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| 1 | Novel 3-dimensional virtual hepatectomy simulation combined with real-time deformation显示文摘AIM:To develop a novel 3-dimensional(3D) virtual hepatectomy simulation software,Liversim,to visualize the real-time deformation of the liver.METHODS:We developed a novel real-time virtual hepatectomy simulation software program called Liversim. The software provides 4 basic functions:viewing 3D models from arbitrary directions,changing the colors and opacities of the models,deforming the models based on user interaction,and incising the liver parenchyma and intrahepatic vessels based on user operations. From April 2010 through 2013,99 patients underwent virtual hepatectomies that used the conventional software program SYNAPSE VINCENT preoperatively. Between April 2012 and October 2013,11 patients received virtual hepatectomies using the novel software program Liversim; these hepatectomies were performed both preoperatively and at the same that the actual hepatectomy was performed in an operating room. The perioperative outcomes were analyzed between the patients for whom SYNAPSE VINCENT was used and those for whom Liversim wasused. Furthermore,medical students and surgical residents were asked to complete questionnaires regarding the new software.RESULTS:There were no obvious discrepancies(i.e.,the emergence of branches in the portal vein or hepatic vein or the depth and direction of the resection line) between our simulation and the actual surgery during the resection process. The median operating time was 304 min(range,110 to 846) in the VINCENT group and 397 min(range,232 to 497) in the Liversim group(P = 0.30). The median amount of intraoperative bleeding was 510 m L(range,18 to 5120) in the VINCENT group and 470 m L(range,130 to 1600) in the Liversim group(P = 0.44). The median postoperative stay was 12 d(range,6 to 100) in the VINCENT group and 13 d(range,9 to 21) in the Liversim group(P = 0.36). There were no significant differences in the preoperative outcomes between the two groups. Liversim was not found to be clinically inferior to SYNAPSE VINCENT. Both students and surgical residents reported that the Liversim image was almost the same as the actual hepatectomy.CONCLUSION:Virtual hepatectomy with real-time deformation of the liver using Liversim is useful for the safe performance of hepatectomies and for surgical education. | Yukio Oshiro Hiroaki Yano Jun Mitani Sangtae Kim Jaejeong Kim Kiyoshi Fukunaga Nobuhiro Ohkohchi | 2015 | World Journal of Gastroenterology2015，21，34： | 23 |
| 2 | Useful detection of CD147 (EMMPRIN) for pathological diagnosis of early hepatocellular carcinoma in needle biopsy samples显示文摘AIM:To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC). METHODS:Twenty-two patients (15 men and 7 women; median age 68 years,range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC. Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition,the degree of staining within tumor tissue was compared according to a number of clinicopathological variables. RESULTS:The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues,even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP. | Satoshi Mamori Keisuke Nagatsuma Tomokazu Matsuura Kiyoshi Ohkawa Hiroshi Hano Masaharu Fukunaga Masato Matsushima Yoshifumi Masui Nao Fushiya Hiroshi Onoda Yasuyuki Searashi Ichiro Takagi Hisao Tajiri | 2007 | World Journal of Gastroenterology2007，13，21： | 20 |
| 3 | Human platelets inhibit liver fibrosis in severe combined immunodeficiency mice显示文摘AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,respectively.Phosphorylations of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using densitometry.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling.Furthermore,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody.RESULTS:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g liver vs 39±6 ng/g liver,P=0.02).Phosphorylation of Met was more prevalent in the hPLT group than in the PBS group(37%±4%/GAPDH vs 20%±8%/GAPDH,P=0.03).Phosphorylation of SMAD3was weaker in the hPLT group than in the PBS group(60%±12%/GAPDH vs 84%±12%/GAPDH,P=0.1),although this difference was not significant.Furthermore,a lower rate of hepatocyte apoptosis was observed in the hPLT group than in the PBS group(5.9%±1.7%vs 2.9%±2.1%,P=0.02).Significant human platelet accumulation was observed in the fibrotic liver tissues,whereas few platelets accumulated in the normal liver.CONCLUSION:Human platelets inhibit liver fibrosis in SCID mice.Increased concentration of HGF in the liver suppresses hepatic stellate cell activation,induces MMPs,and inhibits hepatocyte apoptosis. | Kazuhiro Takahashi Soichiro Murata Kiyoshi Fukunaga Nobuhiro Ohkohchi | 2013 | World Journal of Gastroenterology2013，19，32： | 17 |
| 4 | Antibody markers in the diagnosis of inflammatory boweldisease显示文摘Inflammatory bowel disease(IBD), including Crohn's disease and ulcerative colitis, is a chronic intestinal inflammation of unknown etiology. The diagnosis of IBD is based on endoscopic, radiologic and histopathologic criteria. Recently, the search for a noninvasive marker that could augment or replace part of this diagnostic process has become a focus of IBD research. In this review, antibody markers, including microbial antibodies, autoantibodies and peptide antibodies, will be described, focusing on their common features. At present, no single marker with qualities that are satisfactory for the diagnosis and treatment of IBD has been identified, although panels of some antibodies are being evaluated with keen interest. The discovery of novel IBD-specific and sensitive markers is anticipated. Such markers could minimize the use of endoscopic and radiologic examinations and could enable clinicians to implement individualized treatment plans designed to improve the long-term prognosis of patients with IBD. | Keiichi Mitsuyama Mikio Niwa Hidetoshi Takedatsu Hiroshi Yamasaki Kotaro Kuwaki Shinichiro Yoshioka Ryosuke Yamauchi Shuhei Fukunaga Takuji Torimura | 2016 | World Journal of Gastroenterology2016，22，3： | 12 |
| 5 | study to determine guidelines for pediatric colonoscopy显示文摘AIM To investigated characteristics, diagnosis, bowelcleansing preparation, sedation, and colonoscope length and diameter in Japanese pediatric patients receiving total colonoscopy.METHODS The present study evaluated consecutive patients aged ≤ 15 years who had undergone their first colonoscopy in Kurume University between January 2007 and February 2015. Data were retrospectively analyzed. We identified 110 pediatric patients who had undergone colonoscopy that had reached the cecum, allowing the observation of the total colon.RESULTS Hematochezia, abdominal pain, and diarrhea were the most common symptoms. For bowel-cleansing preparation, pediatric patients aged ≤ 12 years were treated with magnesium citrate, and patients aged 13-15 years were treated with polyethylene glycol 4000. For sedation, thiamylal with pentazocine, which has an analgesic effect, was used in patients aged ≤ 6 years, and midazolam with pentazocine was used in patients aged ≥ 7 years. Regarding the choice of endoscope, short and thin endoscopes were selected for younger patients, particularly patients aged ≤ 3 years. Positive diagnoses were made in 78 patients(70.9%). Inflammatory bowel disease(n = 49, 44.5%), including ulcerative colitis(n = 37, 33.6%) and Crohn's disease(n = 12, 10.9%), was the most common diagnosis. CONCLUSION Colonoscopy offers a high diagnostic capability for pediatric patients with gastrointestinal symptoms. The selection of appropriate management the performance of colonoscopy is important in pediatric patients. | Shinichiro Yoshioka Hidetoshi Takedatsu Shuhei Fukunaga Kotaro Kuwaki Hiroshi Yamasaki RyosukeYamauchi Atsushi Mori Hiroshi Kawano Tadahiro Yanagi Tatsuki Mizuochi Kosuke Ushijima Keiichi Mitsuyama Osamu Tsuruta Takuji Torimura | 2017 | World Journal of Gastroenterology2017，23，31： | 10 |
| 6 | Current surgical treatment of esophagogastric junction adenocarcinoma显示文摘The incidence of esophagogastric junction(EGJ)adenocarcinoma has shown an upward trend over the past several decades worldwide.In this article,we review previous studies and aimed to provide an update on the factors related to the surgical treatment of EGJ adenocarcinoma.The Siewert classification has implications for lymph node spread and is the most commonly used classification.Different types of EGJ cancer have different incidences of mediastinal and abdominal lymph node metastases,and different surgical approaches have unique advantages and disadvantages.Minimally invasive surgeries have been increasingly applied in clinical practice and show comparable oncologic outcomes.Endoscopic resection may be a good therapy for early EGJ cancer.Additionally,there is still a great need for well-designed,large RCTs to forward our knowledge on the surgical treatment of EGJ cancer. | Shun Zhang Hajime Orita Tetsu Fukunaga | 2019 | World Journal of Gastrointestinal Oncology2019，11，8： | 8 |
| 7 | Progress in the mechanism and targeted drug therapy for COPD显示文摘Chronic obstructive pulmonary disease(COPD)is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it,such as glucocorticoids and bronchodilators,have significant therapeutic effects;however,they also cause side effects,including infection and immunosuppression.Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.Among these new drugs,we focussed on thioredoxin(Trx).Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance,blocking the NF-κB and MAPK signalling pathways,suppressing the activation and migration of inflammatory cells and the production of cytokines,inhibiting the synthesis and the activation of adhesion factors and growth factors,and controlling the cAMP-PKA and PI3K/Akt signalling pathways.The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.In addition,Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor(MIF).Taken together,these findings suggest that Trx may be the ideal drug for treating COPD. | Cuixue Wang Jiedong Zhou Jinquan Wang Shujing Li Atsushi Fukunaga Junji Yodoi Hai Tian | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 8 |
| 8 | Laparoscopic hemicolectomy in a patient with situs inversustotalis显示文摘As among persons with normal anatomy, occasional patients with situs inversus develop malignant tumors. Recently, several laparoscopic operations have been reported in patients with situs inversus. We describe laparoscopic hemicolectomy with radical lymphadenectomy in such a patient. Careful consideration of the mirror-image anatomy permitted safe operation using techniques not otherwise differing from those in ordinary cases. Thus, curative laparoscopic surgery for colon cancer in the presence of situs inversus is feasible and safe. | Yushi Fujiwara Yosuke Fukunaga Masayuki Higashino Shinya Tanimura Masashi Takemura Yoshinori Tanaka Harushi Osugi | 2007 | World Journal of Gastroenterology2007，13，37： | 6 |
| 9 | Three-dimensional imaging identified the accessory bile duct in a patient with cholangiocarcinoma显示文摘The development of diagnostic imaging technology, such as multidetector computed tomography(MDCT) and magnetic resonance cholangiopancreatography(MRCP), has made it possible to obtain detailed images of the bile duct. Recent reports have indicated that a 3-dimensional(3D) reconstructed imaging system would be useful for understanding the liver anatomy before surgery. We have investigated a novel method that fuses MDCT and MRCP images. This novel system easily made it possible to detect the anatomical relationship between the vessels and bile duct in the portal hepatis. In this report, we describe a very rare case of extrahepatic cholangiocarcinoma associated with an accessory bile duct from the caudate lobe connecting with the intrapancreatic bile duct. We were unable to preoperatively detect this accessory bile duct using MDCT and MRCP. However, prior to the second operation, we were able to clearly visualise the injured accessory bile duct using our novel 3D imaging modality. In thisreport, we suggest that this imaging technique can be considered a novel and useful modality for understanding the anatomy of the portal hepatis, including the hilar bile duct. | Ryoichi Miyamoto Yukio Oshiro Shinji Hashimoto Keisuke Kohno Kiyoshi Fukunaga Tatsuya Oda Nobuhiro Ohkohchi | 2014 | World Journal of Gastroenterology2014，20，32： | 6 |
| 10 | Influence of Kupffer cells and platelets on ischemia-reperfusion injury in mild steatotic liver显示文摘AIM: To investigate the effect of mild steatotic liver on ischemia-reperfusion injury by focusing on Kupffer cells (KCs) and platelets. METHODS: Wistar rats were divided into a normal liver group (N group) and a mild steatotic liver group (S group) induced by feeding a choline-deficient diet for 2 wk. Both groups were subjected to 20 min of warm ischemia followed by 120 min of reperfusion. The number of labeled KCs and platelets in sinusoids and the blood perfusion in sinusoids were observed by intravital microscopy (IVM), which was performed at 30, 60 and 120 min after reperfusion. To evaluate serum alanine aminotransferase as a marker of liver deterioration, blood samples were taken at the same time as IVM.RESULTS: In the S group, the number of platelets adhering to KCs decreased significantly compared with the N group (120 after reperfusion; 2.9±1.1 cells/acinus vs 4.8±1.2 cells/acinus, P<0.01). The number of KCs in sinusoids was significantly less in the S group than in the N group throughout the observation periods (before ischemia, 19.6±3.3 cells/acinus vs 28.2±4.1 cells/acinus, P<0.01 and 120 min after reperfusion, 29.0±4.3 cells/acinus vs 40.2±3.3 cells/acinus, P<0.01). The blood perfusion of sinusoids 120 min after reperfusion was maintained in the S group more than in the N group. Furthermore, elevation of serum alanine aminotransferase was lower in the S group than in the N group 120 min after reperfusion (99.7±19.8 IU/L vs 166.3±61.1 IU/L, P=0.041), and histological impairment of hepatocyte structure was prevented in the S group. CONCLUSION: Ischemia-reperfusion injury in mild steatotic liver was attenuated compared with normal liver due to the decreased number of KCs and the reduction of the KC-platelet interaction. | Koichi Ogawa Tadashi Kondo Takafumi Tamura Hideki Matsumura Kiyoshi Fukunaga Tatsuya Oda Nobuhiro Ohkohchi | 2013 | World Journal of Gastroenterology2013，19，9： | 6 |
| 11 | Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative resection显示文摘 | Yutaka Saito Masakatsu Fukuzawa Takahisa Matsuda Shusei Fukunaga Taku Sakamoto Toshio Uraoka Takeshi Nakajima Hisatomo Ikehara Kuang-I Fu Takao Itoi Takahiro Fujii | 2010 | Surgical Endoscopy2010，，2： | 5 |
| 12 | Superiority of laparoscopic rectal surgery:Towards a new era显示文摘While laparoscopic colon surgery has been established to some degree over this decade,laparoscopic rectal surgery is not standard yet because of the difficulty of making a clear surgical field,the lack of precise anatomy of the pelvis,immature procedures of rectal transaction and so on.On the other hand,maintaining a clear surgical field via the magnified laparoscopy may allow easier mobilization of the rectum as far as the levetor muscle level and may result less blood loss and less invasiveness.However,some unique techniques to keep a clear surgical field and knowledge about anatomy of the pelvis are required to achieve the above superior operative outcomes.This review article discusses how to keep a clear operative field,removing normally existing abdominal structures,and how to transact the rectum and restore the discontinuity based on anatomical investigations.According to this review,laparoscopic rectal surgery will become a powerful modality to accomplish a more precise procedure which has been technically impossible so far,actually entering a new era. | Yosuke Fukunaga | 2011 | World Journal of Gastrointestinal Surgery2011，3，10： | 5 |
| 13 | Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative resection显示文摘 | Yutaka Saito Masakatsu Fukuzawa Takahisa Matsuda Shusei Fukunaga Taku Sakamoto Toshio Uraoka Takeshi Nakajima Hisatomo Ikehara Kuang-I Fu Takao Itoi Takahiro Fujii | 2010 | Surgical Endoscopy2010，，2： | 5 |
| 14 | Successful resection of metachronous para-aortic, Virchow lymph node and liver metastatic recurrence of rectal cancer显示文摘A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, c SS, c N0, c H0, c P0, c M0 c Stage Ⅱ, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, p SS, p N3, p H0, p P1, p M1(para-aortic lymph node, dissemination) f Stage Ⅳ. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography(CT) detected an 11 mm of liver metastasis in the posteroinferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of paraaortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in paraaortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine aloneand continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome(Grade 3), we managed to continue capecitabine administration with extension of interval period and dose reduction. After 2 years and 2 mo from starting capecitabine plus bevacizumab regimen, Virchow lymph nodes had slowly grown up to 17 mm. Because no recurrence had been detected besides Virchow lymph nodes for this follow up period, considering the side effects and quality of life, surgical resection was selected. We performed left supraclavicular lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer. After the fourth operation, the patient selected follow up without chemotherapy. Now we follow up her without recurrence and keep her quality of life high. | Nobuyoshi Takeshita Toru Fukunaga Masayuki Kimura Yuji Sugamoto Kentaro Tasaki Isamu Hoshino Takumi Ota Tetsuro Maruyama Tomohide Tamachi Takashi Hosokawa Yo Asai Hisahiro Matsubara | 2015 | World Journal of Gastroenterology2015，21，44： | 4 |
| 15 | Roles of lipoprotein receptors in the entry of hepatitis C virus显示文摘Infection by hepatitis C virus(HCV), a plus-stranded RNA virus that can cause cirrhosis and hepatocellular carcinoma, is one of the major health problems in the world. HCV infection is considered as a multistep complex process and correlated with abnormal metabolism of lipoprotein. In addition, virus attacks hepatocytes by the initial attaching viral envelop glycoprotein E1/E2 to receptors of lipoproteins on host cells. With the development of HCV model system, mechanisms of HCV cell entry through lipoprotein uptake and its receptor have been extensively studied in detail. Here we summarize recent knowledge about the role of lipoprotein receptors, scavenger receptor class B type Ⅰ and low-density lipoprotein receptor in the entry of HCV, providing a foundation of novel targeting therapeutic tools against HCV infection. | Jingya Lyu Hitomi Imachi Kensaku Fukunaga Takuo Yoshimoto Huanxiang Zhang Koji Murao | 2015 | World Journal of Hepatology2015，7，24： | 3 |
| 16 | Laparoscopic and endoscopic cooperative surgery for gastrointestinal stromal tumor dissection显示文摘 | N. Hiki Y. Yamamoto T. Fukunaga T. Yamaguchi S. Nunobe M. Tokunaga A. Miki S. Ohyama Y. Seto | 2008 | Surgical Endoscopy2008，，7： | 3 |
| 17 | Laparoscopic Appendectomy for Complicated Appendicitis: A Comparison with Open Appendectomy显示文摘 | Goutaro Katsuno Kunihiko Nagakari Seiichiro Yoshikawa Kazuyoshi Sugiyama Masaki Fukunaga | 2009 | World Journal of Surgery2009，，2： | 3 |
| 18 | Laparoscopic and endoscopic cooperative surgery for gastrointestinal stromal tumor dissection显示文摘 | N. Hiki Y. Yamamoto T. Fukunaga T. Yamaguchi S. Nunobe M. Tokunaga A. Miki S. Ohyama Y. Seto | 2008 | Surgical Endoscopy2008，，7： | 3 |
| 19 | Signalling pathways in autism spectrum disorder:mechanisms and therapeutic implications显示文摘Autism spectrum disorder(ASD)is a prevalent and complex neurodevelopmental disorder which has strong genetic basis.Despite the rapidly rising incidence of autism,little is known about its aetiology,risk factors,and disease progression.There are currently neither validated biomarkers for diagnostic screening nor specific medication for autism.Over the last two decades,there have been remarkable advances in genetics,with hundreds of genes identified and validated as being associated with a high risk for autism.The convergence of neuroscience methods is becoming more widely recognized for its significance in elucidating the pathological mechanisms of autism.Efforts have been devoted to exploring the behavioural functions,key pathological mechanisms and potential treatments of autism.Here,as we highlight in this review,emerging evidence shows that signal transduction molecular events are involved in pathological processes such as transcription,translation,synaptic transmission,epigenetics and immunoinflammatory responses.This involvement has important implications for the discovery of precise molecular targets for autism.Moreover,we review recent insights into the mechanisms and clinical implications of signal transduction in autism from molecular,cellular,neural circuit,and neurobehavioural aspects.Finally,the challenges and future perspectives are discussed with regard to novel strategies predicated on the biological features of autism. | Chen-Chen Jiang Li-Shan Lin Sen Long Xiao-Yan Ke Kohji Fukunaga Ying-Mei Lu Feng Han | 2022 | Signal Transduction and Targeted Therapy2022，7，8： | 3 |
| 20 | Fatty acid-binding protein 7 triggersα-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress显示文摘We previously show that fatty acid-binding protein 3(FABP3)triggersα-synuclein(Syn)accumulation and induces dopamine neuronal cell death in Parkinson disease mouse model.But the role of fatty acid-binding protein 7(FABP7)in the brain remains unclear.In this study we investigated whether FABP7 was involved in synucleinopathies.We showed that FABP7 was co-localized and formed a complex with Syn in Syn-transfected U251 human glioblastoma cells,and treatment with arachidonic acid(100 M)significantly promoted FABP7-induced Syn aggregation,which was associated with cell death.We demonstrated that synthetic FABP7 ligand 6 displayed a high affinity against FABP7 with Kd value of 209 nM assessed in 8-anilinonaphthalene-1-sulfonic acid(ANS)assay;ligand 6 improved U251 cell survival via disrupting the FABP7–Syn interaction.We showed that activation of phospholipase A2(PLA2)by psychosine(10 M)triggered oligomerization of endogenous Syn and FABP7,and induced cell death in both KG-1C human oligodendroglia cells and oligodendrocyte precursor cells(OPCs).FABP7 ligand 6(1 M)significantly decreased Syn oligomerization and aggregation thereby prevented KG-1C and OPC cell death.This study demonstrates that FABP7 triggersα-synuclein oligomerization through oxidative stress,while FABP7 ligand 6 can inhibit FABP7-induced Syn oligomerization and aggregation,thereby rescuing glial cells and oligodendrocytes from cell death. | An Cheng Yi-fei Wang Yasuharu Shinoda Ichiro Kawahata Tetsunori Yamamoto Wen-bin Jia Hanae Yamamoto Tomohiro Mizobata Yasushi Kawata Kohji Fukunaga | 2022 | Acta Pharmacologica Sinica2022，43，3： | 2 |
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