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Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease

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Translational Neurodegeneration 2019年第1期8卷 63-76页

作者： Zhi Dong Zhou Thevapriya Selvaratnam Ji Chao Tristan lee yin Xia Chao Eng-king Tan Department of Research National Neuroscience Institute11 Jalan Tan Tock SengSingapore 308433Singapore Department of Neurology Singapore General HospitalOutram RoadSingapore 169608Singapore Signature Research Program in Neuroscience and Behavioural Disorders Duke-NUS Medical School Singapore8 College RoadSingaporeSingapore

Parkinson’s disease(PD)is the most common neurodegenerative movement disorder,which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain *** detailed pathogenic mechanisms underlying the selective loss of dopaminergic neurons in PD are unclear,and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in ***,the formation ofα-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD,possibly stemming from the consequence of protein misfolding and dysfunctional *** is the mechanism for maintaining protein homeostasis via modulation of protein translation,enhancement of chaperone capacity and the prompt clearance of misfolded protein by the ubiquitin proteasome system and *** protein translation and impaired capacities of chaperone or protein degradation can disturb proteostasis processes,leading to pathological protein aggregation and neurodegeneration in *** recent years,multiple molecular targets in the modulation of protein translation vital to proteostasis and dopaminergic neuron degeneration have been *** potential pathophysiological and therapeutic significance of these molecular targets to neurodegeneration in PD is highlighted.

关键词： Molecular targets Neuron degeneration Parkinson’s disease Protein aggregation Protein translation Proteostasis

Immune checkpoint pathways in immunotherapy for head and neck squamous cell carcinoma

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International Journal of Oral Science 2020年第2期12卷 114-122页

作者： Zi Mei Junwen Huang Bin Qiao Alfred king-yin Lam Department of Oral and Maxillofacial Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Cancer Molecular Pathology and Griffith Medical School Griffith UniversityGold CoastQueenslandAustralia

With the understanding of the complex interaction between the tumour microenvironment and immunotherapy,there is increasing interest in the role of immune regulators in the treatment of head and neck squamous cell carcinoma(HNSCC).Activation of T cells and immune checkpoint molecules is important for the immune response to *** checkpoint molecules include cytotoxic T lymphocyte antigen 4(CTLA-4),programmed death 1(PD-1),T-cell immunoglobulin mucin protein 3(TIM-3),lymphocyte activation gene 3(LAG-3),T cell immunoglobin and immunoreceptor tyrosine-based inhibitory motif(TIGIT),glucocorticoid-induced tumour necrosis factor receptor(GITR)and V-domain Ig suppressor of T cell activation(VISTA).Many clinical trials using checkpoint inhibitors,as both monotherapies and combination therapies,have been initiated targeting these immune checkpoint *** review summarizes the functional mechanism and use of various immune checkpoint molecules in HNSCC,including monotherapies and combination therapies,and provides better treatment options for patients with HNSCC.

关键词： Immune immunotherapy squamous

The Long Road to Understanding the Baculovirus P10 Protein

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Virologica Sinica 2009年第4期24卷 227-242页

作者： David C. J. Carpentier linda A. king School of Life Sciences Oxford Brookes University Headington Campus Oxford United Kingdom Oxford Expression Technologies Ltd Oxford Brookes University Headington Campus Oxford United Kingdom

The baculovirus P 10 protein has always represented a mystery in the field of insect virology. Like the baculovirus polyhedrin protein it is expressed at high levels very late in infection. Homologues of the Autographa californica nucleopolyhedrovirus p10 gene are conserved in all Alphabaculoviruses and in other viruses of lepidopteran hosts yet is completely dispensable for virus replication and transmission. PIO is a microtubule interacting protein whose expression has been associated with the formation of a variety of complex and extensive cytoplasmic and nuclear structures. PIO has been associated with a number of roles during infection ranging from the formation of virus occlusion bodies, to affecting the rate of cellular and/or nuclear lysis during the final stages of the virus replication cycle. In this article we review recent work aimed at understanding the role of this enigmatic protein, putting them into context with recent advances in understanding of protein structure and function. We look back at a number of historical studies and observations, reanalysing their conclusions based on recent data and our own observations. The role of the P 10 protein during baculovirus replication remains elusive, however, novel avenues of investigation have been identified that will, we are sure, eventually lead to an understanding of this protein.

关键词： Baculovirus P10 microtubule Polyhedral occlusion body Fibrous body/fibrillar structure

Synchronous colorectal cancer: Clinical, pathological and molecular implications

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World Journal of Gastroenterology 2014年第22期20卷 6815-6820页

作者： Alfred king-yin Lam Sally Sze-Yan Chan Melissa Leung Cancer Molecular Pathology Griffith Health InstituteGriffith UniversityGold Coast QLD 4222QueenslandAustralia

Synchronous colorectal carcinoma refers to more than one primary colorectal carcinoma detected in a single patient at initial presentation. A literature review has shown that the prevalence of the disease is approximately 3.5% of all colorectal carcinomas. This disease has a male to female ratio of 1.8:1. The mean age at presentation of patients with synchronous colorectal cancer is in the early half of the seventh decade. Patients with inflammatory bowel diseases (ulcerative colitis and Crohn’s disease), hereditary non-polyposis colorectal cancer, familial adenomatous polyposis and serrated polyps/hyperplastic polyposis are known to have a higher risk of synchronous colorectal carcinoma. These predisposing factors account for slightly more than 10% of synchronous colorectal carcinomas. Synchronous colorectal carcinoma is more common in the right colon when compared to solitary colorectal cancer. On pathological examination, some synchronous colorectal carcinomas are mucinous adenocarcinomas. They are usually associated with adenomas and metachronous colorectal carcinomas. Most of the patients with synchronous colorectal cancer have two carcinomas but up to six have been reported in one patient. Patients with synchronous colorectal carcinoma have a higher proportion of microsatellite instability cancer than patients with a solitary colorectal carcinoma. Also, limited data have revealed that in many synchronous colorectal carcinomas, carcinomas in the same patient have different patterns of microsatellite instability status, p53 mutation and K-ras mutation. Overall, the prognosis of patients with synchronous colorectal carcinoma is not significantly different from that in patients with solitary colorectal carcinoma, although a marginally better prognosis has been reported in patients with synchronous colorectal carcinoma in some series. A different management approach and long-term clinical follow-up are recommended for some patients with synchronous colorect

关键词： Synchronous carcinoma Colorectal carcinoma Prevalence Microsatellite instability Review

Leaf Gas Exchange,Chlorophyll Fluorescence,and Fruit Yield in Hot Pepper (Capsicum anmuum L.) Grown Under Different Shade and Soil Moisture During the Fruit Growth Stage

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Journal of Integrative Agriculture 2012年第6期11卷 927-937页

作者： ZHU Juan-juan PENG Qiang LIANG yin-li WU king HAO Wang-lin College of Life Sciences Northwest A&F University Yangling 712100 P.R.China Extension Center of Agricultural Technology Fengxian Agricultural Bureau Fengxian 721700 P.R.China Institute of Soil and Water Conservation the Chinese Academy of Sciences/Ministry of Water Resources Yangling 712100 P..R.China

Relative leaf chlorophyll （Chl.） content, leaf gas exchange, Chl. fluorescence, plant biological biomass, and fruit yield were evaluated in growing hot pepper （Capsicum annuum L.） during the fruit-growing stages in hot summer under three shade levels （un-shade, 30% shade, and 70% shade） and four soil water contents （SWC） of 40-55%, 55-70%, 70-85%, and 85- 100% of field moisture capacity （FMC）. Hot pepper crops were more affected by light irradiance than by soil moisture and by their interaction during the whole observed periods. Hot pepper attained greatest relative leaf Chl. content （expressed as SPAD value） and photosynthetic activity when cultivated with 30% shade, resulting in the highest plant biological biomass and fruit yield. Although 70% shade improved leaf photosynthetic efficiency （expressed as Fv/Fm or Fv＇/Fm＇）, crops obtained the lowest photosynthetic rate, photochemical quenching coefficient （qP）, and non-photochemical quenching coefficient （NPQ）. This showed that light irradiance was insufficiency in S70% （70% shade） treatment. The leaf net photosynthetic rates （PN）, Fc/Fm, and fruit yield increased gradually as SWC levels increased from 40-55% to 70- 85% FMC, but decreased as SWC was higher than 70-85% FMC. The water consumption increased progressively with SWC levels, but water-use efficiency （WUE） was the highest when soil moisture was 55-70% FMC. Interaction of shade and soil moisture had significant effects on PN and FJFm, but not on other parameters. Under drought stress （40-55% and 55-70% FMC）, 30% shade could relieve the droughty damage of crops and improve photosynthetic capacity and WUE, but 70% shade could not, oppositely, aggravate the damage. The positive correlation （r2 =0.72） between leaf PN and fruit yield was existent. This indicated that improvement of leaf photosynthesis would increase potentially marketable yield in hot pepper crops during the full fruit-growing stages. For agricultural purposes, approximately S30% （30% shade） with

关键词： leaf chlorophyll content photosynthetic capacity interaction

Tai Ji Quan as antihypertensive lifestyle therapy:A systematic review and meta-analysis

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Journal of Sport and Health Science 2021年第2期10卷 211-221页

作者： yin Wu Blair T.Johnson Shiqi Chen Yiyang Chen Jill Livingston linda S.Pescatello Department of Kinesiology University of ConnecticutStorrsCT 06269USA Institute for Collaboration on Health Interventionand PolicyUniversity of ConnecticutStorrsCT 06269USA Department of Psychological Sciences University of ConnecticutStorrsCT 06269USA Department of Kinesiology University of MichiganAnn ArborMI 48109USA School of Kinesiology Shanghai University of SportShanghai 200438China Homer Babbidge Library University of ConnecticutStorrsCT 06269USA

Background:Professional health organizations are not currently recommending Tai Ji Quan alongside aerobic exercise to treat *** aimed to examine the efficacy of Tai Ji Quan as antihypertensive lifestyle ***:Tai Ji Quan interventions published in English and Chinese were included when they involved healthy adults,reported pre-and postintervention blood pressure(BP),and had a non-exercise/non-diet control *** systematically searched 11 electronic databases for studies published through July 31,2018,yielding 31 qualifying controlled ***(1)evaluated the risk of bias and methodological study quality,(2)performed meta-regression analyses following random-effects assumptions,and(3)generated additive models representing the largest possible clinically relevant BP ***:Participants(n=3223)were middle-aged(56.6±15.1 years of age,mean±SD)adults with prehypertension(systolic BP(SBP)=136.9±15.2 mmHg,diastolic BP(DBP)=83.4±8.7 mmHg).Tai Ji Quan was practiced 4.0±1.4 sessions/week for 54.0§10.6 min/session for 22.3±20.2 ***,Tai Ji Quan elicited significant reductions in SBP(-11.3 mmHg,95%CI:-14.6 to-8.0;d+=-0.75)and DBP(-4.8 mmHg,95%CI:-6.4 to-3.1;d+=-0.53)***(p<0.001).Controlling for publication bias among samples with hypertension,Tai Ji Quan trials published in English elicited SBP reductions of 10.4 mmHg and DBP reductions of 4.0 mmHg,which was half the magnitude of trials published in Chinese(SBP reductions of 18.6 mmHg and DBP reductions of 8.8 mmHg).Conclusion:Our results indicate that Tai Ji Quan is a viable antihypertensive lifestyle therapy that produces clinically meaningful BP reductions(i.e.,10.4 mmHg and 4.0 mmHg of SBP and DBP reductions,respectively)among individuals with *** magnitude of BP reductions can lower the incidence of cardiovascular disease by up to 40%.

关键词： Blood pressure Complementary medicine Exercise training HypertensionTagedEnd

GLABROUS INFLORESCENCE STEMS regulates trichome branching by genetically interacting with SIM in Arabidopsis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第7期14卷 563-569页

作者： Li-li SUN Zhong-jing ZHOU Li-jun AN Yan AN Yong-qin ZHAO Xiao-fang MENG Clare STEELE-king yin-bo GAN Department of Agronomy College of Agriculture and Biotechnology Zhejiang University Centre for Novel Agricultural Products Department of Biology University of York

Arabidopsis trichomes are large branched single cells that protrude from the epidermis. The first mor- phological indication of trichome development is an increase in nuclear content resulting from an initial cycle of endoreduplication. Our previous study has shown that the C2H2 zinc finger protein GLABROUS INFLORESCENCE STEMS (GIS) is required for trichome initiation in the inflorescence organ and for trichome branching in response to gibberellic acid signaling, although GIS gene does not play a direct role in regulating trichome cell division. Here, we describe a novel role of GIS, controlling trichome cell division indirectly by interacting genetically with a key endoreduplication regulator SIAMESE (SIM). Our molecular and genetic studies have shown that GIS might indireclty control cell division and trichome branching by acting downstream of SIM. A loss of function mutation of SIM signficantly reduced the expression of GIS. Futhermore, the overexpression of GIS rescued the trichome cluster cell phenotypes of sim mutant. The gain or loss of function of GIS had no significant effect on the expression of SIM. These results suggest that GIS may play an indirect role in regulating trichome cell division by genetically interacting with SIM.

关键词： Arabidopsis thaliana GLABROUS INFLORESCENCE STEMS (GIS) Endoreduplication SIAMESE (SIM) Trichome branching Genetic interaction

Temperature variable and the efficiency of sperm mediated transfection of HPV16 DNA into cells

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Asian Journal of Andrology 2002年第3期4卷 169-173页

作者： Ruslana Kadze Philip J.Chan John D.Jacobson Johannah U.Corselli Alan king Center for Fertility and In Vitro Fertilization Department of Gynecology and Obstetricsand Department of Physiology and PharmacologyLoma Linda University School of MedicineLoma LindaCalifornia 92350USA

Aim:To pretreat sperm at various temperatures before exposure to human papillomavirus(HPV)16 DNA fragments and to assess the efficiency of HPV carrier sperm to transfect cumulus ***:Cumulus cells from follicular aspirates were obtained,pooled and divided into culture dishes containing Sybr Gold-stained HPV DNA carrying sperm that were either pretreated at 4℃,37℃or 40℃(n=5).The cells were incubated in 5%CO_(2) in air mixture at 37℃for 24 *** efficiency of sperm to take up fluorescent HPV DNA was determined at hour *** incubation,cumulus cell viability was assessed using the e0sin method and the percentages of fluorescent cumulus cells ***:Over half of all the cumulus cells became fluorescent with the highest percentage in the 37℃*** pretreated at 4℃had the greatest amount of HPV DNA *** sperm motility was similar for the 3 pretreatment *** were no differences in cumulus viability among the ***:Sperm pretreated at 37℃transferred the greatest amount of fluorescent HPV DNA fragments to the cumulus *** HPV DNA was observed in the nuclear and cytoplasmic *** data suggested the possibility of sperm as a vector for the transmission of HPV DNA to the cumulus cells surrounding ovulated oocytes,which might lead to early implantation failures.

关键词： spermatozoa human papillomavirus gene transfer cumulus fertility

Irinotecan therapy and molecular targets in colorectal cancer: A systemic review

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World Journal of Gastroenterology 2009年第29期15卷 3597-3602页

作者： Jessica Weekes Alfred king-yin Lam Sabe Sebesan Yik-Hong Ho Discipline of Surgery (School of Medicine) and North Queensland Centre for Cancer Research (Australian Institute of Tropical Medicine) James Cook University Townsville Queensland 4811 Australia Discipline of Pathology Griffith Medical School Medicine and Oral Health Centre Gold Coast Campus Gold Coast Queensland 4222 Australia Medical Oncology Townsville Hospital Townsville Queensland 4811 Australia

Irinotecan is the second line chemotherapy for advanced stage colorectal cancer (CRC) after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irinotecan as second line chemotherapy for advanced CRC and the potential roles of the molecular markers, p53 and vascular endothelial growth factor (VEGF) in the management of advanced CRC. Thus, the English literature from 1980 to 2008 concerning irinotecan, p53, VEGF and CRC was reviewed. On review, Phase and clinical trials showed thatirinotecan improves pain-free survival, quality of life, 1-year survival, progression-free survival and overall survival in advanced CRC. p53 and VEGF were expressed in CRC and had a predictive power of aggressive clinical behaviour in CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fasmediated cell apoptosis in CRC cells. Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is onlylimited by irinotecan toxicity levels. To conclude, irinotecan improves the patient's quality of life and the survival rates of patients with advanced CRC. p53 and VEGF status of the patients' tumour is likely to affect the responsiveness of CRC to irinotecan. It is recommended that studies of the expression of these molecular markers in relation to chemoresponsiveness ofirinotecan should be carried out for better management of patients with advanced CRC.

关键词： Colorectal cancer Irinotecan Molecular p53 Vascular endothelial growth factor