JP2020513232A - 糖代謝異常の検出方法と予防及び治療 - Google Patents
糖代謝異常の検出方法と予防及び治療 Download PDFInfo
- Publication number
- JP2020513232A JP2020513232A JP2019525832A JP2019525832A JP2020513232A JP 2020513232 A JP2020513232 A JP 2020513232A JP 2019525832 A JP2019525832 A JP 2019525832A JP 2019525832 A JP2019525832 A JP 2019525832A JP 2020513232 A JP2020513232 A JP 2020513232A
- Authority
- JP
- Japan
- Prior art keywords
- gpx2
- expression level
- expression
- diabetes
- individual
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
- C12Q1/28—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving peroxidase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y111/00—Oxidoreductases acting on a peroxide as acceptor (1.11)
- C12Y111/01—Peroxidases (1.11.1)
- C12Y111/01009—Glutathione peroxidase (1.11.1.9)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
- G01N2333/08—RNA viruses
- G01N2333/18—Togaviridae; Flaviviridae
- G01N2333/183—Flaviviridae, e.g. pestivirus, mucosal disease virus, bovine viral diarrhoea virus, classical swine fever virus (hog cholera virus) or border disease virus
- G01N2333/186—Hepatitis C; Hepatitis NANB
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/902—Oxidoreductases (1.)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/902—Oxidoreductases (1.)
- G01N2333/908—Oxidoreductases (1.) acting on hydrogen peroxide as acceptor (1.11)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
- G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/50—Determining the risk of developing a disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/70—Mechanisms involved in disease identification
- G01N2800/7057—(Intracellular) signaling and trafficking pathways
- G01N2800/7066—Metabolic pathways
- G01N2800/7071—Carbohydrate metabolism, e.g. glycolysis, gluconeogenesis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/576—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis
- G01N33/5767—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis non-A, non-B hepatitis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- General Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
Abstract
Description
レプリコン細胞Huh7.5及びHuh7.5/Con1(遺伝子型1b)を高グルコースのDulbecco’s Modified Eagle’s培地(DMEM)で培養した。これを5%二酸化炭素/37℃のインキュベーター内で培養し、10%熱不活性化ウシ胎児血清(heat−inactivated fetal bovine serum,heat−inactivated FBS)、5%抗生物質−抗菌薬(antibiotic−antimycotic)溶液、100U/mLのペニシリン、100μg/mLのストレプトマイシン、及び5%非必須アミノ酸溶液を補充した。そして、細胞株に24時間の飢餓処理を施した後、10%FBS及びアンノナシンを含有する新鮮培地を加えて細胞実験を行った。一方、Con1細胞株については引き続き完全培地(0.5mg/mLのG418を含有)で培養した。
30μgの細胞溶解物サンプルを10%SDS−polyacrylamideゲル上に配置し、電気泳動してから、PVDF膜にブロットした。ブロッキングの後、当該膜を標的タンパクであるGPx2、GLUT1、PCK1(PEPCK)、GLUT2、及びG6PC(G6Pase)抗体(一次抗体)を含有する溶液にそれぞれ浸漬し、2時間インキュベートしてから、0.1%tween 20を含有するPBSで5分間洗浄した。続いて、当該膜をHRP複合二次抗体で1時間インキュベートした。そして、増強化学発光試薬(ECL)を膜に加えて照射し、タンパク質分布を観察した。
細胞を各ウェル1.2×105の数量で6ウェルプレート培地に配置し、一晩成長させた。次に、特定の所定時間だけLipofectAMINE(登録商標)を用い、GPx2過剰発現プラスミド及びsiGPx2(GPx2 siRNA)を当該細胞にトランスフェクションした。また、対照群として、担体にpcDNA(空担体,vihecle)又はsiNC(control siRNA)のみをトランスフェクションした。
24週間:高脂肪餌による糖代謝異常誘発マウス:6週齢のC57BL/6オスマウスを病原無し環境で2週間飼育した。その後、各群が少なくとも5匹のマウスを有するよう、全てのマウスをランダムに6群に分けた。群1には正常餌を与えた。群2には正常餌を与え、且つ、毎週1回マウスの尾部からプラスミド担体を静脈注射した(Turbofectに溶解したものを50μg/plasmid/マウス/週)。群3には正常餌を与え、且つ、毎週1回マウスの尾部からGPx2過剰発現プラスミドを静脈注射した(Turbofectに溶解したものを50μg/plasmid/マウス/週)。群4には、正常餌よりも30%増しの高脂肪餌を与えた。群5には、正常餌よりも30%増しの高脂肪餌を与え、且つ、毎週1回マウスの尾部からプラスミド担体を静脈注射した(Turbofectに溶解したものを50μg/plasmid/マウス/週)。群6には、正常餌よりも30%増しの高脂肪餌を与え、且つ、毎週1回マウスの尾部からGPx2過剰発現プラスミドを静脈注射した(Turbofectに溶解したものを50μg/plasmid/マウス/週)。24週間後に全てのマウスを殺処理し、組織を採取して3つの部分に分けた。第1部分については4%ホルムアルデヒドで固定してパラフィンで包埋し、組織切片として研究した。第2部分の組織については組織用RNAサンプル保存液(RNAlater)に保存し、後の遺伝子発現検出に備えて−80℃環境下に置いた。第3部分の組織については液体窒素に保存した。
全てのマウスを12時間絶食させてから、腹膜内にグルコースを注射した(グルコース2g/体重kg)。次に、グルコース注射から0分、30分、60分及び120分の時点で尾部から採血し、血糖検出器を用いて血糖濃度を検出した。
パラフィンで包埋した肝臓組織を4μmサイズの切片に切断し、100℃でマイクロ波を30分間かけて、非特異性反応をブロッキングした。次に、一次抗体により切片を4℃下で一晩培養した後、0.2%Tween 20を含有するPBSで10分間の洗浄を2度行った。次に、ビオチン標識二次抗体で当該切片を1時間培養した後、0.2%Tween 20を含有するPBSで10分間の洗浄を2度行った。最後に、当該切片を染色し、各種タンパクの発現を観察した。
48名のC型肝炎患者を募集して、それぞれを経口ブドウ糖負荷試験及びグリコヘモグロビンに基づき分類したところ(表1参照)、19名が正常血糖患者、11名が耐糖能異常患者、18名が2型糖尿病患者であった。
患者ごとにウィルスの定型分析を行い、ウィルスの遺伝子型を特定するとともに、ウィルスの定量分析を行った。次に、5名の正常血糖患者、3名の耐糖能異常患者、3名の2型糖尿病患者をランダムに抽出した。且つ、インスリン又は経口血糖降下薬の服用経験のない者をサンプルとし、遺伝子チップ実験を行うことで候補遺伝子を選別した。その他のサンプルについては検証群とし、候補遺伝子の検証に用いた。2つのサンプル群の基本データについては表2に示す通りであった。
各患者の肝臓切片を収集し、各々よりRNAを抽出してRNA濃度を測定してから、それぞれをcDNAに変換して完全性を確認した。結果は図4に示す通りであった。
マイクロアレイチップ実験により全遺伝子の発現検出を行い、全チップの結果を正則化したところ、図5に示すようになった。
遺伝子ネットワーク解析の結果、GPx2は、脂肪酸の酸化、耐糖能、グルコースの取り込み、及び糖新生の遺伝子との間にいずれも密接な関係を有すると推測された。
細胞実験で、糖代謝におけるGPx2の役割を検証した。C型肝炎ウィルス(Hepatitis C virus,HCV)は、GPx2の発現を抑制することでHCVによる肝細胞の糖代謝異常(グルコース輸送の低下と糖新生の増加)を招来し得る。これに対し、GPx2の発現を増加させれば、HCVに起因する糖代謝異常現象を明らかに改善可能である。
Claims (8)
- 所望個体の糖代謝異常を検出する方法であって、
(a)前記所望個体の検体におけるGPx2遺伝子発現、GPx2タンパク発現量、又はGPx2タンパク活性を検出し、
(b)正常個体のGPx2発現量と比較して、前記所望個体のGPx2発現量が前記正常個体のGPx2発現量よりも著しく低い場合には、前記所望個体が糖代謝異常状態を有することを意味する方法。 - 前記検体は、組織、糞便、尿、均質化細胞、血液、血清、血漿、1又は複数の生体液又はこれらの任意の組み合わせからなる群より選択する請求項1に記載の方法。
- 前記個体は動物であり、ヒト及び哺乳類を含む請求項1に記載の方法。
- 前記個体はヒトである請求項1に記載の方法。
- 前記所望個体とは、2型糖尿病のハイリスク群である請求項1に記載の方法。
- GPx2を利用して2型糖尿病を予防又は治療する医薬組成物を調製する用途であって、前記組成物は、有効投与量のGPx2及び医薬的に許容可能な担体を含む用途。
- 前記2型糖尿病は、C型肝炎ウィルスへの感染又は高脂肪食の摂取により招来される請求項6に記載の用途。
- 前記有効投与量とは、少なくとも、投与対象の前記GPx2を正常発現量まで回復させられる投与量である請求項6に記載の用途。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CN2016/105759 WO2018086126A1 (zh) | 2016-11-14 | 2016-11-14 | 一种检测糖代谢异常的方法及其预防及治疗 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2020513232A true JP2020513232A (ja) | 2020-05-14 |
JP7066209B2 JP7066209B2 (ja) | 2022-05-13 |
Family
ID=62110166
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019525832A Active JP7066209B2 (ja) | 2016-11-14 | 2016-11-14 | 糖代謝異常の検出方法と予防及び治療 |
Country Status (6)
Country | Link |
---|---|
US (1) | US11439689B2 (ja) |
EP (1) | EP3540072A4 (ja) |
JP (1) | JP7066209B2 (ja) |
KR (1) | KR20190077037A (ja) |
CN (1) | CN110168098A (ja) |
WO (1) | WO2018086126A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103470194B (zh) * | 2013-09-07 | 2015-12-23 | 中国石油集团西部钻探工程有限公司 | 易上卸套管母扣护丝装置 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005058142A2 (en) * | 2003-12-16 | 2005-06-30 | Emory University | Diabetes diagnostic |
WO2010005533A2 (en) * | 2008-06-30 | 2010-01-14 | The Johns Hopkins University | Compositions and methods for the treatment of ocular oxidative stress and retinitis pigmentosa |
JP2013208117A (ja) * | 2003-10-23 | 2013-10-10 | Illumigen Biosciences Inc | ウイルス感染に対する抵抗性に関連する遺伝子である、oas1における変異の検出 |
JP2016104775A (ja) * | 2009-04-16 | 2016-06-09 | 大正製薬株式会社 | 併用医薬 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1256312A (zh) * | 1998-10-29 | 2000-06-14 | 复旦大学 | 新的人谷胱苷肽过氧化酶、其编码序列及制法和用途 |
WO2005046718A1 (en) * | 2003-11-06 | 2005-05-26 | Ohio University | Diagnosis and hyperinsulinemia and type ii diabetes and protection against same based on genes differentially expressed in pancreas cells (12.1) |
WO2006056080A1 (en) | 2004-11-29 | 2006-06-01 | Diagnocure Inc. | Gpx2 a specific and sensitive target for lung cancer diagnosis, prognosis and/or theranosis |
CN104651329A (zh) | 2014-02-18 | 2015-05-27 | 吉林大学 | 一种含有丝氨酸的谷胱甘肽过氧化物酶gpx2突变体及其制备方法 |
US11718832B2 (en) * | 2014-10-06 | 2023-08-08 | Memorial Sloan-Kettering Cancer Center | Method to reduce oncogenic potential of induced pluripotent stem cells from aged donors |
-
2016
- 2016-11-14 EP EP16921143.0A patent/EP3540072A4/en active Pending
- 2016-11-14 WO PCT/CN2016/105759 patent/WO2018086126A1/zh unknown
- 2016-11-14 KR KR1020197015338A patent/KR20190077037A/ko not_active Application Discontinuation
- 2016-11-14 US US16/349,286 patent/US11439689B2/en active Active
- 2016-11-14 JP JP2019525832A patent/JP7066209B2/ja active Active
- 2016-11-14 CN CN201680090803.8A patent/CN110168098A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013208117A (ja) * | 2003-10-23 | 2013-10-10 | Illumigen Biosciences Inc | ウイルス感染に対する抵抗性に関連する遺伝子である、oas1における変異の検出 |
WO2005058142A2 (en) * | 2003-12-16 | 2005-06-30 | Emory University | Diabetes diagnostic |
WO2010005533A2 (en) * | 2008-06-30 | 2010-01-14 | The Johns Hopkins University | Compositions and methods for the treatment of ocular oxidative stress and retinitis pigmentosa |
JP2016104775A (ja) * | 2009-04-16 | 2016-06-09 | 大正製薬株式会社 | 併用医薬 |
Also Published As
Publication number | Publication date |
---|---|
CN110168098A (zh) | 2019-08-23 |
US20200093897A1 (en) | 2020-03-26 |
KR20190077037A (ko) | 2019-07-02 |
EP3540072A1 (en) | 2019-09-18 |
US11439689B2 (en) | 2022-09-13 |
WO2018086126A1 (zh) | 2018-05-17 |
EP3540072A4 (en) | 2020-05-20 |
JP7066209B2 (ja) | 2022-05-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Forini et al. | Triiodothyronine prevents cardiac ischemia/reperfusion mitochondrial impairment and cell loss by regulating miR30a/p53 axis | |
AU2013266086B2 (en) | Methods of treating a metabolic syndrome by modulating heat shock protein (HSP) 90-beta | |
Esposito et al. | Myostatin: Basic biology to clinical application | |
Zhang et al. | Stat3 activation induces insulin resistance via a muscle-specific E3 ubiquitin ligase Fbxo40 | |
Murfitt et al. | Targeting caveolin-3 for the treatment of diabetic cardiomyopathy | |
Sharma et al. | Decreased Cyclic Guanosine Monophosphate–Protein Kinase G Signaling Impairs Angiogenesis in a Lamb Model of Persistent Pulmonary Hypertension of the Newborn | |
AU2021107213A4 (en) | Use of sphondin as an effective component in preparing medicine for treating hepatitis b | |
KR20140027594A (ko) | 항당뇨 및 항비만 활성을 갖는 약학 조성물 | |
US9693994B2 (en) | Class IIa HDAC inhibitors for the treatment of infection | |
US20110047633A1 (en) | Control of Exocrine Pancreatic Function Using Bone Morphogenetic Proteins | |
JP2020513232A (ja) | 糖代謝異常の検出方法と予防及び治療 | |
EP4299076A1 (en) | Novel method and agent for treating, diagnosing and detecting diabetes and complications | |
US20180030102A1 (en) | Application of metrnl protein in preparing hypolipidemic, hypoglycemic medicine | |
TWI620933B (zh) | 一種檢測醣類代謝異常的方法及其預防及治療 | |
US20100330098A1 (en) | Methods to regulate glucose metabolism | |
CN112891561A (zh) | 一种基因治疗脂肪肝的生物药剂及其制备方法 | |
EP1631291B1 (en) | Use of tyrosine kinase inhibitors to treat diabetes | |
Stephenson et al. | Skeletal muscle mTORC1 activation increases energy expenditure and reduces longevity in mice | |
US20210145783A1 (en) | Compositions and Methods for Treating Sickle Cell Disease | |
WO2023074794A1 (ja) | Hdac調節剤による糖尿病ならびに合併症の治療方法または治療剤 | |
Weeks et al. | Cardiac-selective gene delivery of medium-chain acyl-CoA dehydrogenase (MCAD) does not protect against diabetes-induced cardiac dysfunction | |
Salgado et al. | GKRP-dependent modulation of feeding behavior by tanycyte-released monocarboxylates | |
CN111529689A (zh) | 转录因子klf16蛋白在制备防治脂质和糖代谢异常相关疾病药物中的应用 | |
CN107184956B (zh) | Metrnl蛋白或基因在防治脓毒血症方面的应用 | |
WO2022173818A1 (en) | Use of biliverdin reductase b inhibitors to allow malaria eradication in patients with g6pd deficiency |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190625 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190920 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200707 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20201005 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20201207 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210105 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210622 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210921 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211014 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20211014 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220301 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220314 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220412 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220420 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7066209 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |