Pomegranate-Derived Exosome-Like Nanovesicles Alleviate Binge Alcohol-Induced Leaky Gut and Liver Injury.

Alcoholic liver disease (ALD) is damage to the liver and mainly caused by binge alcohol. ALD have decreased junctional protein expression and modulated intestinal permeability. We investigated whether plant-releasing exosome-like nanovesicles can prevent liver damage and leaky gut from binge alcohol. In this study, we characterized the exosome-like nanovesicles from pomegranate juice and confirmed the round shape of a lipid bilayer. After 14 days of pomegranate-derived exosome-like nanovesicle (PNVs) pretreatment, binge alcohol (6 g/kg/dose) was administered to mice three times orally every 12 h. Exposure to binge alcohol increased levels of oxidative and nitric oxide stress marker proteins such as CYP2E1, 3-Nitrotyrosine, and inducible nitric oxide synthase in both liver and gut damage. Also, binge alcohol significantly elevated the plasma endotoxemia, inflammatory fatty liver, and leaky gut. However, PNVs reduced the oxidative stress and apoptosis marker proteins and prevented the leaky gut and endotoxemia. Markedly, PNV treatment significantly prevented a decrease in the amount of intestinal junctional proteins and an increase in leaky gut in mice exposed to alcohol. These results showed that PNVs can prevent leaky gut and liver damage caused by binge alcohol and suggest that it may be useful hepatoprotective or intestinal protective agents for the first time.

Plum-Derived Exosome-like Nanovesicles Induce Differentiation of Osteoblasts and Reduction of Osteoclast Activation.

Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 µg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.

The Effect of Apple-Derived Nanovesicles on the Osteoblastogenesis of Osteoblastic MC3T3-E1 Cells.

Osteoporosis is characterized by low bone mass and elevated structural deterioration of the bone tissue, resulting in bone weakness with an increased risk of fracture. Considering biological activities of various phytochemicals extracted from apples, we herein demonstrated the potential antiosteoporotic effects of apple-derived nanovesicles (apple NVs) using osteoblastic MC3T3-E1 cells. Apple NVs significantly stimulated the growth of MC3T3-E1 cells. The cellular alkaline phosphatase (ALP) activity was significantly upregulated in the 5 µg/mL apple NVs-treated group. In addition, the concentrarion of mineralized nodules was significantly increased in the apple NVs-treated groups. Furthermore, apple NVs increased the expression of the genes and proteins associated with osteoblast growth and differentiation, such as Runx2, ALP, OPN, and BMP2/4, which further activated ERK- and JNK-related mitogen-activated protein kinase signaling. These results demonstrate that apple NVs have a potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells through regulating the BMP2/Smad1 pathways.

Plasmon-Triggered Upconversion Emissions and Hot Carrier Injection for Combinatorial Photothermal and Photodynamic Cancer Therapy.

Despite the unique ability of lanthanide-doped upconversion nanoparticles (UCNPs) to convert near-infrared (NIR) light to high-energy UV-vis radiation, low quantum efficiency has rendered their application unpractical in biomedical fields. Here, we report anatase titania-coated plasmonic gold nanorods decorated with UCNPs (Au NR@aTiO2@UCNPs) for combinational photothermal and photodynamic therapy to treat cancer. Our novel architecture employs the incorporation of an anatase titanium dioxide (aTiO2) photosensitizer as a spacer and exploits the localized surface plasmon resonance (LSPR) properties of the Au core. The LSPR-derived near-field enhancement induces a threefold boost of upconversion emissions, which are re-absorbed by neighboring aTiO2 and Au nanocomponents. Photocatalytic experiments strongly infer that LSPR-induced hot electrons are injected into the conduction band of aTiO2, generating reactive oxygen species. As phototherapeutic agents, our hybrid nanostructures show remarkable in vitro anticancer effect under NIR light [28.0% cancer cell viability against Au NR@aTiO2 (77.3%) and UCNP@aTiO2 (98.8%)] ascribed to the efficient radical formation and LSPR-induced heat generation, with cancer cell death primarily following an apoptotic pathway. In vivo animal studies further confirm the tumor suppression ability of Au NR@aTiO2@UCNPs through combinatorial photothermal and photodynamic effect. Our hybrid nanomaterials emerge as excellent multifunctional phototherapy agents, providing a valuable addition to light-triggered cancer treatments in deep tissue.

Efficacy of nano-particulated, water-soluble erlotinib against intracranial metastases of EGFR-mutant lung cancer.

Central nervous system (CNS) metastasis is one of the serious complications of epidermal growth factor receptor (EGFR)-mutant lung cancer, which arises due to poor penetration of the brain-blood barrier by EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Although osimertinib, a third-generation EGFR-TKI, has efficacy against CNS metastases, further treatment modalities are still needed as some of these lesions do not respond to osimertinib, or undergo progression after an initial response to this drug if radiotherapy has already been conducted. Here, we investigated the efficacy of water-soluble erlotinib (NUFS-sErt) against these metastases. This agent was synthesized using a nano-particulation platform technology utilizing fat and supercritical fluid (NUFS™) to resolve the low solubility problem that typically prevents the creation of injectable forms of EGFR-TKIs. The average NUFS-sErt particle size was 236.4 nm, and it showed time-dependent dissolution in culture media. The effects of NUFS-sErt were similar to those of conventional erlotinib in terms of inhibiting the proliferation of EGFR-mutant lung cancer cells and suppressing EGFR signaling. In an intraperitoneal xenograft model of HCC827 cells, intraperitoneal administration of NUFS-sErt produced a dose-dependent inhibition of tumor growth and enhanced survival rate. Notably, the injection of NUFS-sErt into the brain ventricle caused significant tumor growth inhibition in an intracranial xenograft model. Hence, our current findings indicate that NUFS-sErt is a novel, water-soluble form of erlotinib that can be administered using intraventricular or intrathecal injections. The target cases would be patients with a progressive CNS metastasis and no other therapeutic options. This drug could also be given intravenously to patients with swallowing difficulties or an inability to ingest due to a medical condition.

A Longitudinal Analysis of Antiretroviral Adherence Among Young Black Men Who Have Sex With Men.

PURPOSE: Young black men who have sex with men (YBMSM) experience poorer antiretroviral therapy (ART) medication adherence relative to their white counterparts. However, few studies have longitudinally examined factors that may correlate with various classifications of ART adherence among this population, which was the primary aim of this study. METHODS: Project nGage was a randomized controlled trial conducted across five Chicago clinics from 2012 to 2015. Survey and medical records data were collected at baseline and 3- and 12-month periods to assess whether psychological distress, HIV stigma, substance use, family acceptance, social support, and self-efficacy predicted ART medication adherence among 92 YBMSM ages 16-29 years. RESULTS: Major results controlling for the potential effects of age, education level, employment, and intervention condition indicated that participants with high versus low medication adherence were less likely to report daily/weekly alcohol or marijuana use, had higher family acceptance, and exhibited greater self-efficacy. CONCLUSIONS: These findings identity important factors that can be targeted in clinical and program interventions to help improve ART medication adherence for YBMSM.

Inhibitory effects of Saururi chinensis extracts on melanin biosynthesis in B16F10 melanoma cells.

Saururus chinensis has been used in folk medicine in Korea for the treatment of edema, jaundice, gonorrhea, and several inflammatory diseases. Saururi chinensis extracts (SCE) have demonstrated anti-inflammatory and anti-oxidant activities, as well as anti-asthmatic, antihypertensive, anti-angiogenic, and therapeutic activities for atopic dermatitis. However, the inhibitory activity of SCE on the melanogenesis signaling pathway is not completely understood. This study examined the effects of SCE on the melanogenesis signaling pathway activated by α-melanocyte-stimulating hormone (α-MSH). We found that SCE inhibited melanin production in a dose-dependent manner without causing cytotoxicity in B16F10 cells. Interestingly, SCE decreased α-MSH-induced tyrosinase activity in B16F10 cells but did not inhibit tyrosinase activity under cell-free conditions. The results of this study indicate that SCE may reduce pigmentation by way of an indirect, nonenzymatic mechanism. We also found that SCE decreased α-MSH-induced microphthalmia-associated transcription factor (MITF) and tyrosinase expression and induced the activation of extracellular signal-regulated kinase (ERK). These results suggest that the depigmenting effect of SCE may result from downregulation of MITF and tyrosinase expression due to increased ERK activity. Thus, our results provide evidence that SCE might be useful as a potential skin-whitening agent.

Carbon/metal nanotubes with tailored order and configuration by direct carbonization of inverse block copolymer micelles inside nanoporous alumina.

Carbonaceous nanotubes decorated with metal nanoparticles were obtained by heating inverse block copolymer micelles loaded with metal precursors inside nanoporous alumina. Simple changes in the applied temperature profile allowed tailoring of the wall morphology of the nanotubes and the spatial arrangement of the metal nanoparticles.

Ordered arrays of <100>-oriented silicon nanorods by CMOS-compatible block copolymer lithography.

Dense, ordered arrays of <100>-oriented Si nanorods with uniform aspect ratios up to 5:1 and a uniform diameter of 15 nm were fabricated by block copolymer lithography based on the inverse of the traditional cylindrical hole strategy and reactive ion etching. The reported approach combines control over diameter, orientation, and position of the nanorods and compatibility with complementary metal oxide semiconductor (CMOS) technology because no nonvolatile metals generating deep levels in silicon, such as gold or iron, are involved. The Si nanorod arrays exhibit the same degree of order as the block copolymer templates.

Hybrid organic-inorganic nanostructures fabricated from layer-by-layer self-assembled multilayers of hyperbranched polyglycerols and phosphorus dendrimers.

Multilayer thin films of cationic phosphorous dendrimers and anionic hyperbranched polyglycerols were fabricated by electrostatic layer-by-layer (LbL) self-assembly (SA). The film formation was monitored by surface plasmon resonance (SPR) spectroscopy and UV-visible spectroscopy, and it was found that the stepwise, alternating deposition results in a linear growth up to four bilayers. Hybrid organic-TiO2 nanostructures were generated by exposing the supramolecular multilayers to TiCl4 precursors. The amounts of TiO2 incorporated inside the scaffolds could be tuned by controlling the porosity of the multilayers with the addition of a small amount of salts. The resulting hybrid films exhibit characteristic photoluminescence (PL) properties.

Assembly and mechanical properties of phosphorus dendrimer/polyelectrolyte multilayer microcapsules.

We report the preparation, characterization, and mechanical properties of polyelectrolyte/phosphorus dendrimer multilayer microcapsules. The shells of these microcapsules are composed either by alternating poly(styrenesulfonate) (PSS) and positively charged dendrimer G4(NH+Et2Cl-)96 or by alternating poly(allylamine hydrochloride) (PAH) and negatively charged dendrimer G4(CH-COO-Na+)96. The same multilayers were constructed on planar support to examine their layer-by-layer growth and to measure the multilayer thickness. Surface plasmon resonance spectroscopy (SPR) showed regular linear growth of the assembly upon each bilayer deposited. We probe the mechanical properties of these polyelectrolyte/dendrimer microcapsules by measuring force-deformation curves with the atomic force microscope (AFM). The experiment suggests that they are much softer than PSS/PAH microcapsules studied before. This softening is attributed to an enhanced permeability of the polyelectrolyte/dendrimer multilayer shells as compared with multilayers formed by linear polyelectrolytes. In contrast, Young's modulus of both dendrimer-based multilayers was found to be on the same order as that of PSS/PAH multilayers.