Classes of Stem Cells: From Biology to Engineering.

Purpose: The majority of adult tissues are limited in self-repair and regeneration due to their poor intrinsic regenerative capacity. It is widely recognized that stem cells are present in almost all adult tissues, but the natural regeneration in adult mammals is not sufficient to recover function after injury or disease. Historically, 3 classes of stem cells have been defined: embryonic stem cells (ESCs), adult mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs).

Animal Models of Osteoarthritis: Updated Models and Outcome Measures 2016-2023.

Purpose: Osteoarthritis (OA) is a global musculoskeletal disorder that affects primarily the knee and hip joints without any FDA-approved disease-modifying therapies. Animal models are essential research tools in developing therapies for OA; many animal studies have provided data for the initiation of human clinical trials. Despite this, there is still a need for strategies to recapitulate the human experience using animal models to better develop treatments and understand pathogenesis.

Development of porcine skeletal muscle extracellular matrix-derived hydrogels with improved properties and low immunogenicity.

Hydrogels derived from decellularized extracellular matrices (ECM) of animal origin show immense potential for regenerative applications due to their excellent cytocompatibility and biomimetic properties. Despite these benefits, the impact of decellularization protocols on the properties and immunogenicity of these hydrogels remains relatively unexplored. In this study, porcine skeletal muscle ECM (smECM) underwent decellularization using mechanical disruption (MD) and two commonly employed decellularization detergents, sodium deoxycholate (SDC) or Triton X-100.

Luminogenic and Bactericidal Studies of an Acrylonitrile-Based AIEgen.

We have synthesized an aggregation-induced emissive molecule that exhibits promising photophysical characteristics. The aggregating aptitude is demonstrated by binary solvent mixture and it is emissive in both solution and solid state. The luminogenic characteristics are employed in creating fluorescent inks as well as for the detection of nitro antibiotics in biofluids and in solid support.

Amphiphilic polyphenol incorporated hydrogel derived from mucoadhesive of Dillenia indica: Potential antioxidant and adsorbent.

In this work, the mucoadhesive substances from the fruits and seeds of Dillenia indica (DI), a plant present abundantly in India, have been extracted and utilised to prepare a hydrogel. A synthetically prepared amphiphilic polyphenol (L) has been incorporated within the hydrogel network to enhance the hydrogelation property. Moreover, the DI-L hydrogel's total phenolic content and radical scavenging prospects have been investigated.

Osteochondral regenerative engineering: challenges, state-of-the-art and translational perspectives.

Despite quantum leaps, the biomimetic regeneration of cartilage and osteochondral regeneration remains a major challenge, owing to the complex and hierarchical nature of compositional, structural and functional properties. In this review, an account of the prevailing challenges in biomimicking the gradients in porous microstructure, cells and extracellular matrix (ECM) orientation is presented. Further, the spatial arrangement of the cues in inducing vascularization in the subchondral bone region while maintaining the avascular nature of the adjacent cartilage layer is highlighted.

Quinoxaline-probe embedded injectable fluorogenic hydrogels: Comparative detection of mesitylene in guar gum and i-carrageenan hydrogels.

The innovation of novel chemosensor probes for the recognition of trace volatile organic compounds is critical due to their hazardous effect on the environment and human health. A nitro-group integrated quinoxaline probe with a profound discriminative fluorescence 'turn-on' response to mesitylene was fabricated into guar gum and i-carrageenan, two biopolymer-based hydrogel matrices, to develop compact, portable fluorogenic hydrogel sensors and assess their fluorescence properties. A comparative characterization-based analysis of native, probe-associated, and probe-analyte-associated hydrogels, (comprising of FT-IR, XRD, TGA) was investigated to ascertain the overall compatibility of the hydrogel-based sensors for use as a smart rapid detection tool.

Inhibition of CGRP signaling impairs fracture healing in mice.

Calcitonin gene-related peptide (CGRP) is a neuropeptide produced by sensory nerves and functions as a pain sensor. It acts by binding to the calcitonin-like receptor (CLR, protein; Calcrl, gene). CGRP inhibition has been recently introduced as therapeutic treatment of migraine-associated pain.

Transcriptional regulation of neural stem cell expansion in the adult hippocampus.

Experience governs neurogenesis from radial-glial neural stem cells (RGLs) in the adult hippocampus to support memory. Transcription factors (TFs) in RGLs integrate physiological signals to dictate self-renewal division mode. Whereas asymmetric RGL divisions drive neurogenesis during favorable conditions, symmetric divisions prevent premature neurogenesis while amplifying RGLs to anticipate future neurogenic demands.

Inhibitor of the tyrosine phosphatase STEP reverses cognitive deficits in a mouse model of Alzheimer's disease.

STEP (STriatal-Enriched protein tyrosine Phosphatase) is a neuron-specific phosphatase that regulates N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking, as well as ERK1/2, p38, Fyn, and Pyk2 activity. STEP is overactive in several neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease (AD). The increase in STEP activity likely disrupts synaptic function and contributes to the cognitive deficits in AD.

External cys/cySS redox state modification controls the intracellular redox state and neurodegeneration via Akt in aging and Alzheimer's disease mouse model neurons.

The extracellular redox environment of cells is mainly set by the redox couple cysteine/cystine (cys/cySS) while intracellular redox is buffered by reduced/oxidized glutathione (GSH/GSSG), but controlled by NAD(P)H/NAD(P). With aging, the extracellular redox environment shifts in the oxidized direction beyond middle-age. Since aging is the primary risk factor in Alzheimer's disease (AD), here our aim was to determine if a reduced extracellular cys/cySS redox potential of cultured primary mouse neurons changes the intracellular redox environment, affects pAkt levels, and protects against neuron loss.

Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons.

Aging, a major risk factor in Alzheimer's disease (AD), is associated with an oxidative redox shift, decreased redox buffer protection, and increased free radical reactive oxygen species (ROS) generation, probably linked to mitochondrial dysfunction. While NADH is the ultimate electron donor for many redox reactions, including oxidative phosphorylation, glutathione (GSH) is the major ROS detoxifying redox buffer in the cell. Here, we explored the relative importance of NADH and GSH to neurodegeneration in aging and AD neurons from nontransgenic and 3xTg-AD mice by inhibiting their synthesis to determine whether NADH can compensate for the GSH loss to maintain redox balance.

Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS.

A reversible early oxidized redox state that precedes macromolecular ROS damage in aging nontransgenic and 3xTg-AD mouse neurons.

The brain depends on redox electrons from nicotinamide adenine dinucleotide (reduced form; NADH) to produce ATP and oxyradicals (reactive oxygen species [ROS]). Because ROS damage and mitochondrial dysregulation are prominent in aging and Alzheimer's disease (AD) and their relationship to the redox state is unclear, we wanted to know whether an oxidative redox shift precedes these markers and leads to macromolecular damage in a mouse model of AD. We used the 3xTg-AD mouse model, which displays cognitive deficits beginning at 4 months.