Influence of Magnesium Ions and Crowding Agents on Structure and Stability of RNA Aptamers.

Aptamers bind to their targets with exceptional affinity and specificity. However, their intracellular application is hampered by the lack of knowledge about the effect of the cellular milieu on the RNA structure/stability. In this study, cellular crowding was mimicked using polyethylene glycol (PEG), and the crucial role of Mg ions in stabilizing the structure of an RNA aptamer was investigated.

3D Melt-Extrusion Printing of Medium Chain Length Polyhydroxyalkanoates and Their Application as Antibiotic-Free Antibacterial Scaffolds for Bone Regeneration.

In this work, we investigated, for the first time, the possibility of developing scaffolds for bone tissue engineering through three-dimensional (3D) melt-extrusion printing of medium chain length polyhydroxyalkanoate (mcl-PHA) (i.e., poly(3-hydroxyoctanoate--hydroxydecanoate--hydroxydodecanoate), P(3HO--3HD--3HDD)).

Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation.

Parkinson's disease (PD) is a neurodegenerative disorder associated with mitochondrial dysfunctions and oxidative stress. However, to date, therapeutics targeting these pathological events have not managed to translate from bench to bedside for clinical use. One of the major reasons for the lack of translational success has been the use of classical model systems that do not replicate the disease pathology and progression with the same degree of robustness.

Immunotherapy: An emerging treatment option for neurodegenerative diseases.

Accumulation of misfolded proteins and protein aggregates leading to degeneration of neurons is a hallmark of several neurodegenerative diseases. Therapy mostly relies on symptomatic relief. Immunotherapy offers a promising approach for the development of disease-modifying routes.

Modern pollen dispersal in relation to present vegetation distribution and land use in the Baspa valley, Kinnaur, western Himalayas.

Interpretation of a fossil pollen data for the vegetation and climate reconstruction of any region needs a modern pollen-vegetation analogue for its calibration. We analyzed the surface sediments and moss polsters for the pollen and microcharcoal records to understand the modern pollen-vegetation relationship and human activities in the Baspa Valley, Kinnaur, Himachal Pradesh. Presently, valley is occupied by the arboreal and non-arboreal vegetation of temperate to subalpine habitats and land use activities.

Bacterial Cellulose Electrospun Fiber Mesh Coated with Chitin Nanofibrils for Eardrum Repair.

In this study, we develop a bio-based and bioactive nanofibrous patch based on bacterial cellulose (BC) and chitin nanofibrils (CNs) using an ionic liquid as a solvent for BC, aimed at tympanic membrane (TM) repair. Electrospun BC nanofiber meshes were produced via electrospinning, and surface-modified with CNs using electrospray. The rheology of the BC/ionic liquid system was investigated.

Medium chain length polyhydroxyalkanoates as potential matrix materials for peripheral nerve regeneration.

Polyhydroxyalkanoates are natural, biodegradable, thermoplastic and sustainable polymers with a huge potential in fabrication of bioresorbable implantable devices for tissue engineering. We describe a comparative evaluation of three medium chain length polyhydroxyalkanoates (mcl-PHAs), namely poly(3-hydroxyoctanoate), poly(3-hydroxyoctanoate-co-3-hydoxydecanoate) and poly(3-hydroxyoctanoate-co-3-hydroxydecanoate-co-3-hydroxydodecanoate), one short chain length polyhydroxyalkanoate, poly(3-hydroxybutyrate), P(3HB) and synthetic aliphatic polyesters (polycaprolactone and polylactide) with a specific focus on nerve regeneration, due to mechanical properties of mcl-PHAs closely matching nerve tissues. biological studies with NG108-15 neuronal cell and primary Schwann cells did not show a cytotoxic effect of the materials on both cell types.

Renal tissue engineering for regenerative medicine using polymers and hydrogels.

Chronic Kidney Disease (CKD) is a growing worldwide problem, leading to end-stage renal disease (ESRD). Current treatments for ESRD include haemodialysis and kidney transplantation, but both are deemed inadequate since haemodialysis does not address all other kidney functions, and there is a shortage of suitable donor organs for transplantation. Research in kidney tissue engineering has been initiated to take a regenerative medicine approach as a potential treatment alternative, either to develop effective cell therapy for reconstruction or engineer a functioning bioartificial kidney.

Aminosilane Functionalized Aligned Fiber PCL Scaffolds for Peripheral Nerve Repair.

Silane modification is a simple and cost-effective tool to modify existing biomaterials for tissue engineering applications. Aminosilane layer deposition has previously been shown to control NG108-15 neuronal cell and primary Schwann cell adhesion and differentiation by controlling deposition of ─NH groups at the submicron scale across the entirety of a surface by varying silane chain length. This is the first study toreport depositing 11-aminoundecyltriethoxysilane (CL11) onto aligned Polycaprolactone (PCL) scaffolds for peripheral nerve regeneration.

Amelioration of Parkinson's disease by pharmacological inhibition and knockdown of redox sensitive TRPC5 channels: Focus on mitochondrial health.

Aims: Transient receptor potential canonical 5 (TRPC5) channels are redox-sensitive cation-permeable channels involved in temperature and mechanical sensation. Increased expression and over-activation of these channels has been implicated in several central nervous system disorders such as epilepsy, depression, traumatic brain injury, anxiety, Huntington's disease and stroke. TRPC5 channel activation causes increased calcium influx which in turn activates numerous downstream signalling pathways involved in the pathophysiology of neurological disorders.

Aptamer Reduces Aggregation of Mutant Huntingtin and Rescues Proteostasis Network in Non-Neuronal and Neuronal Cells.

Aggregation of mutant huntingtin is a pathological hallmark of Huntington's disease (HD). Protein aggregation results in various cellular dysfunctions, such as increase in oxidative stress, mitochondrial damage, proteostasis imbalance, etc., which finally cause cell death.

Meclofenoxate Inhibits Aggregation of Alpha-synuclein .

Background: α-Synuclein, a natively disordered protein, is a key component of Lewy bodies, the ubiquitinated protein aggregates which are the pathological hallmark of Parkinson's disease (PD). Meclofenoxate (centrophenoxine) is a nootropic drug which has shown beneficial therapeutic effects in various neuronal diseases. Administration of meclofenoxate enhanced levels of dopamine and improved motor function in animal models of Parkinson's disease (PD).

Aligned Polyhydroxyalkanoate Blend Electrospun Fibers as Intraluminal Guidance Scaffolds for Peripheral Nerve Repair.

The use of nerve guidance conduits (NGCs) to treat peripheral nerve injuries is a favorable approach to the current "gold standard" of autografting. However, as simple hollow tubes, they lack specific topographical and mechanical guidance cues present in nerve grafts and therefore are not suitable for treating large gap injuries (30-50 mm). The incorporation of intraluminal guidance scaffolds, such as aligned fibers, has been shown to increase neuronal cell neurite outgrowth and Schwann cell migration distances.

The functional role of Ire1 in regulating autophagy and proteasomal degradation under prolonged proteotoxic stress.

Inhibition of endoribonuclease/kinase Ire1 has shown beneficial effects in many proteotoxicity-induced pathology models. The mechanism by which this occurs has not been elucidated completely. Using a proteotoxic yeast model of Huntington's disease, we show that the deletion of Ire1 led to lower protein aggregation at longer time points.

Bacterial Cellulose-Based Blends and Composites: Versatile Biomaterials for Tissue Engineering Applications.

Cellulose of bacterial origin, known as bacterial cellulose (BC), is one of the most versatile biomaterials that has a huge potential in tissue engineering due to its favourable mechanical properties, high hydrophilicity, crystallinity, and purity. Additional properties such as porous nano-fibrillar 3D structure and a high degree of polymerisation of BC mimic the properties of the native extracellular matrix (ECM), making it an excellent material for the fabrication of composite scaffolds suitable for cell growth and tissue development. Recently, the fabrication of BC-based scaffolds, including composites and blends with nanomaterials, and other biocompatible polymers has received particular attention owing to their desirable properties for tissue engineering.

Additive Manufacturing of Polyhydroxyalkanoate-Based Blends Using Fused Deposition Modelling for the Development of Biomedical Devices.

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes.

Impact of nanoparticles on amyloid β-induced Alzheimer's disease, tuberculosis, leprosy and cancer: a systematic review.

Nanotechnology is an interdisciplinary domain of science, technology and engineering that deals with nano-sized materials/particles. Usually, the size of nanoparticles lies between 1 and 100 nm. Due to their small size and large surface area-to-volume ratio, nanoparticles exhibit high reactivity, greater stability and adsorption capacity.

Neuroprotective Potential of HC070, a Potent TRPC5 Channel Inhibitor in Parkinson's Disease Models: A Behavioral and Mechanistic Study.

Transient receptor potential canonical 5 (TRPC5) channels are predominantly expressed in the striatum and substantia nigra of the brain. These channels are permeable to calcium ions and are activated by oxidative stress. The physiological involvement of TRPC5 channels in temperature and mechanical sensation is well documented; however, evidence for their involvement in the pathophysiology of neurodegenerative disorders like Parkinson's disease (PD) is sparse.

The role of the glycerol transporter channel Fps1p in cellular proteostasis during enhanced proteotoxic stress.

In response to osmotic shock, the components of high-osmolarity glycerol (HOG) pathway regulate the level of intracellular glycerol in yeast and ensure cell survival. Glycerol is a compatible solute and a stabiliser of proteins. Its role in maintaining proteostasis is less explored.

3D Disease Modelling of Hard and Soft Cancer Using PHA-Based Scaffolds.

Tumour cells are shown to change shape and lose polarity when they are cultured in 3D, a feature typically associated with tumour progression in vivo, thus making it significant to study cancer cells in an environment that mimics the in vivo milieu. In this study we established hard (MCF7 and MDA-MB-231, breast cancer) and soft (HCT116, colon cancer) 3D cancer tumour models utilizing a blend of P(3HO--3HD) and P(3HB). P(3HO--3HD) and P(3HB) belong to a group of natural biodegradable polyesters, PHAs, that are synthesised by microorganisms.

Role of ATP-Small Heat Shock Protein Interaction in Human Diseases.

Adenosine triphosphate (ATP) is an important fuel of life for humans and species. Its potential role in modulating cellular functions and implications in systemic, pulmonary, and ocular diseases is well studied. Plasma ATP has been used as a diagnostic and prognostic biomarker owing to its close association with disease's progression.

Polyhydroxyalkanoates and their advances for biomedical applications.

Polyhydroxyalkanoates (PHAs) are sustainable, versatile, biocompatible, and bioresorbable polymers that are suitable for biomedical applications. Produced via bacterial fermentation under nutrient-limiting conditions, they are uncovering a new horizon for devices in biomedical applications. A wide range of cell types including bone, cartilage, nerve, cardiac, and pancreatic cells, readily attach grow and are functional on PHAs.