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Selective toxicity of hydroxyl-rich carbon nanodots for cancer research

Nano Research 2018年第4期11卷 2204-2216页

作者： Tak H. Kim Joseph P. Sirdaarta Qian Zhang Ehsan Eftekhari James St. John derek kennedy Ian E. Cock Qin Li Queensland Micro and Nano Technology Center & School of Engineering Griffith University 170 Kessels Rd Nathan OLD 4111 Australia Australian Rivers Institute & School of Natural Sciences Griffith University 170 Kessels Rd Nathan QLD 4111 Australia Griffith Institute for Drug Discovery Gfiffith University 46 Don Young Rd Nathan QLD 4111 Australia Menzies Health Institute Queensland Griffith University Parkland Drive Southport QLD 4222 Australia

The toxicity of nanoparticles in a biological system is an integration of effects arising from surface functionali~ particle size, ionic dissolution, etc. This complexity suggests that generalization of a material＇s toxicity may be inappropriate. Moreover, from a medicinal point of view, toxicity can be used for treatment of malignant cells, such as cancer. In this stud~ highly biocompatible carbon nanodots （gCDs） were synthesized by reacting citric acid and urea in glycerol, which resulted in abundant hydroxyl functional groups on the particle surface. gCDs show excitation-dependent photoluminescence but with bright green to yellow emission. Importantly, a series of toxicity assessments showed that as-synthesized gCDs possessed exceptional biocompatibilities to various biological entities including 18 bacteria species, Petunia axillaris seedlings, and Artemia franciscana nauplii. Furthermore, the particles were shown to have low to no toxic effects on human embryonic kidney （HEK-293）, breast （MCF-7）, and oral squamous （CAL-27） carcinoma cell lines. Of particular interest, the gCDs displayed antiproliferative activities against ovarian choriocarcinoma cells （JAr/Jeg-3 cell lines）, which may be further explored for cancer drug discovery.

关键词： carbon nanodots nanotoxicity fluorescence choriocarcinoma cells thioredoxin reductase

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“技术先锋”企业的五种范式

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商学院 2013年第12期 102-105页

作者：麦维德 Neeraj Aggarwal derek kennedy John Wenstrup Michael Rüβmann Ruba Bomo Julia Chen Julio Bezerra 波士顿咨询公司

技术先锋企业运用各类技术来推动自身的业务发展，它们的业绩表现显著优于其它中小企业。它们欣然地接受新一轮的信息技术浪潮，并因此在市场中脱颖而出。

关键词：信息技术中小企业范式业务发展业绩表现市场

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Maternal and fetal T cells in term pregnancy and preterm labor

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Cellular & Molecular Immunology 2020年第7期17卷 693-704页

作者： derek Miller Meyer Gershater Rebecca Slutsky Roberto Romero Nardhy Gomez-Lopez Perinatology Research Branch Division of Obstetrics and Maternal–Fetal MedicineDivision of Intramural ResearchEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthU.S.Department of Health and Human ServicesDetroitMIUSA Department of Obstetrics and Gynecology Wayne State University School of MedicineDetroitMIUSA Department of Obstetrics and Gynecology University of MichiganAnn ArborMIUSA Department of Epidemiology and Biostatistics Michigan State UniversityEast LansingMIUSA Center for Molecular Medicine and Genetics Wayne State UniversityDetroitMIUSA Detroit Medical Center DetroitMIUSA Department of Obstetrics and Gynecology Florida International UniversityMiamiFLUSA Department of Biochemistry Microbiology and ImmunologyWayne State University School of MedicineDetroitMIUSA

Pregnancy is a state of immunological balance during which the mother and the developing fetus must tolerate each other while maintaining sufficient immunocompetence to ward off potential *** site of closest contact between the mother and fetus is the decidua,which represents the maternal–fetal *** of the immune cell subsets present at the maternal–fetal interface have been well described;however,the importance of the maternal T cells in this compartment during late gestation and its complications,such as preterm labor and birth,has only recently been ***,pioneer and recent studies have indicated that fetal T cells are activated in different subsets of preterm labor and may elicit distinct inflammatory responses in the amniotic cavity,leading to preterm *** this review,we describe the established and proposed roles for maternal T cells at the maternal–fetal interface in normal term parturition,as well as the demonstrated contributions of such cells to the pathological process of preterm labor and *** also summarize the current knowledge of and proposed roles for fetal T cells in the pathophysiology of the preterm labor *** is our hope that this review provides a solid conceptual framework highlighting the importance of maternal and fetal T cells in late gestation and catalyzes new research questions that can further scientific understanding of these cells and their role in preterm labor and birth,the leading cause of neonatal mortality and morbidity worldwide.

关键词： maternal-fetal interface decidua amniotic fluid adaptive immunity parturition

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Immune cells in term and preterm labor

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Cellular & Molecular Immunology 2014年第6期11卷 571-581页

作者： Nardhy Gomez-Lopez derek StLouis Marcus A Lehr Elly N Sanchez-Rodriguez Marcia Arenas-Hernandez Department of Obstetrics & Gynecology and Immunology & Microbiology Wayne State University Detroit MI USA Perinatology Research Branch NICHD/NIH School of Medicine Wayne State University Detroit MI USA

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells （neutrophils, macrophages and mast cells） mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells （T-cell subsets and B cells） participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems （natural killer T （NKT） cells and dendritic cells （DCs）） seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm.

关键词： B cells cytotoxic T cells dendritic cells macrophages mast cells neutrophils NKT cells parturition preterm delivery regulatory T cells T cells

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An imbalance between innate and adaptive immune cells at the maternal-fetal interface occurs prior to endotoxin-induced preterm birth

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Cellular & Molecular Immunology 2016年第4期13卷 462-473页

作者： Marcia Arenas-Hernandez Roberto Romero derek St Louis Sonia S Hassan Emily B Kaye Nardhy Gomez-Lopez Department of Obstetrics & Gynecology Wayne State University School of Medicine Detroit Michigan USA perinatology Research Branch Program for Perinatal Research and Obstetrics Division of Intramural Research Eunice Kennedy ShriverNational Institute of Child l~ealth and Human DevelopmentNIC.HD/NIHDHHS Bethesda Maryland and Detroit Michigan USA Departme.nt of Obstetrics and Gynecology University of M chigan Ann ArborMichigan USA Department of Epidemiology and Biostatistics Michigan State University East Lansing Michigan USA Department of Molecular Obstetrics and Genetics Wayne State University Detroit Michigan USA Department of ImmunoLogy & MicrobioLogy Wayne State University School of Medicine Detroit Michigan USA

Preterm birth （PTB） is the leading cause of neonatal morbidity and mortality worldwide. A transition from an anti-inflammatory state to a pro-inflammatory state in the mother and at the maternal-fetal interface has been implicated in the pathophysiology of microbial-induced preterm labor. However, it is unclear which immune cells mediate this transition. We hypothesized that an imbalance between innate and adaptive immune cells at the maternal-fetal interface will occur prior to microbial-induced preterm labor. Using an established murine model of endotoxin-induced PTB, our results demonstrate that prior to delivery there is a reduction of CD4 ＋ regulatory T cells （Tregs） in the uterine tissues. This reduction is neither linked to a diminished number of Tregs in the spleen, nor to an impaired production of ILIO, CCL17, or CCL22 by the uterine tissues. Endotoxin administration to pregnant mice does not alter effector CD4＋ T cells at the maternal-fetal interface. However, it causes an imbalance between Tregs （CD4＋ and CD8＋）, effector CD8＋ T cells, and Th17 cells in the spleen. In addition, endotoxin administration to pregnant mice leads to an excessive production of CCL2, CCL3, CCL17, and CCL22 by the uterine tissues as well as abundant neutrophils. This imbalance in the uterine microenvironment is accompanied by scarce APC-like cells such as macrophages and MHC II ＋ neutrophils. Collectively, these results demonstrate that endotoxin administration to pregnant mice causes an imbalance between innate and adaptive immune cells at the maternal-fetal interface.

关键词： antigen-presenting cells effector T cells inflammation labor lipopolysaccharide macrophages microbial product neutrophils pregnancy preterm labor regulatory T cells

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Measurement of Metabolic and Inflammatory Serum Markers and Immune Marker Gene Expression during Superovulation in Beef Cattle

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Open Journal of Animal Sciences 2021年第2期11卷 175-196页

作者： Alexandria P. Snider derek J. McLean Alfred R. Menino 112 Withycombe Hall Department of Animal and Rangeland Sciences Oregon State University Corvallis USA USDA ARS U.S. Meat Animal Research Center Livestock Biosystems Unit Clay Center NE USA Eunice kennedy Shriver National Institute of Child Health and Human Development Bethesda MD USA

Health status of donor cows during superovulation is important to ensure optimal embryo quality at time of collection. Because nutritional and metabolic status impact embryo quality some form of nutritional supplementation is often provided before and during superovulation. OmniGen-AF® (OG) feeding has been shown to assist in the maintenance of animal health through regulation of metabolic status and balance and supporting aspects of immune function. We observed feeding donor cows OG decreased percent degenerate embryos recovered following superovulation increased serum progesterone concentration and improved in vitro embryo development. Evaluation of OG feeding on markers of metabolic function and inflammatory and immune function in beef cattle embryo donors are reported here. Similarly, cow metabolic and inflammatory response with repeated superovulation protocols is not known. Biomarkers to monitor and evaluate cow health during superovulation may provide management options to improve embryo recovery and quality. Twenty-four Angus cross-bred cattle were randomly assigned to four treatment groups, fed 0 or 56 g/hd/day for 49 days and superovulated with 200 or 400 mg Folltropin V (FSH). Blood was collected weekly for analyses. The protocol was repeated on all cows 90 - 120 d later with cows reassigned to their original groups. No differences (P > 0.10) were observed due to OG feeding or FSH dose on metabolic and inflammatory markers. Replicate exerted a significant effect where serum concentration of albumin, IL1β, IL6, PGE2 and leptin were lower (P<

关键词： Bovine Metabolism Estrous Cycle Follicle Stimulating Hormone Inflammation

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Effects of Feeding OmniGen-AF<sup>®</sup>during Superovulation on <i>in Vitro</i>Development of Embryos Recovered from Donor Beef Cows

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Open Journal of Animal Sciences 2021年第1期11卷 37-49页

作者： Alexandria P. Snider derek J. Mclean Alfred R. Menino Jr. 112 Withycombe Hall Department of Animal and Rangeland Sciences Oregon State University Corvallis USA Eunice kennedy Shriver National Institute of Child Health and Human Development Bethesda USA

Embryo quality is crucial when selecting embryos for transfer. Variation in quality may be attributed to poor oocytes, semen, stress, inflammation, and potential immune system dysregulation. OmniGen-AF® (OG) feeding supports immune system function and animal health. Our laboratory recently reported lower percent degenerate embryos recovered and increased plasma progesterone in beef cattle donors fed OG during superovulation. In vitro development of embryos recovered from donor cows fed OG prior to collection is presented here. Embryos were recovered from 24 beef cows assigned to four treatment groups: 0 g OG/hd/d and 200 mg Folltropin®-V (FSH) (0/200);0 g OG/hd/d and 400 mg FSH (0/400), 56 g OG/hd/d, 200 mg FSH (56/200) and 56 g OG/hd/d and 400 mg FSH (56/400). Good to excellent quality early blastocysts were cultured for 8 d. and development through hatching, embryonic volume and plasminogen activator (PA) production were quantified. The complete protocol was repeated 90 - 120 d later as Replicate 2. Optimal development was observed by embryos recovered from 0/200 cows where percent blastocysts hatching was greater (P compared to 56/200 and 0/400 cows and embryonic volume was greatest (P was similar (P

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