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Mitochondrial neuronal uncoupling proteins:a target for potential disease-modification in Parkinson’s disease Philip

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Translational Neurodegeneration 2012年第1期1卷 11-19页

作者： WL ho Jessica WM ho Hui-Fang Liu Danny HF So Zero HM Tse koon-ho chan David B Ramsden Shu-Leong ho Division of Neurology Department of MedicineUniversity of Hong KongPokfulamHong Kong SARChina School of Medicine and School of Biosciences University of BirminghamBirminghamUK Research Centre of Heart BrainHormone and Healthy Aging(HBHA)University of Hong KongPokfulamHong Kong SARChina

This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson’s disease(PD).Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation,but as an integral part of this process,superoxides and other reactive oxygen species are also *** free radical production contributes to oxidative *** have evolved to handle such stress via various endogenous anti-oxidant *** such family of proteins is the mitochondrial uncoupling proteins(UCPs),which are anion carriers located in the mitochondrial inner *** are five known homologues(UCP1 to 5),of which UCP4 and 5 are predominantly expressed in neural *** a series of previous publications,we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium(MPP+;toxic metabolite of MPTP)and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential,and reducing oxidative *** also showed how their expression can be influenced by nuclear factor kappa-B(NF-B)signaling pathway specifically in ***,we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin(hormone produced by adipocytes)acting via UCP2 against MPP+-induced *** is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with *** expression,which can be induced,may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.

关键词： uncoupling proteins mitochondria Parkinson??s disease ATP oxidative stress neuroprotection

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A converged ubiquitin-proteasome pathway for the degradation of TOC and TOM tail-anchored receptors

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Journal of Integrative Plant Biology 2024年第5期66卷 1007-1023页

作者： Meijing Yang Shuai Chen Shey-Li Lim Lang Yang Jia Yi Zhong koon Chuen chan Zhizhu Zhao Kam-Bo Wong Junqi Wang Boon Leong Lim School of Biological Sciences University of Hong KongPokfulam 999077Hong KongChina Department of Biology Southern University of Science and TechnologyShenzhen 518055China School of Biomedical Engineering Shenzhen UniversityShenzhen 518060China School of Life Sciences The Chinese Universityof Hong KongShatin 999077HongKongChina State Key Laboratory of Agrobiotechnology The Chinese University of Hong KongShatin 999077Hong KongChina HKU Shenzhen Institute of Research and Innovation Shenzhen 518052China

In plants,thousands of nucleus-encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC(translocon on the outer chloroplast membrane)and the TOM(translocon on the outer mitochondrial membrane)complexes for import into those *** degradation pathways for these receptors are ***,we discovered a converged ubiquitin-proteasome pathway for the degradation of Arabidopsis thaliana TOC and TOM tail-anchored *** receptors are ubiquitinated by E3 ligase(s)and pulled from the outer membranes by the AAA+adenosine triphosphatase CDC48,after which a previously uncharacterized cytosolic protein,transmembrane domain(TMD)-binding protein for tail-anchored outer membrane proteins(TTOP),binds to the exposed TMDs at the C termini of the receptors and CDC48,and delivers these complexes to the 26S proteasome.

关键词： 26S proteasome CDC48 SP1 TOC TOM ubiquitination

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Immunomodulation by mesenchymal stem cells:Interplay between mesenchymal stem cells and regulatory lymphocytes

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World Journal of Stem Cells 2016年第9期8卷 268-278页

作者： Oscar Ka-Fai Ma koon ho chan Department of Medicine Li Ka Shing Faculty of Medicine the University of Hong Kong

Mesenchymal stem cells(MSCs) possess immunomodulatory properties, which confer enormous potential for clinical application. Considerable evidence revealed their efficacy on various animal models of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus and uveitis. MSCs elicit their immunomodulatory effects by inhibiting lymphocyte activation and proliferation, forbidding the secretion of proinflammatory cytokines, limiting the function of antigen presenting cells, and inducing regulatory T(Treg) and B(Breg) cells. The induction of Treg and Breg cells is of particular interest since Treg and Breg cells have significant roles in maintaining immune tolerance. Several mechanisms have been proposed regarding to the MSCs-mediated induction of Treg and Breg cells. Accordingly, MSCs induce regulatory lymphocytes through secretion of multiple pleiotropic cytokines, cell-to-cell contact with target cells and modulation of antigen-presenting cells. Here, we summarized how MSCs induce Treg and Breg cells to provoke immunosuppression.

关键词： Mesenchymal stem cells Regulatory T cells Regulatory B cells Immunomodulation Autoimmunity

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Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

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World Journal of Gastroenterology 2016年第48期22卷 10653-10662页

作者： Way Seah Lee Ruey Terng Ng koon-Wing chan Yu-Lung Lau Department of Paediatrics University Malaya Medical Center University Malaya Paediatric and Child Health Research Group University Malaya Department of Paediatrics and Adolescent Medicine Queen Mary Hospital LKS Faculty of Medicine The University of Hong Kong

AIM Infantile-onset inflammatory bowel disease(IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10(IL-10) and interleukin-10 receptors(IL-10R) in Asian children with IO-IBD. METhoDS All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10 R genes in patients with presenting clinical features of Crohn's disease(CD).RESULTS Six [13%; CD = 3, ulcerative colitis(UC) = 2, IBDunclassified(IBD-U) = 1] of the 48 children(CD = 25; UC = 23) with IBD have IO-IBD. At final review [median(range) duration of follow-up: 6.5(3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy(IBD-U), after standard immunosuppression(CD), and after total colectomy(UC)]. Three patients were on immunosuppression:one(UC) was in remission while two(both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea(100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease(0% vs 19%, P = 0.31), requiring biologics therapy(50% vs 36%, P = 0.40), surgery(50% vs 29%, P = 0.27), or achieving remission(50% vs 64%, P = 0.40). No mutations in either IL10 or IL10 R in the three patients with CD and the only patient with IBD-U were *** The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10 R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.

关键词： Infantile-onset inflammatory bowel disease Pediatric

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Prenatal diagnosis of choledochal cyst using magnetic resonance imaging: A case report

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World Journal of Gastroenterology 2005年第32期11卷 5082-5083页

作者： Alex Mun-Ching Wong Yun-Chung Cheung Yu-Hung Liu koon-Kwan Ng Siu-Cheung chan Shu-Hang Ng Department of Diagnostic Radiologychang Gung Memorial hospital Kwei-ShanTao-YuanTaiwanChina Obstetrics and Gynecologychang Gung Memorial hospital 222Mei Chin RoadKeelungTaiwanChina

Choledochal cysts are congenital anomalies of the biliary ducts, characterized by cystic dilatation of the *** diagnosis of this anomaly using ultrasonography (US) has been well documented. Magnetic resonance imaging (MRI) has recently become an important complement to US in prenatal diagnosis of fetal anomalies. We herein report a patient in whom at 24 wk' gestation US suggested a right upper quadrant abdominal cyst and in whom at 26 wk' gestation MRI more clearly delineated the cyst and its surrounding structures and suggested a choledochal cyst, which was confirmed at postnatal surgery and histopathology.

关键词：出生前诊断胆囊疾病胎儿磁共振成像病例报告胆囊扩张术

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Computed tomography findings in fatal cases of enormous hepatic portal venous gas

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World Journal of Gastroenterology 2005年第19期11卷 2953-2955页

作者： Siu-Cheung chan Yung-Liang Wan Yun-Chung Cheung Shu-Hang Ng Alex Mun-Ching Wong koon-Kwan Ng Department of Diagnostic Radiology chang Gung Memorial hospital Linko Medical Center and Keelung HospitalTaoyuanTaiwanChina

AIM: To assess the computed tomography (CT) findings in the patients with hepatic portal venous gas (HPVG) who presented with a short fatal clinical course in our hospital in order to demonstrate if there was any sign for ***: Between January 1997 and December 2000, CT scan of the abdomen was performed on 949 patients with acute abdominal pain in our emergency *** patients were found having HPVG. The CT images and clinical presentations of all these five patients were reviewed. RESULTS: In reviewing the CT findings of the cases, HPVG in bilateral hepatic lobes, abnormal gas in the superior mesenteric veins, small bowel intramural gas, and bowel distension were observed in all patients. Dry gas in multiple branches of the mesenteric vein was also revealed in all cases. All the patients expired due to irreversible septic shock within 48 h after their initial clinical presentation in emergency room. Two patients had acute pancreatitis with grade D and E Balthazar classification and they expired within 24 h due to progressing septic shock under aggressive medical treatment and life support. Two patients with underlying end stage renal disease expired within 48 h even though emergent surgical intervention was undertaken. The excited bowels revealed severe ischemic change. One patient expired only a few hours after the CT examination. CONCLUSION: HPVG is a diagnostic clue in patients with acute abdominal conditions, and CT is the most specific diagnostic tool for its evaluation. The dry mesenteric veins are the suggestive fatal sign, especially for the deteriorating patients, with the direct effect on gastrointestinal perfusion.

关键词： CT诊断肝静脉疾病肠系膜胃肠灌注

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伴有特殊表型的Wiskott-Aldrich综合征3例

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中国当代儿科杂志 2017年第2期19卷 250-253页

作者：贺建新 chan koon Wing 徐保平刘秀云桂晋刚申昆玲江载芳 Lau Yu Lung 首都医科大学附属北京儿童医院呼吸科北京100045 香港大学儿童与青少年科学系首都医科大学附属北京儿童医院免疫研究室北京100045

病例1 患儿,男,4个月。因发现血小板减少4月余,咳嗽50 d,发热4 d入院。患儿4个月前（生后2 d）发现血小板减少（PLT 22×10^9/L）,外院经骨髓细胞学检查诊断为血小板减少性紫癜,口服泼尼松及静脉丙种球蛋白治疗,血小板正常后出院。出院... 详细信息

病例1 患儿,男,4个月。因发现血小板减少4月余,咳嗽50 d,发热4 d入院。患儿4个月前（生后2 d）发现血小板减少（PLT 22×10^9/L）,外院经骨髓细胞学检查诊断为血小板减少性紫癜,口服泼尼松及静脉丙种球蛋白治疗,血小板正常后出院。出院后不规律口服泼尼松,2个月前停用,血小板波动于50～60×10^9/L。

关键词： Wiskott-Aldrich综合征血小板减少性紫癜静脉丙种球蛋白表型骨髓细胞学检查诊断泼尼松出院后

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同一家族内IL-12β1受体缺陷引起的卡介苗播散性感染二例

同一家族内IL-12β1受体缺陷引起的卡介苗播散性感染二例

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中华医学会第十四次全国儿科学术会议

作者：王晓川章迁王晓红王莹吕志宝刘宇隆 chan koon Wing 复旦大学附属儿科医院香港大学医学院

目的:报道同一家族中两例IL-12Rβ1受体缺陷引起的卡介苗播散性感染。方法:对第1例患儿进行的是回顾性诊断,对第2例患儿结合其家族史、临床表现和基因诊断进行诊断。结果:例1患儿男性,2000年9月27日出生,生后2小时接种卡介苗,4月龄时发...

目的:报道同一家族中两例IL-12Rβ1受体缺陷引起的卡介苗播散性感染。方法:对第1例患儿进行的是回顾性诊断,对第2例患儿结合其家族史、临床表现和基因诊断进行诊断。结果:例1患儿男性,2000年9月27日出生,生后2小时接种卡介苗,4月龄时发现其左腋下淋巴结结核,给予异烟肼+ 利福平+丁胺卡娜霉素治疗,于2001年4月17日行左腋下淋巴结团块切除术,同年8月行右侧腹股沟淋巴结清扫术,术后继续抗痨治疗。于2001年11月起,患儿出现发热、白蛋白降低并有腹水,继续给

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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi Lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei chang Lingyan Wu Brian K.P.Goh Alexander Yaw-Fui Chung Chung Yip chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak chanwat Jidapa Thammasiri Boon koon Yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-hon Lim Glenn Bonney Wei Qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam Han Chong Toh Roger Sik-Yin Foo Pierce Kah-hoe Chow Genome Institute of Singapore Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Cancer Science Institute of Singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System Singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： NADH oxidase H2O2 production oxidative phosphorylation

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A new prognostic histopathologic classification of nasopharyngeal carcinoma

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Chinese Journal of Cancer 2016年第6期35卷 30-45页

作者： Hai-Yun Wang Yih-Leong chang Ka-Fai To Jacqueline S.G.Hwang Hai-Qiang Mai Yan-Fen Feng Ellen T.chang Chen-Ping Wang Michael koon Ming Kam Shie-Lee Cheah Ming Lee Li Gao Hui-Zhong Zhang Jie-Hua He Hao Jiang Pei-Qing Ma Xiao-Dong Zhu Liang Zeng Chun-Yan Chen Gang Chen Ma-Yan Huang Sha Fu Qiong Shao An-Jia Han Hai-Gang Li Chun-Kui Shao Pei-Yu Huang Chao-Nan Qian Tai-Xiang Lu Jin-Tian Li Weimin Ye Ingemar Ernberg ho Keung Ng Joseph T.S.Wee Yi-Xin Zeng Hans-Olov Adami Anthony T.C.chan Jian-Yong Shao State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center Department of Molecular Diagnostics Sun Yat-sen University Cancer Center Department of Pathology National Taiwan University HospitalNational Taiwan University College of Medicine Department of Anatomical and Cellular Pathology Hong Kong Cancer Institute and Sir YK Pao Centre for CancerFaculty of MedicineThe Chinese University of Hong Kong Department of Pathology Singapore General Hospital Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer Center Department of Pathology Sun Yat-sen University Cancer Center Division of Epidemiology Department of Health Research and PolicyStanford University School of Medicine Health Sciences Practice ExponentInc. Department of Otolaryngology National Taiwan University HospitalNational Taiwan University College of Medicine Department of Clinical Oncology Hong Kong Cancer Institute and Sir YK Pao Centre for CancerFaculty of MedicineThe Chinese University of Hong Kong Division of Radiation Oncology National Cancer CenterSingapore Department of Radiation Oncology Cancer Institute and HospitalChinese Academy of Medical Sciences Department of Radiation Oncology The Affiliated Hospital of Bengbu Medical College Department of Pathology Cancer Institute and HospitalChinese Academy of Medical Sciences Department of Radiation Oncology Guangxi Medical University Department of Pathology Hunan Provincial Cancer Hospital Department of Radiation Oncology Sun Yat-sen University Cancer Center Department of Pathology Fujian Provincial Cancer Hospital Department of Pathology The First Affiliated HospitalSun Yat-sen University Department of Pathology Sun Yat-sen Memorial HospitalSun Yat-sen University Department of Pathology The Third Affiliated HospitalSun Yat-sen University Department of Experiment Research Sun Yat-sen University Cancer Center Department of Medical Epidemiology and Biostatistics Karolinska Institutet Departments of Mi

Background:The current World Health Organization(Who) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic *** study aimed to propose an NPC histopathologic classification that can poten?tially be used to predict prognosis and treatment ***:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from *** efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed *** used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P horter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the Who classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.

关键词： Nasopharyngeal carcinoma Pathologic classification Prognosis

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