Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms.

Azacitidine is a mainstay of therapy for myelodysplastic syndrome (MDS)-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their posttreatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms.

Amplified EPOR/JAK2 Genes Define a Unique Subtype of Acute Erythroid Leukemia.

Unlabelled: Acute erythroid leukemia (AEL) is a unique subtype of acute myeloid leukemia characterized by prominent erythroid proliferation whose molecular basis is poorly understood. To elucidate the underlying mechanism of erythroid proliferation, we analyzed 121 AEL using whole-genome, whole-exome, and/or targeted-capture sequencing, together with transcriptome analysis of 21 AEL samples. Combining publicly available sequencing data, we found a high frequency of gains and amplifications involving EPOR/JAK2 in TP53-mutated cases, particularly those having >80% erythroblasts designated as pure erythroid leukemia (10/13).

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing.

Discovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors.

Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC values of 0.004 μM and 0.

Discovery of 4-Chromen-4-one Derivatives as a New Class of Selective Rho Kinase (ROCK) Inhibitors, which Showed Potent Activity in ex Vivo Diabetic Retinopathy Models.

Diabetic retinopathy (DR) is a major cause of blindness, and there is a lack of effective treatment at present. Rho-associated coiled-coil containing serine/threonine protein kinases (ROCKs) have recently been suggested as potential targets for the DR treatment. We herein report the discovery of 4-chromen-4-one derivatives as a new class of ROCK inhibitors.

Molecular heterogeneity in peripheral T-cell lymphoma, not otherwise specified revealed by comprehensive genetic profiling.

Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a diagnosis of exclusion, being the most common entity in mature T-cell neoplasms, and its molecular pathogenesis remains significantly understudied. Here, combining whole-exome and targeted-capture sequencing, gene-expression profiling, and immunohistochemical analysis of tumor samples from 133 cases, we have delineated the entire landscape of somatic alterations, and discovered frequently affected driver pathways in PTCL, NOS, with and without a T-follicular helper (TFH) cell phenotype. In addition to previously reported mutational targets, we identified a number of novel recurrently altered genes, such as KMT2C, SETD1B, YTHDF2, and PDCD1.

Description and initial characterization of metatranscriptomic nidovirus-like genomes from the proposed new family Abyssoviridae, and from a sister group to the Coronavirinae, the proposed genus Alphaletovirus.

Transcriptomics has the potential to discover new RNA virus genomes by sequencing total intracellular RNA pools. In this study, we have searched publicly available transcriptomes for sequences similar to viruses of the Nidovirales order. We report two potential nidovirus genomes, a highly divergent 35.

transcriptome assembly for the lung of the ornamented pygmy frog ().

, belonging to Neobatrachia, is a new model organism to study developmental biology, adaptive mechanisms from aquatic to terrestrial life, environmental toxicology, and human disease. use of lungs soon after hatching makes it extremely valuable for the study of lung function and development mechanisms. However, our knowledge of genes and pathways associated with lung development in is very limited.

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease.

Background: The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.

Research proceedings on amphibian model organisms.

Model organisms have long been important in biology and medicine due to their specific characteristics. Amphibians, especially Xenopus, play key roles in answering fundamental questions on developmental biology, regeneration, genetics, and toxicology due to their large and abundant eggs, as well as their versatile embryos, which can be readily manipulated and developed in vivo. Furthermore, amphibians have also proven to be of considerable benefit in human disease research due to their conserved cellular developmental and genomic organization.

Transcriptome profiles of metamorphosis in the ornamented pygmy frog Microhyla fissipes clarify the functions of thyroid hormone receptors in metamorphosis.

Anuran metamorphosis is an excellent system in which to study postembryonic development. Studies on Xenopus (Mesobatrachia) show that thyroid hormone receptors (TRs) regulate metamorphosis in a ligand-dependent manner by coordinating the action of hundreds of genes. However, whether this mechanism is conserved among amphibians is still unknown.

Complete mitochondrial genomes of two relatively closed species from Gymnocypris (Cypriniformes: Cyprinidae): genome characterization and phylogenetic considerations.

The complete mitochondrial genome for Gymnocypris eckloni and Gymnocypris przewalskii ganzihonensis is 16,686 and 16,682 bp in size, respectively. Both of the mitochondrial genomes have identical genomic organization and structure including 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes and 1 control region as found in other vertebrates, with the exception of 86 bp non-coding nucleotides between tRNA(Thr) and tRNA(Pro). The phylogenetic analyses based on the concatenated nucleotide sequence of 12 PCGs on the heavy strand supported a relatively closed relationship among G.

[cDNA cloning and expression analysis of MSTN gene from Schizopygopsis pylzovi].

Myostatin (MSTN) is a member of the TGF-β superfamily that acts as a negative regulator of skeletal muscle growth. A full-length, 2 180 bp, cDNA sequence of the myostatin gene from Schizopygopisis pylzovi was cloned with RT-PCR,5'-RACE and 3'-RACE and the cDNA clone included a 1 128 bp ORF, encoding a 375 amino acid peptide. Using PCR, we obtained the sequences of two introns of the MSTN gene and found that its structure in Schizopygopsis pylzovi was similar to that of other vertebrates, including three exons and two introns.

Convergent, parallel and correlated evolution of trophic morphologies in the subfamily schizothoracinae from the Qinghai-Tibetan plateau.

Schizothoracine fishes distributed in the water system of the Qinghai-Tibetan plateau (QTP) and adjacent areas are characterized by being highly adaptive to the cold and hypoxic environment of the plateau, as well as by a high degree of diversity in trophic morphology due to resource polymorphisms. Although convergent and parallel evolution are prevalent in the organisms of the QTP, it remains unknown whether similar evolutionary patterns have occurred in the schizothoracine fishes. Here, we constructed for the first time a tentative molecular phylogeny of the schizothoracine fishes based on the complete sequences of the cytochrome b gene.

[Construction and expression of recombinant human serum albumin-EPO fusion protein].

Unlabelled: OBJECTIVE To construct the recombinant plasmid pCI-HLE encoding human serum album-EPO (HSA-EPO) fusion protein and to express it in CHO cell.

Methods: The cDNA encoding human serum album and EPO were amplified by PCR, and then spliced with the synsitic DNA fragment encoding GS (GGGGS), by overlap PCR extension to form LEPO. After BamH I digestion, the HSA and LEPO was ligated to generate the fusion HSA-EPO gene and was then cloned into the expression vector pCI-neo to generate the recombinant plasmid pCI-HLE.

Sonic hedgehog is involved in formation of the ventral optic cup by limiting Bmp4 expression to the dorsal domain.

Accumulating evidence suggests that Sonic hedgehog (Shh) signaling plays a crucial role in eye vesicle patterning in vertebrates. Shh promotes expression of Pax2 in the optic stalk and represses expression of Pax6 in the optic cup. Shh signaling contributes to establishment of both proximal-distal and dorsal-ventral axes by activating Vax1, Vax2, and Pax2.

[Construction of recombinant adenovirus vector carrying human TIMP-1 cDNA and its expression in vitro].

The full-length cDNA of hTIMP-1 was obtained from a surgical patient with HCC by the method of RT-PCR. Then it was cloned into the adenoviral shuttle plasmid pAdTrack-CMV, and subsequently cotransformed into competent BJ5183 cells with the adenoviral backbone plasmid pAdEasy-1. Thereupon, a recombinant adenoviral plasmid containing full-length cDNA of hTIMP-1 was generated by homologous recombination in E.

Effects of multidrug resistance, antisense RNA on the chemosensitivity of hepatocellular carcinoma cells.

Background: Multidrug resistance is a major obstacle in cancer chemotherapy. We examined whether the antisense RNA of multidrug resistance gene 1 (mdr1) could reverse multidrug resistance in the human hepatocellular carcinoma (HCC) cell line SMMC7721/ADM.

Methods: The recombinant adenoviruses pAdEasy-GFP-ASmdr1 product was produced by the adenoviral vector AdEasy system, which can express antisense RNA against the mdr1 gene.

Overexpression of TIMP-1 mediated by recombinant adenovirus in hepatocellular carcinoma cells inhibits proliferation and invasion in vitro.

Background: Matrix metalloproteinases (MMPs) and its natural tissue inhibitors of metalloproteinases (TIMPs) are involved in cancer progression. This study was undertaken to determine the effects of overexpression of TIMP-1 on human hepatocellular carcinoma (HCC) cell growth, proliferation, and invasion.

Methods: Employing the efficient AdEasy(TM) system, recombinant adenovirus AdTIMP-1 containing full-length cDNA of TIMP-1 was generated by homologous recombination and amplified in 293 cells.

[Recombinant adenovirus vectors carrying antisense matrix metalloproteinase-2 inhibits hepatocellular carcinoma growth in vivo].

Objective: To investigate the inhibitory effect of a recombinant adenoviral vector carrying antisense matrix metalloproteinase-2(MMP2) on the growth of hepatocellular carcinoma(HCC) in vivo.

Methods: The recombinant adenoviral vector carrying antisense MMP2(Ad-MMP2(AS))which had been constructed by us in readiness was used to infect the human HCC cell line (Bel-7402). Then the invasiveness of the Bel-7402 cells was assayed in Matrigel, and the production of MMP2 in the Bel-7402 cells was detected with Western blot analysis and Gelatin zymography.

Construction of the recombinant adenovirus vector carrying antisense multidrug resistance gene.

Background: Multidrug resistance proteins serve as transporters for chemical drugs in human malignancies. The objective of this study was to construct a homologous recombinant adenovirus carrying a reversal fragment of multidrug resistance gene 1 (mdr1) gene cDNA sequence.

Methods: The fragment of the mdr1 gene from the plasmid pHaMDR1-1 carrying the whole human mdr1 cDNA sequence was inserted reversely into the shuttle plasmid pAdTrack-CMV of adenoviral vector system AdEasy.

[Construction of recombinant adeno-associated virus vectors carrying double gene of antisense multidrug resistance-associated protein and antisense multidrug resistance].

Objective: To construct a recombinant adeno-associated virus vectors carrying double gene of antisense multidrug resistance-associated protein (MRP) and antisense multidrug resistance (MDR1) for use in studying the gene therapy to reverse the multidrug resistance (MDR) in hepatocellular carcinoma (HCC).

Methods: The 500 bp fragment (mrp) of MRP cDNA 5' region and the 600 bp fragment (mdr1) of MDR1 cDNA 5' region were amplified through polymerase chain reaction (PCR), and then they were linked to a combined gene fragment (mrp+mdrl) by overlapping technique. The combined gene fragment(mrp+mdrl) was cloned reversely into the multiple cloning site (MCS) of the expression plasmid pAAV-IRES-hrGFP in AAV Helper-Free System to construct the recombinant expression plasmid pAAV-IRES-hrGFP-(mrp + mdr1)AS.

[Inhibition of adenovirus-mediated gene transfer of antisense matrix metalloproteinase-2 on hepatocellular carcinoma growth in vivo].

Objective: To investigate if a recombinant adenoviral vector carrying antisense matrix metalloproteinase-2 (MMP2) gene would inhibit the growth of hepatocellular carcinoma (HCC) in vivo.

Methods: Using the recombinant adenoviral vector carrying antisense MMP2 gene (Ad-MMP2AS) which was constructed by us previously, to infect the human HCC cell line (Bel-7402). Then the invasiveness of the Bel-7402 cells was assayed in Matrigel, and the production of MMP2 in the Bel-7402 cells was detected with Western blotting analysis and Gelatin zymography.