Co-administration of indacaterol and tiotropium bromide for the treatment of chronic obstructive pulmonary disease and bronchiectasis, and effect on IL-8 and CRP levels

Purpose: To investigate the efficacy of indacaterol plus tiotropium bromide in chronic obstructive pulmonary disease (COPD) complicated by bronchiectasis and the impact on IL-8 and C reactive protein (CRP) levels.Methods: Sixty enrolled patients with COPD and bronchiectasis who received treatment in Yantai Qishan Hospital, Yuyan, China from June 2017 to December 2019 were randomly allocated to group A (n = 30) and group B (n = 30). Group A received inhalation of indacaterol plus tiotropium bromide. Group B received only tiotropium bromide inhalation therapy. Therapeutic effects and appropriate serum indicators were compared.Results: Maximal mid-expiratory flow (MMF), maximal voluntary ventilation (MVV), and forced expiratory volume in one second (FEV1.0) levels of the patients were significantly elevated, and group A showed a significantly higher values than group B (p < 0.05). The serum levels of IL-8, CRP, and serum calcitonin (PCT) in both groups were lower than before treatment, but the decrease in group A was significantly greater than that in group B (p < 0.05). The SaO2, PaO2, and PaO2/FiO2 levels in both groups increased, but the increase in group A was higher than that in group B (p < 0.05). Group A showed a significantly lower total incidence of complications than group B (p < 0.05).Conclusion: Indacaterol plus tiotropium bromide produced significant effects in the treatment of COPD with bronchiectasis, which ameliorate lung function and inflammation status in the body and therefore have the potential of being utilized in clinical practice

Preparation and Characterisation of Nobiletin-Loaded Nanostructured Lipid Carriers

The objective of this manuscript was to investigate and optimise the potential of nanostructured lipid carriers (NLCs) as a carrier system for nobiletin (NOB), which was prepared by high-pressure homogenisation method. Additionally, this study was focused on the application of NOB-loaded NLC (NOB-NLC) in functional food. Response surface method with a three-level Box–Behnken design was validated through analysis of variance, and the robustness of the design was confirmed through the correspondence between the values measured in the experiments and the predicted ones. Properties of the prepared NOB-NLC, such as Z-average, polydispersity, entrapment efficiency, zeta potential, morphology, and crystallinity, were investigated. NOB-NLC exhibited a spherical shape with a diameter of 112.27 ± 5.33 nm, zeta potential of −35.1 ± 2.94 mV, a polydispersity index of 0.251 ± 0.058, and an EE of 81.06%  ±  6.02%. Results from X-ray diffraction and differential scanning calorimetry of NOB-NLC reviewed that the NOB crystal might be converted to an amorphous state. Fourier transform infrared spectroscopic analysis demonstrated that chemical interaction was absent between the compound and lipid mixture in NOB-NLC

A Novel YY1-miR-1 Regulatory Circuit in Skeletal Myogenesis Revealed by Genome-Wide Prediction of YY1-miRNA Network

microRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally, and mounting evidence supports the prevalence and functional significance of their interplay with transcription factors (TFs). Here we describe the identification of a regulatory circuit between muscle miRNAs (miR-1, miR-133 and miR-206) and Yin Yang 1 (YY1), an epigenetic repressor of skeletal myogenesis in mouse. Genome-wide identification of potential down-stream targets of YY1 by combining computational prediction with expression profiling data reveals a large number of putative miRNA targets of YY1 during skeletal myoblasts differentiation into myotubes with muscle miRs ranking on top of the list. The subsequent experimental results demonstrate that YY1 indeed represses muscle miRs expression in myoblasts and the repression is mediated through multiple enhancers and recruitment of Polycomb complex to several YY1 binding sites. YY1 regulating miR-1 is functionally important for both C2C12 myogenic differentiation and injury-induced muscle regeneration. Furthermore, we demonstrate that miR-1 in turn targets YY1, thus forming a negative feedback loop. Together, these results identify a novel regulatory circuit required for skeletal myogenesis and reinforce the idea that regulatory circuitries involving miRNAs and TFs are prevalent mechanisms

IKK/NF-κB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis

Nuclear factor κB (NF-κB) is involved in multiple skeletal muscle disorders, but how it functions in differentiation remains elusive given that both anti- and promyogenic activities have been described. In this study, we resolve this by showing that myogenesis is controlled by opposing NF-κB signaling pathways. We find that myogenesis is enhanced in MyoD-expressing fibroblasts deficient in classical pathway components RelA/p65, inhibitor of κB kinase β (IKKβ), or IKKγ. Similar increases occur in myoblasts lacking RelA/p65 or IKKβ, and muscles from RelA/p65 or IKKβ mutant mice also contain higher fiber numbers. Moreover, we show that during differentiation, classical NF-κB signaling decreases, whereas the induction of alternative members IKKα, RelB, and p52 occurs late in myogenesis. Myotube formation does not require alternative signaling, but it is important for myotube maintenance in response to metabolic stress. Furthermore, overexpression or knockdown of IKKα regulates mitochondrial content and function, suggesting that alternative signaling stimulates mitochondrial biogenesis. Together, these data reveal a unique IKK/NF-κB signaling switch that functions to both inhibit differentiation and promote myotube homeostasis

Pax3/7BP Is a Pax7- and Pax3-Binding Protein that Regulates the Proliferation of Muscle Precursor Cells by an Epigenetic Mechanism

SummaryIn mouse skeletal muscles, Pax7 uniquely marks muscle satellite cells and plays some important yet unknown functions at the perinatal stage. To elucidate its in vivo functions, we initiated a yeast two-hybrid screening to look for Pax7-interacting proteins and identified a previously uncharacterized Pax7- and Pax3-binding protein (Pax3/7BP). Pax3/7BP is a ubiquitously expressed nuclear protein, enriched in Pax7+ muscle precursor cells (MPCs), and serves as an indispensable adaptor for Pax7 to recruit the histone 3 lysine 4 (H3K4) methyltransferase (HMT) complex by bridging Pax7 and Wdr5. Knockdown of Pax3/7BP abolished the Pax3/7-associated H3K4 HMT activity and inhibited the proliferation of Pax7+ MPCs from young mice both in culture and in vivo. Id3 and Cdc20 were direct target genes of Pax7 and Pax3/7BP involved in the proliferation of Pax7+ MPCs. Collectively, our work establishes Pax3/7BP as an essential adaptor linking Pax3/7 with the H3K4 HMT to regulate the proliferation of MPCs

Dystrophin glycoprotein complex dysfunction:a regulatory link between muscular dystrophy and cancer cachexia

SummaryCachexia contributes to nearly a third of all cancer deaths, yet the mechanisms underlying skeletal muscle wasting in this syndrome remain poorly defined. We report that tumor-induced alterations in the muscular dystrophy-associated dystrophin glycoprotein complex (DGC) represent a key early event in cachexia. Muscles from tumor-bearing mice exhibited membrane abnormalities accompanied by reduced levels of dystrophin and increased glycosylation on DGC proteins. Wasting was accentuated in tumor mdx mice lacking a DGC but spared in dystrophin transgenic mice that blocked induction of muscle E3 ubiquitin ligases. Furthermore, DGC deregulation correlated positively with cachexia in patients with gastrointestinal cancers. Based on these results, we propose that, similar to muscular dystrophy, DGC dysfunction plays a critical role in cancer-induced wasting

DRAC: Diabetic Retinopathy Analysis Challenge with Ultra-Wide Optical Coherence Tomography Angiography Images

Computer-assisted automatic analysis of diabetic retinopathy (DR) is of great importance in reducing the risks of vision loss and even blindness. Ultra-wide optical coherence tomography angiography (UW-OCTA) is a non-invasive and safe imaging modality in DR diagnosis system, but there is a lack of publicly available benchmarks for model development and evaluation. To promote further research and scientific benchmarking for diabetic retinopathy analysis using UW-OCTA images, we organized a challenge named "DRAC - Diabetic Retinopathy Analysis Challenge" in conjunction with the 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2022). The challenge consists of three tasks: segmentation of DR lesions, image quality assessment and DR grading. The scientific community responded positively to the challenge, with 11, 12, and 13 teams from geographically diverse institutes submitting different solutions in these three tasks, respectively. This paper presents a summary and analysis of the top-performing solutions and results for each task of the challenge. The obtained results from top algorithms indicate the importance of data augmentation, model architecture and ensemble of networks in improving the performance of deep learning models. These findings have the potential to enable new developments in diabetic retinopathy analysis. The challenge remains open for post-challenge registrations and submissions for benchmarking future methodology developments