0.05) by application of CS-ZnO NPs. The interaction of supplementary irrigation water and CS-ZnO-NPs treatments gave clear variation in water use efficiency. The highest relative increase of WUE (23.03%) was at the highest rate of CS-ZnO-NPs (150 ppm). Overall, the data suggested that the foliar application of CS-ZnO-NPs can be an efficient strategy for improving wheat yield, water use efficiency under deficit water and one of the solutions for Zn deficiency in wheat grains

Future regenerative medicine developments and their therapeutic applications

: Although the currently available pharmacological assays can cure most pathological disorders, they have limited therapeutic value in relieving certain disorders like myocardial infarct, peripheral vascular disease, amputated limbs, or organ failure (e.g. renal failure). Pilot studies to overcome such problems using regenerative medicine (RM) delivered promising data. Comprehensive investigations of RM in zebrafish or reptilians are necessary for better understanding. However, the precise mechanisms remain poorly understood despite the tremendous amount of data obtained using the zebrafish model investigating the exact mechanisms behind their regenerative capability. Indeed, understanding such mechanisms and their application to humans can save millions of lives from dying due to potentially life-threatening events. Recent studies have launched a revolution in replacing damaged human organs via different approaches in the last few decades. The newly established branch of medicine (known as Regenerative Medicine aims to enhance natural repair mechanisms. This can be done through the application of several advanced broad-spectrum technologies such as organ transplantation, tissue engineering, and application of Scaffolds technology (support vascularization using an extracellular matrix), stem cell therapy, miRNA treatment, development of 3D mini-organs (organoids), and the construction of artificial tissues using nanomedicine and 3D bio-printers. Moreover, in the next few decades, revolutionary approaches in regenerative medicine will be applied based on artificial intelligence and wireless data exchange, soft intelligence biomaterials, nanorobotics, and even living robotics capable of self-repair. The present work presents a comprehensive overview that summarizes the new and future advances in the field of RM

Pathogenic pathways of copper deficiency in Parkinson disease

Parkinson disease, the fastest growing neurodegenerative disorder, is characterized by the progressive loss of dopamine neurons in the substantia nigra pars compacta. A growing body of evidence implicates biometal dyshomeostasis as a primary aetiological factor participating in aberrant pathways that result in the degeneration of the nigrostriatal pathway. Through the Bradford Hill analysis, I demonstrate that previous empirical evidence supports an aetiological role for iron accumulation and copper deficiency observed in nigral dopamine neuron loss in Parkinson disease. While many pathogenic pathways of copper deficiency remain uncharacterised, the cuproprotein, superoxide dismutase 1 (SOD1), has been shown to exhibit impaired antioxidant capacity and structural misfolding in degenerating regions of the Parkinson disease brain. Our research group posits that SOD1 proteinopathy contributes to dopamine neuron loss, and thus developed a novel murine model to test this hypothesis. I describe, for the first time, that these mice express high levels of wild-type human SOD1 and brain copper deficiency, emulating the specific biochemistry observed in the Parkinson’s disease substantia nigra. Importantly, I demonstrate that these biochemical conditions act synergistically to precipitate wild-type SOD1 proteinopathy in these mice, and that this proteinopathy is associated with nigral dopamine neuron loss and motor deficits in an age-related manner. Further, I demonstrate atypical post-translational modification of key SOD1 protein residues likely potentiates the formation of structurally disordered SOD1 aggregates in this model. The observed findings are consistent with our hypothesis that mis-metalation of SOD1 by copper increases its propensity to misfold and aggregate and results in downstream neurotoxic effects. Together, these data suggest that stabilising SOD1 protein structure by replenishing brain copper levels may constitute a viable therapeutic avenue

MRI as an accurate tool for the diagnosis and characterization of different knee joint meniscal injuries

Background: The knee menisci are compound anatomical structures with important purposes within the knee. In the long term, meniscal losing results in high risk of developing degenerative osteoarthritis. MRI is an accurate and non-invasive diagnostic method for the knee injuries providing satisfactory guide for conservative treatment and guarding the patients from uncritical arthroscopy. Objective: This study aimed to detect the MRI accuracy in diagnosis of meniscal lesions compared to arthroscopy. Patients & methods: This study included 13 females and 17 males presented by pain, swelling, limitation of movement, in the duration from April 2015 to June 2016. All patients were subjected to MRI followed by arthroscopy. Results: The study revealed that specificity, sensitivity, NPV, PPV and accuracy, in MRI diagnosis of medial meniscal abnormal signals were 50%, 95.8%, 88.4%, 86.6%, and 90% respectively, whereas those for lateral meniscus signals were 84.6% 88.2%, 84.6%, 88.2% and 86.7% respectively. Conclusion: MRI of the knee will give the orthopedic surgeons ability to select suitable treatment and arthroscopic interference for their patients. MRI has high accuracy in meniscal tears diagnosis allowing accurate grading of them

Mechanochemical functionalization of disulfide linked hydrogels

interior, nave and choi

Influence of Biophysical Parameters on Maintaining the Mesenchymal Stem Cell Phenotype

The maintenance of the mesenchymal stem cell (MSC) phenotype in vivo is influenced by the precise orchestration of biochemical and biophysical signals in the stem cell “niche”. However, when MSCs are removed from the body and expanded in vitro, there is a loss of multipotency. Here, we employ micropatterned hydrogels to explore how biophysical cues influence the retention of MSC multipotency marker expression. At the single-cell level, soft substrates and patterns that restrict spreading and cytoskeletal tension help maintain the expression of MSC markers. When MSCs are patterned in multicellular geometries, both high cell density and regions of low tension within the pattern are shown to assist the maintenance of multipotency. Combining experiment and simulation along with cytoskeleton disrupting agents reveals spatial patterns of cytoskeletal tension in multicellular architectures that guides the expression of markers associated with MSC multipotency. These findings uncover a relationship between multiple biophysical parameters in maintaining the MSC phenotype, which may shed light on the structure of the MSC “niche” and prove useful in guiding the selection of in vitro expansion materials for regenerative therapies