Porous organic framework membranes based on interface-induced polymerisation: design, synthesis and applications.

Porous organic frameworks (POFs) are novel porous materials that have attracted much attention due to their extraordinary properties, such as high specific surface area, tunable pore size, high stability and ease of functionalisation. However, conventional synthesised POFs are mostly large-sized particles or insoluble powders, which are difficult to recycle and have low mass transfer efficiencies, limiting the development of their cutting-edge applications. Therefore, processing POF materials into membrane structures is of great significance. In recent years, interface engineering strategies have proved to be efficient methods for the formation of POF membranes. In this perspective, recent advances in the use of interfaces to prepare POF membranes are reviewed. The challenges of this strategy and the potential applications of the formed POF membranes are discussed.

Tailored preparation of porous aromatic frameworks in a confined environment.

The growth of porous aromatic frameworks (PAFs) on the surface of polymer brushes is reported for the first time. In contrast to PAFs formed in solution, polymer brushes provide a confined environment for PAF growth, resulting in nanosized and homogeneous spherical PAFs formed amongst the polymer brushes. 4-Bromobenzene functionalities from the polymer brushes are utilized to induce PAF growth by a Yamamoto-type Ullman coupling reaction. The size of PAFs can be tailored from 30 nm to 500 nm by subtly changing the structural parameters: e.g. reaction time, grafting density, and concentration of 4-bromobenzene on the surface. The established strategy is not only applicable to the preparation of PAF-1, but can also be extended to the controlled preparation of PAF-5. In addition, free-standing and flexible PS/PAF-1 hybrid membranes are obtained via dissolving the oxidized layer between the polymer layer and the silicon substrate, which can be transferred to any flat substrate. The obtained PS/PAF-1 membrane is proven to show high efficiency in removing dye from water and is promising for eliminating other foulants, such as microorganisms and trace organics.

7-Amino acid peptide (7P) decreased airway inflammation and hyperresponsiveness in a murine model of asthma.

A 7-amino acid peptide (7P), (Gly-Gln-Thr-Tyr-Thr-Ser-Gly) is one of the synthesized mimic polypeptides, which is the second envelope protein at hypervariable region 1 of chronic hepatitis C virus (HCV HVR1). It contributed to the anti-inflammatory reaction and inhibited lung Th9 responses in asthma through binding to CD81. In this study, we examined the effects of 7P on bronchoconstriction, acute inflammation of the airways, and lung Th2-type responses during allergic lung inflammation. Our results determined that 7P decreased bronchoconstriction and inhibited both acute inflammatory cytokines (TNFα, IL-1ß, and IL-6) and Th2 cell cytokine responses (IL-5, IL-4, and IL-13) during allergic lung inflammation. 7P directly inhibited lung Th2 cell differentiation (7P: 5.1% vs. vehicle:12.2% and control 7P:12.2%) and suppressed airway inflammatory cytokine signal transduction to decrease Th2 cell response. Overall, 7P significantly decreased airway hyperresponsiveness (AHR), airway inflammation, and Th2 responses, which may serve as a novel therapeutic candidate during allergic lung inflammation.

A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung Inflammation.

T helper (Th) cells orchestrate allergic lung inflammation in asthma pathogenesis. Th9 is a novel Th cell subset that mainly produces IL-9, a potent proinflammatory cytokine in asthma. A 7-amino acid peptide (7P) of the hypervariable region 1 (HVR1) of hepatitis C virus has been identified as an important regulator in the type 2 cytokine (IL-4, IL-5, and IL-13) immune response. However, it is unknown whether 7P regulates Th9 cell differentiation during ovalbumin- (OVA-) induced allergic lung inflammation. To address this, we studied wild-type mice treated with 7P and a control peptide in an in vivo mouse model of OVA-induced allergic inflammation and an in vitro cell model of Th9 differentiation, using flow cytometry, cytokine assays, and quantitative PCR. The binding of 7P to CD81 on naïve CD4+ T cells during lung Th9 differentiation was determined using CD81 overexpression and siRNA knockdown analyses. Administration of 7P significantly reduced Th9 cell differentiation after OVA sensitization and exposure. 7P also inhibited Th9 cell differentiation from naïve and memory CD4+ T cells in vitro. Furthermore, 7P inhibited the differentiation of human Th9 cells with high CD81 expression from naïve CD4+ T cells by blocking CD81 signaling. CD81 siRNA significantly reduced Th9 cell differentiation from naïve CD4+ T cells in vitro. Interestingly, CD81 overexpression in human naïve CD4+ T cells also enhanced Th9 development in vitro. These data indicate that 7P may be a good candidate for reducing IL-9 production in asthma.

Peptide PD29 treats bleomycin-induced pulmonary fibrosis by inhibiting the TGF-ß/smad signaling pathway.

Pulmonary fibrosis (PF) is an end-stage change in lung disease characterized by fibroblast proliferation, massive extracellular matrix (ECM) aggregation with inflammatory damage, and severe structural deterioration. PD29 is a 29-amino acid peptide which has the potential to alleviate PF pathogenesis via three mechanisms: anti-angiogenesis, inhibition of matrix metalloproteinase activities, and inhibition of integrins. In this study, fibrotic lung injuries were induced in SD rats by a single intratracheal instillation of 5 mg/kg bleomycin (BLM). Then, these rats were administered 7.5, 5, or 2.5 mg/kg PD29 daily for 30 days. BLM induced-syndromes including structure distortion, excessive deposition of ECM, excessive inflammatory infiltration, and pro-inflammatory cytokine release were used to evaluate the protective effect of PD-29. Oxidative stress damage in lung tissues was attenuated by PD29 in a dose-dependent manner. The expression of TGF-ß1 and the phosphorylation of Smad-2/-3-its downstream targets-were enhanced by BLM and weakened by PD29. In vitro, PD29 inhibited TGF-ß1-induced epithelial-mesenchymal transition (EMT) and transformation in A549 cells and mouse primary fibroblasts into myofibroblasts. In summary, PD29 reversed EMT and transformation of fibroblasts into myofibroblasts in vitro and prevented PF in vivo possibly by suppressing the TGF-ß1/Smad pathway.

The wound healing potential of collagen peptides derived from the jellyfish Rhopilema esculentum.

PURPOSE: Wound represents a major health challenge as they consume a large amount of healthcare resources to improve patient's quality of life. Many scientific studies have been conducted in search of ideal biomaterials with wound-healing activity for clinical use and collagen has been proven to be a suitable candidate biomaterial. This study intended to investigate the wound healing activity of collagen peptides derived from jellyfish following oral administration. METHODS: In this study, collagen was extracted from the jellyfish--Rhopilema esculentum using 1% pepsin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fourier transform infrared (FTIR) were used to identify and determine the molecular weight of the jellyfish collagen. Collagenase II, papain and alkaline proteinase were used to breakdown jellyfish collagen into collagen peptides. Wound scratch assay (in vitro) was done to determine migration potential of human umbilical vein endothelial cells (HUVEC) covering the artificial wound created on the cell monolayer following treatment with collagen peptides. In vivo studies were conducted to determine the effects of collagen peptides on wound healing by examining wound contraction, re-epithelialization, tissue regeneration and collagen deposition on the wounded skin of mice. Confidence level (p < 0.05) was considered significant using GraphPad Prism software. RESULTS: The yield of collagen was 4.31%. The SDS-PAGE and FTIR showed that extracted collagen from jellyfish was type I. Enzymatic hydrolysis of this collagen using collagenase II produced collagen peptides (CP1) and hydrolysis with alkaline proteinase/papain resulted into collagen peptides (CP2). Tricine SDS-PAGE revealed that collagen peptides consisted of protein fragments with molecular weight <25 kDa. Wound scratch assay showed that there were significant effects on the scratch closure on cells treated with collagen peptides at a concentration of 6.25 µg/mL for 48 h as compared to the vehicle treated cells. Overall treatment with collagen peptide on mice with full thickness excised wounds had a positive result in wound contraction as compared with the control. Histological assessment of peptides treated mice models showed remarkable sign of re-epithelialization, tissue regeneration and increased collagen deposition. Immunohistochemistry of the skin sections showed a significant increase in ß-fibroblast growth factor (ß-FGF) and the transforming growth factor-ß1 (TGF-ß1) expression on collagen peptides treated group. CONCLUSION: Collagen peptides derived from the jellyfish-Rhopilema esculentum can accelerate the wound healing process thus could be a therapeutic potential product that may be beneficial in wound clinics in the future.

Rationally Designed α-Conotoxin Analogues Maintained Analgesia Activity and Weakened Side Effects.

A lack of specificity is restricting the further application of conotoxin from Conus bullatus (BuIA). In this study, an analogue library of BuIA was established and virtual screening was used, which identified high α7 nicotinic acetylcholine receptor (nAChR)-selectivity analogues. The analogues were synthesized and tested for their affinity to functional human α7 nAChR and for the regulation of intracellular calcium ion capacity in neurons. Immunofluorescence, flow cytometry, and patch clamp results showed that the analogues maintained their capacity for calcium regulation. The results of the hot-plate model and paclitaxel-induced peripheral neuropathy model indicated that, when compared with natural BuIA, the analgesia activities of the analogues in different models were maintained. To analyze the adverse effects and toxicity of BuIA and its analogues, the tail suspension test, forced swimming test, and open field test were used. The results showed that the safety and toxicity of the analogues were significantly better than BuIA. The analogues of BuIA with an appropriate and rational mutation showed high selectivity and maintained the regulation of Ca2+ capacity in neurons and activities of analgesia, whereas the analogues demonstrated that the adverse effects of natural α-conotoxins could be reduced.

Deoxycholic acid inhibits the growth of BGC-823 gastric carcinoma cells via a p53­mediated pathway.

The aim of the present study was to investigate the effects of deoxycholic acid (DCA) on BGC­823 human gastric carcinoma cells and to explore the possible mechanisms underlying any such effects. Cell proliferation was detected using a 3­(4,5­Dimethylthiazol­2­yl)­2,5­diphenyl tetrazolium bromide assay, cell morphology was observed by inverted microscopy, and cell cycle progression and the mitochondrial membrane potential were analyzed using flow cytometry. The expression of Bcl­2, Bax, p53, Cyclin D1 and cyclin­dependent kinase (CDK)2 proteins in BGC­823 cells was analyzed with western blotting. The results demonstrated that DCA significantly inhibited cell growth, and that the cell cycle was arrested at the G1 phase. DCA was also shown to induce BGC­823 cell apoptosis, which was associated with the collapse of the mitochondrial membrane potential. The mitochondria­dependent pathway was activated via an increase in the ratio of Bax:Bcl­2 in BGC­823 cells. In addition, the expression of p53, cyclin D1 and CDK2 was altered following DCA treatment. These results suggest that DCA induces apoptosis in gastric carcinoma cells through activation of an intrinsic mitochondrial­dependent pathway, in which p53 is involved.