ABBV-744 alleviates LPS-induced neuroinflammation via regulation of BATF2-IRF4-STAT1/3/5 axis.

Suppression of neuroinflammation using small molecule compounds targeting the key pathways in microglial inflammation has attracted great interest. Recently, increasing attention has been gained to the role of the second bromodomain (BD2) of the bromodomain and extra-terminal (BET) proteins, while its effect and molecular mechanism on microglial inflammation has not yet been explored. In this study, we evaluated the therapeutic effects of ABBV-744, a BD2 high selective BET inhibitor, on lipopolysaccharide (LPS)-induced microglial inflammation in vitro and in vivo, and explored the key pathways by which ABBV-744 regulated microglia-mediated neuroinflammation.

Unique Advantages of Dendrimers-Structured Mesoporous Silica Nanoparticles over Traditional Hollow Ones in Delivering Bcl2-Functional Converting Peptide for Multidrug Resistant Cancer Treatment.

Innovative silica nanomaterials have made the significant advancements in curative therapy against cancers with multidrug resistance (MDR). The study on different-nanostructured mesoporous silica nanoparticles (MSNs) with discrepant pore sizes affecting biomacromolecules in resisting cancer MDR hasn't been reported yet. In this study, a systematic comparison of 6 nm-pore sized hollow-structured MSNs (HMSNs) and 10 nm-pore sized dendrimers-structured MSNs (LMSNs) for delivering Bcl-2-functional converting peptide (N9) or doxorubicin (DOX) to overcome cancer MDR is comprehensively carried out both in in vitro and in vivo resistant tumor models.

JE-133 Suppresses LPS-Induced Neuroinflammation Associated with the Regulation of JAK/STAT and Nrf2 Signaling Pathways.

Neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, and interrupting the microglial-mediated neuroinflammation has been suggested as a promising strategy to delay or prevent the progression of neurodegeneration. In this study, we investigated the effects of JE-133, an optically active isochroman-2-chromene conjugate containing a 1,3-disubstituted isochroman unit, on lipopolysaccharide (LPS)-induced microglial neuroinflammation and underlying mechanisms both in vitro and in vivo. First, JE-133 treatment decreased LPS-induced overproduction of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitrite, and nitric oxide synthase (iNOS) in BV2 microglial cells.

PDPOB Exerts Multiaspect Anti-Ischemic Effects Associated with the Regulation of PI3K/AKT and MAPK Signaling Pathways.

The discovery of new therapeutic agents for ischemic stroke remains an urgent need. Here, we identified a novel phenyl carboxylic acid derivative, -pentyl 4-(3,4-dihydroxyphenyl)-4-oxobutanoate (PDPOB), with anti-ischemic activities. The anti-ischemic neuroprotective and anti-inflammatory capacities of PDPOB were investigated using neuronal cells suffering from oxygen-glucose deprivation/reperfusion (OGD/R) and microglial cells stimulated by lipopolysaccharide (LPS).

Impact of macroporous silica nanoparticles at sub-50nm on bio-behaviors and biosafety in drug-resistant cancer models.

The in vivo bio-behaviors and biosafety of nanoparticles were demonstrated to be closely correlated with particle sizes, which illustrated whether they could be used as the effective drug delivery carriers. Though tumor penetration capabilities of the small pore sized-mesoporous silica nanoparticles (MSNs) were reported to be in a particle size-dependent manner, the size effects of large pore sized-MSNs on the safe and effective cancer resistance treatment, especially at sub-50 nm, were not explicitly evaluated. In this study, we fabricate the 20 nm and 50 nm MSNs, and aim at investigating their difference in tumor accumulation, penetration, retention and toxicity both in vitro and in vivo.

Novel urethral sheath to manage bladder calculi.

Purpose: To explore the role of a new urethral sheath in transurethral lithotripsy for bladder calculi.

Methods: The 120 cases with bladder stone (BS) models were divided into three groups. One stone was placed in the bladder for each case.