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In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions

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Acta Pharmaceutica Sinica B 2021年第4期11卷 989-1002页

作者： Ana LMartínez-López Carlos JGonzález-Navarro Paula Aranaz JoséLVizmanos Juan MIrache NANO-VAC Research Group Department of Chemistry and Pharmaceutical TechnologySchool of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Center for Nutrition Research School of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Department of Biochemistry&Genetics School of ScienceUniversity of NavarraPamplona 31080Spain Navarra Institute for Health Research(IdiSNA) Pamplona 31080Spain

The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of insulin.These nanocarriers,based on the coating of zein nanoparticles with a polymer conjugate containing PEG,displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 mg/mg.In intestinal pig mucus,the diffusivity of these nanoparticles(PPA-NPs)was found to be 20-fold higher than bare nanoparticles(NPs).These results were in line with the biodistribution study in rats,in which NPs remained trapped in the mucus,whereas PPA-NPs were able to cross this layer and reach the epithelium surface.The therapeutic effcacy was evaluated in Caenorhabditis elegans grown under high glucose conditions.In this model,worms treated with insulin-loaded in PPA-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in NPs.This finding was associated with a signifcant reduction in the formation of reactive oxygen species(ROS)as well as an important decrease in the glucose and fat content in worms.These effects would be related with the mucus-permeating ability of PPA-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms(similar to mucus)and,thus,the absorption of insulin.

关键词： Nanoparticles Oral delivery Mucus-permeating Biodistribution Insulin Caenorhabditis elegans ROS

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The role of serratiopeptidase in the resolution of inflammation

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Asian Journal of Pharmaceutical Sciences 2017年第3期12卷 209-215页

作者： Manju Tiwari department of biochemistry and genetics Barkatullah University

Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a protective measure to remove cause of inflammation and failure of resolution lead to chronic inflammation. Over a period of time, a number of drugs mostly chemical have been deployed to combat acute and chronic inflammation. Recently, enzyme based anti-inflammatory drugs became popular over conventional chemical based drugs. Serratiopeptidase, a proteolytic enzyme from trypsin family, possesses tremendous scope in combating inflammation. Serine protease possesses a higher affinity for cyclooxygenase(COX-Ⅰ and COX-Ⅱ), a key enzyme associated with production of different inflammatory mediators including interleukins(IL),prostaglandins(PGs) and thromboxane(TXs) etc. Currently, arthritis, sinusitis, bronchitis,fibrocystic breast disease, and carpal tunnel syndrome, etc. are the leading inflammatory disorders that affected the entire the globe. In order to conquer inflammation, both acute and chronic world, physician mostly relies on conventional drugs. The most common drugs to combat acute inflammation are Nonsteroidal anti-inflammatory drugs(NSAIDs) alone and or in combination with other drugs. However, during chronic inflammation, NSAIDs are often used with steroidal drugs such as autoimmune disorders. These drugs possess several limitations such as side effects, ADR, etc. In order to overcome these limitations and complications, enzyme based drugs(anti-inflammatory) emerged, and aim for a new high since the last decade. Serine protease, the largest proteolytic family has been reported for several therapeutic applications, including anti-inflammatory. Serratiopeptidase is a leading enzyme which has a very long history in medical as an effective anti-inflammatory drug. Current study emphasizes present scenario and future prospect of serratiopeptidase as an antiinflammatory drug. The study also illustrates a comparative analysis of conventional drugs a

关键词： Inflammation Cyclooxygenase NSAIDs Serratiopeptidase Steroids Enzyme therapeutics

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Glucose 6 phosphatase dehydrogenase (G6PD) and neurodegenerative disorders:Mapping diagnostic and therapeutic opportunities

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Genes & Diseases 2017年第4期4卷 196-203页

作者： Manju Tiwari department of biochemistry and genetics Barkatullah UniversityBhopalMadhya PradeshIndia

Glucose 6 phosphate dehydrogenase(G6PD)is a key and rate limiting enzyme in the pentose phosphate pathway(PPP).The physiological significance of enzyme is providing reduced energy to specific cells like erythrocyte by maintaining co-enzyme nicotinamide adenine dinucleotide phosphate(NADPH).There are preponderance research findings that demonstrate the enzyme(G6PD)role in the energy balance,and it is associated with bloodrelated diseases and disorders,primarily the anemia resulted from G6PD deficiency.The Xlinked genetic deficiency of G6PD and associated non-immune hemolytic anemia have been studied widely across the globe.Recent advancement in biology,more precisely neuroscience has revealed that G6PD is centrally involved in many neurological and neurodegenerative disorders.The neuroprotective role of the enzyme(G6PD)has also been established,as well as the potential of G6PD in oxidative damage and the Reactive Oxygen Species(ROS)produced in cerebral ischemia.Though G6PD deficiency remains a global health issue,however,a paradigm shift in research focusing the potential of the enzyme in neurological and neurodegenerative disorders will surely open a new avenue in diagnostics and enzyme therapeutics.Here,in this study,more emphasis was made on exploring the role of G6PD in neurological and inflammatory disorders as well as non-immune hemolytic anemia,thus providing diagnostic and therapeutic opportunities.

关键词： Glucose 6 phosphate dehydrogenase Hemolytic anemia Metabolic disorders Neurodegenerative disorders

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A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem and progenitor cells

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Journal of Molecular Cell Biology 2020年第1期12卷 4-16页

作者： Kushani Shah Gwendalyn D.King Hao Jiang department of biochemistry and Molecular genetics University of Alabama at BirminghamBirminghamAL 35294USA department of Neurobiology University of Alabama at BirminghamBirminghamAL 3529AUSA department of biochemistry and Molecular genetics University of VirginiaCharlottesvilleVA 22908USA

It remains unknown whether H3K4 methylation,an epigenetic modification associated with gene activation,regulates fate determination of the postnatal neural stem and progenitor cells(NSPCs).By inactivating the Dpy30 subunit of the major H3K4 methyltransferase complexes in specific regions of mouse brain,we demonstrate a crucial role of efficient H3K4 methylation in maintaining both the self-renewal and differentiation capacity of postnatal NSPCs.Dpy30 deficiency disrupts development of hippocampus and especially the dentate gyrus and subventricular zone,the major regions for postnatal NSC activities.Dpy30 is indispensable for sustaining the self-renewal and proliferation of NSPCs in a cell-intrinsic manner and also enables the differentiation of mouse and human neural progenitor cells to neuronal and glial lineages.Dpy30 directly regulates H3K4 methylation and the induction of several genes critical in neurogenesis.These findings link a prominent epigenetic mechanism of gene expression to the fundamental properties of NSPCs and may have implications in neurodevelopmental disorders.

关键词： neural stem cell self-renewal differentiation epigenetics H3K4 methylation Dpy30

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利用基因组数据挖掘对人类长非编码RNA进行功能注释（英文）

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第6期20卷 476-487页

作者： Brian L.GUDENAS Jun WANG Shu-zhen KUANG An-qi WEI Steven B.COGILL Liang-jiang WANG department of genetics and biochemistry Clemson University

越来越多证据表明RNA在生物系统中扮演着重要的角色,而这些发现支持了生命起源于RNA的假设。在人类基因组中,大部分的基因并不编码蛋白质,被称为非编码RNA基因。长非编码RNA(lncRNA)是其中最大的一类,其转录本长度大于200个核苷酸。虽... 详细信息

越来越多证据表明RNA在生物系统中扮演着重要的角色,而这些发现支持了生命起源于RNA的假设。在人类基因组中,大部分的基因并不编码蛋白质,被称为非编码RNA基因。长非编码RNA(lncRNA)是其中最大的一类,其转录本长度大于200个核苷酸。虽然一些lncRNA已被证明是调控基因表达和3D基因组结构的重要元件,但是大部分lncRNA还未被研究和注释。本课题组利用大量基因组数据,提出一些基于数据挖掘和机器学习的方法,对人类lncRNA进行功能注释。我们与其他同领域课题组的近期研究结果表明,基因组数据挖掘可帮助加深对lnc RNA功能的理解,并为与疾病相关lncRNA的实验研究提供重要信息。

关键词：长非编码RNA(lncRNA) 功能注释基因组数据挖掘机器学习

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Granulation of m A-modified mRNAs protects their functionality through cellular stress

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Journal of Molecular Cell Biology 2020年第11期12卷 821-822页

作者： Hao Jiang department of biochemistry and Molecular genetics University of Virginia School of MedicineCharlottesvilleVA 22908USA

To cope with various stress conditions,cells turn off house-keeping processes and turn on stress-protective pathways(Rabouille and Alberti,2017).A successful strategy would also require cells to efficiently reactivate the essential cellular processes once the stress is over.In addition to activation of signaling events,recent studies have shown that formation of certain membraneless assemblies plays a role in stress adaptation(Rabouille and Alberti,2017).

关键词： stress protective activation

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Model systems to study the life cycle of human papillomaviruses and HPV-associated cancers

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Virologica Sinica 2015年第2期30卷 92-100页

作者： Louise T.Chow department of biochemistry and Molecular genetics University of Alabama at Birmingham Birmingham 35294-0005 USA

The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of p RB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.

关键词： human papillomaviruses(HPVs) productive program HPV-associated cancers model systems

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对氨基苯甲酸掺杂的微槽结构碳纤维用于改善PLA-PEG的强度及生物相容性（英文）

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Science China Materials 2016年第11期59卷 911-920页

作者：史燕妮李敏王宁 Malcolm xing 吴琪琳 State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Shanghai 201620China College of Materials Science and Engineering Donghua UniversityShanghai 201620China department of Mechanical Engineering Faculty of Engineering and Department of Biochemistry&GeneticsFaculty of Medicine P.I.@Manitoba Institute of Child Healththe University of ManitobaWinnipeg R3T 2N2Canada

本文利用一种叶酸代谢产物,对氨基苯甲酸(PABA),来改性碳纤维(CFs),通过在其表面形成微槽结构以达到改善其亲水性的目的.采用溶液浇注/粒子沥滤法制备了CFs/PLA-PEG复合生物支架.研究发现,引入小的PABA疏水分子可以在CFs和聚乳酸-聚乙二... 详细信息

本文利用一种叶酸代谢产物,对氨基苯甲酸(PABA),来改性碳纤维(CFs),通过在其表面形成微槽结构以达到改善其亲水性的目的.采用溶液浇注/粒子沥滤法制备了CFs/PLA-PEG复合生物支架.研究发现,引入小的PABA疏水分子可以在CFs和聚乳酸-聚乙二醇(PLA-PEG)基体之间形成良性结合界面.CFs/PLA-PEG生物支架的抗压强度从3.98MPa提高到5.48MPa.由于PABA的改性,低毒性的CFs/PLA-PEG复合材料显著加速了预成骨细胞的粘附,对细胞增殖没有明显影响.通过比较支架上的L929细胞和MC_3T_3细胞的生物相容性,可以认为PABA-CFs不仅克服了PLA-PEG强度差的缺陷,而且可以促进细胞的生长,证明了PABA-CFs增强PLA-PEG生物复合材料可作为一种潜在的组织工程支架材料.

关键词： carbon fibers PABA modification biocomposites mechanical strength biocompatibihty

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Mitochondrial GPX1 silencing triggers differential photosynthesis impairment in response to salinity in rice plants

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Journal of Integrative Plant Biology 2016年第8期58卷 737-748页

作者： Yugo Lima-Melo Fabricio E.L.Carvalho Márcio O.Martins Gisele Passaia Rachel H.V.Sousa Milton C.Lima Neto Márcia Margis-Pinheiro Joaquim A.G.Silveira department of biochemistry and Molecular Biology Federal University of Ceará department of genetics Federal University of Rio Grande do Sul

The physiological role of plant mitochondrial glutathione peroxidases is scarcely known. This study attempted to elucidate the role of a rice mitochondrial isoform（GPX1） in photosynthesis under normal growth and salinity conditions. GPX1 knockdown rice lines（GPX1s） were tested in absence and presence of 100 mM NaCl for 6 d.Growth reduction of GPX1 s line under non-stressful conditions, compared with non-transformed（NT） plants occurred in parallel to increased H_2O_2 and decreased GSH contents. These changes occurred concurrently with photosynthesis impairment, particularly in Calvin cycle＇s reactions, since photochemical efficiency did not change.Thus, GPX1 silencing and downstream molecular/metabolic changes modulated photosynthesis differentially. In contrast, salinity induced reduction in both phases of photosynthesis, which were more impaired in silenced plants.These changes were associated with root morphology alterations but not shoot growth. Both studied lines displayed increased GPX activity but H_2O_2 content did not change in response to salinity. Transformed plants exhibited lower photorespiration, water use efficiency and root growth, indicating that GPX1 could be important to salt tolerance. Growth reduction of GPX1 s line might be related to photosynthesis impairment, which in turn could have involved a cross talk mechanism between mitochondria and chloroplast originated from redox changes due to GPX1 deficiency.

关键词： CO2 assimilation glutathione peroxidase Oryza sativa photochemistry redox homeostasis

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Evolutionary Lineages and Functional Diversification of Plant Hexokinases

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Molecular Plant 2010年第2期3卷 334-346页

作者： Rucha Karve Michael Lauria Annie Virnig Xiaoxia Xia Bradley L. Rauh Brandon d. Moore department of genetics and biochemistry Clemson University Clemson SC 29634 USA

Sequencing data from 10 species show that a plant hexokinase （HXK） family contains 5-11 genes. Functionally, a given family can include metabolic catalysts, glucose signaling proteins, and non-catalytic, apparent regulatory enzyme homologs. This study has two goals. The first aim is to develop a predictive method to determine which HXK proteins within a species have which type of function. The second aim is to determine whether HXK-dependent glucose signaling proteins occur among more primitive plants, as well as among angiosperms. Using a molecular phylogeny ap- proach, combined with selective experimental testing, we found that non-catalytic HXK homologs might occur in all plants, including the relatively primitive Selaginella moellendorffi. We also found that different lineages of angiosperm HXKs have apparent conserved features for catalytic activity and for sub-cellular targeting. Most higher-plant HXKs are expressed predominantly at mitochondria, with HXKs of one lineage occurring in the plastid, and HXKs of one monocot lineage occurring in the cytosol. Using protoplast transient expression assays, we found that HXK glucose signaling pro- teins occur likely in all higher plants and in S. moellendorffi as well. Thus, the use of glucose by plant HXK isoforms in metabolism and/or as a regulatory metabolite occurs as widespread, conserved processes.

关键词： Hexokinase molecular phylogeny moonlighting proteins plant glucose signaling Selaginella.

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