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Deneddylase 1 regulates deneddylase activity of the Cop9 signalosome in Drosophila melanogaster

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Insect Science 2017年第1期24卷 27-34页

作者： Kiyoung Kim Jeongsook Yoon Jeongbin Yim Hyung-Jun Kim Department of Medical Biotechnology Soonchunhyang University Asan 336-745 division of intractable diseases CenterforBiomedical Sciences National Institute of Health Cheongwon 361-951 Department of Neural Development and Disease Korea Brain Research Institute Daegu 701-300 Korea

NEDD8 conjugation of Cullin has an important role in ubiquitin-mediated protein degradation. The COP9 signalosome, of which CSN5 is the major catalytic subunit, is a major Cullin deneddylase, Another deneddylase, Deneddylase 1, has also been shown to process the Nedd8 precursor. In Drosophila, the DEN1 mutants do not have increased levels of Cullin neddylation, but instead show a significant decrease in neddylated Cullin. This characteristic decrease in neddylated Cullins in the DEN1^null background can be rescued by UAS-dDEN1^WT overexpression but not by overexpression of mature NEDDS, indicating that this phenotype is distinct from the NEDD8-processing function of DENI. We examined the role of DEN 1-CSN interaction in regulating Cullin neddylation. Overexpression of DEN1 in a CSN5^hypo background slightly reduced unneddylated Cullin levels. The CSN5, DEN1 double mutation partially rescues the premature lethality associated with the CSN5 single mutation. These results suggest that DEN1 regulates Cullin neddylation by suppressing CSN deneddylase activity.

关键词： COP9 signalosome Cullin DEN1 Drosophila NEDD8

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工程化干细胞的前沿生物医学策略（英文）

Science Bulletin 2024年第2期 248-279页

作者：王经琳张筱萱陈涵旭任昊桢周敏赵远锦 Department of Vascular Surgery Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University division of Hepatobiliary Surgery and Transplantation Surgery Department of General Surgery Nanjing Drum Tower Hospital School of Biological Science and Medical Engineering Southeast University Shenzhen Research Institute Southeast University

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders. As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical applications. Despite the achievements, the therapeutic benefits of stem cells for diseases are limited, and the data of clinical researches are *** optimize tthe effectiveness of stem cells, engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities, paving the way for the next generation of stem cell therapies. This review offers a detailed analysis of engineered stem cells, including their clinical applications and potential for future development. We begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(i PSCs), embryonic stem cells(ESCs), mesenchymal stem cells(MSCs) and hematopoietic stem cells(HSCs)). Furthermore, we present the latest developments of engineered strategies in stem cells, including engineered methods in molecular biology and biomaterial fields, and their application in biomedical research. Finally, we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

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Platycodon grandiflorum extract represses up-regulated adipocyte fatty acid binding protein triggered by a high fat feeding in obese rats

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World Journal of Gastroenterology 2007年第25期13卷 3493-3499页

作者： Yoon Shin Park Yoosik Yoon Hong Seok Ahn division of intractable diseases Center for Biomedical Sciences National Institute of Health 194 Tongillo Eunpyeong-gu Seoul 122-701 South Korea College of Medicine Chung Ang University 221 Heukseok-dong Dongjak-gu Seoul 156-756 South Korea Sungshin Women's University Department Food and Nutrition 5 Dongsun-Dong Sungbuk-Gu Seoul 136-742 South Korea

AIM: To investigate the effect of Platycodon grandi- florum extract (PGE) on lipid metabolism and FABP mRNA expression in subcutaneous adipose tissue of high fat diet-induced obese rats. METHODS: PGE was treated to investigate the inhibitory effect on the pre-adipocyte 3T3-L1 differentiation and pancreatic lipase activity. Male Sprague-Dawley rats with an average weight of 439.03 ± 7.61 g were divided into four groups: the control groups that fed an experimental diet alone (C and H group) and PGE treatment groups that administered PGE along with a control diet or HFD at a concentration of 150 mg/kg body weight (C + PGE and H + PGE group, respectively) for 7 wk. Plasma total cholesterol (TC) and triglycerol (TG) concentrations were measured from the tail vein of rats. Adipocyte cell area was measured from subcutaneous adipose tissue and the fatty acid binding protein (FABP) mRNA expression was analyzed by northern blot analysis. RESULTS: PGE treatment inhibited 3T3-L1 pre-adipocyte differentiation and fat accumulation, and also decreased pancreatic lipase activity. In this experiment, PGE signifi cantly reduced plasma TC and TG concentrations as well as body weight and subcutaneous adipose tissue weight. PGE also significantly decreased the size of subcutaneous adipocytes. Furthermore, it significantly repressed the up-regulation of FABP mRNA expression induced by a high-fat feeding in subcutaneous adipose tissue. CONCLUSION: PGE has a plasma lipid lowering-effect and anti-obesity effect in obese rats fed a high fat *** these results, we can suggest the possibility that PGE can be used as a food ingredient or drug component to therapeutically control obesity.

关键词：肥胖脂肪酸蛋白质脂肪细胞

Vagus nerve stimulation for refractory epilepsy:long term efficacy and side-effects

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Chinese Medical Journal 2004年第1期117卷 58-61页

作者：許志輝蓝明權黄家星祈理治潘偉生 division of Neurology Department of MedicineDivision of NeurosurgeryDepartment of SurgeryPrince of Wales Hospital the Chinese University of Hong KongHong Kong Special Administrative Region

Background In general vagus nerve stimulation (VNS) can serve as an adjunctive treatment for patients with refractory partial -onset seizures. And we evaluated the long-term efficacy and safety of VNS in a group of Chinese patients with refratory epilepsy. Methods Of 127 patients with refractory epilepsy,13 patients who were not eligible for surgical intervention were implanted with the Cyberonics VNS system. Seizure frequency,physical examination and side effects profile were recorded at follow-up visits for a minimum of 18 months. Results Mean duration of treatment was 47.4 months,and the longest follow-up period was 71 months. Mean baseline seizure frequency was 26.6 seizures per month. The mean percentage reductions in convulsions were 33.2%,47.1% and 40.0% at 6,12 and 18 months,respectively. One patient became seizure free,and six (46%) had 50% or more reduction in seizure frequency. Response was poor (intractable convulsions.

关键词： refractory epilepsy·vagus nerve stimulation·epilepsy surgery·Chinese population

Neutrophil-sourced TNF in cancer:deciphering an intricate orchestrator of immunosuppressive communication in the tumor microenvironment

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3558-3560页

作者： Xinyuan Zhao Ye Lu Li Cui Stomatological Hospital School of StomatologySouthern Medical UniversityGuangzhou 510280 GuangdongChina division of Oral Biology and Medicine School of DentistryUniversity of CaliforniaLos AngelesLos Angeles 90095 CAUSA

In a recent Cancer Discovery publication,Bianchi et *** a crucial mechanism driving therapeutic resistance in pancreatic ductal adenocarcinoma(PDAC),orchestrated by cell-autonomous Cxcl1 and TNF from polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs).This insight provides fresh perspectives for surmounting such resistance in PDAC.1 PDAC represents a highly aggressive malignancy exhibiting substantial therapeutic resistance,attributable to factors such as intractable genomic aberrations,immunosuppression mediated by myeloid cells,and pro-inflammatory activation of cancerassociated fibroblasts.

关键词： cancer Cancer

Emerging Therapeutic Strategies in The Fight Against Primary Biliary Cholangitis

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 949-957页

作者： Abigail Medford Jonathan Childs Ashleigh Little Sanjukta Chakraborty Leonardo Baiocchi Gianfranco Alpini Shannon Glaser Department of Medical Physiology Texas A&M University School of MedicineBryanTXUSA Hepatology Unit University of Tor VergataRomeItaly division of Gastroenterology and Hepatology Department of MedicineIndiana University School of MedicineIndianapolisINUSA

The liver has a vital role in many metabolic and regulatory processes in the *** biliary cholangitis(PBC),previously known as primary biliary cirrhosis,is a chronic cholestatic autoimmune disease of the intrahepatic bile ducts associated with loss of tolerance to mitochondrial *** this time there is no definitive cure for PBC;however,ursodeoxycholic acid(UDCA)has been shown to reduce injury when administered as the first line of *** therapeutics can be given concurrently or as an alternative to UDCA to manage the symptoms and further curb disease ***,a liver transplant is the only potentially curative option when the patient has developed end-stage liver disease or intractable *** review aims to delineate the pathogenesis of primary biliary cholangitis and shed light on current therapeutic strategies in the treatment of PBC.

关键词： Cholestatic liver disease Therapeutic approaches Biliary epithelia ursodeoxycholic acid

What constitutes failure of medical therapy in the changing landscape of Crohn's disease?

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Laparoscopic, Endoscopic and Robotic Surgery 2022年第4期5卷 158-160页

作者： Nguyen Huynh Henry Wang Kar Yin Fok James Wei Tatt Toh division of Colorectal Surgery Department of SurgeryWestmead HospitalSydneyNew South WalesAustralia Westmead Clinical School The University of SydneySydneyNew South WalesAustralia

The management of Crohn's disease has evolved rapidly in the era of immunomodulators and *** this,a significant proportion of patients with Crohn's disease ultimately require surgical *** of the indications for operative management includes failure of medical *** report two cases of patients with complicated Crohn's disease who have exhausted medical therapy and failed medical *** both cases,the patients developed large complex intra-abdominal phlegmons and intractable symptoms of intermittent pain,partial obstruction and/or infectious complications requiring operative ***'s disease can present with a wide spectrum of *** the complexity of management in Crohn's disease,it is important for both physicians and surgeons to be aware of what constitutes failure of medical therapy and when it may be important to consider surgical involvement.

关键词： Crohn's disease Phlegmon Laparoscopic surgery Failure of medical therapy Ileocecal resection

Chemical ablation of the gallbladder using alcohol in cholecystitis after palliative biliary stenting

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World Journal of Gastroenterology 2009年第16期15卷 2041-2043页

作者： Tae Hoon Lee Sang-Heum Park Sang Pil Kim Ji-Young Park Chang Kyun Lee Il-Kwun Chung Hong Soo Kim Sun-Joo Kim division of Gastroenterology Department of Internal MedicineSoonchunhyang University College of MedicineCheonan Hospital

Chemical ablation of the gallbladder is effective in patients at high risk of complications after surgery. Percutaneous gallbladder drainage is an effective treatment for cholecystitis; however, when the drain tube cannot be removed because of recurrent symptoms, retaining it can cause problems. An 82-year-old woman presented with cholecystitis and cholangitis caused by biliary stent occlusion and suspected tumor invasion of the cystic duct. We present successful chemical ablation of the gallbladder using pure alcohol, through a percutaneous gallbladder drainage tube, in a patient who developed intractable cholecystitis with obstruction of the cystic duct after receiving a biliary stent. Our results suggest that chemical ablation therapy is an effective alternative to surgical therapy for intractable cholecystitis.

关键词：化学消融治疗胆道内支架置入术胆囊炎纯酒精姑息胆道支架胆囊引流术高危患者

Multiple bowel intussusceptions from metastatic localized malignant pleural mesothelioma:A case report

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World Journal of Gastroenterology 2010年第31期16卷 3984-3986页

作者： Hsien Liu Yu-Jen Cheng Hsin-Pao Chen Jau-Chung Hwang Po-Chih Chang division of General Surgery Department of Sur-geryE-DA Hospital/I-Shou University division of Thoracic Surgery Department of SurgeryE-DA Hospital/I-Shou University division of Colon and Rectal Surgery Depart-ment of SurgeryE-DA Hospital/I-Shou University Department of Pathology E-DA Hospital/I-Shou University

Localized malignant pleural mesothelioma (LMPM) is a rare occurrence, and gastrointestinal intra-luminal metastases have not previously been reported. Herein, we report a patient with LMPM who presented with a local recurrence 10 mo after initial en bloc surgical resection. Abdominal computed tomography was performed for intractable, vague abdominal pain with episodic vomiting, which showed a "target sign" over the left lower quadrant. Laparotomy revealed several intra-luminal metastatic tumors in the small intestine and colon and a segmental resection of metastatic lesions was performed. Unfortunately, the patient died of sepsis despite successful surgical intervention. Though local recurrence is more frequent in LMPM, the possibility of distant metastasis should not be ignored in patients with non-specifi c abdominal pain.

关键词： Localized malignant pleural mesothelioma Intussusception Distant metastasis