Enhancement of Bone Tissue Regeneration with Multi-Functional Nanoparticles by Coordination of Immune, Osteogenic, and Angiogenic Responses.

Inorganic nanoparticles are promising materials for bone tissue engineering due to their chemical resemblance to the native bone structure. However, most studies are unable to capture the entirety of the defective environment, providing limited bone regenerative abilities. Hence, this study aims to develop a multifunctional nanoparticle to collectively control the defective bone niche, including immune, angiogenic, and osteogenic systems. The nanoparticles, self-assembled by biomimetic mineralization and tannic acid (TA)-mediated metal-polyphenol network (MPN), are released sustainably after the incorporation within a gelatin cryogel. The released nanoparticles display a reduction in M1 macrophages by means of reactive oxygen species (ROS) elimination. Consequently, osteoclast maturation is also reduced, which is observed by the minimal formation of multinucleated cells (0.4%). Furthermore, the proportion of M2 macrophages, osteogenic differentiation, and angiogenic potential are consistently increased by the effects of magnesium from the nanoparticles. This orchestrated control of multiple systems influences the in vivo vascularized bone regeneration in which 80% of the critical-sized bone defect is regenerated with new bones with mature lamellar structure and arteriole-scale micro-vessels. Altogether, this study emphasizes the importance of the coordinated modulation of immune, osteogenic, and angiogenic systems at the bone defect site for robust bone regeneration.

Molecular Characteristics of Catalytic Nitrogen Removal from Coal Tar Pitch over γ-Alumina-Supported NiMo and CoMo Catalysts.

The removal of nitrogen from coal tar pitch (CTP) through the hydrodenitrogenation (HDN) of CTP and its molecular behavior were evaluated in the presence of NiMo/γ-alumina and CoMo/γ-alumina catalysts. Fourier transform ion cyclotron resonance mass spectrometry with atmospheric pressure photoionization was used to analyze the complicated chemical classes and species of CTP and the treated products at the molecular level. Nitrogen species were qualitatively analyzed before and after hydrotreatment. A single-stage hydrotreatment with an HDN catalyst resulted in a high sulfur removal performance (85.6-94.7%) but a low nitrogen removal performance (26.8-29.2%). Based on relative abundance analyses of nitrogen and binary nitrogen species, CcHh-NnSs was the most challenging species to remove during HDN treatment. Furthermore, prior hydrodesulfurization was combined with HDN treatment, and the dual hydrotreatments yielded a significantly improved nitrogen removal performance (46.4-48.7%).

Role of Gasdermin E in the Biogenesis of Apoptotic Cell-Derived Exosomes.

The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in pyroptosis. In this study, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell-derived exosomes. In apoptotic human HeLa and HEK293 cells, GSDMA, GSDMC, GSDMD, and GSDME increased the release of apoptotic exosomes. GSDMB and DFNB59, in contrast, negatively affected the release of apoptotic exosomes. GSDME at its full-length and cleaved forms was localized in the exosomes and exosomal membrane. Full-length and cleaved forms of GSDME are suggested to increase Ca2+ influx to the cytosol through endosomal pores and thus increase the biogenesis of apoptotic exosomes. In addition, the GSDME-mediated biogenesis of apoptotic exosomes depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins, that is, annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of apoptotic exosomes begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that GSDME-bearing tumors released apoptotic exosomes to induce inflammatory responses in the in vivo mouse 4T1 orthotropic model of BALB/c breast cancer. The data indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.

Itch and Janus Kinase Inhibitors.

Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for pruritus in atopic dermatitis, psoriasis, and other diseases, such as prurigo nodularis and lichen planus, with rapid itch relief compared with conventional treatments. The most common adverse effects reported include nasopharyngitis, acne, and elevated blood creatine phosphokinase levels. Janus kinase inhibitors are currently prescribed with warnings about a potential increase in malignancies and cardiovascular diseases and usage in people of older ages. This review aims to provide knowledge about itch and the Janus kinase and signal transducer and activator of transcription pathway and to analyse the current evidence for itch relief by Janus kinase inhibitors.

Effects of CALR-Mutant Type and Burden on the Phenotype of Myeloproliferative Neoplasms.

Somatic CALR mutations occur in approximately 70% of patients with JAK2 V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF). We evaluated the effects of the CALR mutant type and burden on the phenotype of CALR-mutated myeloproliferative neoplasms (MPN). Of the 510 patients with suspected or diagnosed MPN, all 49 patients detected with CALR mutations were diagnosed with ET (n = 32) or PMF (n = 17). The CALR mutant burden was significantly higher in PMF than in ET (45% vs. 34%), and type 1-like and type 2-like mutations were detected in 49% and 51% patients, respectively. Patients with MPN and type 2-like mutation showed a significantly higher median platelet count than those with type 1-like mutation. Particularly, patients with ET and type 2-like mutation had no thrombotic events, despite higher platelet counts. The effect of CALR mutant burden differed depending on the mutant type. A higher mutant burden tended to be associated with a cytopenic phenotype (i.e., lower hemoglobin levels and platelet counts) in patients with the type 1-like mutation and a proliferative hematological phenotype (i.e., higher platelet and neutrophil counts) in patients with the type 2-like mutation. This study suggests that the disease phenotype of MPN may be altered through CALR mutant burden and mutant type.

Utilization of bioelectrical impedance analysis for detection of lymphedema in breast Cancer survivors: a prospective cross sectional study.

BACKGROUND: Breast cancer survivors are at risk of developing breast cancer-related lymphedema (BCRL) after surgical treatment, which may have a negative effect on quality of life. The purpose of this study was to investigate the clinical role of bioelectrical impedance analysis (BIA) and the relationship between the development of BCRL in breast cancer survivors who have undergone axillary surgery. METHODS: A total of 228 patients with breast cancer were enrolled in the study between May 2016 and January 2017. BCRL was assessed by measuring the circumference of both arms at 15 cm below the acromion process and the olecranon process. Patients were classified as BCRL (n = 22) and non-BCRL (n = 206) based on the difference of the arm circumference of 2 cm. Data including lymphedema, anthropometry, BIA measurements, food frequency questionnaire, type of surgery, total number of dissected lymph nodes, and post-operative treatment were collected. RESULTS: Of the breast cancer survivors, 10.4% had BCRL by the definition. The BCRL group contained 22 patients, while the non-BCRL group contained 206 patients. Compared to the non-BCRL group, the BCRL group had a higher body mass index, a larger percentage of ideal body weight, more dissected lymph nodes, and higher single frequency BIA (SFBIA) ratio (P = 0.027, P = 0.031, P < 0.001, and P < 0.001, respectively). The SFBIA ratio provided 63.64% sensitivity and 95.15% specificity in estimating the risk of BCRL. CONCLUSION: Our data provides evidence to support that the use of SFBIA ratio can serve as an alternative method to monitor and/or diagnose BCRL. TRIAL REGISTRATION: This trial was retrospectively registered at Clinicaltrials.gov identifier ( NCT03391206 ) on the 5 January 2018.

WO3/Conducting Polymer Heterojunction Photoanodes for Efficient and Stable Photoelectrochemical Water Splitting.

An efficient and stable heterojunction photoanode for solar water oxidation was fabricated by hybridization of WO3 and conducting polymers (CPs). Organic/inorganic hybrid photoanodes were readily prepared by the electropolymerization of various CPs and the codeposition of tetraruthenium polyoxometalate (Ru4POM) water-oxidation catalysts (WOCs) on the surface of WO3. The deposition of CPs, especially polypyrrole (PPy) doped with Ru4POM (PPy:Ru4POM), resulted in a remarkably improved photoelectrochemical performance by the formation of a WO3/PPy p-n heterojunction and the incorporation of efficient Ru4POM WOCs. In addition, there was also a significant improvement in the photostability of the WO3-based photoanode after the deposition of the PPy:Ru4POM layer due to the suppression of the formation of hydrogen peroxide, which was responsible for corrosion. This study provides insight into the design and fabrication of novel photosynthetic and photocatalytic systems with excellent performance and stability through the hybridization of organic and inorganic materials.