Novel chromenedione derivatives displaying inhibition of protein tyrosine phosphatase 1B (PTP1B) from Flemingia philippinensis

Wang, Y.,Yuk, H.J.,Kim, J.Y.,Kim, D.W.,Song, Y.H.,Tan, X.F.,Curtis-Long, M.J.,Park, K.H. Pergamon Press 2016 Bioorganic & medicinal chemistry letters Vol.26 No.2

Protein tyrosine phosphatase 1B (PTP1B) is an important target to treat obesity and diabetes due to its key roles in insulin and leptin signaling. The MeOH extracts of the root bark of Flemingia philippinensis yielded eight inhibitory molecules (1-8) capable of targeting PTP1B. Three of them were identified to be novel compounds, philippin A (1), philippin B (2), and philippin C (3) which have a rare 3-phenylpropanoyl chromenedione skeleton. The other compounds (4-8) were known prenylated isoflavones. All compounds (1-8) inhibited PTP1B in a dose dependent manner with IC<SUB>50</SUB>s ranging between 2.4 and 29.4μM. The most potent compound emerged to be prenylated isoflavone 5 (IC<SUB>50</SUB>=2.4μM). In kinetic studies, chromenedione derivatives (1-3) emerged to be reversible, competitive inhibitors, whereas prenylated isoflavones (5-8) were noncompetitive inhibitors.

Autologous hybrid cell fusion vaccine in a spontaneous intermediate model of breast carcinoma

R. Curtis Bird,Patricia DeInnocentes,Allison E. Church Bird,Farruk M. Lutful Kabir,E. Gisela Martinez-Romero,Annette N. Smith,Bruce F. Smith 대한수의학회 2019 Journal of Veterinary Science Vol.20 No.5

Breast cancer is among the most common malignancies affecting women and reproductivelyintact female dogs, resulting in death from metastatic disease if not treated effectively. Tobetter manage the disease progression, canine mammary tumor (CMT) cells derived frommalignant canine mammary cancers were fused to autologous dendritic cells (DCs) toproduce living hybrid-cell fusion vaccines for canine patients diagnosed with spontaneousmammary carcinoma. The high-speed sorting of rare autologous canine patient DCs fromthe peripheral blood provides the autologous component of fusion vaccines, and fusion tomajor histocompatibility complex-unmatched CMT cells were produced at high rates. Thevaccinations were delivered to each patient following a surgical resection 3 times at 3-weekintervals in combination with immuno-stimulatory oligonucleotides and Gemcitabineadjunct therapy. The immunized patient animals survived 3.3-times longer (median survival611 days) than the control patients (median survival 184 days) and also appeared to exhibit anenhanced quality of life. A comparison of vaccinated patients diagnosed with inflammatorymammary carcinoma resulted in a very short median survival (42 days), suggesting no effectof vaccination. The data showed that the development of autologous living DC-based vaccinestrategies in patient animals designed to improve the management of canine mammarycarcinoma can be successful and may allow an identification of the antigens that can betranslatable to promote effective immunity in canine and human patients.

Estrogen receptor-α, progesterone receptor, and c-erbB/HER-family receptor mRNA detection and phenotype analysis in spontaneous canine models of breast cancer

Farruk M. Lutful Kabir,Patricia DeInnocentes,Payal Agarwal,Christopher P. Mill,David J. Riese 2nd,R. Curtis Bird 대한수의학회 2017 Journal of Veterinary Science Vol.18 No.2

Well characterized, stable, p16-defective canine mammary cancer (CMT) cell lines and normal canine mammary epithelial cells were used to investigate expression of the major breast cancer-specific hormone receptors estrogen receptor alpha (ER1) and progesterone receptor (PR) as well as luminal epithelial-specific proto-oncogenes encoding c-erbB-1 (epidermal growth factor receptor/EGFr), c-erbB-2/HER2, c-erbB-3, and c-erbB-4 receptors. The investigation developed and validated quantitative reverse transcriptase polymerase chain reaction assays for each transcript to provide rapid assessment of breast cancer phenotypes for canine cancers, based on ER1, PR, and c-erbB-2/HER2 expressions, similar to those in human disease. Roles for relatively underexplored c-erbB-3 and c-erbB-4 receptor expressions in each of these breast cancer phenotypes were also evaluated. Each quantitative assay was validated by assessment of amplicon size and DNA sequencing following amplification. Differential expression of ER1, PR, and c-erbB-2 in CMT cell lines clearly defined distinct human-like breast cancer phenotypes for a selection of CMT-derived cell lines. Expression profiles for EGFr family genes c-erbB-3 and c-erbB-4 in CMT models also provided an enriched classification of canine breast cancer identifying new extended phenotypes beyond the conventional luminal-basal characterization used in human breast cancer.

Graphene as interface modifier in ITO and ITO-Cr electrodes

Leticia A. Silva,Jéssica M.M. Luzardo,Sanair M. Oliveira,Rafael V. Curti,Alexander M. Silva,Rogerio Valaski,Rodrigo B. Capaz,Joyce R. Araujo 한국물리학회 2020 Current Applied Physics Vol.20 No.7

We explore graphene as interface modifier for electrodes in optoelectronic organic devices by measuring the electrical properties of ITO/graphene and ITO/Cr/graphene. For this purpose, exfoliated graphene (EG) was electrochemically synthesized and deposited by spray-pyrolysis. The built-in voltage (Vbi) values were 450 mV for the ITO/CuPc/Al reference, 750 mV for ITO/Cr/graphene/CuPc/Al and 1000 mV for ITO/graphene/CuPc/Al device structures. From these results, we estimate the work functions as 3.20 eV, 3.45 eV and 4.75 eV for ITO/ EG, ITO/Cr/EG and ITO. To understand how the work function changes, we carried out first-principles calculations based on density-functional theory (DFT) where Cr work function (~4.2 eV) is not modified by the deposition of pristine graphene; however there is a substantial increase (from 4.2 eV to 5.2 eV), upon deposition of graphene oxide (GO), resulting from a complete transfer of O atoms from the GO sheet to the Cr surface forming a thin layer of chromium oxide.

비스(트리메틸실릴메틸) 1,2-비스(디페닐포스피노)에탄니켈(II)의 합성 및 반응

진종식,Chong Shik Chin,M. D. Curtis Korean Chemical Society 1981 대한화학회지 Vol.25 No.5

새로운 니켈(II) 화합물, 비스(트리메틸실릴메틸)1,2-(비스디페닐포스피노) 에탄니켈(II)(1)이 디클로로-1,2-비스(디페닐포스피노)에탄니켈(Ⅱ)와 트리메틸실릴메틸리튬의 반응으로부터 합성되었다. 화합물 1은 질소하, 상온에서 안정하다. 화합물 1은 열분해하여 환원성짝지음 생성물, 1,2-비스(트리메틸실릴)에탄을 생성한다. 화합물 1은 상온에서 일산화탄소 및 산소와, 그리고 80${\circ}$C에서 1,2-비스(디페닐포스피노)에탄과 반응하여 역시 1,2-비스(트리메틸실릴)에탄을 생성한다. A new nickel(II) compound, $Ni(CH_2SiMe_3)_2((C_6H_5)_2PCH_2CH_2P(C_6H_5)_2)$, 1, has been prepared by the reaction of $NiCl_2((C_6H_5)_2PCH_2CH_2P(C_6H_5)_2)$ with $Me_3SiCH_2Li$. The compound, 1, is stable under nitrogen at room temperature both in solution and in the solid state. Thermal decomposition of 1 in solution or in the solid produces the reductive coupling product, $Me_3SiCH_2CH_2SiMe_3$ which is also afforded by the reactions of 1 with CO and $O_2$ at room temperature, and with $(C_6H_5)_2PCH_2CH_2P(C_6H_5)_2$ at 80${\circ}$C.

CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7– and IL-15–dependent niches

Jung, Yong Woo,Kim, Hyun Gyung,Perry, Curtis J.,Kaech, Susan M. National Academy of Sciences 2016 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.113 No.29

<P>C-C receptor 7 (CCR7) is important to allow T cells and dendritic cells to migrate toward CCL19- and CCL21-producing cells in the T-cell zone of the spleen and lymph nodes. The role of this chemokine receptor in regulating the homeostasis of effector and memory T cells during acute viral infection is poorly defined, however. In this study, we show that CCR7 expression alters memory CD8 T-cell homeostasis following lymphocytic choriomeningitis virus infection. Greater numbers of CCR7-deficient memory T cells were formed and maintained compared with CCR7-sufficient memory T cells, especially in the lung and bone marrow. The CCR7-deficient memory T cells also displayed enhanced rates of homeostatic turnover, which may stem from increased exposure to IL-15 as a consequence of reduced exposure to IL-7, because removal of IL-15, but not of IL-7, normalized the numbers of CCR7-sufficient and CCR7-deficient memory CD8 T cells. This result suggests that IL-15 is the predominant cytokine supporting augmentation of the CCR7(-/-) memory CD8 T-cell pool. Taken together, these data suggest that CCR7 biases memory CD8 T cells toward IL-7-dependent niches over IL-15-dependent niches, which provides insight into the homeostatic regulation of different memory T-cell subsets.</P>

Demographic and Clinical Correlates of Seizure Frequency: Findings from the Managing Epilepsy Well Network Database

Erdong Chen,Martha Sajatovic,Hongyan Liu,Ashley Bukach,Curtis Tatsuoka,Elisabeth Welter,Samantha S. Schmidt,Yvan A. Bamps,Shelley C. Stoll,Tanya M. Spruill,Daniel Friedman,Charles E. Begley,Ross Shego 대한신경과학회 2018 Journal of Clinical Neurology Vol.14 No.2

Background and Purpose Epilepsy is a chronic neurological disease that represents a tremendousburden on both patients and society in general. Studies have addressed how demographicvariables, socioeconomic variables, and psychological comorbidity are related to thequality of life (QOL) of people with epilepsy (PWE). However, there has been less focus on howthese factors may differ between patients who exhibit varying degrees of seizure control. Thisstudy utilized data from the Managing Epilepsy Well (MEW) Network of the Centers for DiseaseControl and Prevention with the aim of elucidating differences in demographic variables,depression, and QOL between adult PWE. Methods Demographic variables, depression, and QOL were compared between PWE whoexperience clinically relevant differences in seizure occurrence. Results Gender, ethnicity, race, education, income, and relationship status did not differ significantlybetween the seizure-frequency categories (p>0.05). People with worse seizure controlwere significantly younger (p=0.039), more depressed (as assessed using the Patient HealthQuestionnaire) (p=0.036), and had lower QOL (as determined using the 10-item Quality of Lifein Epilepsy for Adults scale) (p<0.001). Conclusions The present results underscore the importance of early screening, detection, andtreatment of depression, since these factors relate to both seizure occurrence and QOL in PWE.

The Inhibition of Epileptogenesis During Status Epilepticus by Ginsenosides of Korean Red Ginseng and Ginseng Cell Culture (Dan25)

Chepurnov S.A.,Chepurnova N.E.,Jin-Kyu Park,Redkozubova O.M.,Pravdukhina A.A.,Abbasova K.R.,Buzinova E.V.,Mirina A.A.,Chepurnova D.A.,Dubina A.A.,Pirogov U.A.,Curtis M.,Uva L. 고려인삼학회 2007 Journal of Ginseng Research Vol.31 No.3

Pharmacology of Korean Red ginseng gives us unique possibility to develop new class of antiepileptic drugs today and to improve one’s biological activity. The chemical structures of ginsenosides (GS) have some principal differences from well-known antiepileptic new generation drugs. The antiepileptic effect of GS was also demonstrated in all models of epilepsy in rats (young and adult), which have studied, in all models of epilepsy including status epilepticus (SE), induced by lithium - pilocarpine. In our experiments in rats new evidences on protective effects were exerted as a result of premedication by GS. Pre-treatment of several GS could induce decrease of the seizures severity and brain structural damage (by MRI), neuronal degeneration in hippocampus. Wave nature of severity of motor seizures during convulsive SE was observed during lithium-pilocarpine model of SE in rats (the first increase of seizures was 30 min after the beginning of SE and the second - 90 min after. The efficacy of treatment on SE by ginsenoside as expected was observed after no less 3 weeks by daily GS i.p. administration. It is blocked SE or significantly decrease the severity of seizures during SE. The implication of presented data is that combination of ginsenosides from Korean Red ginseng and ginseng cell culture Dan25 that could be applied for prevention of epileptical status development. However, a development of optimal ratio of different ginsenosides (Rb1 Rc, Rg, Rf,) should consummate in the new antiepileptic drug development.

PRENYLATED FLAVANONES FROM DERRIS LAXIFLORA

KIM, YOUNG HO,LEE, EUNG-SEOK,KOONCHANOK, NUPHAVAN M.,GEAHLEN, ROBERT L.,ASHENDEL, CURTIS L.,CHANG, CHING-JER 영남대학교 약품개발연구소 1995 영남대학교 약품개발연구소 연구업적집 Vol.5 No.-

A new prenylated flavanone 1 [laxiflorin (2S)-5, 7, 3', 4'-tetrahydroxy-6-(β-hydroxyethyl)-8-(γ, γ-dimethylallyl)flavanone] and four known flavanones (6, 8-diprenyleriodictyol, hiravanone, senegalensein and lupinifolin) were isolated from the leaves and twigs of Derris laxiflora.. Laxiflorin with a β-hydroxyethyl group at C-6 exhibited significant inhibitory activity against protein-tyrosine kinase.