Inhibition of the Early-Stage Cross-Amyloid Aggregation of Amyloid-β and IAPP via EGCG: Insights from Molecular Dynamics Simulations.

Amyloid-β (Aβ) and islet amyloid polypeptide (IAPP) are small peptides that have the potential to not only self-assemble but also cross-assemble and form cytotoxic amyloid aggregates. Recently, we experimentally investigated the nature of Aβ-IAPP coaggregation and its inhibition by small polyphenolic molecules. Notably, we found that epigallocatechin gallate (EGCG) had the ability to reduce heteroaggregate formation.

3D-Printed Microcubes for Catalase Drug Delivery.

Oxidative stress, i.e., excessive production of reactive oxygen species (ROS), plays an important role in the pathogenesis of inflammatory diseases such as cardiovascular diseases, cancer, and neurodegenerative diseases.

Alginate-Based Oral Delivery Systems to Enhance Protection, Release, and Absorption of Catalase.

Oxidative stress, overproduction of reactive oxygen species (ROS), plays an important role in the development of inflammatory bowel diseases. Catalase has great therapeutic potential by scavenging hydrogen peroxide, one of the ROSs produced in cellular metabolisms. However, in vivo application to scavenge ROS is currently limited especially in oral administrations.

Binding Behavior between Transforming-Growth-Factor-Beta1 and Its Receptor Reconstituted in Biomimetic Membranes.

Transforming growth factor β1 (TGF-β1) is critical to cell differentiation, proliferation, and apoptosis. It is important to understand the binding affinity between TGF-β1 and its receptors. In this study, their binding force was measured using an atomic force microscope.

Structural polymorphism and cytotoxicity of brain-derived β-amyloid extracts.

To date, more than 37 amyloidogenic proteins have been found to form toxic aggregates that are implicated in the progression of numerous debilitating protein misfolding diseases including Alzheimer's disease (AD). Extensive literature highlights the role of β-amyloid (Aβ) aggregates in causing excessive neuronal cell loss in the brains of AD patients. In fact, major advances in our understanding of Aβ aggregation process, including kinetics, toxicity, and structures of fibrillar aggregates have been revealed by examining in vitro preparations of synthetic Aβ peptides.

Detection of defects in cellular solids using highly nonlinear solitary waves: a numerical study of the proximal femur.

This study investigates the suitability of a relatively new non-destructive evaluation (NDE) technique for the detection of non-visible defects in cellular solids using highly nonlinear solitary waves (HNSWs) in a one-dimensional granular chain. Specifically, the HNSW-based NDE approach is employed to identify the existence of micro-fractures in trabecular bone within the femoral neck (FN) and the intertrochanteric (IT) region of the proximal femur which are fracture-prone sites due to their relatively low bone density, particularly in osteoporosis patients. The availability of a HNSW-based bone quality assessment tool could not only help in early diagnosis of osteoporosis but also affect surgical decisions and improve clinical outcomes in joint replacement surgeries which motivated this study.

2D MXenes for controlled releases of therapeutic proteins.

MXenes belong to a new class of two dimensional (2D) functional nanomaterials, mainly encompassing transition-metal carbides, nitrides and carbonitrides, with unique physical, chemical, electronic and mechanical properties for various emerging applications across different fields. To date, the potentials of MXenes for biomedical application such as drug delivery have not been thoroughly explored due to the lack of information on their biocompatibility, cytotoxicity and biomolecule-surface interaction. In this study, we developed novel drug delivery system from MXene for the controlled release of a model therapeutic protein.

Phosphorylation Induced Conformational Transitions in DNA Polymerase .

DNA polymerase (pol ) is a member of the X- family of DNA polymerases that catalyze the distributive addition of nucleoside triphosphates during base excision DNA repair. Previous studies showed that the enzyme was phosphorylated with PKC at two serines (44 and 55), causing loss of DNA polymerase activity but not DNA binding. In this work, we have investigated the phosphorylation-induced conformational changes in DNA polymerase in the presence of Mg ions.

Linking Alzheimer's Disease and Type 2 Diabetes: Characterization and Inhibition of Cytotoxic Aβ and IAPP Hetero-Aggregates.

The cytotoxic self-aggregation of β-amyloid (Aβ) peptide and islet amyloid polypeptide (IAPP) is implicated in the pathogenesis of Alzheimer's disease (AD) and Type 2 diabetes (T2D), respectively. Increasing evidence, particularly the co-deposition of Aβ and IAPP in both brain and pancreatic tissues, suggests that Aβ and IAPP cross-interaction may be responsible for a pathological link between AD and T2D. Here, we examined the nature of IAPP-Aβ40 co-aggregation and its inhibition by small molecules.

Nanocomposite Conductive Bioinks Based on Low-Concentration GelMA and MXene Nanosheets/Gold Nanoparticles Providing Enhanced Printability of Functional Skeletal Muscle Tissues.

There is a growing need to develop novel well-characterized biological inks (bioinks) that are customizable for three-dimensional (3D) bioprinting of specific tissue types. Gelatin methacryloyl (GelMA) is one such candidate bioink due to its biocompatibility and tunable mechanical properties. Currently, only low-concentration GelMA hydrogels (≤5% w/v) are suitable as cell-laden bioinks, allowing high cell viability, elongation, and migration.

Effect of Exogenous pH on Cell Growth of Breast Cancer Cells.

Breast cancer is the most common type of cancer in women and the most life-threatening cancer in females worldwide. One key feature of cancer cells, including breast cancer cells, is a reversed pH gradient which causes the extracellular pH of cancer cells to be more acidic than that of normal cells. Growing literature suggests that alkaline therapy could reverse the pH gradient back to normal and treat the cancer; however, evidence remains inconclusive.

Predictions of the elastic modulus of trabecular bone in the femoral head and the intertrochanter: a solitary wave-based approach.

This paper deals with the numerical prediction of the elastic modulus of trabecular bone in the femoral head (FH) and the intertrochanteric (IT) region via site-specific bone quality assessment using solitary waves in a one-dimensional granular chain. For accurate evaluation of bone quality, high-resolution finite element models of bone microstructures in both FH and IT are generated using a topology optimization-based bone microstructure reconstruction scheme. A hybrid discrete element/finite element (DE/FE) model is then developed to study the interaction of highly nonlinear solitary waves in a granular chain with the generated bone microstructures.

Multi-Compartment Lymph-Node-on-a-Chip Enables Measurement of Immune Cell Motility in Response to Drugs.

Organs On-a-Chip represent novel platforms for modelling human physiology and disease. The lymph node (LN) is a relevant immune organ in which B and T lymphocytes are spatially organized in a complex architecture, and it is the place where the immune response initiates. The present study addresses the utility of a recently designed LN-on-a-chip to dissect and understand the effect of drugs delivered to cells in a fluidic multicellular 3D setting that mimics the human LN.

Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus belonging to the Coronavirus family, is now known to cause Coronavirus Disease (Covid-19) which was first recognized in December 2019. Covid-19 leads to respiratory illnesses ranging from mild infections to pneumonia and lung failure. Strikingly, within a few months of its first report, Covid-19 has spread worldwide at an exceptionally high speed and it has caused enormous human casualties.

Numerical predictions of the interaction between highly nonlinear solitary waves and the microstructure of trabecular bone in the femoral head.

The unique properties of highly nonlinear solitary waves in granular chains have prompted extensive research in the area of non-destructive testing and led to the development of new diagnostic schemes with potential applications in the healthcare industry. Here, we study numerically the interaction between highly nonlinear solitary waves in a granular chain and the microstructure of trabecular bone in the femoral head. High-resolution finite element models of bone microstructures with varying bone volume fraction are generated using a topology optimization-based bone microstructure reconstruction scheme.

Aggregation and Cellular Toxicity of Pathogenic or Non-pathogenic Proteins.

More than 20 unique diseases such as diabetes, Alzheimer's disease, Parkinson's disease are caused by the abnormal aggregations of pathogenic proteins such as amylin, β-amyloid (Aβ), and α-synuclein. All pathogenic proteins differ from each other in biological function, primary sequences, and morphologies; however, the proteins are toxic when aggregated. Here, we investigated the cellular toxicity of pathogenic or non-pathogenic protein aggregates.

Inhibition of lysozyme aggregation and cellular toxicity by organic acids at acidic and physiological pH conditions.

The misfolding of proteins can lead to fibrillar and non-fibrillar deposits that are the hallmark of numerous human diseases. Inhibition of protein aggregation is considered as a promising strategy for the prevention of such diseases. Here we induced the fibrillar and non-fibrillar aggregates of hen egg white lysozyme (HEWL) at acidic (pH 3) and physiological (pH 7.

Computational and Experimental Approaches to Design Inhibitors of Amylin Aggregation.

Amylin is a neuroendocrine peptide hormone secreted by pancreatic ß-cells; however, amylin is toxic to ß-cells when it is aggregated in type 2 diabetes mellitus (T2DM). It is important to understand amylin's structures and aggregation mechanism for the discovery and design of effective drugs to inhibit amylin aggregation. In this review, we investigated experimental and computational studies on amylin structures and inhibitors.

Genetic Associations With Diabetic Retinopathy and Coronary Artery Disease in Emirati Patients With Type-2 Diabetes Mellitus.

Type 2 Diabetes Mellitus (T2DM) is associated with both microvascular complications such as diabetic retinopathy (DR), and macrovascular complications like coronary artery disease (CAD). Genetic risk factors have a role in the development of these complications. In the present case-control study, we investigated genetic variations associated with DR and CAD in T2DM patients from the United Arab Emirates.

Inhibition of Human Amylin Aggregation and Cellular Toxicity by Lipoic Acid and Ascorbic Acid.

More than 30 human degenerative diseases result from protein aggregation such as Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Islet amyloid deposits, a hallmark in T2DM, are found in pancreatic islets of more than 90% of T2DM patients. An association between amylin aggregation and reduction in β-cell mass was also established by post-mortem studies.

Clinical profiles, comorbidities and complications of type 2 diabetes mellitus in patients from United Arab Emirates.

Objective: To assess clinical profiles of patients with type 2 diabetes in the United Arab Emirates (UAE), including patterns, frequencies, and risk factors of microvascular and macrovascular complications.

Research Design And Methods: Four hundred and ninety patients with type 2 diabetes were enrolled from two major hospitals in Abu Dhabi. The presence of microvascular and macrovascular complications was assessed using logistic regression, and demographic, clinical and laboratory data were collected.

Gait alterations in the UAE population with and without diabetic complications using both traditional and entropy measures.

Diabetic foot, one of the most common and debilitating manifestations of type 2 diabetes mellitus (T2DM), is the leading cause of worldwide non-traumatic lower extremity amputations. Diabetics who are at risk of ulceration are currently mainly identified by a thorough clinical examination of the feet, which typically does not show clear symptoms during the early stages of disease progression. In this study, we used a non-linear dynamics tool, gait entropy (GaitEN), in addition to traditional linear gait analysis methods, to investigate gait alterations amongst diabetic patients with combinations of three types of T2DM related complications: retinopathy, diabetic peripheral neuropathy (DPN) and nephropathy.

Ultrasound-mediated drug delivery by gas bubbles generated from a chemical reaction.

Highly echogenic and ultrasound-responsive microbubbles such as nitrogen and perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here, we propose an innovative method for drug delivery using microbubbles generated from a chemical reaction. In a novel drug delivery system, luminol encapsulated in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate nitrogen gas (N) by chemical reaction when it reacts with hydrogen peroxide (HO), one of reactive oxygen species (ROS).

Association of Diabetes Related Complications with Heart Rate Variability among a Diabetic Population in the UAE.

Microvascular, macrovascular and neurological complications are the key causes of morbidity and mortality among type II diabetes mellitus (T2DM) patients. The aim of this study was to investigate the alterations of cardiac autonomic function of diabetic patients in relation to three types of diabetes-related complications. ECG recordings were collected and analyzed from 169 T2DM patients in supine position who were diagnosed with nephropathy (n = 55), peripheral neuropathy (n = 64) and retinopathy (n = 106) at two hospitals in the UAE.