Efficiency of PGK1 proteins delivered to the brain via a liposomal system through intranasal route administration for the treatment of spinocerebellar ataxia type 3.

A patient-friendly and efficient treatment method for patients with spinocerebellar ataxia type 3 (SCA3) was provided through a nose-to-brain liposomal system. Initially, PGK1 was overexpressed in HEK 293-84Q-GFP diseased cells (HEK 293-84Q-GFP-PGK1 cells) to confirm its effect on the diseased protein polyQ. A decrease in polyQ expression was demonstrated in HEK 293-84Q-GFP-PGK1 cells compared to HEK 293-84Q-GFP parental cells.

Mucin-mediated mucosal retention via end-terminal modified Pluronic F127-based hydrogel to increase drug accumulation in the lungs.

Noninvasive lung drug delivery is critical for treating respiratory diseases. Pluronic-based copolymers have been used as multifunctional materials for medical and biological applications. However, the Pluronic F127-based hydrogel is rapidly degraded, adversely affecting the mechanical stability for prolonged drug release.

Investigation into the crystal structure-dielectric property correlation in barium titanate nanocrystals of different sizes.

For high capacitance multilayer ceramic capacitors, high dielectric constant and lead-free ceramic nanoparticles are highly desired. However, as the particle size decreases to a few tens of nanometers, their dielectric constant significantly decreases, and the underlying mechanism has yet to be fully elucidated. Herein, we report a systematic investigation into the crystal structure-dielectric property relationship of combustion-made BaTiO (BTO) nanocrystals.

Towards a Diagnosis of Cardiac Amyloidosis: Single Center Experience with Technetium Pyrophosphate Planar Imaging and Opportunities for Standardization of Diagnostic Workflow.

: Cardiac amyloidosis is a disorder caused by amyloid fibril deposition in the extracellular space of the heart. Almost all forms of clinical cardiac amyloidosis are transthyretin amyloidosis (ATTR) or light chain amyloidosis. technetium pyrophosphate (Tc PYP scan) has changed the landscape of the non-biopsy diagnosis of ATTR cardiac amyloidosis (ATTR-CA) by providing remarkably high diagnostic accuracy.

Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas.

Oral cancer is one of the most common cancers worldwide, especially in South Central Asia. It has been suggested that cancer stem cells (CSC) play crucial roles in tumor relapse and metastasis, and approaches to target CSC may lead to promising results. Here, aldehyde dehydrogenase 1 (ALDH1) and CD44 were utilized to isolate CSCs of oral cancer.

Interstitial Control-Released Polymer Carrying a Targeting Small-Molecule Drug Reduces PD-L1 and MGMT Expression in Recurrent High-Grade Gliomas with TMZ Resistance.

In recurrent glioblastoma, Gliadel wafer implantation after surgery has been shown to result in incomplete chemical removal of residual tumor and development of brain edema. Furthermore, temozolomide (TMZ) resistance caused by O-methylguanine-DNA-methyltransferase (MGMT) activation and programmed cell death-ligand 1 (PD-L1) expression leads to immune-cold lesions that result in poorer prognosis. Cerebraca wafer, a biodegradable polymer containing (Z)--butylidenephthalide (BP), is designed to eliminate residual tumor after glioma resection.

Combination of ovalbumin-coated iron oxide nanoparticles and poly(amidoamine) dendrimer-cisplatin nanocomplex for enhanced anticancer efficacy.

Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR)-based tumor targeted 4.5 generation poly(amidoamine) dendrimer(4.

-Butylidenephthalide Modulates Autophagy to Ameliorate Neuropathological Progress of Spinocerebellar Ataxia Type 3 through mTOR Pathway.

Spinocerebellar ataxia type 3 (SCA3), a hereditary and lethal neurodegenerative disease, is attributed to the abnormal accumulation of undegradable polyglutamine (polyQ), which is encoded by mutated ataxin-3 gene (). The toxic fragments processed from mutant can induce neuronal death, leading to the muscular incoordination of the human body. Some treatment strategies of SCA3 are preferentially focused on depleting the abnormal aggregates, which led to the discovery of small molecule -butylidenephthalide (-BP).

Conversational Vocal Intensity in Parkinson's Disease: Treatment and Environmental Comparisons.

Background: Vibrotactile Feedback (VF) using wearable devices is an emerging treatment option for hypophonia in Individuals with Parkinson's disease (IwPD). Studies evaluating the effectiveness of VF in improving conversational vocal intensity in real-life environment in IwPD are limited.

Objective: To determine the effect of VF on conversational vocal intensity and compare vocal intensity between a) clinic and real-life environment b) VF and Lee Silverman Voice Treatment (LSVT LOUD®)vs.

Use of Videos and Digital Media in Parent-implemented Interventions for Parents of Children with Primary Speech Sound And/or Language Disorders: A Scoping Review.

No review to date has focused on evaluating the use of videos and digital media in parent-implemented interventions for parents of children with primary language or speech sound disorder (LD/SSD). Research objectives guiding this scoping review included an evaluation of (a) use of videos and/or other digital media in parent-implemented interventions; (b) use of videos and/or other digital media in asynchronous content; (c) the role of the parent as learner; and (d) the program impact on parents and children. This review followed a five-stage framework: (a) identify research questions; (b) identify relevant studies; (c) select studies; (d) chart the data; and (e) collate, summarize and report the results.

Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain.

Although butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailability, drug stability, and encapsulation efficiency (EE, up to 95%) of BP were improved by using cyclodextrin-encapsulated BP in liposomal formulations (CDD1).

Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado-Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive motor disease with no broadly effective treatment. However, most current therapies are based on symptoms rather than the underlying disease mechanisms. In this review, we describe potential therapeutic strategies based on known pathological biomarkers and related pathogenic processes.

Prediction of Symptomatic Venous Thromboembolism in Critically Ill Patients: The ICU-Venous Thromboembolism Score.

Objectives: To identify risk factors and develop a prediction score for in-hospital symptomatic venous thromboembolism in critically ill patients.

Design: Retrospective cohort study.

Setting: Henry Ford Health System, a five-hospital system including 18 ICUs.

CTA-for-All: Impact of Emergency Computed Tomographic Angiography for All Patients With Stroke Presenting Within 24 Hours of Onset.

Background and Purpose- We sought to evaluate the impact of a Computed Tomographic Angiography (CTA) for All emergency stroke imaging protocol on outcome after large vessel occlusion (LVO). Methods- On July 1, 2017, the Henry Ford Health System implemented the policy of performing CTA and noncontrast computed tomography together as an initial imaging study for all patients with acute ischemic stroke (AIS) presenting within 24 hours of last known well, regardless of baseline National Institutes of Health Stroke Scale score. Previously, CTA was reserved for patients presenting within 6 hours with a National Institutes of Health Stroke Scale score ≥6.

Epigenetic targeting DNMT1 of pancreatic ductal adenocarcinoma using interstitial control release biodegrading polymer reduced tumor growth through hedgehog pathway inhibition.

Annually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the DNA methyltransferase 1 (DNMT1) protein.

The Role of Biomaterials in Implantation for Central Nervous System Injury.

Permanent deficits that occur in memory, sensation, and cognition can result from central nervous system (CNS) trauma that causes dysfunction and/or unregulated CNS regeneration. Some therapeutic approaches are preferentially applied to the human body. Therefore, cell transplantation, one of the therapeutic strategies, may be used to benefit people.

The Molecular Mechanisms of Plant-Derived Compounds Targeting Brain Cancer.

Glioblastoma multiforme (GBM) is one of the most aggressive and malignant forms of brain tumors. Despite recent advances in operative and postoperative treatments, it is almost impossible to perform complete resection of these tumors owing to their invasive and diffuse nature. Several natural plant-derived products, however, have been demonstrated to have promising therapeutic effects, such that they may serve as resources for anticancer drug discovery.

Vibrio vulnificus MARTX cytotoxin causes inactivation of phagocytosis-related signaling molecules in macrophages.

Background: Vibrio vulnificus is a marine bacterial species that causes opportunistic infections manifested by serious skin lesions and fulminant septicemia in humans. We have previously shown that the multifunctional autoprocessing repeats in toxin (MARTX) of a biotype 1 V. vulnificus strain promotes survival of this organism in the host by preventing it from engulfment by the phagocytes.

Targeting the pathway of GSK-3β/nerve growth factor to attenuate post-infarction arrhythmias by preconditioned adipose-derived stem cells.

Adipose-derived stem cell (ADSC) transplantation is a promising new therapy to improve cardiac function after myocardial infarction. However, its low efficacy of transdifferentiation hampers its usefulness. Glycogen synthase kinase-3β (GSK-3β) signal has been shown to play a role in preconditioning-induced cardioprotection.

Transgenic Cabbage Expressing Cry1Ac1 Does Not Affect the Survival and Growth of the Wolf Spider, Pardosa astrigera L. Koch (Araneae: Lycosidae).

Both herbivores that consume transgenic crops and their predators can be exposed to insecticidal proteins expressed in those crops. We conducted a tritrophic bioassay to evaluate the ecotoxicological impacts that Bt cabbage (Brassica oleracea var. capitata) expressing Cry1Ac1 protein might have on the wolf spider (Pardosa astrigera), a non-target generalist predator.

Spatial distribution of filament elasticity determines the migratory behaviors of a cell.

Any cellular response leading to morphological changes is highly tuned to balance the force generated from structural reorganization, provided by actin cytoskeleton. Actin filaments serve as the backbone of intracellular force, and transduce external mechanical signal via focal adhesion complex into the cell. During migration, cells not only undergo molecular changes but also rapid mechanical modulation.

A Neoglycoconjugate Containing the Human Milk Sugar LNFPIII Drives Anti-Inflammatory Activation of Antigen Presenting Cells in a CD14 Dependent Pathway.

The milk pentasaccharide LNFPIII has therapeutic action for metabolic and autoimmune diseases and prolongs transplant survival in mice when presented as a neoglycoconjugate. Within LNFPIII is the Lewisx trisaccharide, expressed by many helminth parasites. In humans, LNFPIII is found in human milk and also known as stage-specific embryonic antigen-1.

Crystal Structure of the Minor Pilin CofB, the Initiator of CFA/III Pilus Assembly in Enterotoxigenic Escherichia coli.

Type IV pili are extracellular polymers of the major pilin subunit. These subunits are held together in the pilus filament by hydrophobic interactions among their N-terminal α-helices, which also anchor the pilin subunits in the inner membrane prior to pilus assembly. Type IV pilus assembly involves a conserved group of proteins that span the envelope of Gram-negative bacteria.