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Engineering of Bacteria for the Visualization of Targeted Delivery of a Cytolytic Anticancer Agent
Jiang, Sheng-Nan,Park, Seung-Hwan,Lee, Hee Jung,Zheng, Jin Hai,Kim, Hyung-Seok,Bom, Hee-Seung,Hong, Yeongjin,Szardenings, Michael,Shin, Myung Geun,Kim, Sun-Chang,Ntziachristos, Vasilis,Choy, Hyon E,Mi Elsevier 2013 Molecular therapy Vol.21 No.11
Effect of Salmonella Treatment on an Implanted Tumor (CT26) in a Mouse Model
윤미선,반상오,Sheng- Nan Jiang,Vu Hong Nguyen,박승환,정제훈,김형석,민정준,최현일,홍영진 한국미생물학회 2012 The journal of microbiology Vol.50 No.3
The use of bacteria has contributed to recent advances in targeted cancer therapy especially for its tumor-specific accumulation and proliferation. In this study, we investigated the molecular events following bacterial therapy using an attenuated Salmonella Typhimurium defective in ppGpp synthesis (ΔppGpp), by analyzing those proteins differentially expressed in tumor tissues from treated and untreated mice. CT26 murine colon cancer cells were implanted in BALB/c mice and allowed to form tumors. The tumor-bearing mice were treated with the attenuated Salmonella Typhimurium. Tumor tissues were analyzed by 2D-PAGE. Fourteen differentially expressed proteins were identified by mass spectrometry. The analysis revealed that cytoskeletal components, including vimentin, drebrin-like protein, and tropomyosinalpha 3, were decreased while serum proteins related to heme or iron metabolism, including transferrin, hemopexin, and haptoglobin were increased. Subsequent studies revealed that the decrease in cytoskeletal components occurred at the transcriptional level and that the increase in heme and iron metabolism proteins occurred in liver. Most interestingly, the same pattern of increased expression of transferrin, hemopexin, and haptoglobin was observed following radiotherapy at the dosage of 14 Gy.
Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death
( Yu Ji Jiang ),( Sheng Cui ),( Kang Luo ),( Jun Ding ),( Qi Yan Nan ),( Shang Guo Piao ),( Mei Ying Xuan ),( Hai Lan Zheng ),( Yong Jie Jin ),( Ji Zhe Jin ),( Jung Pyo Lee ),( Byung Ha Chung ),( Bum 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.6
Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal in-jury. Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinflammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. Conclusions: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.
Zheng, Jin Hai,Nguyen, Vu H.,Jiang, Sheng-Nan,Park, Seung-Hwan,Tan, Wenzhi,Hong, Seol Hee,Shin, Myung Geun,Chung, Ik-Joo,Hong, Yeongjin,Bom, Hee-Seung,Choy, Hyon E.,Lee, Shee Eun,Rhee, Joon Haeng,Min, American Association for the Advancement of Scienc 2017 Science Translational Medicine Vol.9 No.376
<P>We report a method of cancer immunotherapy using an attenuated Salmonella typhimurium strain engineered to secrete Vibrio vulnificus flagellin B (FlaB) in tumor tissues. Engineered FlaB-secreting bacteria effectively suppressed tumor growth and metastasis inmousemodels and prolonged survival. By using Toll-like receptor 5 (TLR5)-negative colon cancer cell lines, we provided evidence that the FlaB-mediated tumor suppression upon bacterial colonization is associated with TLR5-mediated host reactions in the tumor microenvironment. These therapeutic effects were completely abrogated in TLR4 and MyD88 knockout mice, and partly in TLR5 knockout mice, indicating that TLR4 signaling is a requisite for tumor suppression mediated by FlaB-secreting bacteria, whereas TLR5 signaling augmented tumor-suppressive host reactions. Tumor microenvironment colonization by engineered Salmonella appeared to induce the infiltration of abundant immune cells such as monocytes/macrophages and neutrophils via TLR4 signaling. Subsequent secretion of FlaB from colonizing Salmonella resulted in phenotypic and functional activation of intratumoral macrophages with M1 phenotypes and a reciprocal reduction in M2-like suppressive activities. Together, these findings provide evidence that nonvirulent tumor-targeting bacteria releasing multiple TLR ligands can be used as cancer immunotherapeutics.</P>
Kim, Dong-Yeon,Kim, Hyeon-Sik,Le, Uyenchi Nguyen,Jiang, Sheng Nan,Kim, Hee-Jung,Lee, Kyo-Chul,Woo, Sang-Keun,Chung, Jihwa,Kim, Hyung-Seok,Bom, Hee-Seung,Yu, Kook-Hyun,Min, Jung-Joon Society of Nuclear Medicine 2012 The Journal of nuclear medicine Vol.53 No.11
<P>Radiolabeled lipophilic cationic compounds, such as (18)F-labeled phosphonium salt, accumulate in the mitochondria through a negative inner transmembrane potential. The purpose of this study was to develop and evaluate ((18)F-fluoropentyl)triphenylphosphonium salt ((18)F-FPTP) as a myocardial PET agent.</P>
( Wen Qian Wei ),( Fang Qi Liu ),( Lei Liu ),( Zuo Feng Li ),( Xiao Yan Zhang ),( Fan Jiang ),( Qu Shi ),( Xiao Yan Zhou ),( Wei Qi Sheng ),( San Jun Cai ),( Xuan Li ),( Ye Xu ),( Peng Nan ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.5
Hereditary non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inheritance syndrome. HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions. Our study aimed to identify the patterns of hMSH2 and hMLH1 mutations in Chinese HNPCC patients. Ninety-eight unrelated families from China meeting Amsterdam or Bethesda criteria were included in our study. Germline mutations in MLH1 and MSH2 genes, located in the exons and the splice-site junctions, were screened in the 98 probands by direct sequencing. Eleven mutations were found in ten patients (11%), with six in MLH1 (54.5%) and five in MSH2 (45.5%) genes. One patient had mutations in both MLH1 and MSH2 genes. Three novel mutations in MLH1 gene (c.157_160delGAGG, c.2157dupT and c.-64G>T) were found for the first time, and one suspected hotspot in MSH2 (c.1168C>T) was revealed. [BMB reports 2011; 44(5): 317-322]
Engineering and Visualization of Bacteria for Targeting Infarcted Myocardium
Le, Uyenchi N,Kim, Hyung-Seok,Kwon, Jin-Sook,Kim, Mi Yeon,Nguyen, Vu H,Jiang, Sheng Nan,Lee, Byeong-Il,Hong, Yeongjin,Shin, Myung Geun,Rhee, Joon Haeng,Bom, Hee-Seung,Ahn, Youngkeun,Gambhir, Sanjiv S Elsevier Science B.V., Amsterdam 2011 Molecular therapy Vol.19 No.5