Diclofenac transdermal patch versus the sustained release tablet: A randomized clinical trial in rheumatoid arthritic patients

Purpose: To prepare and characterize transdermal films of diclofenac diethanolamine as a safer and more effective alternative than the sustained release (SR) tablet equivalent for prolonged relief from pain and inflammation in arthritis.Methods: Transdermal films of diclofenac were prepared using sodium carboxymethyl cellulose and polyvinyl pyrrolidone K30, with turpentine oil and sesame oil as penetration enhancers. The films were characterized for  physicochemical properties and for ex vivo permeation in a randomized clinical trial(RCT) for analgesic activities in arthritic patients.Results: The transdermal films were uniform in weight and thickness, flat, with high drug content (94.40 ± 1.04 to 98.62 ± 1.08 %) and with high folding endurance (149 ± 9.09 to 192 ± 10.12). Drug permeation through excised rat abdominal skin was prolonged. Films containing penetration enhancers showed higher ex vivo drug permeation than those without the enhancer; furthermore, drug permeation increased with increase in the concentration of enhancer. The films were  non-irritating to the skin. In RCT, F3 (containing turpentine oil, 1 %v/w) decreased the pain score from 9.87 ± 1.14 to 4.94 ± 0.78 units, compared with the SR tablet (once daily) which decreased pain from 9.59 ± 0.42 to 6.49 ± 1.20 units, 48 h post-administration. Turpentine oil showed better permeation enhancement than sesame oil in the transdermal films.Conclusion: Transdermal films of diclofenac, formulated with permeation enhancers, may have greater therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of patient compliance in rheumatoid arthritis.Keywords: Analgesic activity, Diclofenac, Permeation enhancer, Rheumatoid arthritis, Transdermal film

New advances of DNA methylation in liver fibrosis, with special emphasis on the crosstalk between microRNAs and DNA methylation machinery

AbstractEpigenetics refers to the study of heritable changes in the pattern of gene expression that is controlled by a mechanism specifically not due to changes the primary DNA sequence. Well-known epigenetic mechanisms include DNA methylation, post-translational histone modifications and RNA-based mechanisms including those controlled by small non-coding RNAs (miRNAs). Recent studies have shown that epigenetic modifications orchestrate the hepatic stellate cell (HSC) activation and liver fibrosis. In this review we focus on the aberrant methylation of CpG island promoters of select genes is the prominent epigenetic mechanism to effectively silence gene transcription facilitating HSC activation and liver fibrosis. Furthermore, we also discuss epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation and the interaction of DNA methylation with miRNAs involved in the regulation of HSC activation and liver fibrosis. Recent advances in epigenetics alterations in the pathogenesis of liver fibrosis and their possible use as new therapeutic targets and biomarkers

DNA methylation repatterning accompanying hybridization, whole genome doubling and homoeolog exchange in nascent segmental rice allotetraploids

Allopolyploidization, which entails interspecific hybridization and whole genome duplication (WGD), is associated with emergent genetic and epigenetic instabilities that are thought to contribute to adaptation and evolution. One frequent genomic consequence of nascent allopolyploidization is homoeologous exchange (HE), which arises from compromised meiotic fidelity and generates genetically and phenotypically variable progenies. Here, we used a genetically tractable synthetic rice segmental allotetraploid system to interrogate genome‐wide DNA methylation and gene expression responses and outcomes to the separate and combined effects of hybridization, WGD and HEs. Progenies of the tetraploid rice were genomically diverse due to genome‐wide HEs that affected all chromosomes, yet they exhibited overall methylome stability. Nonetheless, regional variation of cytosine methylation states was widespread in the tetraploids. Transcriptome profiling revealed genome‐wide alteration of gene expression, which at least in part associates with changes in DNA methylation. Intriguingly, changes of DNA methylation and gene expression could be decoupled from hybridity and sustained and amplified by HEs. Our results suggest that HEs, a prominent genetic consequence of nascent allopolyploidy, can exacerbate, diversify and perpetuate the effects of allopolyploidization on epigenetic and gene expression variation, and hence may contribute to allopolyploid evolution

Chlamydia psittaci pneumonia in Wuxi, China: retrospective analysis of 55 cases and predictors of severe disease

PurposeMore and more patients with community-acquired pneumonia have been detected with Chlamydia psittaci (C. psittaci) infected using metagenomic next-generation sequencing (mNGS). Previously, this was unheard of, and several patients presented with severe pneumonia and even required ECMO. We aimed to clarify the clinical characteristics of C. psittaci pneumonia and find out if there are any possible predictors of severe C. psittaci pneumonia.MethodsIn this retrospective study, we included all confirmed cases of C. psittaci pneumonia in Wuxi. Epidemiological, clinical, and radiological features, as well as laboratory data, were collected and analyzed.ResultsWe enrolled 55 patients with C. psittaci pneumonia, with 30 (54.5%) having a history of exposure to birds or their internal organs. 50 (90.9%) patients were diagnosed by mNGS. Patients with C. psittaci pneumonia had many complications, among which, that deserve sufficient attention from clinicians were vascular embolic events (3, 5.5%). High fever was the most common clinical manifestation (41, 74.5%). The majority of patients had a significant increase in neutrophils ratio, neutrophils to lymphocytes ratio (NLR), rapid c-reactive protein, creatine kinase (CK), and lactate dehydrogenase (LDH), as well as a decrease in lymphocytes ratio, albumin, serum sodium, serum potassium, and serum phosphorus. Chest computed tomography scans revealed unilateral pneumonia (70.9%), consolidation (87.3%), air bronchogram (76.4%), and ground-glass opacity (69.1%). The neutrophil ratio, NLR, LDH, and CK were all factors that could identify severe pneumonia. Both AUCs exceeded 0.8; the respective 95% CIs were 0.715–0.944, 0.710–0.963, 0.677–0.937, and 0.718–0.950; all p < 0.05 (0.01, 0.001, 0.007, 0.007 respectively). The ORs were 10.057, 9.750, 10.057, and 9.667, respectively; the 95% CIs were 2.643–38.276, 2.339–40.649, and 2.643–38.276, respectively; all p-values were less than 0.05 (0.001, 0.002, 0.001, 0.001 respectively).ConclusionC. psittaci pneumonia is a very complex disease that changes all the time. Some patients showed severe pneumonia. Patients will have a poor prognosis if they are not treated promptly and effectively. We discovered that many clinical indicators were typical. Meanwhile, significant increases in neutrophil ratio, NLR, LDH, and CK predicted severe pneumonia. Timely detection of mNGS provided substantial help for clinical diagnosis and early treatment

Well-width dependence of the emission linewidth in ZnO/MgZnO quantum wells

Photoluminescence (PL) spectra were measured as a function of well width (L(W)) and temperature in ZnO/Mg(0.1)Zn(0.9)O single quantum wells (QWs) with graded thickness. The emission linewidth (full width at half maximum) was extracted from the emission spectra, and its variation as a function of L(W) was studied. The inhomogeneous linewidth obtained at 5 K was found to decrease with increasing L(W) from 1.8 to 3.3 nm due to the reduced potential variation caused by the L(W) fluctuation. Above 3.3 nm, however, the linewidth became larger with increasing L(W), which was explained by the effect related with defect generation due to strain relaxation and exciton expansion in the QW. For the homogenous linewidth broadening, longitudinal optical (LO) phonon scattering and impurity scattering were taken into account. The LO phonon scattering coefficient Γ(LO) and impurity scattering coefficient Γ(imp) were deduced from the temperature dependence of the linewidth of the PL spectra. Evident reduction of Γ(LO) with decreasing L(W) was observed, which was ascribed to the confinement-induced enhancement of the exciton binding energy. Different from Γ(LO), a monotonic increase in Γ(imp) was observed with decreasing L(W), which was attributed to the enhanced penetration of the exciton wave function into the barrier layers

Effect of Laser Pulse Width on the Laser Lift-off Process of GaN Films

Major Research Plan of the National Natural Science Foundation of China [91023048]; National Natural Science Foundation of China [61106044, 10974165]; Doctoral Program Foundation of Institutions of Higher Education of China [20110121110029]Laser lift-off (LLO), by which GaN is separated from sapphire, is demonstrated to be a promising technique for advanced GaN-based optoelectronic devices. Its physical insight, however, is still not fully understood. We study systematically the effect of laser pulse width on the LLO process and the property of GaN. To estimate accurately the temperature distribution and the decomposed thickness of GaN, fluctuation in the pulse laser energy is taken into account. It is found that the temperature at the interface is increased in a higher speed for a narrower pulse width. In addition, less damage to the GaN film is expected for a narrower pulse width owing to the smaller heated area, lower transient temperature and lower N-2 vapor pressure encountered during LLO. Some experimental results reported in literature are explained well. Our results are useful in understanding the effect of laser pulse width and can be taken as references in LLO of GaN/sapphire structures

Tuning Properties of External Cavity Violet Semiconductor Laser

National Natural Science Foundation of China [91023048, 61106044, 61274052]A tunable grating-coupled external cavity (EC) laser is realized by employing a GaN-based laser diode as the gain device. A tuning range of 4.47 nm from 403.82 to 408.29 nm is achieved. Detailed investigations reveal that the injection current strongly influences the performance of the EC laser. Below the free-running lasing threshold, EC laser works stably. While above the free-running lasing threshold, a Fabry-Perot (F-P) resonance peak in the emission spectrum and a smooth kink in the output power-injection current characteristic curve are observed, suggesting the competition between the inner F-P cavity resonance and EC resonance. Furthermore, the tuning range is found to be asymmetric and occurs predominantly on the longer wavelength side. This is interpreted in terms of the asymmetric gain distribution of GaN-based quantum well material

Coevolution in Hybrid Genomes: Nuclear-Encoded Rubisco Small Subunits and Their Plastid-Targeting Translocons Accompanying Sequential Allopolyploidy Events in Triticum

The Triticum/Aegilops complex includes hybrid species resulting from homoploid hybrid speciation and allopolyploid speciation. Sequential allotetra- and allohexaploidy events presumably result in two challenges for the hybrids, which involve 1) cytonuclear stoichiometric disruptions caused by combining two diverged nuclear genomes with the maternal inheritance of the cytoplasmic organellar donor; and 2) incompatibility of chimeric protein complexes with diverged subunits from nuclear and cytoplasmic genomes. Here, we describe coevolution of nuclear rbcS genes encoding the small subunits of Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase) and nuclear genes encoding plastid translocons, which mediate recognition and translocation of nuclear-encoded proteins into plastids, in allopolyploid wheat species. We demonstrate that intergenomic paternal-to-maternal gene conversion specifically occurred in the genic region of the homoeologous rbcS3 gene from the D-genome progenitor of wheat (abbreviated as rbcS3D) such that it encodes a maternal-like or B-subgenome-like SSU3D transit peptide in allohexaploid wheat but not in allotetraploid wheat. Divergent and limited interaction between SSU3D and the D-subgenomic TOC90D translocon subunit is implicated to underpin SSU3D targeting into the chloroplast of hexaploid wheat. This implicates early selection favoring individuals harboring optimal maternal-like organellar SSU3D targeting in hexaploid wheat. These data represent a novel dimension of cytonuclear evolution mediated by organellar targeting and transportation of nuclear proteins