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Nanoparticle-linked antagonist for leptin signaling inhibition in breast cancer

World Journal of clinical Oncology 2017年第1期8卷 54-66页

作者： Tia Harmon Adriana Harbuzariu Viola Lanier crystal c lipsey Ward Kirlin Lily Yang Ruben R Gonzalez-Perez Department of Microbiology Biochemistry and Immunology Morehouse School of Medicine Department of Pathology and Laboratory Medicine Emory University School of Medicine

AIM To develop a leptin peptide receptor antagonist linked to nanoparticles and determine its effect on viability of breast cancer *** The leptin antagonist, LPrA2, was coupled via EDAc [1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide] to iron oxide nanoparticles(IONP-LPrA2) to increase its ***-LPrA2 conjugation was confirmed by Western blot and nanoparticle tracking *** triple negative breast cancer(TNBc) MDA-MB-231, Hcc1806 and estrogen receptor positive(ER+) McF-7 cells were analyzed for the expression of the leptin receptor, *** effects of leptin and antagonist on levels of leptin-induced STAT3 phosphorylation and cyclin D1, cell cycle progression, cell proliferation, and tumorsphere formation in breast cancer cells were *** of the chemotherapeutics [cisplatin(cis), cyclophosphamide(cTX), doxorubicin(Dox) and paclitaxel(PTX)] to effectively reduce cell viability were *** effects of combination treatments of IONP-LPrA2 and chemotherapeutics on cell viability were *** Western blot analysis of coupling reaction products identified IONP-LPrA2 at approximately 100 ***2 significantly decreased leptin-induced p STAT3 levels in Hcc1806 cells and drastically decreased cyclin D1 levels in all cell ***-LPrA2 significantly reduced leptin-induced S phase progression and cell proliferation in all breast cancer cell lines and the formation of tumorspheres in MDA-MB-231 ***, IONP-LPrA2 showed an additive effect on the reduction of breast cancer cell survival with *** plus IONP-LPrA2 produced a significant reduction in the survival of MDA-MB-231 and Hcc1806 *** plus IONP-LPrA2 caused a significant decrease in the survival of MDA-MB-231 *** plus IONP-LPrA2 caused a marked reduction in the survival of Hcc1806 ***, PTX plus IONP-LPrA2 did not have a major effect on the viability of the breast cancer cells when compared to PTX *** Prese

关键词： Triple negative breast cancer Obesity Leptin Leptin peptide receptor antagonist 2 Iron oxide nanoparticles chemotherapy adjuvant

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Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer

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World Journal of Methodology 2016年第1期6卷 43-55页

作者： crystal c lipsey Adriana Harbuzariu Danielle Daley-Brown Ruben R Gonzalez-Perez Department of Microbiology Biochemistry and ImmunologyGraduate Education in Bio-medical SciencesMorehouse School of Medicine

Obesity is a global pandemic characterized by high levels of body fat(adiposity) and derived-cytokines(i.e., leptin). Research shows that adiposity and leptin provide insight on the link between obesity and cancer progression. Leptin's main function is to regulate energy balance. However, obese individuals routinely develop leptin resistance, which is the consequence of the breakdown in the signaling mechanism controlling satiety resulting in the accumulation of leptin. Therefore, leptin levels are often chronically elevated in human obesity. Elevated leptin levels are related to higher incidence, increased progression and poor prognosis of several human cancers. In addition to adipose tissue, cancer cells can also secrete leptin and overexpress leptin receptors. Leptin is known to act as a mitogen, inflammatory and pro-angiogenic factor that induces cancer cell proliferation and tumor angiogenesis. Moreover, leptin signaling induces cancer stem cells, which are involved in cancer recurrence and drug resistance. A novel and complex signaling crosstalk between leptin, Notch and interleukin-1(IL-1) [Notch, IL-1 and leptin crosstalk outcome(NILcO)] seems to be an important driver of leptin-induced oncogenic actions. Leptin and NILcO signaling mediate the activation of cancer stem cells that can affect drug resistance. Thus, leptin and NILcO signaling are key links between obesity and cancer progression. This review presents updated data suggesting that adiposity affects cancer incidence, progression, and response to treatment. Here we show data supporting the oncogenic role of leptin in breast, endometrial, and pancreatic cancers.

关键词： Obesity Leptin Breast cancer Endometrial cancer Pancreatic cancer Notch interleukin-1 and leptin crosstalk outcome

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Glymphatic imaging and modulation of the optic nerve

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Neural Regeneration Research 2022年第5期17卷 937-947页

作者： Anisha Kasi crystal Liu Muneeb A.Faiq Kevin c.chan Department of Ophthalmology NYU Grossman School of MedicineNYU Langone HealthNew York UniversityNew YorkNYUSA Department of Radiology NYU Grossman School of MedicineNYU Langone HealthNew York UniversityNew YorkNYUSA Neuroscience Institute NYU Grossman School of MedicineNYU Langone HealthNew York UniversityNew YorkNYUSA center for Neural Science College of Arts and ScienceNew York UniversityNew YorkNYUSA

Optic nerve health is essential for proper function of the visual ***,the pathophysiology of certain neurodegenerative disease processes affecting the optic nerve,such as glaucoma,is not fully ***,it was hypothesized that a lack of proper clearance of neurotoxins contributes to neurodegenerative *** ability to clear metabolic waste is essential for tissue homeostasis in mammals,including *** the brain lacks the traditional lymphatic drainage system identified in other anatomical regions,there is growing evidence of a glymphatic system in the central nervous system,which structurally includes the optic *** to acknowledge the supportive role of astroglial cells,this perivascular fluid drainage system is essential to remove toxic metabolites from the central nervous ***,we review existing literature describing the physiology and dysfunction of the glymphatic system specifically as it relates to the optic *** summarize key imaging studies demonstrating the existence of a glymphatic system in the optic nerves of wild-type rodents,aquaporin 4-null rodents,and humans;glymphatic imaging studies in diseases where the optic nerve is impaired;and current evidence regarding pharmacological and lifestyle interventions that may help promote glymphatic function to improve optic nerve *** conclude by highlighting future research directions that could be applied to improve imaging detection and guide therapeutic interventions for diseases affecting the optic nerve.

关键词： aquaporin-4 cerebrospinal fluid glaucoma glymphatic system hydrocephalus imaging metabolic waste clearance optic nerve perivascular pharmacological and lifestyle interventions

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characterization of energy and performance of swine fed a novel corn-soybean extruded product

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Journal of Animal Science and Biotechnology 2015年第3期6卷 322-329页

作者： Katherine M Koch Robert c Thaler Sam K Baidoo crystal L Levesque Rebecca c Bott South Dakota State University University of Minnesota Southern Research and Outreach center

Background： A novel extruded product was characterized with a metabolism and lactation trial to establish the product＇s energy content, and its effects on lactating sow performance. The product was composed of a 60：40 corn-soybean blend, which was then extruded. This product containing the co-extruded 60：40 corn-soybean blend was commercially developed and is used extensively in swine diets in southwest Minnesota. GE of dietary treatments were determined by isoperibol bomb calorimetry. Twelve barrows （59.9 ± 1.4 kg）, were used to determine the digestible and metabolizable energy of the extruded product. DE of treatments was determined by subtracting fecal energy from GE provided to barrows by each respective treatment. ME was determined by subtracting urinary energy from calculated digestible energy. Sixty-three sows were used for the lactation trial. Three dietary treatments were utilized： cONTROL （an industry standard diet）; PRODUcT （contained the product, vitamins and minerals）; OIL （matched the lysine：ME ratio of PRODUcT by addition of soy oil）. Sow weight, backfat thickness at the right and left last ribs, body condition score, number of piglets, and litter weights were recorded on the date of farrowing （d 0）, （d 9）, and at weaning. Blood and milk samples were obtained at weaning, and blood was analyzed for plasma urea nitrogen （PUN）, milk was analyzed for total protein and fat content. Results： On a dry-matter basis, the test diet provided 3,908 kcal/kg DE and 3,833 kcal/kg ME, which was significantly greater than the basal diet, which provided 3,633 kcal/kg DE and 3,567 kcal/kg ME （P 〈 0.0001）. These data were used to establish the DE and ME of the product, which were 3,882 kcal/kg and 3,798 kcal/kg, respectively, on an as-fed basis. No effect of diet was observed for changes in sow backfat （RBF P = 0.24; LBF P = 0.07） or body condition score （P = 0.12） during lactation. Milk total protein （P = 0.69）, fat （P = 0.66）, PUN, average piglet gain （P = 0.55） and pi

关键词： corn Extruded Lactation ME Soybean Swine

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THE SYNTHESIS OF 4,5-BIS(4'-BROMOBENZYLTHIODITHIOLE-2-THIONE WITH ONE DIMENSIONAL INTERMOLEcULAR INTERAcTIONS

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chinese chemical Letters 1996年第2期7卷 103-104页

作者： Fang QI(Institute of crystal Materials, Shandong University, Jinan, 250100) Institute of crystal Materials Shandong University Jinan 250100 China

The title compound BBBT-Dry (c17H12Br2S5, Mr=536.42) has been synthesized and its structure feature has been described. BBBT-DTT is characterized by one dimensional chains formed by S…S (head to head) and Br…Br (tai... 详细信息

关键词： BIS THIONE WITH INTERMOLEcULAR INTERAcTIONS OF SYNTHESIS DITHIOLE DIMENSIONAL BROMOBENZYLTHIO

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chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas

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World Journal of Gastrointestinal Oncology 2016年第4期8卷 358-365页

作者： crystal S Seldon Lauren E colbert William A Hall Sarah B Fisher David S Yu Jerome c Landry Department of Radiation Oncology Winship Cancer Institute Emory University School of Medicine Department of Radiation Oncology Memorial Sloan Kettering Cancer Center Department of Radiation Oncology the Medial College of Wisconsin Division of Surgical Oncology Department of Surgery Emory University School of Medicine

Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.

关键词： chromodomain-helicase-DNA binding protein 5 chromodomain-helicase-DNA binding protein 7 Mixed lineage kinase domain-like protein Pancreatic adenocarcinoma Biomarker

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Impact of prehospital medical evacuation (MEDEVAc) transport time on combat mortality in patients with noncompressible torso injury and traumatic amputations: a retrospective study

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Military Medical Research 2019年第1期6卷 23-30页

作者： Joseph K.Maddry crystal A.Perez Alejandra G.Mora Jill D.Lear Shelia c.Savell Vikhyat S.Bebarta US Air Force En route care Research center 59th MDW/ST Chief Scientist's Office –US Army Institute of Surgical research JBSA Ft.Sam Houston Department of Emergency Medicine San Antonio Military Medical CenterJBSA Ft. Sam Houston US Air Force En route care Research center 59th MDW/ST Chief Scientist's Office –US Army Institute of Surgical researchJBSA Ft.Sam Houston Department of Emergency Medicine University of Colorado School of Medicine

Background: In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality. Limited data exist on the influence of transport time on patient outcomes with specific injury types. The objective of this study was to determine the impact of the duration of time from the initial request for medical evacuation to arrival at a medical treatment facility on morbidity and mortality in casualties with traumatic extremity amputation and noncompressible torso injury(NcTI).Methods: We completed a retrospective review of MEDEVAc patient care records for United States military personnel who sustained traumatic amputations and NcTI during Operation Enduring Freedom between January 2011 and March 2014. We grouped patients as traumatic amputation and NcTI(AMP+NcTI), traumatic amputation only(AMP),and neither AMP nor NcTI(Non-AMP/NcTI). Analysis was performed using chi-squared tests, Fisher's exact tests,cochran-Armitage Trend tests, Shapiro-Wilks tests, Wilcoxon and Kruskal-Wallis techniques and cox proportional hazards regression ***: We reviewed 1267 records, of which 669 had an injury severity score(ISS) of 10 or greater and were included in the analysis. In the study population, 15.5% sustained only amputation injuries(n=104, AMP only), 10.8% sustained amputation and NcTI(n=72, AMP+NcTI), and 73.7% did not sustain either an amputation or an NcTI(n=493,Non-AMP/NcTI). AMP+NcTI had the highest mortality(16.7%) with transport time greater than 60 min. While the AMP+NcTI group had decreasing survival with longer transport times, AMP and Non-AMP/NcTI did not exhibit the same ***: A decreased transport time from the point of injury to a medical treatment facility was associated with decreased mortality in patients who suffered a combination of amputation injury and NcTI. No significant association between transport time

关键词： Transport time Non-compressible torso injury Traumatic amputation combat

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Toll-like receptor agonists shape the immune responses to a mannose receptor-targeted cancer vaccine

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cellular & Molecular Immunology 2015年第6期12卷 719-728页

作者： Li-Zhen He Jeffrey Weidlick crystal Sisson Henry c Marsh Tibor Keler celldex Therapeutics Inc. Hampton N J USA and celldex Therapeutics Inc. Needham MA USA

Previous studies have documented that selective delivery of protein antigens to cells expressing mannose receptor （MR） can lead to enhanced immune responses. We postulated that agents that influenced the MR expression level, and the activation and migration status of MR-expressing antigen presenting cells, would modulate immune responses to MR-targeted vaccines. To address this question, we investigated the effect of clinically used adjuvants in human MR transgenic （hMR-Tg） mice immunized with an MR-targeting cancer vaccine composed of the human anti-MR monoclonal antibody B 11 fused with the oncofetal protein, human chorionic gonadotropin beta chain （hcGβ）, and referred to as B 11-hcGβ. We found that humoral responses to low doses of B11-hcGβ could be enhanced by prior administration of GM-cSF, which upregulated MR expression in vivo. However, co-administration of the Toll-like receptor （TLR） agonists, poly-IcLc and/or cpG with B11-hcGβ was required to elicit Thl immunity, as measured by antigen-specific T-cell production of IFN-γ. The TLR agonists were shown to increase the number of vaccine-containing cells in the draining lymph nodes of immunized hMR-Tg mice. In particular, with B11-hcGβand poly-IcLc, a dramatic increase in vaccine-positive cells was observed in the T-ceU areas of the lymph nodes, compared to the vaccine alone or combined with GM-cSF. Importantly, the absence of the TLR agonists during the priming immunization led to antigen-specific tolerance. Therefore, this study provides insight into the mechanisms by which adjuvants can augment immune responses to B11-hcGβ and have implications for the rationale design of clinical studies combining MR-targeted vaccination with TLR agonists.

关键词： GM-cSF hcGβ mannose receptor Toll-like receptor agonists

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Dynamic interplay of T helpercell subsets in experimental autoimmune encephalomyelitis

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World Journal of Immunology 2012年第1期2卷 1-13页

作者： crystal c Walline Saravanan Kanakasabai John J Bright Neuroscience Research Laboratory Methodist Research Institute Indiana University Health Indianapolis IN 46202 United States Department of Medicine Indiana University School of Medicine Indianapolis IN 46202 United States

AIM： To investigate the temporal onset and dynamic interplay of cD4^＋ T helper cell subsets in experimental autoimmune encephalomyelitis （EAE）.METHODS： EAE was induced in c57BL/6 mice by im-munization with myelin oligodendrocyte glycoprotein peptide p35-55. The clinical signs were scored and the tissue samples and immune cells isolated for analysis at different phases of EAE. The expression levels of inflammatory cytokines and related transcription fac-tors were detected by quantitative reverse transcription polymerase chain reaction （PcR） and enzyme linked immunosorbant assay （ELISA）. The percentages of Th1, Th17, Th2, Treg and memory T cell subsets in EAE were analyzed by immunostaining and fow cytometry. The data were analyzed by statistical ***： Quantitative real-time PcR analysis showed that EAE mice express elevated levels of Th1 [interferon gamma （ IFNγ ）, interleukin （ IL ） -12p40 ], Th17 [ IL-17 , related orphan receptor gamma （RORγ ）, IL-12p40] and Treg [ Foxp3, Epstein-Barr virus induced gene 3 （EBI3）, IL-10] genes in the central nervous system at the peak of the disease. Whereas, the expression of Th1 （ IFNγ , T-bet, IL-12p35, IL-12p40 ）, Th17 （RORγ, IL-12p40 ）, Th2 （ IL-4） and Treg （ Foxp3, EBI3） response genes was reduced in the spleen during pre-disease but gradually recovered at the later phases of EAE. ELISA and fow cytometry analyses showed an increase in Th17 re-sponse in the periphery, while Th1 response remained unchanged at the peak of disease. The mRNA levels of IFNγ, IL-17 and IL-12p40 in the brain were increased by 23 （P 〈 0.001）, 9 （P 〈 0.05） and 14 （P 〈 0.01） fold, respectively, on day 21 of EAE. conversely, the mRNA expression of IL-10 was increased by 2 fold （P 〈 0.05） in the spleen on day 21. cD4^＋cD25^＋Foxp3＋Treg response was reduced at pre-disease but recovered to na？ve levels by disease onset. The percentage of cD25 Foxp3 regulatory T cells decreased from 7.7% in the na？ve to 3.2% （P 〈 0.05） on day 7 of EAE, which the

关键词： Autoimmune disease Experimental autoimmune encephalomyelitis Multiple sclerosis T helper cells Th1/Th17

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Branched chain amino acids alter fatty acid profile in colostrum of sows fed a high fat diet

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Journal of Animal Science and Biotechnology 2020年第2期11卷 468-479页

作者： chang Ma Yajng Liu Shaoshuai Liu crystal L.Lévesque Fengqi Zhao Jindong Yin Bing Dong State Key Laboratory of Animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Department of Animal Science College of Agriculture and Biological SciencesSouth Dakota State UniversityBrookingsSD 57007USA Department of Animal and Veterinary Sciences University of VermontBurlingtonVT 05405USA

Background:Branched chain amino acids(BcAAs)are important substrates for milk protein synthesis in the mammary gland,and are tightly related to lipid *** study has been performed examining the role of BcAAs with high fat diets on milk fat *** study was designed to investigate the effect of dietary BcAAs on growth performance of piglets,progeny body weight,and milk fat composition in sows fed a high fat *** diets(cON=control diet;HF=high fat diet with 8%soybean oil;HF-MB=HF plus 0.39%BcAAs;HF-HB=HF plus 0.78%BcAAs)were fed to sows from late gestation to ***:compared to HF,BcAAs(HF-MB and HF-HB)increased the litter weight(Pcreased colostrum fat content by 27.3–35.8%(Pcid profiles between the two doses of BcAAs were *** with HF,HF-MB tended to decrease the percentage of c18:3n3(P=0.063)and increased the percentage of c18:1n9c(P=0.03).In addition,BcAAs in HF-MB increased the concentration of total fatty acid by 22.1%in colostrum(P=0.03)but decreased that in serum at parturition by 53.2%(P=0.027).The fatty acids in colostrum that increased with BcAAs were c15:0,c17:0,c20:3n6,c20:4n6,c20:5n3 and c22:6n3(P=0.00~0.04).colostrum fatty acids of c20:0,c21:0,c22:0,c16:1,c20:1,c18:1n9c also tended to be increased(0.05change in sow serum fatty acid profile due to BcAAs was different from that in ***:BcAAs in high fat diet of sows altered the fatty acid composition in colostrum and enhanced litter *** study indicated that BcAAs supplementation can enhance mammary fatty acid uptake and mammary fat synthesis and that supplemental BcAAs and fat in late gestation and lactation diets for sows can improve reproductive performance.

关键词： Dietary lipids Fatty acid composition Milk Odd chain fatty acid Pig Poly unsaturated fatty acid Sow

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