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Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver

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cellular & Molecular Immunology 2022年第7期19卷 834-847页

作者： Wenshu Tang Jingying Zhou Weiqin Yang Yu Feng haoran Wu Myth T.S.Mok Lingyun Zhang Zhixian Liang Xiaoyu Liu Zhewen Xiong Xuezhen Zeng Jing Wang Jiahuan Lu Jingqing Li hanyong Sun Xiaoyu Tian Philip chun Yeung Yong hou heung Man Lee candice c.h.lam howard h.W.Leung Anthony W.h.chan Ka Fai To John Wong Paul B.S.Lai Kelvin K.c.Ng Simon K.h.Wong Vincent W.S.Wong Alice P.S.Kong Joseph J.Y.Sung Alfred S.L.cheng school of Biomedical Sciences The Chinese University of Hong KongHong Kong SAR 999077China Department of Anatomical and cellular Pathology The Chinese University of Hong KongHong Kong SAR 999077China Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of Surgery The Chinese University of Hong KongHong Kong SAR 999077China Department of Medicine and Therapeutics The Chinese University of Hong Kong.Hong Kong SAR 999077China State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SAR 999077China Lee Kong chian School of Medicine Nanyang Technological UniversitySingapore 639798Singapore Institute of Precision Medicine The First Affliated HospitalSun Yat-sen UniversityGuangzhou 510080China

Obesity is a major risk factor for cancers including hepatocellular carcinoma(hcc)that develops from a background of non-alcoholic fatty liver disease(NAFLD).hypercholesterolemia is a common comorbidity of *** cholesterol biosynthesis mainly occurs in the liver,its role in hcc development of obese people remains *** high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-hcc mouse models,we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T(NKT)cell-mediated antitumor *** analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD ***,cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted hcc ***,suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by NKT inactivation but not cD8^(+)T cell ***,sterol regulatory element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells,which were supported by findings in people with obesity,NAFLD and *** study highlights mTORc1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control hcc in the obesity epidemic.

关键词： cancer microenvironment cancer models Tumour immunology

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A novel role for tissue-nonspecific alkaline phosphatase at the blood-brain barrier during sepsis

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Neural Regeneration Research 2021年第1期16卷 99-100页

作者： Divine c.Nwafor candice M.Brown Department of Neuroscience West Virginia University Health Science CenterMorgantownWVUSA Department of Microbiology Immunologyand Cell BiologySchool of MedicineWest Virginia University Health Science CenterMorgantownWVUSA

Sepsis and the blood-brain barrier(BBB):Sepsis is a life threatening systemic inflammatory condition involving multi-organ *** World health Organization estimates that about 30 million people are affected by sepsis every year,and at least 6 million people die from sepsis each *** of approximately 24 million sepsis survivors,it is estimated that 70%of these individuals will experience some form of long-term neurological impairment(Iwashyna et al.,2010).Thus,when combined with prevention,diagnosis,and therapeutic management strategies,a functional understanding of the mechanisms that promote sepsis-associated neurological impairment is necessary to address the clinical challenges and economic burdens faced when treating sepsis.

关键词： prevention diagnosis barrier

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Immanant positivity for catalan-Stieltjes matrices

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Frontiers of Mathematics in china 2022年第5期17卷 887-903页

作者： Ethan Y.h.LI Grace M.X.LI Arthur L.B.YANG candice X.T.ZhANG center for combinatorics LPMCNankai UniversityTianjin 300071China

We give some sufficient conditions for the nonnegativity of immanants of square submatrices of catalan-Stieltjes matrices and their corresponding hankel *** obtain these sufficient conditions,we construct new planar networks with a recursive nature for catalan-Stieltjes *** applications,we provide a unified way to produce inequalities for many combinatorial polynomials,such as the Eulerian polynomials,Schröder polynomials,and Narayana polynomials.

关键词： Immanant character catalan-Stieltjes matrices hankel matrices planar network

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Alpha-adrenoceptor antagonism by crassostrea gigas oyster extract inhibits noradrenalineinduced vascular contraction in Wistar rats

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Journal of Integrative Medicine 2015年第3期13卷 194-200页

作者： Kylie connolly Douglas Jackson candice Pullen Andrew Fenning School of Medical and Applied Sciences CQUniversity Australia

OBJEcTIVE： crassostrea gigas oyster extract has been reported to have antioxidant, antihypertensive and lipid-lowering properties that may be useful for treating cardiovascular diseases. This study aimed to evaluate the effect of c. gigas oyster extract on cardiovascular function in tissues from healthy rats. METhODS： Single-cell microelectrode and isolated thoracic aortic organ bath studies were performed on tissues from 8-week-old healthy Wistar rats, using varying concentrations of c. gigas oyster extract. To elucidate a mechanism of action for the oyster’s vasoactive properties, concentration response curves were carried out in the presence of a calcium channel inhibitior（verapamil）, a nitric oxide synthase inhibitor（N G-nitro-L-arginine methyl ester）, a potassium channel inhibitor（4-aminopyridine）, in addition to the α-adrenoceptor inhibitor prazosin. RESULTS： Oyster solution at 7 500 mg/m L inhibited noradrenaline-induced contraction in isolated aortic rings. cardiac electrophysiology results showed that neither concentration of oyster solution was able to significantly reduce action potential duration at all phases of repolarisation in left ventricular papillary muscles from healthy animals. cONcLUSION： When administered to healthy vascular tissue, c. gigas oyster extract inhibits contraction induced by noradrenaline. This effect is likely to be mediated through α-adrenoceptor inhibition, and to a lesser extent, calcium modulating activity.

关键词： crassostrea hypertension calcium channels receptors,adrenergic rats

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Dynamic Patterns of Gene Expression Additivity and Regulatory Variation throughout Maize Development

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Molecular Plant 2019年第3期12卷 410-425页

作者： Peng Zhou candice N.hirsch Steven P.Briggs Nathan M.Springer Department of Plant and Microbial Biology University of MinnesotaSaint PaulMN 55108USA Department of Agronomy and Plant Genetics University of MinnesotaSaint PaulMN 55108USA Division of Biological Sciences University of CaliforniaSanDiegoLaJollaCA92093USA

Gene expression variation is a key component underlying phenotypic variation and heterosis. Transcriptome profiling was performed on 23 different tissues or developmental stages of two maize inbreds, B73 and Mo17, as well as their hybrid. The obtained large-scale datasets provided opportunities to monitor the developmental dynamics of differential expression, additivity for gene expression, and regulatory variation. The transcriptome can be divided into .30 000 genes that are expressed in at least one tissue of one in bred and an additional ~10 000 “silent” genes that are not expressed in any tissue of any genotype, 90% of which are non-syntenic relative to other grasses. Many (.74%) of the expressed genes exhibit differential expression in at least one tissue. however, the majority of genes with differential expression do not exhibit consistent differential expression in different tissues. These genes often exhibit tissue-specific differential expression with equivalent expression in other tissues, and in many cases they switch the directionality of differential expression in different tissues. This suggests widespread variation for tissue-specific regulation of gene expression between the two maize inbreds B73 and Mo17. Nearly 5000 genes are expressed in only one parent in at least one tissue (single parent expression) and 97% of these genes are expressed at mid-parent levels or higher in the hybrid, providing extensive opportunities for hybrid complementation in heterosis. In general, additive expression patterns are much more common than non-additive patterns, and this trend is more pronounced for genes with strong differential expression or single pare nt expressi on. There is relatively little evidence for non-additive expression patterns that are maintained in multiple tissues. The analysis of allele-specific expression allowed classification of cis. and trans-regulatory variation. Genes with c/s-regulatory variation often exhibit additive expression and tend

关键词： maize gene expression heterosis differential expression non-additive expression allele-specific expression

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Lactate reloaded–reevaluation of the importance of lactate monitoring in the management of adult sepsis in the emergency department

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BIOcELL 2021年第3期45卷 445-449页

作者： GABOR XANTUS BALINT KISS GYULA MOLNAR candice MAThESON V.A NNA GYARMAThY PETER L.KANIZSAI cardiff University CardiffCF103ATUK Semmelweis University Budapest1085Hungary Dalhuis University halifax HalifaxNS B3H 4R2Canada Epiconsult Biomedical consulting and Medical communications Agency DoverDE 19901USA Pecs University Clinical CentrePecs7626Hungary

For about a quarter of a century,monitoring lactate levels and/or lactate clearance has been an unquestionable cornerstone in sepsis *** elevated lactate level appeared to be an independent predictor of mortality,and the consequent metabolic acidosis was thought to explain a number of pathophysiological changes seen in septic *** physiological and clinical findings seem to challenge the adverse role of lactic acidosis in *** suggests that lactate levels are not necessarily directly proportional to either tissue or cellular hypoxia,and conversely,despite high lactate levels,increased peripheral tissue oxygen pressure can be measured in adult patients with septic *** to the most recent understanding of in vitro and in vivo evidence,the elevated lactate level in sepsis might be a normal reaction due to adrenergic stress with potential beneficial/protective physiological effects,as *** the one hand,burning lactic may help fuel the body during critical illness,but on the other hand,with a slight drop in ph,the body may counteract certain deleterious changes during the dysregulated host response;reduce the chances of reperfusion myocardial injury,and improve tissue oxygenation by shifting the haemoglobin dissociation curve to the *** the pathophysiological process in sepsis resulting in elevated lactate levels may aid management in an emergency,medicine,and intensive care *** more in-depth physiological knowledge,physicians may inevitably surpass normalisation heuristics and deliver personalized rather than protocolised sepsis resuscitation.

关键词： Reevaluation Lactate Sepsis Resuscitation

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2003和2004年春季台北大气悬浮物中的水溶性离子(英文)

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干旱区资源与环境 2004年第S1期18卷 173-177页

作者： Shih-chun candice Lung charles c-K chou Shaw c. Liu Institute of Earth Sciences Academia Sinica P. O. BOX 1-55 Nankang Taipei Taiwan 11529 R.O.CpresenterInstitute of Earth Sciences Academia Sinica Nankang Taipei Taiwan 115Institute of Earth Sciences Academia Sinica Nankang Taipei Taiwan 115

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cT of hepatocellular carcinoma in non-alcoholic fatty liver disease: imaging characteristics and inter-rater agreement

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hepatoma Research 2019年第10期5卷 42-52页

作者： Ishan Garg Scott M.Thompson Shannon P.Sheedy Taofic Mounajjed Ashish Khandelwal Eric c.Ehman candice A.Bookwalter Sudhakar K.Venkatesh Department of Radiology Mayo Clinic College of MedicineRochesterMN 55905USA Department of Laboratory Medicine and Pathology Mayo Clinic College of MedicineRochesterMN 55905USA

Aim:To determine the computed tomography(cT)features of non-alcoholic fatty liver disease(NAFLD)associated hepatocellular carcinoma(hcc).Methods:In this institutional review board approved study,we reviewed 38 patients with NAFLD(68.4%male;mean age 63 years)with histology confirmed hcc and triphasic liver *** images were independently reviewed by four readers blinded to clinical and pathology *** reviewers assessed hcc for arterial phase hyper enhancement(APhE),portal venous phase washout(PVWO),delayed phase washout(DPWO),and enhancing *** of cirrhotic morphology and portal hypertension(Ph)were also *** final cT features were determined by majority and a fifth reader reviewed cases lacking ***-rater agreement was determined by prevalence-adjusted ***:Mean hcc size was 3.6±2.8 cm(range,1.1-16.0 cm).The hccs showed APhE in 92.1%,PVWO in 55.3%,DPWO in 81.6%,and enhancing capsule in 44.7%.cirrhotic morphology was present in 65.8%and Ph in 63.2%.Inter-rater agreement was moderate to almost perfect for APhE(0.74-1.0),cirrhosis(0.79-0.89),and Ph(0.79-0.95),weak to perfect for DPWO(0.47-0.95)and poor for PVWO(0-0.42). ;conclusion:NAFLD associated hcc demonstrate less frequent portal venous washout on cT which may affect their imaging diagnosis.

关键词： hepatocellular carcinoma computed tomography fatty liver inter-rater agreement non-alcoholic fatty liver disease

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Adsorptive Removal from Aqueous Solution of cr(VI) by Green Moringa Tea Leaves Biomass

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Journal of Encapsulation and Adsorption Sciences 2017年第2期7卷 108-119页

作者： candice c. Timbo Martha Kandawa-Schulz Marta Amuanyena habauka M. Kwaambwa Department of chemistry and Biochemistry University of Namibia Windhoek Namibia Faculty of health and Applied Sciences Namibia University of Science and Technology Windhoek Namibia

hexavalent chromium, cr(VI), is a toxic metal present in industrial effluents. The study was carried to test the use of green Moringa leaves biomass as adsorbent for cr(VI) from aqueous solutions. Batch adsorption method was used and the concentration of cr(VI) measured using an ultraviolet-visible (UV-Vis) spectrophotometry. The effects of the adsorption contact time, adsorbent dosage, ph, initial adsorbate concentration and temperature were studied. Results show maximum removal of cr(VI) of 99% ± 1%, with maximum adsorption capacity of 33.9 mg/g at a ph 2, 60 minutes contact time and 100 mg/l initial cr(IV) concentration. The Langmuir and Freundlich adsorption isotherm models were used to fit the experimental data. The data showed that adsorption on green Moringa oleifera leaves tea biomass fitted well to Freundlich isotherm (r2 = 0.9432) compared to the Langmuir isotherm (r2 = 0.9122). M. oleifera leaves biomass can be used in water purification systems. The sludge of M. oleifera leaves is biodegradable, cost effective and environmentally friendly and therefore attractive in hexavalent chromium removal in water.

关键词： Adsorbent Adsorption Isotherm heavy Metals hexavalent chromium Moringa oleifera

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FOLFIRI3-aflibercept in previously treated patients with metastatic colorectal cancer

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World Journal of clinical Oncology 2018年第5期9卷 110-118页

作者： candice carola Fran?ois Ghiringhelli Stefano Kim Thierry ANDré Juliette Barlet Le?la Bengrine-Lefevre hélène Marijon Marie-Line Garcia-Larnicol christophe Borg Linda Dainese Nils Steuer hubert Richa Magdalena Benetkiewicz Annette K Larsen Aimery de Gramont Benoist chibaudel Department of Medical Oncology Franco-British Institute Department of Medical Oncology Centre George Fran?ois Leclerc Department of Medical Oncology CHU Besan?on Department of Medical Oncology Saint-Antoine Hospital and Sorbonne Universités UMPC Department of Anatomy-Pathology Paris Pathology Institute Department of Gastrointestinal Surgery Franco-British Institute Fondation ARcAD cancer Biology and Therapeutics Centre de Recherche Saint-Antoine INSERM U938 Faculté de Médecine Sorbonne Université

AIM To evaluate the efficacy and safety of the modified FOLFIRI3-aflibercept as second-line therapy in patients with metastatic colorectal *** This is a retrospective multicenter cohort, evaluating the efficacy and safety of the association of aflibercept with FOLFIRI3(day 1: aflibercept 4 mg/kg, folinic acid 400 mg/m^2, irinotecan 90 mg/m^2, 5-fluorouracil infusion 2400 mg/m^2 per 46 h; day 3: irinotecan 90 mg/m^2) in patients with previously treated metastatic colorectal cancer. The primary endpoint was overall response rate(ORR). Secondary endpoints were disease control rate(DcR), progression-free survival(PFS), overall survival(OS), and *** Among 74 patients treated in four French centers, nine were excluded due to prior use of aflibercept(n = 3), more than one prior treatment line in irinotecanna?ve patients(n = 3), and inadequate liver function(n = 3). In the "irinotecan-na?ve" patients(n = 30), ORR was 43.3% and DcR was 76.7%. Median PFS and OS were 11.3 mo(95%cI: 6.1-29.0) and 17.0 mo(95%cI: 13.0-17.3), respectively. The most common(> 5%) grade 3-4 adverse events were diarrhea(37.9%), neutropenia(14.3%), stomatitis and anemia(10.4%), and hypertension(6.7%). In the "pre-exposed irinotecan" patients(n = 35), 20(57.1%) received ≥ 2 prior lines of treatment. ORR was 34.3% and DcR was 60.0%. Median PFS and OS were 5.7 mo(95%cI: 3.9-10.4) and 14.3 mo(95%cI: 12.8-19.5), *** Minimally modified FOLFIRI has improvement dramatically the FOLFIRI3-aflibercept efficacy, whatever prior use of irinotecan. A prospective randomized trial is warranted to compare FOLFIRI-aflibercept to FOLFIRI3-aflibercept.

关键词： chemotherapy Irinotecan Aflibercept Second-line colorectal cancer

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