Brain Delivery of Protein Therapeutics by Cell Matrix-Inspired Biomimetic Nanocarrier.

Protein therapeutics are anticipated to offer significant treatment options for central nervous system (CNS) diseases. However, the majority of proteins are unable to traverse the blood-brain barrier (BBB) and reach their CNS target sites. Inspired by the natural environment of active proteins, the cell matrix components hyaluronic acid (HA) and protamine (PRTM) are used to self-assemble with proteins to form a protein-loaded biomimetic core and then incorporated into ApoE3-reconstituted high-density lipoprotein (rHDL) to form a protein-loaded biomimetic nanocarrier (Protein-HA-PRTM-rHDL).

Intracerebral fate of organic and inorganic nanoparticles is dependent on microglial extracellular vesicle function.

Nanoparticles (NPs) represent an important advance for delivering diagnostic and therapeutic agents across the blood-brain barrier. However, NP clearance is critical for safety and therapeutic applicability. Here we report on a study of the clearance of model organic and inorganic NPs from the brain.

The effect of drug loading and multiple administration on the protein corona formation and brain delivery property of PEG-PLA nanoparticles.

The presence of protein corona on the surface of nanoparticles modulates their physiological interactions such as cellular association and targeting property. It has been shown that -mangostin (M)-loaded poly(ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles (NP-M) specifically increased low density lipoprotein receptor (LDLR) expression in microglia and improved clearance of amyloid beta (A) after multiple administration. However, how do the nanoparticles cross the blood‒brain barrier and access microglia remain unknown.

Autonomic Tone Variations Prior to Onset of Paroxysmal Atrial Fibrillation.

BACKGROUND Variations of heart rate variability (HRV) before paroxysmal atrial fibrillation (PAF) onset are still controversial. We aimed to observe the autonomic tone variations before PAF onset based on HRV analysis. MATERIAL AND METHODS We prospectively investigated 24-h Holter recordings of 60 patients with PAF (M/F: 34/26) and 40 healthy people in sinus rhythm (M/F: 18/12).

C-Phycocyanin Ameliorates Mitochondrial Fission and Fusion Dynamics in Ischemic Cardiomyocyte Damage.

Mitochondrial dysfunction is a predominant risk factor in ischemic heart disease, in which the imbalance of mitochondrial fusion and fission deteriorates mitochondrial function and might lead to cardiomyocyte death. C-phycocyanin (C-pc), an active component from blue-green algae, such as , has been reported to have anti-apoptosis and anti-oxidation functions. In this study, the effects of C-pc on mitochondrial dynamics of cardiomyocytes was examined using an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, an model to study the ischemia in the heart.

Decreased immunoglobulin G in brain regions of elder female APOE4-TR mice accompany with Aβ accumulation.

Background: Apolipoprotein E4 (APOE4) and ageing are the most important known risk factors for late-onset Alzheimer's disease (AD). In the present study, we determined the alterations of IgG, CD19, and Aβ in various brain regions of uninfected male and female APOE3- and APOE4-TR mice at the age of 3 and 10 months to elucidate impacts of AD risk factors on alterations of brain IgG.

Results: Positive staining for IgG was distributed across the brain, including neocortex, entorhinal cortex, hippocampus, thalamus and cerebellum.

CD200-, CX3CL1-, and TREM2-mediated neuron-microglia interactions and their involvements in Alzheimer's disease.

Neurons and microglia are two major components in the central nervous system (CNS). The interactions between them play important roles in maintaining homeostasis of the brain. In recent years, substantial studies have focused on the interactions between neurons and microglia, revealing that microglia become reactive when the interactions are pathophysiologically interfered, usually accompanying neuronal injury, which is a common feature for Alzheimer's disease (AD).

Theanine enhanced both the toxicity of strychnine and anticonvulsion of pentobarbital sodium.

Context: Theanine, an additive, holds several effects on the central nervous system without toxicity and affects CNS drugs. Theanine bilaterally alters β wave of the EEG with or without caffeine and pentobarbital-induced locomotor activity. Theanine also enhances hypnosis of pentobarbital sodium (PB) and antidepression of midazolam, suggesting there are complicated interactions between theanine and CNS drugs.