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| 1 | Hepatitis B virus pathogenesis: Fresh insights into hepatitis B virus RNA显示文摘Hepatitis B virus(HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host mi RNAs and may deregulate mi RNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viralderived mi RNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBVderived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBVinduced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics. | Kazuma Sekiba Motoyuki Otsuka Motoko Ohno Mari Yamagami Takahiro Kishikawa Tatsunori Suzuki Rei Ishibashi Takahiro Seimiya Eri Tanaka Kazuhiko Koike | 2018 | World Journal of Gastroenterology2018，24，21： | 10 |
| 2 | Circulating RNAs as new biomarkers for detecting pancreatic cancer显示文摘Pancreatic cancer remains difficult to treat and has a high mortality rate.It is difficult to diagnose early mainly due to the lack of screening imaging modalities and specific biomarkers.Consequently,it is important to develop biomarkers that enable the detection of early stage tumors.Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses.These circulating RNAs are upregulated in the serum and plasma of cancer patients,including those with pancreatic cancer,compared with healthy controls.The majority of RNA biomarker studies have assessed circulating microRNAs(miRs),which are often tissue-specific.There are few reports of the tumorspecific upregulation of other types of small noncoding RNAs(ncRNAs),such as small nucleolar RNAs and Piwi-interacting RNAs.Long ncRNAs(IncRNAs),such as HOTAIR and MALAT1,in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers.Among tissuederived RNAs,some miRs show increased expression even in pre-cancerous tissues,and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma.Additionally,some miRs and IncRNAs have been reported with significant alterations in expression according to disease progression,and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established.Furthermore,recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers.Although much work is required to clarify the release mechanism,origin of tumor-specific circulating RNAs,and selectivity of carrier complexes,and technical advances must also be achieved,such as creating a consensus normalization protocol for quantitative data analysis,circulating RNAs are largely unexplored and might represent novel clinical biomarkers. | Takahiro Kishikawa Motoyuki Otsuka Motoko Ohno Takeshi Yoshikawa Akemi Takata Kazuhiko Koike | 2015 | World Journal of Gastroenterology2015，21，28： | 8 |
| 3 | Diagnostic and therapeutic application of noncoding RNAs for hepatocellular carcinoma显示文摘Micro RNAs(mi RNAs) are small,noncoding RNA molecules that regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncoding RNAs(lnc RNAs),another class of noncoding RNAs,have been determined to be also involved in transcription regulation and translation of target genes. Since deregulated expression levels or functions of miR NAs and lncR NAs in hepatocellular carcinoma(HCC) are frequently observed,clinical use of noncoding RNAs for novel diagnostic and therapeutic applications in the management of HCCs is highly and emergently e xpe c t e d. H e r e,we s ummar iz e r e c e nt f indings regarding deregulated mi RNAs and lnc RNAs for their potential clinical use as diagnostic and prognostic biomarkers of HCC. Specifically,we emphasize the deregulated expression levels of such noncoding RNAs in patients' sera as noninvasive biomarkers,a field that requires urgent improvement in the clinical surveillance of HCC. Since nucleotide-based strategies are being applied to clinical therapeutics,we further summarize clinical and preclinical trials using oligonucleotides involving the use of miR NAs and small interfering RNAs against HCC as novel therapeutics. Finally,we discuss current open questions,which must be clarified in the near future for realistic clinical applications of these new strategies. | Chikako Shibata Motoyuki Otsuka Takahiro Kishikawa Motoko Ohno Takeshi Yoshikawa Akemi Takata Kazuhiko Koike | 2015 | World Journal of Hepatology2015，7，1： | 7 |
| 4 | Novel therapeutic approaches for hepatitis B virus covalently closed circular DNA显示文摘Hepatitis B virus(HBV) infection is a major global health problem. Although current therapies, such as the use of nucleos(t)ide analogs, inhibit HBV replication efficiently, they do not eliminate covalently closed circular DNA(ccc DNA), which persists in hepatocyte nuclei. As HBV ccc DNA is a viral transcription template, novel therapeutic approaches to directly target HBV ccc DNA are necessary to completely eradicate persistent HBV infections. HBV ccc DNA levels in HBV-infected human liver cells are extremely low; thus, more reliable and simple measurement methods are needed to correctly monitor their levels during therapeutic treatment. Although reverse transcription-polymerase chain reaction or Southern blot procedures are currently used in research studies, these methods are not completely reliable and are also time-consuming and labor-intensive. Genome editing technologies, such as zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeats/Cas9(CRISPR/Cas9) system, which are designed to target specific DNA sequences, represent highly promising potential therapeutic tools. In particular, the CRISPR/Cas9 system is an easily customizable sequencespecific nuclease with high flexibility and may be the most feasible approach to target HBV ccc DNA. Further research to develop easier, safer, and more effective protocols should be pursued. | Motoko Ohno Motoyuki Otsuka Takahiro Kishikawa Takeshi Yoshikawa Akemi Takata Kazuhiko Koike | 2015 | World Journal of Gastroenterology2015，21，23： | 5 |
| 5 | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells显示文摘 | Hsu, TL Hanson, SR Kishikawa, K Wang, SK Sawa, M Wong, CH | 2007 | 中国生物学文摘2007，21，10： | 5 |
| 6 | Flow Range Enhancement by Secondary Flow Effect in Low Solidity Circular Cascade Diffusers显示文摘High-pressure ratio and wide operating range are highly required for compressors and blowers. The technical issue of the design is achievement of suppression of flow separation at small flow rate without deteriorating the efficiency at design flow rate. A numerical simulation is very effective in design procedure, however, cost of the numerical simulation is generally high during the practical design process, and it is difficult to confirm the optimal design which is combined with many parameters. A multi-objective optimization technique is the idea that has been proposed for solving the problem in practical design process. In this study, a Low Solidity circular cascade Diffuser(LSD) in a centrifugal blower is successfully designed by means of multi-objective optimization technique. An optimization code with a meta-model assisted evolutionary algorithm is used with a commercial CFD code ANSYS-CFX. The optimization is aiming at improving the static pressure coefficient at design point and at low flow rate condition while constraining the slope of the lift coefficient curve. Moreover, a small tip clearance of the LSD blade was applied in order to activate and to stabilize the secondary flow effect at small flow rate condition. The optimized LSD blade has an extended operating range of 114 % towards smaller flow rate as compared to the baseline design without deteriorating the diffuser pressure recovery at design point. The diffuser pressure rise and operating flow range of the optimized LSD blade are experimentally verified by overall performance test. The detailed flow in the diffuser is also confirmed by means of a Particle Image Velocimeter. Secondary flow is clearly captured by PIV and it spreads to the whole area of LSD blade pitch. It is found that the optimized LSD blade shows good improvement of the blade loading in the whole operating range, while at small flow rate the flow separation on the LSD blade has been successfully suppressed by the secondary flow effect. | Daisaku Sakaguchi Min Thaw Tun Kanata Mizokoshi Daiki Kishikawa | 2014 | Journal of Thermal Science2014，23，4： | 4 |
| 7 | Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study显示文摘 | Yasuo Ohkubo Hideki Kishikawa Eiichi Araki Takao Miyata Satoshi Isami Sadatoshi Motoyoshi Yujiro Kojima Naohiko Furuyoshi Motoaki Shichiri | 1995 | Diabetes Research and Clinical Practice1995，，2： | 3 |
| 8 | Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation显示文摘 | Itasaka H Kishikawa K Suehiro T | 1994 | Surg Today1994，24，8： | 1 |
| 9 | Lysophosphatidylserine stimulates chemotactic migration of colorectal cancer cells through GPR34 and PI3K/Akt pathway显示文摘 | Iida Y H Tsuno N Kishikawa J | 2014 | Anticancer Res2014，34，10： | 1 |
| 10 | Impact of inhaled corticosteroid treatment on 15-year longitudinal respiratory function changes in adult patients with bronchial asthma显示文摘 | Shimoda T Obase Y Kishikawa R | 2013 | International archives of allergy and immunology2013，，4： | 1 |
| 11 | The effects of dexme- detomidine on human neutrophil apoptosis 显示文摘 | Kishikawa H Kobayashi K Takemori K | 2008 | Biomed Res2008，29，4： | 1 |
| 12 | Pulmonary contusion causes long-term respiratory dysfunction with decreased functional residual capacity显示文摘 | Kishikawa M Yoshioka T Shimazu T | 1991 | J Trauma1991，31，9： | 1 |
| 13 | Initial non-weight-bearing therapy is im- portant for preventing vertebral body collapse in elderly patients with clinical vertebral fractures 显示文摘 | Kishikawa Y | 2012 | Int J Gen Med2012，5，4： | 1 |
| 14 | Effect of intra- portal infusion to improve small for size graft injury in living donor adult liver transplantation显示文摘 | Suehiro T Shimada M Kishikawa K el al | 2005 | Transpl Int2005，18，8： | 1 |
| 15 | Molecular scanning of insulin receptor substrate-1 ( IRS-1 ) genre in Japanese patients with NIDDM : Identification of five novel polymorphisms 显示文摘 | Ura S Araki E Kishikawa H | 1996 | Diabetologia1996，39，10： | 1 |
| 16 | Effect of in- traportal infusion to improve small for size graft injury in livingdonor adult liver transplantation 显示文摘 | Suehim T Shimada M Kishikawa K eta/ | 2005 | Transpl Int2005，18，： | 1 |
| 17 | Inhibi- tion of neutrophil elastase reduces lung injury and bacterial count in Hamsters 显示文摘 | Hagio T Kishikawa K Kawabata K | 2008 | Pulm Pharmacol Ther2008，21，6： | 1 |
| 18 | Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with noninsulindependent diabetes mellitus-arand omized prospective 6-year study显示文摘 | Oh kuboY kishikawa ArakiE | 1995 | Diabetes Res Clin Pract1995，28，： | 1 |
| 19 | Bromocriptine protects dopaminergic neurons from levodopa-induced toxicity by stimulating D2 receptors显示文摘 | Tsujihata M Kishikawa M | 1999 | Exp Neurol1999，159，： | 1 |
| 20 | Physiological functions of enzymatic hydrolysates of collagen or keratin contained in livestock and fish waste 显示文摘 | OHBA R DEGUCHI T KISHIKAWA M | 2003 | Food Sci Technol Res2003，9，1： | 1 |
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