Hydrophobic residues in the α-synuclein NAC domain drive seed-competent fibril formation and are targeted by peptide inhibitors.

Alpha-synuclein (αSyn) is a 14-kDa intrinsically disordered protein that aggregates into insoluble fibrils in synucleinopathies, including Lewy bodies, multiple system atrophy, and Parkinson's disease, contributing to neurotoxicity and disease progression. The ability of these fibrils to seed further aggregation of native protein is central to αSyn pathology. Here, we examined the broader non-amyloid component (NAC) domain, focusing on how residues flanking the hydrophobic 68-71 (GAVV) motif of αSyn (residues 8-11 in NAC35) modulate nucleation, stability, and pathological seeding.

In Silico, In Vitro, and In Vivo Investigations of Anticancer Properties of a Novel Platinum (II) Complex and Its PLGA Encapsulated Form.

In recent years, the development of multinuclear platinum complexes has introduced a new era in platinum-based chemotherapy, offering improved cytotoxicity and the ability to overcome resistance. However, these complexes still face challenges related to water solubility, biodistribution, and targeted delivery. This study provides a comprehensive investigation of a novel platinum (II) complex, [Pt(μ-bpy-2H) (Me)(dmso)] (C1), focusing on its DNA binding ability and anticancer activity.

Clinical Correlation of Altered Molecular Signatures in Epileptic Human Hippocampus and Amygdala.

Widespread alterations in the expression of various genes could contribute to the pathogenesis of epilepsy. The expression levels of various genes, including major inhibitory and excitatory receptors, ion channels, cell type-specific markers, and excitatory amino acid transporters, were assessed and compared between the human epileptic hippocampus and amygdala, and findings from autopsy controls. Moreover, the potential correlation between molecular alterations in epileptic brain tissues and the clinical characteristics of patients undergoing epilepsy surgery was evaluated.

Comparison of swallowing disorder in patients with tongue cancer undergoing reconstruction with either a radial forearm free flap or a submental island flap.

Purpose: In this study, the swallowing status of patients with tongue cancer undergone tongue reconstruction using radial forearm free flaps (RFFF) and submental flaps were compared.

Methods: A total of 26 patients with tongue cancer undergone tongue resection were randomly treated by tongue reconstruction with either submental flap or RFFF approach. Swallowing status of the patients was investigated using fiberoptic endoscopic evaluation of swallowing (FEES) by measurement of pharyngeal residue and penetration scales.

Design and preparation of a theranostic peptideticle for targeted cancer therapy: Peptide-based codelivery of doxorubicin/curcumin and graphene quantum dots.

Although chemotherapy has been known as a powerful medication for cancer treatment over the years, there is an important necessity for designing a novel targeted drug delivery system to overcome the drawbacks of this conventional method including undesired side effects on normal cells and drug resistance. The structural differences between the surface of cancerous and normal cells allow to design and engineer targeted drug delivery systems for cancer treatment. Integrins as one of the cell surface receptors over-expressed in cancer cells could potentially be suitable candidates for targeting cancer cells.

Glutamate Signaling Pathway in Absence Epilepsy: Possible Role of Ionotropic AMPA Glutamate Receptor Type 1 Subunit.

AMPA receptors, consisting of glutamate receptor type1 (GluR1) subunit are involved in the pathophysiology of some neurological disorders. In this study, the role of the GluR1 subunit in the development, as well as features of absence seizures were assessed. Both Wistar and WAG/Rij (a genetic animal model of absence epilepsy) rats with 2 and 6-month ages were included in the study.

The effect of GABAergic neurotransmission on the seizure-related activity of the laterodorsal thalamic nuclei and the somatosensory cortex in a genetic model of absence epilepsy.

The present study aimed to investigate the alterations of the GABAergic system in the laterodorsal nucleus (LDN) of the thalamus and the somatosensory cortex (SC) in an experimental model of absence seizure. The effects of pharmacological manipulation of both GABA and GABA receptor subunits in the LDN on the generation of spike-wave discharges (SWD) were evaluated. The experiments were carried out in four groups of both WAG/Rij and Wistar rats with 2 and 6 months of age.

Differentiation of spermatogonial stem cells by soft agar three-dimensional culture system.

Since proliferation and differentiation of spermatogonial stem cells (SSCs) in culture system provide successful transplantation in this study, culture of human SSCs was compared to SACS (soft agar culture system), gelatin and control groups. The cells were isolated from seminiferous tubules of non-azoospermia patients (NOA) and cultured in DMEM for 3 weeks. The presence of SSCs in culture system was confirmed by immunocytochemistry of GFR-α1 and ITGα6 antibodies.

Discrepancies of Notch 1 receptor during development of chronic seizures.

The critical role of Notch signaling has been shown in the pathogenesis of some neurological disorders including schizophrenia, epilepsy and Alzheimer's disease. This study was aimed to evaluate the role of Notch 1 receptor in epileptogenesis as well as seizure characteristics. The animals were divided into three groups of sham, early stage and end stage.

Cell injury and receptor expression in the epileptic human amygdala.

Neuropathological findings in the amygdala obtained from patients with mesial temporal lobe epilepsy (MTLE) indicate varying degrees of histopathological alterations, such as neuronal loss and gliosis. The mechanisms underlying cellular damage in the amygdala of patients with MTLE have not been fully elucidated. In the present study, we assess cellular damage, determine the receptor expression of major inhibitory and excitatory neurotransmitters, and evaluate the correlation between the expression of various receptors and cell damage in the basolateral complex and the centromedial areas in the amygdala specimens resected during brain surgery on 30 patients with medically intractable MTLE.

Switching from high-fat diet to foods containing resveratrol as a calorie restriction mimetic changes the architecture of arcuate nucleus to produce more newborn anorexigenic neurons.

Purpose: These days, obesity threatens the health for which one of the main interventions is calorie restriction (CR). Due to the difficulty of compliance with this treatment, CR mimetics such as resveratrol (RSV) have been considered. The present study compared the effects of RSV and CR on hypothalamic remodeling in a diet-switching experiment.

Resveratrol promotes the arcuate nucleus architecture remodeling to produce more anorexigenic neurons in high-fat-diet-fed mice.

Objective: Adult hypothalamic neurogenesis has been considered a central regulator of energy balance. Resveratrol (RSV), a natural polyphenol, influences the body fat mass and reduces the amount of adipose tissue. The present study was designed to evaluate the effect of RSV on dynamic of hypothalamic neurons in a diet-induced obesity model of mice.

Developmental changes in Notch1 and NLE1 expression in a genetic model of absence epilepsy.

Childhood absence epilepsy (CAE) is an epilepsy syndrome with seizures occurring in the early childhood, highlighting that seizures susceptibility in CAE is dependent on brain development. The Notch 1 signalling pathway is important in brain development, yet the role of the Notch1 signalling pathway in CAE remains elusive. We here explored Notch1 and its modulator notchless homologue 1 (NLE1) expression in WAG/Rij and control rats using immunohistochemistry.

Survival, proliferation, and migration of human meningioma stem-like cells in a nanopeptide scaffold.

Objectives: In order to grow cells in a three-dimensional (3D) microenvironment, self-assembling peptides, such as PuraMatrix, have emerged with potential to mimic the extracellular matrix. The aim of the present study was to investigate the influence of the self-assembling peptide on the morphology, survival, proliferation rate, migration potential, and differentiation of human meningioma stem-like cells (hMgSCs).

Materials And Methods: The efficacy of a novel method for placing hMgSCs in PuraMatrix (the injection approach) was compared to the encapsulation and surface plating methods.

Enhancement of Neural Stem Cell Survival, Proliferation, Migration, and Differentiation in a Novel Self-Assembly Peptide Nanofibber Scaffold.

Considerable efforts have been made to combine biologically active molecules into the self-assembling peptide in order to improve cells growth, survival, and differentiation. In this study, a novel three-dimensional scaffold (RADAGGSIKVAV; R-GSIK) was designed by adding glycine and serine between RADA4 and IKVAV to promote the strength of the peptide. The cell adhesion, viability, proliferation, migration, and differentiation of rat embryonic neural stem cells (NSCs) in R-GSIK were investigated and compared to laminin-coated, two-dimensional, and Puramatrix cultures.

Mechano-Transduction Signals Derived from Self-Assembling Peptide Nanofibers Containing Long Motif of Laminin Influence Neurogenesis in In-Vitro and In-Vivo.

Astroglial scaring and limited neurogenesis are two problematic issues in recovery of spinal cord injury (SCI). In the meantime, it seems that mechanical manipulations of scaffold to inhibit astroglial scarring and improve neurogenesis is worthy of value. In the present investigation, the effect of nanofiber (gel) concentration as a mechanical-stimuli in neurogenesis was investigated.

The Modulatory Effect of Metabotropic Glutamate Receptor Type-1α on Spike-Wave Discharges in WAG/Rij Rats.

Modulatory function of metabotropic glutamate type 1 (mGlu1) receptors plays a crucial role in the pathophysiology of some neurological disorders, including schizophrenia and epilepsy. In this study, the expression of mGlu1α receptors in the thalamic nuclei was assessed during development of absence seizures in the WAG/Rij rats, a valid genetic animal model of absence epilepsy. In addition, the effect of pharmacological modulation of mGlu1α receptors in the laterodorsal (LD) nucleus of the thalamus on the characteristic features of bioelectrical brain activities in the WAG/Rij rats was assessed.

Comparison of Capability of Human Bone Marrow Mesenchymal Stem Cells and Endometrial Stem Cells to Differentiate into Motor Neurons on Electrospun Poly(ε-caprolactone) Scaffold.

Human endometrial and bone marrow-derived mesenchymal stem cells can be differentiated into a number of cell lineages. Mesenchymal stem cells (MSCs) are potential candidates for cellular therapy. The differentiation of human bone marrow MSCs (hBM-MSCs) and endometrial stem cells (hEnSCs) into motor neuron-like cells has been rarely investigated previously; however, the comparison between these stem cells when they are differentiated into motor neuron-like cell is yet to be studied.

Effects of TRPV1 on the hippocampal synaptic plasticity in the epileptic rat brain.

Temporal lobe epilepsy is often presented by medically intractable recurrent seizures due to dysfunction of temporal lobe structures, mostly the temporomesial structures. The role of transient receptor potential vaniloid 1 (TRPV1) activity on synaptic plasticity of the epileptic brain tissues was investigated. We studied hippocampal TRPV1 protein content and distribution in the hippocampus of epileptic rats.

A novel traumatic brain injury model for induction of mild brain injury in rats.

Background: Due to the marked heterogeneity of human traumatic brain injury (TBI), none of the available animal model can reproduce the entire spectrum of TBI, especially mild focal TBI. This study was designed to develop a modified TBI weight drop model for induction of focal mild cerebral injury.

New Method: A stereotaxic coupled weight drop device was designed.

The effect of Noggin supplementation in Matrigel nanofiber-based cell culture system for derivation of neural-like cells from human endometrial-derived stromal cells.

A very important obstacle in axonal regeneration after spinal cord injury is astroglial scaring. Noggin as bone morphogenic protein inhibitor plays a critical role in decreasing GFAP(+) cells and reducing the number of astrocytes in the site of injury. Human endometrial-derived stromal cells (hEnSCs) were isolated and cultured in two different neural inductive mediums consisting of neural progenitor maintenance medium (NPMM)/BDNF or NPMM/BDNF/Noggin in Matrigel 3D cell culture.