Contribution of Fcγ receptors to human respiratory syncytial virus pathogenesis and the impairment of T‐cell activation by dendritic cells

Human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization related to respiratory disease. Infection with hRSV produces abundant infiltration of immune cells into the airways, which combined with an exacerbated pro‐inflammatory immune response can lead to significant damage to the lungs. Human RSV re‐infection is extremely frequent, suggesting that this virus may have evolved molecular mechanisms that interfere with host adaptive immunity. Infection with hRSV can be reduced by administering a humanized neutralizing antibody against the virus fusion protein in high‐risk infants. Although neutralizing antibodies against hRSV effectively block the infection of airway epithelial cells, here we show that both, bone marrow‐derived dendritic cells (DCs) and lung DCs undergo infection with IgG‐coated virus (hRSV‐IC), albeit abortive. Yet, this is enough to negatively modulate DC function. We observed that such a process is mediated by Fcγ receptors (FcγRs) expressed on the surface of DCs. Remarkably, we also observed that in the absence of hRSV‐specific antibodies FcγRIII knockout mice displayed significantly less cellular infiltration in the lungs after hRSV infection, compared with wild‐type mice, suggesting a potentially harmful, IgG‐independent role for this receptor in hRSV disease. Our findings support the notion that FcγRs can contribute significantly to the modulation of DC function by hRSV and hRSV‐IC. Further, we provide evidence for an involvement of FcγRIII in the development of hRSV pathogenesis.     

Iron(III) Porphyrin‐Based Porous Material as Photocatalyst for Highly Efficient and Selective Degradation of Congo Red

A highly efficient and selective photocatalyst, UPC‐CMP‐1 has been successfully synthesized by a Sonogashira–Hagihara coupling reaction between iron(III) 5,10,15,20‐tetrakis‐(4′‐bromophenyl) porphine and 1,4‐diethynylbenzene. The scanning electron microscopy shows UPC‐CMP‐1 possesses a dendrite‐like nanostructure. Interestingly, within 120 s, UPC‐CMP‐1 can decompose 88.3% of Congo red (CR) molecules under visible light irradiation. Furthermore, UPC‐CMP‐1 exhibits high selectivity to CR over other dyes. These results reveal that conjugated microporous polymer should be an excellent candidate on the application of dye degradation.

     

美法仑-甘草次酸复合物的合成及其体外抗肿瘤活性研究

目的设计合成美法仑–甘草次酸复合物,并对其体内外抗肿瘤活性进行研究。方法以美法仑和18α-甘草次酸为原料,通过酯化、氧化、酰化和缩合反应制备目标化合物3a和3b,结构经元素分析、MS、1H-NMR确证,并采用MTT法对其体外抗肿瘤活性进行研究,同时考察了其对正常大鼠肝细胞BRL和小鼠成纤维细胞L929的细胞毒性。结果目标化合物3a、3b的体外抗肿瘤活性明显优于母体药物18α-甘草次酸和美法仑,且对正常细胞的毒性小于氮芥类药物美法仑。结论美法仑–甘草次酸复合物3a和3b抗肿瘤活性良好,具有开发成抗肿瘤候选药物的前景。     

Ternary Dinuclear Copper(II) Complexes of a Reduced Schiff Base Ligand with Diimine Coligands: DNA Binding,Cytotoxic Cell Apoptosis,and Apoptotic Mechanism

A serial of mixed‐ligand Cu(II) complexes of the type [Cu(phens)(H₂PDILeu)]H₂O (1 ‐ 4 ) containing phens as 2,2′‐bipyridyl (bpy, 1 ), 1,10‐phenanthroline (phen, 2 ), dipyrido[3,2‐d:2′,3′‐f]quinoxaline (dpq, 3 ), and dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz, 4 ) have been isolated and characterized. The interaction of the complexes with calf‐thymus DNA has been explored by physical methods to propose modes of DNA binding of the complexes, which indicate that 4 interacts with DNA more strongly than all of the other complexes through intercalation interaction. Furthermore, cell apoptosis was detected by AnnexinV/PI flow cytometry and TUNEL assay and by Western blotting to detect the protein expression of p53, Bax, and Bcl‐2. All the three copper complexes can effectively induce apoptosis of the three human tumor cells, which was accompanied with upregulation of the expression of p53 and Bax, while Bcl‐2 decreased.     

In situ-forming PLGA implants loaded with leuprolide acetate/β-cyclodextrin complexes: mathematical modelling and degradation

Drug release mechanism of in situ-forming implants (ISIs) based on poly(lactic acid-co-glycolic acid) (PLGA) loaded with leuprolide acetate/β-cyclodextrin (LA/β-CD) complexes via fitting with four diffusion-based semi-empirical models were studied. The release rate constants and release exponent of ISIs were calculated. The main drug release mechanism was Fickian diffusion. The LA diffusion coefficient and release constant were decreased via increasing the portion of β-CD in complexes. The release curve was parabolic, with a higher initial slope and then consistent with the exponential. All ISIs containing LA/β-CD complexes better fitted with the Korsmeyer–Peppas, Weibull and Peppas–Sahlin models rather than first-order model. Furthermore, the effect of LA/β-CD complexation on the degradation of ISIs was studied through scanning electron microscopy (SEM). Results showed that hydrophilic nature of β-CD facilitated the surface erosion of PLGA chains, however after 18 d, ISI-1/10 had still a proper structural strength, due to no hydrolytic degradation of β-CD in this implant.     

Exploring versatile applications of cyclodextrins: an overview

Context: Ever since the discovery of cyclodextrins, a family of cyclic oligosaccharides based on α (1?→?4) linkage among glucopyranose subunits, these versatile supramolecular hosts have received tremendous attention for scientific explorations. Due to their property of forming host–guest type inclusion complex, cyclodextrins and their synthetic derivatives exhibit wide range of utilities in different areas viz. pharmaceuticals, drug delivery systems, cosmetics, food and nutrition, textile and chemical industry etc.

Objective: The purpose of this review is to highlight properties, advantages, recent studies and versatile benefits of cyclodextrins and to re-strengthen their prospective applications in novel directions for future research.

Methods: This article summarizes a variety of applications of cyclodextrins in various industrial products, technologies, analytical and chemical processes and recent industrial advancements by extensively literature search on various scientific databases, Google and websites of various associated pharmaceutical industries and patenting authorities across the world.

Results and conclusion: Due to possibility of multidimensional changes in physical and chemical properties of molecules upon inclusion complexation in cyclodextrins, these compounds are of great commercial interest and may offer solution to many of the scientific problems of the current world.     

Cloning and expression of a Porphyromonas gingivalis gene for protoporphyrinogen oxidase by complementation of a hemG mutant of Escherichia coli

Porphyromonas gingivalis, a bacterium implicated in periodontal pathogenesis, has a growth requirement for iron protoporphyrin IX. By complementation with a P. gingivalis 381 chromosomal DNA library, we were able to isolate a clone that enhanced the poor growth of a hemG mutant of Escherichia coli. The DNA sequence analysis of this clone revealed three open reading frames (ORFs). ORF3 encoded a protein of 466 amino acids with a calculated molecular weight of 51 695 Da. The deduced amino acid sequence of the ORF3 gene had significant similarity to sequences of protoporphyrinogen oxidase (PPO) from Myxococcus xanthus (30% identical residues). When the ORF3 gene was overexpressed in E. coli, the extract had much higher PPO activity than a control extract, and this activity was inhibited by acifluorfen, a specific inhibitor of PPO. Thus, ORF3 was named PgHemG. Furthermore, several porphyrin-related genes, including hemD, hemN and hemH, were identified in the data bases on the websites available on-line. We postulated that a porphyrin biosynthetic pathway to heme from preuroporphyrin may be conserved in P. gingivalis.     

Ion-exchange voltammetry of tris(2,2′-bipyridyl) ruthenium(II), iron(II), osmium(II) and tris(2,2′-bipyrazyl) ruthenium(II) in acetonitrile solutions at poly(ester-sulphonate) coated electrodes

Glassy carbon electrodes modified with the poly(ester-sulphonate) ionomer Kodak AQ 55 D are used and characterized in acetonitrile solutions. The potential window accessible in acetonitrile + tetrabutylammonium hexafluorophosphate extends from ?1.750 V to +1.900 V vs. an aqueous KCl saturated Ag/vbAgCl reference electrode.The electrochemical behaviour of [Ru(bpy)₃]²⁺, [Fe(bpy)₃]²⁺, [Os(bpy)₃]²⁺ and [Ru(bpz)₃]²⁺ (where bpy = 2,2′bipyridyl and bpz = 2,2′bipyrazyl) is studied at the modified electrode. All the electroactive cations are preconcentrated efficiently in the polymeric coating. In the case of bpy complexes both a one-electron oxidation as well as two one-electron steps of the stepwise reduction of the starting complex are detected at the modified electrode.In the case of [Ru(bpz)₃]²⁺, three consecutive reduction steps can be observed, while no oxidation process is observed in the direct positive scan before reaching the upper limit of the potential range accessible at the modified electrode.The relative order in the ion-exchange selectivity coefficients in acetonitrile solutions for the cations studied is evaluated by comparison with the electrochemical behaviour observed at unmodified electrodes. The possibility of gaining information on preconcentration effects for ion-exchange voltammetry in non-aqueous solvents from the Gibbs energies of transfer from water to hydrophobic media is also discussed.     

Covalent modification of a glassy carbon surface by electrochemical oxidation of r-aminobenzene sulfonic acid in aqueous solution

R-aminobenzene sulfonic acid (r-ABSA) was covalently modified on a glassy carbon electrode (GCE) by electrochemical oxidation in 0.1 M KCl aqueous solution. The presence of an r-ABSA monolayer on the GCE was proven by X-ray photoelectron spectroscopy (XPS). Electron transfer to Fe(CN)₆^3? was investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) on the modified electrodes in solutions of various pHs. Changes in the solution pH value result in the variation of the terminal group (sulfonic acid group) charge state, based on which its surface pK_a values are estimated. The r-ABSA monolayer film on GCE has good stability and can be used as a charge-rich precursor to assemble oppositely charged species by layer-by-layer electrostatic interaction. For example, multilayer films of anionic Fe(III) tetrakis(p-sulfonatophenyl) porphyrin (FeTSPP) and cationic polymer diazo-resins (DAR) can be obtained on the r-ABSA/GCE based on electrostatic and covalently attached interaction and the resulting modified electrodes have good electrochemical response and stability.