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rFliC prolongs allograft survival in association with the activation of recipient Tregs in a TLR5-dependent manner

Cellular & Molecular Immunology 2014年第2期11卷 206-214页

作者： Jing Hao Chao Zhang Jing Song Guihua Hou Key laboratory for experimental Teratology of the Ministry of Education and Institute of experimental Nuclear Medicine Shandong University MedicalSchool Jinan 250012 China

AIIorejection remains an obstacle for successful organ transplantation. Although different types of immunosuppressive agents are effective for controlling rejection and prolonging graft survival, drug treatment is limited because of side effects and toxicity. Therefore, it is necessary and urgent to identify new candidate drugs for inducing allotolerance. Recently, it has been reported that bacterial flagellin induces the immunosuppressive activity of regulatory T cells （Tregs） in humans in vitro. In the present study, we analyzed the effects of recombinant flagellin （rFliC） on allograft survival and explored the underlying mechanisms associated with the activation of recipient Tregs in a murine skin allotransplantation model. The results showed that rFliC administration （3 mg/kg, once per day for 3 days, i.p.） prolonged allograft survival （mean survival time： 18.4--.1.1 days） compared to the control group （10___0.7 days, P〈O.01）. Additionally, higher positive expression of Toll-like receptor 5 （TLR5） was detected within the allograft administered with rFliC. The frequency of CD4＋CD25＋Foxp3＋ Tregs; the expression of Treg-related factors TLR5, Foxp3, TGF-I^I and IL-IO; and the proliferation and suppression of Tregs were increased following rFliC administration compared to the control. Moreover, the increased expression of tolerance-related molecules and the proliferation of Tregs induced by rFliC were attenuated by an anti-TLR5 blocking antibody both in vivo and in vitro. In conclusion, rFliC administration prolongs the survival of allografts, which is associated with the activation of recipient Tregs in a TLR5-dependent manner, rFliC may be a new candidate for anti-allorejection therapy.

关键词： allotransplantation flagellin regulatory T cells TLR5

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Bile acids:Chemistry,physiology,and pathophysiology

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World Journal of Gastroenterology 2009年第7期15卷 804-816页

作者： Maria J Monte Jose JG Marin Alvaro Antelo Jose Vazquez-Tato laboratory of experimental Hepatology and Drug Targeting CIBERehdUniversity of Salamanca Facultad de Ciencias Departamento de Quimica FisicaCampus of LugoUniversity of Santiago

The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physical-chemical and biological characteristics.They are synthesized by the liver from cholesterol through several complementary pathways that are controlled by mechanisms involving finetuning by the levels of certain bile acid species.Although their best-known role is their participation in the digestion and absorption of fat,they also play an important role in several other physiological processes.Thus,genetic abnormalities accounting for alterations in their synthesis,biotransformation and/or transport may result in severe alterations,even leading to lethal situations for which the sole therapeutic option may be liver transplantation.Moreover,the increased levels of bile acids reached during cholestatic liver diseases are known to induce oxidative stress and apoptosis,resulting in damage to the liver parenchyma and,eventually,extrahepatic tissues.When this occurs during pregnancy,the outcome of gestation may be challenged.In contrast,the physical-chemical and biological properties of these compounds have been used as the bases for the development of drugs and as pharmaceutical tools for the delivery of active agents.

关键词：物理化学病理生理学胆汁酸诱导氧化应激肝脏疾病生物学特性消化吸收生理过程

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Regulation of mitochondrial carrier SLC25A13 on breast cancer cell cycle in vitro

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上海交通大学学报（医学版） 2019年第8期39卷 848-855页

作者：顾孝平 CHEN Meng-ping LIANG A-juan LIU Yun-xia SUN Hai-peng 黄莹 Key laboratory of Cell Differentiation and Apoptosis of National Ministry of Education Department of Pathophysiology Shanghai Jiao Tong University College of Basic Medical Sciences Shanghai 200025 China Center for Reproductive Medicine Tongji Hospital Tongji University School of Medicine Shanghai 200065 China

Objective·To investigate the role of mitochondrial solute carrier family 25 member 13(SLC25A13)on breast cancer development.Methods·SLC25A13 mRNA and protein expressions in invasive breast cancer tissues and normal breast tissues were from The Cancer Genome Atlas(TCGA)breast cancer dataset.Survival analysis was conducted online by Kaplan-Meier software.MCF-7 cell line was used for in vitro cell assay.Knockdown of SLC25A13 and sirtuin 2(SIRT2)were conducted by siRNA transfection.Cell viability was measured with trypan blue exclusion.Cell cycle arrest was determined by flow cytometry.The mRNA expression of SLC25A13 and P27 were detected by quantitative PCR.The protein level of SLC25A13,P27 and SIRT2 were detected by Western blotting.Protein half-life of P27 was assessed by Western blotting after cycloheximide treatment.Results·SLC25A13 was up-regulated in invasive breast cancer tissues.High expression of SLC25A13 correlated with poor overall survival and breast cancer recurrence.SLC25A13 knockdown inhibited MCF-7 cell cycle progression.P27 and SIRT2 both accumulated after SLC25A13 knockdown.P27 accumulation resulted from prolonged protein half-life.Knockdown of SIRT2 restored cell cycle arrest as well as P27 accumulation caused by SLC25A13 silencing.Conclusion·High expression of SLC25A13 may promote cell cycle progression via SIRT2 in breast cancer development.

关键词： solute carrier family 25 member 13(SLC25A13) sirtuin-2(SIRT2) P27 breast cancer cell cycle

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Negative association between trunk fat, insulin resistance and skeleton in obese women

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World Journal of Diabetes 2013年第2期4卷 31-39页

作者： Emanuela A Greco Davide Francomano Rachele Fornari Chiara Marocco Carla Lubrano Vincenza Papa Francesca Wannenes Luigi Di Luigi Lorenzo M Donini Andrea Lenzi Antonio Aversa Silvia Migliaccio Department of experimental Medicine Section of Medical Pathophysiology Endocrinology and Nutrition University "Sapienza"of Rome Department of experimental Medicine Section of Medical Pathophysiology Endocrinology and Nutrition University "Sapienza" of Rome Unit of Endocrinology Department of Health Sciences University "Foro Italico" of Rome

AIM: To evaluate the potential interference of trunk fat (TF) mass on metabolic and skeletal metabolism. METHODS: In this cross-sectional study, 340 obese women (mean age: 44.8 ± 14 years; body mass index: 36.0 ± 5.9 kg/m 2 ) were included. Patients were evaluated for serum vitamin D, osteocalcin (OSCA), inflammatory markers, lipids, glucose and insulin (homeostasis model assessment of insulin resistance, HOMA-IR) levels, and hormones profile. Moreover, all patients underwent measurements of bone mineral density (BMD;at lumbar and hip site) and body composition (lean mass, total and trunk fat mass) by dual-energy X-ray absorptiometry. RESULTS: Data showed that: (1) high TF mass was inversely correlated with low BMD both at lumbar (P < 0.001) and hip (P < 0.01) sites and with serum vitamin D (P < 0.0005), OSCA (P < 0.0001) and insulin-like growth factor-1 (IGF-1; P < 0.0001) levels; (2) a positive correlation was found between TF and HOMA-IR (P < 0.01), fibrinogen (P < 0.0001) and erythrocyte sedimentation rate (P < 0.0001); (3) vitamin D levels were directly correlated with IGF-1 (P < 0.0005), lumbar (P < 0.006) and hip (P < 0.01) BMD; and (4) inversely with HOMA-IR (P < 0.001) and fibrinogen (P < 0.0005). Multivariate analysis demonstrated that only vitamin D was independent of TF variable. CONCLUSION: In obese women, TF negatively correlates with BMD independently from vitamin D levels. Reduced IGF-1 and increased inflammatory markers might be some important determinants that account for this relationship.

关键词： Obesity Skeleton Vitamin D Osteocalcin Insulin resistance Trunk fat Inflammation

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A novel viewpoint in glaucoma therapeutics: enriched environment

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Neural Regeneration Research 2022年第7期17卷 1431-1439页

作者： María F.González Fleitas Damián Dorfman Ruth E.Rosenstein laboratory of Retinal Neurochemistry and experimental Ophthalmology Department of Human BiochemistrySchool of Medicine/CEFyBOUniversity of Buenos Aires/CONICETBuenos AiresArgentina

Glaucoma is one of the world’s most frequent visual impairment causes and leads to selective damage to retinal ganglion cells and their axons.Despite glaucoma’s most accepted risk factor is increased intraocular pressure(IOP),the mechanisms behind the disease have not been fully elucidated.To date,IOP lowering remains the gold standard;however,glaucoma patients may still lose vision regardless of effective IOP management.Therefore,the exclusive IOP control apparently is not enough to stop the disease progression,and developing new resources to protect the retina and optic nerve against glaucoma is a goal of vast clinical importance.Besides pharmacological treatments,environmental conditions have been shown to prevent neurodegeneration in the central nervous system.In this review,we discuss current concepts on key pathogenic mechanisms involved in glaucoma,the effect of enriched environment on these mechanisms in different experimental models,as well as recent evidence supporting the preventive and therapeutic effect of enriched environment exposure against experimental glaucomatous damage.Finally,we postulate that stimulating vision may become a non-invasive and rehabilitative therapy that could be eventually translated to the human disease,preventing glaucoma-induced terrible sequelae resulting in permanent visual disability.

关键词： brain-derived neurotrophic factor chondroitin sulfate enriched environment glaucoma optic nerve axons optic nerve glia retinal ganglion cells visual stimulation

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T淋巴细胞能量代谢及其生物学意义(英文)

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Science Bulletin 2016年第16期61卷 1270-1280页

作者：杨祎冯娟吕思霖王宪 Department of Physiology and pathophysiology School of Basic Medical Science Peking University Key Laboratory of Molecular Cardiovascular Science Ministry of Education

能量代谢为细胞的基本特性,除满足细胞在各种功能状态下的能量和生物合成需求外,同样参与信号级联反应调控细胞的功能及命运.能量稳态是维持细胞生存和正常功能的重要条件.近年,细胞代谢与功能之间的关系成为对各种代谢性疾病、肿瘤及... 详细信息

能量代谢为细胞的基本特性,除满足细胞在各种功能状态下的能量和生物合成需求外,同样参与信号级联反应调控细胞的功能及命运.能量稳态是维持细胞生存和正常功能的重要条件.近年,细胞代谢与功能之间的关系成为对各种代谢性疾病、肿瘤及自身免疫性疾病研究的热点.T淋巴细胞为一类重要的适应性免疫细胞,参与调节多种炎症性疾病的发生发展.因此T淋巴细胞能量代谢引起了越来越多研究者的关注.本综述中我们主要关注T淋巴细胞能量代谢与其激活、分化和功能之间的关系及相应调节机制,并初步探讨其在免疫炎症性疾病中的潜在治疗前景.

关键词：能量代谢 T细胞生物学意义能量平衡 T淋巴细胞调节机制生理功能疾病

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Novel synthetic adhesive as an effective alternative to Fibrin based adhesives

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World Journal of Hepatology 2017年第24期9卷 1030-1039页

作者： Pramod Kadaba Srinivasan Vera Sperber Mamdouh Afify Hirokazu Tanaka Kenji Fukushima Babette Kogel Felix Gremse RenéTolba Institute for laboratory Animal Science and experimental Surgery University Hospital RWTH Aachen experimental Molecular Imaging University Hospital RWTH Aachen

AIM To compare a novel, fully synthetic, polyurethane based glue(MAR-1) to fibrin sealant in a partial liver resection rat model.METHODS After 50% resection of the lateral left liver lobe in male Wistar rats(n = 7/group/time point), MAR-1, Fibrin or Na Cl was applied. After 14, 21 and 90 postoperative days, sealant degradation, intra-abdominal adhesions were scored, and histological examination of liver tissue was performed.RESULTS(Mean ± SEM)(MAR-1 vs Fibrin vs Na Cl). Bleeding mass was significantly higher in Na Cl(3.36 ± 0.51 g)compared to MAR-1(1.44 ± 0.40 g) and Fibrin(1.16 ± 0.32 g). At 14 and 90 d, bleeding time was significantly lower in MAR-1(6.00 ± 0.9 s; 13.57 ± 3.22 s) and Fibrin(3.00 ± 0.44 s; 22.2 ± 9.75 s) compared to Na Cl(158.16 ± 11.36 s; 127.5 ± 23.3 s). ALT levels were significantly higher in MAR-1(27.66 ± 1 U/L) compared to Fibrin(24.16 ± 0.98 U/L) and Na Cl(23.85 ± 0.80 U/L). Intrabdominal adhesions were significantly lower in MAR-1(11.22% ± 5.5%) compared to Na Cl(58.57% ± 11.83%). Degradation of the glue was observed and MAR-1 showed almost no traces of glue in the abdominal cavity as compared to the Fibrin(10% ± 5% 14 d; 7% ± 3% 21 d). Survival showed no significant differences between the groups.CONCLUSION Compared to Fibrin, MAR-1 showed similar hemostatic properties, no adverse effects, and is biocompatible. Further studies on adhesion strength and biodegradability of synthetic sealants are warranted.

关键词： MAR-1 血纤维蛋白肝切除术 Hemostasis 聚氨酯

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Neuroprotective agents effective against radiation damage of central nervous system

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Neural Regeneration Research 2022年第9期17卷 1885-1892页

作者： Mária Lalkovičová laboratory of Radiation Biology Joint Institute for Nuclear ResearchDubnaRussia Slovak Academy of Sciences Institute of Experimental PhysicsKošiceSlovakia

Ionizing radiation caused by medical treatments,nuclear events or even space flights can irreversibly damage structure and function of brain cells.That can result in serious brain damage,with memory and behavior disorders,or even fatal oncologic or neurodegenerative illnesses.Currently used treatments and drugs are mostly targeting biochemical processes of cell apoptosis,radiation toxicity,neuroinflammation,and conditions such as cognitive-behavioral disturbances or others that result from the radiation insult.With most drugs,the side effects and potential toxicity are also to be considered.Therefore,many agents have not been approved for clinical use yet.In this review,we focus on the latest and most effective agents that have been used in animal and also in the human research,and clinical treatments.They could have the potential therapeutical use in cases of radiation damage of central nervous system,and also in prevention considering their radioprotecting effect of nervous tissue.

关键词： antioxidants biomedical neuroprotectants central nervous system ionizing radiation neuroprotection radiation injury radiomitigators radioprotectants radioprotection therapeutics

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Changes of proteins induced by anticoagulants can be more sensitively detected in urine than in plasma

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中国科学：生命科学英文版 2014年第11期57卷 649-656页

作者： LI MengLin ZHAO MinDi GAO YouHe National Key laboratory of Medical Molecular Biology Department of Physiology and PathophysiologyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical College

The most fundamental property of biomarkers is change.But changes are hard to maintain in plasma since it is strictly controlled by homeostatic mechanisms of the body.There is no homeostatic mechanism for urine.Besides,urine is partly a filtration of blood,and systematic information can be reflected in urine.We hypothesize that change of blood can be reflected in urine more sensitively.Here we introduce the interference into the blood by two anticoagulants heparin or argatroban.Plasma and urine proteins were profiled by LC-MS/MS and then validated by Western blot in totally six SD female rats before and after the drug treatments.In argatroban treated group,with exactly the same experimental procedure and the same cutoff value for both plasma and urine proteins,62 proteins changed in urine,only one of which changed in plasma.In heparin treated group,27 proteins changed in urine but only three other proteins changed in plasma.Both LC-MS/MS and Western blot analyses demonstrated drug-induced increases in transferrin and hemopexin levels in urine but not in plasma.Our data indicates that urine may serve as a source for more sensitive detection of protein biomarkers than plasma.

关键词：血浆蛋白药物诱导尿液抗凝血剂灵敏 Western印迹检测 LC-MS

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Cross-metathesis of biomass to olefins:Molecular catalysis bridging the gap between fossil and bio-energy

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Chinese Journal of Chemical Engineering 2022年第8期35卷 44-60页

作者： Wenjuan Yan Zhenchao You Kexin Meng Feng Du Shuxia Zhang Xin Jin State Key laboratory of Heavy Oil Processing Center for Chemical Engineering Experimental TeachingChina University of PetroleumQingdao 266580China

Terminal olefins are important building blocks for the industry of biofuels,oligomers,and lubricants production.The industrial processes for production of olefins involving oligomerization of ethylene or cracking of petrochemical waxes have several flaws including low yield and high cost in product separation.Cross-metathesis of bio-derived unsaturated fatty esters and olefins with ethylene(ethenolysis),allows the conversion of sustainable waste biomass to various renewable olefins with much safer,less toxic,sustainable,and zero-CO_(2) emission processes.To our best knowledge,however,a comprehensive summary of key advances in this field(since 2017)is yet to be available,particularly on molecular features of homogeneous and heterogeneous catalysts.This paper presents a critical review on molecular structures of metal complex and oxide catalysts for ethenolysis of olefins and oleochemicals.The influence of cationic centers,coordination conditions,nature of ligands,operating conditions on catalyst performances will be systematically discussed along with relevant reaction mechanism.The key challenges for rational design of coordinated cationic hybrids have been summarized,which will provide insights to technological advancement of large-scale production of oleochemical-derived olefins.

关键词： Metathesis Catalysts Metal complex Metal oxide Olefins Oleochemicals

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