AAV-aMTD-Parkin, a therapeutic gene delivery cargo, enhances motor and cognitive functions in Parkinson's and Alzheimer's diseases.

Neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD), have a global prevalence and profoundly impact both motor and cognitive functions. Although adeno-associated virus (AAV)-based gene therapy has shown promise, its application for treating central nervous system (CNS) diseases faces several challenges, including effective delivery of AAV vectors across the blood-brain barrier, determining optimal dosages, and achieving targeted distribution. To address these challenges, we have developed a fusion delivery therapeutic cargo called AAV-aMTD-Parkin, which combines a hydrophobic cell-penetrating peptide sequence with the DNA sequences of AAV and Parkin.

Intracellular delivery of nuclear localization sequence peptide mitigates COVID-19 by inhibiting nuclear transport of inflammation-associated transcription factors.

The novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), can trigger dysregulated immune responses known as the cytokine release syndrome (CRS), leading to severe organ dysfunction and respiratory distress. Our study focuses on developing an improved cell-permeable nuclear import inhibitor (iCP-NI), capable of blocking the nuclear transport of inflammation-associated transcription factors, specifically nuclear factor kappa B (NF-κB). By fusing advanced macromolecule transduction domains and nuclear localization sequences from human NF-κB, iCP-NI selectively interacts with importin α5, effectively reducing the expression of proinflammatory cytokines.

Imipramine Ameliorates Depressive Symptoms by Blocking Differential Alteration of Dendritic Spine Structure in Amygdala and Prefrontal Cortex of Chronic Stress-Induced Mice.

Previous studies have shown disrupted synaptic plasticity and neural activity in depression. Such alteration is strongly associated with disrupted synaptic structures. Chronic stress has been known to induce changes in dendritic structure in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), but antidepressant effect on structure of these brain areas has been unclear.

Nitric Oxide, an Old Molecule With Noble Functions in Pseudomonas aeruginosa Biology.

Pseudomonas aeruginosa, a Gram-negative bacterium, is characterized by its versatility that enables persistent survival under adverse conditions. It can grow on diverse energy sources and readily acquire resistance to antimicrobial agents. As an opportunistic human pathogen, it also causes chronic infections inside the anaerobic mucus airways of cystic fibrosis patients.

KDM4B histone demethylase and G9a regulate expression of vascular adhesion proteins in cerebral microvessels.

Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels.

Mechanisms of Amyloid-β Peptide Clearance: Potential Therapeutic Targets for Alzheimer's Disease.

Amyloid-β peptide (Aβ) is still best known as a molecule to cause Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have been focused on the reduc-tion of Aβ in the brain. Since accumulation of Aβ depends on the rate of its synthesis and clearance, the metabolic pathway of Aβ in the brain and the whole body should be carefully explored for AD research.

Direct detection of methicillin-resistant Staphylococcus aureus from blood cultures using an immunochromatographic immunoassay-based MRSA rapid kit for the detection of penicillin-binding protein 2a.

Using an EZ-Step MRSA rapid kit, a novel screening test for methicillin-resistant Staphylococcus aureus (MRSA) that detects penicillin-binding protein 2a, 34 of 36 MRSA-positive clinical blood culture samples were positive on direct testing (sensitivity, 94.4%), whereas 21 of 21 methicillin-susceptible S. aureus-positive samples were negative (specificity, 100%).

MglA regulates transcription of virulence factors necessary for Francisella tularensis intraamoebae and intramacrophage survival.

Francisella tularensis is able to survive and grow within macrophages, a trait that contributes to pathogenesis. Several genes have been identified that are important for intramacrophage survival, including mglA and iglC. F.