Improvement of side-effects and treatment on the experimental colitis in mice of a resin microcapsule-loading hydrocortisone sodium succinate.

Context: Extensive or long-time use of corticosteroids often causes many toxic side-effects. The ion exchange resins and the coating material, Eudragit, can be used in combination to form a new oral delivery system to deliver corticosteroids.

Objectives: The resin microcapsule (DRM) composed by Amberlite 717 and Eudragit S100 was used to target hydrocortisone (HC) to the colon in order to improve its treatment effect on ulcerative colitis (UC) and reduce its toxic side-effects.

Activation of biologically relevant levels of reactive oxygen species by Au/g-CN hybrid nanozyme for bacteria killing and wound disinfection.

As common reactive oxygen species, HO is widely used for bacterial inactivation and wound disinfection. However, the concentrations used are always higher than physiological levels, which frequently result in potential toxicity to healthy tissue and even delay wound healing. Here we report highly efficient nanozyme hybrids that are capable of activating biologically relevant concentrations of HO for defending bacterial infections.

Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance.

In this study, a type of multifunctional mixed micelles were prepared by a novel biodegradable amphiphilic polymer (MPEG-SS-2SA) and a multidrug resistance (MDR) reversal agent (d-α-tocopheryl polyethylene glycol succinate, TPGS). The mixed micelles could achieve rapid intracellular drug release and reversal of MDR. First, the amphiphilic polymer, MPEG-SS-2SA, was synthesized through disulfide bonds between poly (ethylene glycol) monomethyl ether (MPEG) and stearic acid (SA).

Embedding magnetic nanoparticles into coordination polymers to mimic zinc ion transporters for targeted tumor therapy.

Magnetic nanoparticle-embedded coordination polymers could act as mimics for zinc ion transporters for targeted cancer therapy. Compared with traditional zinc ionophores, our system could realize targeted and internal environment responsive transport of zinc ions to suppress the tumour growth while minimizing nonspecific injury to normal tissues.

Development and validation of a rapid and sensitive UPLC-MS/MS method for quantification of kukoamine B in human plasma: Application to a clinical pharmacokinetic study.

A rapid, accurate and robust method was firstly developed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay to quantify kukoamine B, which is a novel drug under clinical development for the treatment of sepsis, in human plasma. Solid-phase extraction (SPE) was used to extract kukoamine B from human plasma. The extracts were separated on a Waters Acquity HSS T3 column (2.

Bacterial Hyaluronidase Self-Triggered Prodrug Release for Chemo-Photothermal Synergistic Treatment of Bacterial Infection.

A novel platform for targeted on-demand prodrug ascorbic acid (AA) delivery is fabricated using a bacterial hyaluronidase sensitive graphene-mesoporous silica nanosheet@hyaluronic acid-magnetic nanoparticles as the nanocarrier to treat bacterial infections. The released AA can be converted to detrimental •OH in situ on the surface of bacteria. With the chemo-photothermal synergistic effect, the designed antibacterial system can effectively inactivate bacteria and disperse stubborn biofilm.

NBLDA: negative binomial linear discriminant analysis for RNA-Seq data.

Background: RNA-sequencing (RNA-Seq) has become a powerful technology to characterize gene expression profiles because it is more accurate and comprehensive than microarrays. Although statistical methods that have been developed for microarray data can be applied to RNA-Seq data, they are not ideal due to the discrete nature of RNA-Seq data. The Poisson distribution and negative binomial distribution are commonly used to model count data.

Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid.

Context 3,4-Oxo-isopropylidene-shikimic acid (ISA) is an analog of shikimic acid (SA). SA is extracted from the dry fruit of Illicium verum Hook. f.

Copper(II)-Graphitic Carbon Nitride Triggered Synergy: Improved ROS Generation and Reduced Glutathione Levels for Enhanced Photodynamic Therapy.

Graphitic carbon nitride (g-C3 N4 ) has been used as photosensitizer to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). However, its therapeutic efficiency was far from satisfactory. One of the major obstacles was the overexpression of glutathione (GSH) in cancer cells, which could diminish the amount of generated ROS before their arrival at the target site.

Quality of Life in Patients After Maxillectomy and Placement of Prosthetic Obturator.

Purpose: The aim of this study was to assess quality of life (QoL) and obturator functioning in patients having undergone a maxillectomy as a tumor ablative resection and rehabilitation with a prosthetic obturator.

Materials And Methods: The University of Washington Quality of Life scale version 4 (UW-QoLv4) and the Obturator Functioning Scale (OFS) were used to evaluate the self-reported QoL and obturator functioning. The effects of demographic and treatment variables on QoL were assessed using age, defect size, postoperative radiotherapy (RT), neck dissection, and dentition.

Ultra performance liquid chromatography tandem mass spectrometry assay for determination of kukoamine B in human blood and urine.

In this paper, we report a sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method which is capable of quantifying kukoamine B (KB) levels in human blood and urine. Following solid phase extraction and direct dilution process, the analyte and its internal standard (D5-KB) run on an Acquity UPLC(®) HSS T3 column (2.1×50mm i.

Ceria/POMs hybrid nanoparticles as a mimicking metallopeptidase for treatment of neurotoxicity of amyloid-β peptide.

Protein misfolding to amyloid aggregates is the hallmark for neurodegenerative disease. While much attention has been paid to screen natural proteases that can degrade amyloid-β peptides (Aβ), it is difficult to apply them in the clinics with the intractable problem of immunogenicity in living organisms. Herein, we rationally designed an artificial nanozyme, Ceria/Polyoxometalates hybrid (CeONP@POMs) with both proteolytic and superoxide dismutase (SOD) activities.

A β-Lactamase-Imprinted Responsive Hydrogel for the Treatment of Antibiotic-Resistant Bacteria.

Antibiotics play important roles in infection treatment and prevention. However, the effectiveness of antibiotics is now threatened by the prevalence of drug-resistant bacteria. Furthermore, antibiotic abuse and residues in the environment cause serious health issues.

Synergistic eradication of antibiotic-resistant bacteria based biofilms in vivo using a NIR-sensitive nanoplatform.

In this work, a novel multifunctional NIR-sensitive nanoplatform has been developed for synergistic eradication of antibiotic-resistant bacteria based biofilms in vitro and in vivo. With high biocompatibility and an outstanding synergistic effect, our system provides a promising avenue to preventing and combating biofilm-associated infections.

Nicotine Induces Cardiomyocyte Hypertrophy Through TRPC3-Mediated Ca/NFAT Signalling Pathway.

Background: Nicotine is thought to be an important risk factor for the development of cardiovascular diseases. However, the effects of nicotine on cardiomyocyte hypertrophy are poorly understood. The present study was designed to explore the role of nicotine in cardiomyocyte hypertrophy and its underlying mechanism.

A multifunctional upconverting nanoparticle incorporated polycationic hydrogel for near-infrared triggered and synergistic treatment of drug-resistant bacteria.

Recently, antibiotic drug-resistant therapies have become very important due to the emergence of antibiotic-resistant bacterial strains. The development of novel antibacterial materials has received significant attention. Here, quaternized chitosan hydrogels incorporated with NaYF4:Er/Yb/Mn@photosensitizer-doped silica (UCNPs/MB) were synthesized for effective killing of both gram-positive oxacillin-resistant S.

Microarray analysis unmasked two siblings with pure hereditary spastic paraplegia shared a run of homozygosity region on chromosome 3q28-q29.

Hereditary spastic paraplegia (HSP) is a clinical and genetic heterogeneity group of neurodegenerative disorders which is characterized by progressive weakness and spasticity of the lower limbs. More than 70 genetic types of HSP have been described so far. Here we describe a Chinese non-consanguineous family with two affected siblings manifesting early-onset autosomal recessive HSP in pure forms.

Somatic copy number losses on chromosome 9q21.33q22.33 encompassing the PTCH1 loci associated with cardiac fibroma.

Cardiac fibroma is an extremely rare benign tumor that remains poorly characterized genetically. Somatic copy number alterations are common in tumors and have been defined as a crucial factor leading to tumors. In this study, we present a child diagnosed with cardiac fibroma with somatic copy number losses of a total of three discontinuous segments from 9q21.

Biomimetic nanoassembly for targeted antigen delivery and enhanced Th1-type immune response.

A new type of biomimetic nanoassembly for targeted antigen delivery and enhanced Th1-type response is reported for the first time, to combat the major challenges in the treatment of infected cells.

Phosphorylation of Beet black scorch virus coat protein by PKA is required for assembly and stability of virus particles.

Plant virus coat proteins (CPs) play a fundamental role in protection of genomic RNAs, virion assembly, and viral movement. Although phosphorylation of several CPs during virus infection have been reported, little information is available about CP phosphorylation of the spherical RNA plant viruses. Here, we demonstrate that the CP of Beet black scorch virus (BBSV), a member of the genus Necrovirus, can be phosphorylated at threonine-41 (T41) by cAMP-dependent protein kinase (PKA)-like kinase in vivo and in vitro.

In vitro and in vivo application of pH-sensitive colon-targeting polysaccharide hydrogel used for ulcerative colitis therapy.

The aim of this study was to prepare, characterize novel types of pH-sensitive konjac gum-xanthan gum-glycerol-sodium alginate hydrogel (KGM-XG-GLY-SA hydrogel) allowing for the site-specific delivering of drugs to the colon and evaluate its colon-targeting characteristic. In this study, hydrophilic drug of hydrocortisone sodium succinate (HSS) was chosen as a model drug and successfully loaded in hydrogel without any organic solvent. In vitro investigations were carried out to evaluate its release process.

Investigation of the colon-targeting, improvement on the side-effects and therapy on the experimental colitis in mouse of a resin microcapsule loading dexamethasone sodium phosphate.

Context: Dexamethasone is the major drug in the treatment of ulcerative colitis (UC). However, the extensive or long-time use of dexamethasone causes many toxic side-effects. Ion exchange resins react with external-ions through their own functional groups and Eudragit S occurs degradation when pH > 7.

Two amino acids near the N-terminus of Cucumber mosaic virus 2b play critical roles in the suppression of RNA silencing and viral infectivity.

Cucumber mosaic virus (CMV) 2b suppresses RNA silencing primarily through the binding of double-stranded RNA (dsRNA) of varying sizes. However, the biologically active form of 2b remains elusive. Here, we demonstrate that the single and double alanine substitution mutants in the N-terminal 15th leucine and 18th methionine of CMV 2b exhibit drastically attenuated virulence in wild-type plants, but are efficiently rescued in mutant plants defective in RNA-dependent RNA polymerase 6 (RDR6) and Dicer-like 4 (DCL4).

Different concentrations of glucose regulate proliferation and osteogenic differentiation of osteoblasts via the PI3 kinase/Akt pathway.

Introduction: The aim of this study was to investigate the effect of high glucose levels on proliferation and osteogenic ability in MC3T3-E1 osteoblastic cell line and to explore the regulatory mechanism of PI3 kinase (PI3K)/Akt signaling pathway.

Methods: The cultures were divided into 8 treatment groups: 4 concentrations of glucose (5.5, 15.

Assessment of the safety, targeting, and distribution characteristics of a novel pH-sensitive hydrogel.

In our previous study, we synthesized a pH-sensitive hydrogel based on poly (ɛ-caprolactone) (PCL), Pluronic (Poloxamer) and methacrylic acid (MAA) using UV-initiated free-radical polymerization. In the present study, we evaluated the safety of the obtained GMA-PCFC-GMA copolymer and a P(CFC-MAA-MEG) hydrogel both in vitro and in vivo. The pharmacokinetics study and distribution characteristics of dexamethasone in rat blood and mouse colon were investigated in detail.