Phylogenetic examination of crude drugs derived from Yunnanese Swertia plants

Aiming to examine whether the genetic background of the crude drugs derived from four Yunnanese Swertia plants and their chemical constituent profiles correlate, we analyzed the nucleotide sequences of their nuclear ribosomal DNA regions including ITS1, 5.8S ribosomal RNA gene, and ITS2, together with those of Japanese S. japonica and S. pseudochinensis from Hebei Province. The result that two of the Yunnanese Swertia plants, S. binchuanensis and S. punicea, were genetically similar may explain their similarity in chemical constituent profiles. On the other hand, in spite of differences in chemical profile, S. decora and S. pseudochinensis were genetically close. The other Yunnanese Swertia plants, S. delavayi, and S. japonica, stood at intermediate positions between these two genetically similar pairs. The result suggests that although genetic background would have an influence, environmental factors, e.g., soil and weather conditions, might be critical for their production of secondary metabolites. © The Japanese Society of Pharmacognosy and Springer Japan 2013

Gene Expression Profiles of the Cochlea and Vestibular Endorgans: Localization and Function of Genes Causing Deafness

Objectives: We sought to elucidate the gene expression profiles of the causative genes as well as the localization of the encoded proteins involved in hereditary hearing loss. Methods: Relevant articles (as of September 2014) were searched in PubMed databases, and the gene symbols of the genes reported to be associated with deafness were located on the Hereditary Hearing Loss Honnepage using localization, expression, and distribution as keywords. Results: Our review of the literature allowed us to systematize the gene expression profiles for genetic deafness in the inner ear, clarifying the unique functions and specific expression patterns of these genes in the cochlea and vestibular endorgans. Conclusions: The coordinated actions of various encoded molecules are essential for the normal development and maintenance of auditory and vestibular function.ArticleANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY. 124:6S-48S (2015)journal articl

Alternative mRNA Splicing in Three Venom Families Underlying a Possible Production of Divergent Venom Proteins of the Habu Snake, Protobothrops flavoviridis

Snake venoms are complex mixtures of toxic proteins encoded by various gene families that function synergistically to incapacitate prey. A huge repertoire of snake venom genes and proteins have been reported, and alternative splicing is suggested to be involved in the production of divergent gene transcripts. However, a genome-wide survey of the transcript repertoire and the extent of alternative splicing still remains to be determined. In this study, the comprehensive analysis of transcriptomes in the venom gland was achieved by using PacBio sequencing. Extensive alternative splicing was observed in three venom protein gene families, metalloproteinase (MP), serine protease (SP), and vascular endothelial growth factors (VEGF). Eleven MP and SP genes and a VEGF gene are expressed as a total of 81, 61, and 8 transcript variants, respectively. In the MP gene family, individual genes are transcribed into different classes of MPs by alternative splicing. We also observed trans-splicing among the clustered SP genes. No other venom genes as well as non-venom counterpart genes exhibited alternative splicing. Our results thus indicate a potential contribution of mRNA alternative and trans-splicing in the production of highly variable transcripts of venom genes in the habu snake

Up-regulation of ras-GAP genes is reversed by a MEK inhibitor and doxorubicin in v-Ki-ras-transformed NIH/3T3 fibroblasts

金沢大学大学院医学系研究科脳細胞分子学金沢大学薬学部Ras-GTPase-activating proteins (Ras-GAPs) have been implicated both as suppressors of Ras and as effectors in regulating cellular activities. To study whether Ras-GAPs have roles in tumor cell survival or not, mRNA levels of ras-related genes were measured in v-Ki-ras-transformed (DT) and the parental NIH/3T3 cells, using real-time PCR. mRNA levels of p120-Gap, Gap1m, and PIK3CA were increased in DT cells compared with NIH/3T3 cells. p120-Gap and PIK3CA genes were induced by addition of serum or epidermal growth factor to serum-starved DT cells. Three anti-cancer drugs, an ERK kinase (MEK) inhibitor PD98059, a topoisomerase II poison doxorubicin (adriamycin), and a histone deacetylase inhibitor trichostatin A, selectively blocked the overexpression of p120-Gap and Gap1m genes in DT cells. These drugs also caused reversion of DT cells to the adherent shape associated with growth arrest. Our results suggest that p120-Gap and Gap1m genes provide important biomarkers for cancer therapies. © 2007 Elsevier Inc. All rights reserved

Pericardial Effusion With Tamponade in Lung Cancer Patients During Treatment With Nivolumab: A Report of Two Cases

Background: Nivolumab is an immune checkpoint inhibitor (ICI) that has shown efficacy for treating non-small cell lung cancer and has become a standard therapy for previously treated non-small cell lung cancer. Moreover, immune-related adverse events of ICI therapy are well-known. Malignant pericardial effusions occasionally arise in patients with lung cancer. There have been a few reports of pericardial effusion in non-small cell lung cancer after nivolumab administration. However, the cause of this condition is controversial; the possibilities include serositis as an immune-related adverse event or pseudo-progression.Case Presentation: This report presents two cases of pericardial effusion with tamponade in lung cancer during treatment with nivolumab. Both patients experienced temporal increases in pericardial effusions followed by effusion regression. In one case, nivolumab administration was continued after performance of pericardiocentesis, without an increase in pericardial effusion. In the other case, temporal simultaneous increases in both the pericardial effusion and the primary tumor were detected, followed by simultaneous regression in both the effusion and the tumor. These findings support the fact that the pericardial effusions were caused by pseudo-progression.Conclusions: Pericardial effusion with tamponade can occur in lung cancer patients being treated with nivolumab; moreover, some of these effusions might be caused by pseudo-progression. In the case of putative pseudo-progression, continuation of nivolumab administration might be allowable with strict follow up