RNA-Seq analysis for indigo biosynthesis pathway genes in Indigofera tinctoria and Polygonum tinctorium

AbstractNatural indigo is the most important blue dye for textile dyeing and valuable secondary metabolite biosynthesized in Indigofera tinctoria and Polygonum tinctorium plants. Present investigation is made to generation of gene resource for pathway enrichment and to understand possible gene expression involved in indigo biosynthesis. The data about raw reads and the transcriptome assembly project has been deposited at GenBank under the accessions SRA180766 and SRX692542 for I. tinctoria and P. tinctorium, respectively

低出力パルス超音波は自己免疫疾患での唾液腺炎による唾液分泌低下を改善する

Introduction: Low-intensity pulsed ultrasound (LIPUS) has been known to promote bone healing by nonthermal effects. In recent studies, LIPUS has been shown to reduce inflammation in injured soft tissues. Xerostomia is one of the most common symptoms in Sjögren syndrome (SS). It is caused by a decrease in the quantity or quality of saliva. The successful treatment of xerostomia is still difficult to achieve and often unsatisfactory. The aim of this study is to clarify the therapeutic effects of LIPUS on xerostomia in SS. Methods: Human salivary gland acinar (NS-SV-AC) and ductal (NS-SV-DC) cells were cultured with or without tumor necrosis factor-α (TNF-α; 10 ng/ml) before LIPUS or sham exposure. The pulsed ultrasound signal was transmitted at a frequency of 1.5 MHz or 3 MHz with a spatial average intensity of 30 mW/cm2 and a pulse rate of 20 %. Cell number, net fluid secretion rate, and expression of aquaporin 5 (AQP5) and TNF-α were subsequently analyzed. Inhibitory effects of LIPUS on the nuclear factor κB (NF-κB) pathway were determined by Western blot analysis. The effectiveness of LIPUS in recovering salivary secretion was also examined in a MRL/MpJ/lpr/lpr (MRL/lpr) mouse model of SS with autoimmune sialadenitis. Results: TNF-α stimulation of NS-SV-AC and NS-SV-DC cells resulted in a significant decrease in cell number and net fluid secretion rate (p < 0.01), whereas LIPUS treatment abolished them (p < 0.05). The expression changes of AQP5 and TNF-α were also inhibited in LIPUS treatment by blocking the NF-κB pathway. Furthermore, we found that mRNA expression of A20, a negative feedback regulator, was significantly increased by LIPUS treatment after TNF-α or interleukin 1β stimulation (NS-SV-AC, p < 0.01; NS-SV-DC, p < 0.05). In vivo LIPUS exposure to MRL/lpr mice exhibited a significant increase in both salivary flow and AQP5 expression by reducing inflammation in salivary glands (p < 0.01). Conclusions: These results suggest that LIPUS upregulates expression of AQP5 and inhibits TNF-α production. Thus, LIPUS may restore secretion by inflamed salivary glands. It may synergistically activate negative feedback of NF-κB signaling in response to inflammatory stimulation. Collectively, LIPUS might be a new strategic therapy for xerostomia in autoimmune sialadenitis with SS

Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia

Simple Summary Tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of chronic myeloid leukemia (CML). Recently, TKIs were discontinued in patients with CML with deep molecular remission, and some patients have been reported to be able to maintain long-term treatment-free remission (TFR). However, there is no certainty regarding which patients can maintain TFR. We focused on immunity in the TFR phase and investigated the immunological mechanism of continuous TFR or recurrence. Our results suggest that the group that maintains the TFR is immunologically activated. In addition, regulatory T cells can be used as a biomarker. These results may have important implications for future strategies for maintaining TFR in CML treatment. Treatment-free remission (TFR) has become a therapeutic goal in chronic myeloid leukemia (CML), and approximately half of the patients with chronic phase-CML (CML-CP) with deep molecular remission (DMR) by tyrosine-kinase inhibitors (TKIs) have achieved TFR. However, the mechanism of continuous TFR is still unclear, as there are fluctuate patients who have BCR-ABL-positive leukemia cells but do not observe obvious relapse. We focused on the immune response and conducted an immune analysis using clinical samples from the imatinib discontinuation study, JALSG-STIM213. The results showed that, in the group that maintained TFR for 3 years, changes in regulatory T (Treg) cells were observed early after stopping imatinib treatment. The effector Treg (eTreg) cells increased transiently at 1 month after stopping imatinib and then returned to baseline at 3 months after stopping imatinib treatment. There was no difference in the Treg phenotype, and CD8(+) T cells in the TFR group were relatively activated. High concentrations of imatinib before stopping were negatively correlated with eTreg cells after stopping imatinib. These data suggest immunological involvement in the maintenance of the TFR, and that Treg cells after stopping imatinib might be a biomarker for TFR. Furthermore, high imatinib exposure may have a negative immunological impact on the continuous TFR

Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients

Background Axitinib is an oral, potent and selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3. We report on data obtained from 18 Japanese patients with advanced solid tumors in two phase I trials that evaluated the safety, pharmacokinetics and antitumor activity of axitinib and also examined potential biomarkers. Methods Six patients received a single 5-mg dose of axitinib followed by 5 mg twice daily (BID), and an additional six patients received axitinib 5 mg BID only. Another six patients received axitinib at 5-mg, 7-mg and 10-mg single doses followed by 5 mg BID. Results Plasma pharmacokinetics following single doses of axitinib was generally linear. Common treatment-related adverse events were fatigue (83%), anorexia (72%), diarrhea (67%), hand–foot syndrome (67%) and hypertension (61%). Sixteen patients (89%) experienced thyroid-stimulating hormone (TSH) elevation. Grade 3/4 toxicities included hypertension (33%) and fatigue (28%). No grade 3/4 fatigue occurred in patients who started thyroid hormone replacement therapy when TSH was elevated. Thyroglobulin elevation was observed in all patients who continued treatment with axitinib for ≥3 months. Abnormal TSH correlated with exposure to axitinib (r = 0.72). Decrease in soluble (s) VEGFR-2 levels significantly correlated with exposure to axitinib (r = –0.94). Axitinib showed antitumor activity across multiple tumor types. Conclusions Axitinib-related thyroid dysfunction could be due to a direct effect on the thyroid gland. Grade 3/4 fatigue and hypothyroidism appear to be controllable with use of thyroid hormone replacement therapy. sVEGFR-2 and TSH may act as biomarkers of axitinib plasma exposure

The Discovery of LOX-1, its Ligands and Clinical Significance

LOX-1 is an endothelial receptor for oxidized low-density lipoprotein (oxLDL), a key molecule in the pathogenesis of atherosclerosis.The basal expression of LOX-1 is low but highly induced under the influence of proinflammatory and prooxidative stimuli in vascular endothelial cells, smooth muscle cells, macrophages, platelets and cardiomyocytes. Multiple lines of in vitro and in vivo studies have provided compelling evidence that LOX-1 promotes endothelial dysfunction and atherogenesis induced by oxLDL. The roles of LOX-1 in the development of atherosclerosis, however, are not simple as it had been considered. Evidence has been accumulating that LOX-1 recognizes not only oxLDL but other atherogenic lipoproteins, platelets, leukocytes and CRP. As results, LOX-1 not only mediates endothelial dysfunction but contributes to atherosclerotic plaque formation, thrombogenesis, leukocyte infiltration and myocardial infarction, which determine mortality and morbidity from atherosclerosis. Moreover, our recent epidemiological study has highlighted the involvement of LOX-1 in human cardiovascular diseases. Further understandings of LOX-1 and its ligands as well as its versatile functions will direct us to ways to find novel diagnostic and therapeutic approaches to cardiovascular disease

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead