Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury

Yang Hui-Hui,Jiang Hui-Ling,Tao Jia-Hao,Zhang Chen-Yu,Xiong Jian-Bing,Yang Jin-Tong,Liu Yu-Biao,Zhong Wen-Jing,Guan Xin-Xin,Duan Jia-Xi,Zhang Yan-Feng,Liu Shao-Kun,Jiang Jian-Xin,Zhou Yong,Guan Cha-Xi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Modification of a Smoking Motivation Questionnaire for Chinese Medical Students

Jiang, Chao,Sun, Wen-Jie,Wan, Yan-Chun,Wei, Ming-Wei,Mu, Yong-Ping,Tarver, Siobhan L.,Gao, Yong-Qing,Hu, Tian,Xu, Chao,Gordon, James,Feng, Cindy Xin,Wen, Yu-Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Introduction: Smoking prevalence among the medical students is high in China. Therefore, understanding the smoking motivations of medical students is crucial for smoking control, but currently there are no scales questionnaires customized for probing the smoking motivations of medical students. This aim of study was to test and modify a questionnaire for investigating smoking motivations among medical students. Methods: A cross-sectional survey was conducted among 1,125 medical students at Xuzhou Medical College in China in 2012.The model fit and validity was assessed by confirmatory factor analysis (CFA) and the reliability was tested by single-item reliability, composite reliability, and item-total correlation. Results: The prevalence of smoking was 9.84 % among study population. In the modified scales, the global fit indices identified a CFI value of 0.96, TLI was 0.96, and the RMSEA was 0.063. CFA supported the two dimensional structure of the instrument. The average variance extracted ranged from 0.45 to 0.62. All single-item reliability scores were greater than 0.20, and the composite reliability ranged from 0.74 to 0.91. Conclusion: Modified scales could be the preliminary instrument used in evaluating the smoking motivations of medical students. However, it should be further assessed using other forms and methods of validity and reliability, additional motivations of smoking, and the survey of other medical colleges in China.

Marine Collagen Peptides Prepared from Chum Salmon (Oncorhynchus keta) Skin Extend the Life Span and Inhibit Spontaneous Tumor Incidence in Sprague-Dawley Rats

Jiang Liang,Xin-Rong Pei,Nan Wang,Zhao-Feng Zhang,Jun-Bo Wang,Yong Li 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.4

To observe the effects of marine collagen peptides (MCPs) prepared from chum salmon (Oncorhynchus keta) skin on life span and spontaneous tumor incidence, Sprague-Dawley rats were fed diets supplemented with MCP at concentrations of 0%, 2.25%, 4.5%, and 9% (wt/wt) from the age of 4 weeks until natural death. There were 40 rats in each group (male:female ratio=1:1). The results showed that the MCP did not significantly influence body weight or food consumption of rats of either sex throughout the life span; it did dose-dependently inhibit the age-related decrease in the activities of antioxidant enzymes and the age-related increase in the levels of lipid peroxidation product in both sexes. MCP notably increased the mean life span, the life span of the last 30% of the survivors, and the maximal life span; it decreased overall spontaneous tumor incidence of both sexes with significance in the 4.5% and 9% MCP-treated male groups and 9% MCP-treated female group. Compared to the control group, the incidence of death from tumors was decreased in MCP groups in comparison with the control group of both sexes. Therefore, we concluded that MCPs dose-dependently increase life span and decrease spontaneous tumor incidence in Sprague-Dawley rats. Moreover, the antioxidative property of MCPs may be responsible for the increased life span and protection against tumor development.

Diversity and Chemical Defense Role of Culturable Non-Actinobacterial Bacteria Isolated from the South China Sea Gorgonians

( Jiang Peng ),( Xiao Yong Zhang ),( Xin Ya Xu ),( Fei He ),( Shu Hua Qi ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.4

The diversity of culturable non-actinobacterial (NA) bacteria associated with four species of South China Sea gorgonians was investigated using culture-dependent methods followed by analysis of the bacterial 16S rDNA sequence. A total of 76 bacterial isolates were recovered and identified, which belonged to 21 species of 7 genera, and Bacillus was the most diverse genus. Fifty-one percent of the 76 isolates displayed antibacterial activities, and most of them belonged to the Bacillus genus. From the culture broth of gorgonian-associated Bacillus methylotrophicus SCSGAB0092 isolated from gorgonian Melitodes squamata, 11 antimicrobial lipopeptides including seven surfactins and four iturins were obtained. These results imply that Bacillus strains associated with gorgonians play roles in coral defense mechanisms through producing antimicrobial substances. This study, for the first time, compares the diversity of culturable NA bacterial communities among four species of South China Sea gorgonians and investigates the secondary metabolites of gorgonian-associated B. methylotrophicus SCSGAB0092.

Application of Joint Detection of AFP, CA19-9, CA125 and CEA in Identification and Diagnosis of Cholangiocarcinoma

Li, Yong,Li, Da-Jiang,Chen, Jian,Liu, Wei,Li, Jian-Wei,Jiang, Peng,Zhao, Xin,Guo, Fei,Li, Xiao-Wu,Wang, Shu-Guang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Objective: To explore the application of joint detection of serum AFP, CA19-9, CA125 and CEA in identification and diagnosis of cholangiocarcinoma (CC). Materials and Methods: The levels of serum AFP, CA19-9, CA125 and CEA of both 30 patients with CC and 30 patients with hepatocellular carcinoma (HCC) were assessed. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic effects of single and joint detection of those 4 kinds of tumor markers for CC. Results: The levels of serum CA19-9, CA125 and CEA in CC patients were higher than that in HCC patients,whereas that of serum AFP was significantly lower s. The area under ROC curve of single detection of serum AFP, CA19-9, CA125 and CEA were 0.05, 0.86, 0.84 and 0.83, with the optimal cutoff values of 15.4 ng/ml, 125.1 U/ml, 95.7 U/ml and 25.9 ng/ml, correspondingly, and the percentage correct single diagnosis was <79%. With joint detection, the diagnostic effect of combined AFP, CA19-9, CA125 and CEA was the highest, with an area under the ROC curve of 0.94 (95%CI 0.88~0.99). Conclusions: Single detection of serum CA19-9, CA125 and EA is not meaningful. The sensitivity, specificity, the rate of correct diagnosis and the area under ROC curve of joint detection of AFP, CA19-9, CA125 and CEA are highest, indicating that the joint detection of these 4 tumor markers is of great importance in the diagnosis of CC.

New Compounds from Euphorbia helioscopia and Absolute Configuration Determination by Computational Methods

He, Jiang-Bo,Zhu, Hua-Jie,Luo, Gui-Fen,Liu, Guang-Ming,Chen, Hao,Li, Yan,Chen, Shaopeng,Lu, Xin,Zhou, Guochun,Cheng, Yong-Xian Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.8

The whole plant of Euphorbia helioscopia is an important traditional Chinese medicine. Fom its BuOH soluble extract, one new lactam (1), three new terpenoids (2-4) including a new naturally occurring compound, and three known compounds were isolated. Their structures were identified by spectroscopic evidences. In particular, the absolute configurations of side chain of compounds 1 and 2 were determined using computational methods.

Phase-field simulation of radiation-induced bubble evolution in recrystallized U-Mo alloy

Yanbo Jiang,Yong Xin,Wenbo Liu,Zhipeng Sun,Ping Chen,Dan Sun,Mingyang Zhou,Xiao Liu,Di Yun 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.1

In the present work, a phase-field model was developed to investigate the influence of recrystallizationon bubble evolution during irradiation. Considering the interaction between bubbles and grain boundary(GB), a set of modified Cahn-Hilliard and Allen-Cahn equations, with field variables and order parametersevolving in space and time, was used in this model. Both the kinetics of recrystallization characterized inexperiments and point defects generated during cascade were incorporated in the model. The bubbleevolution in recrystallized polycrystalline of UeMo alloy was also investigated. The simulation resultsshowed that GB with a large area fraction generated by recrystallization accelerates the formation andgrowth of bubbles. With the formation of new grains, gas atoms are swept and collected by GBs. Thesimulation results of bubble size and distribution are consistent with the experimental results.

Effect of TLR4 and B7-H1 on Immune Escape of Urothelial Bladder Cancer and its Clinical Significance

Wang, Yong-Hua,Cao, Yan-Wei,Yang, Xue-Cheng,Niu, Hai-Tao,Sun, Li-Jiang,Wang, Xin-Sheng,Liu, Jing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

Expression of Lamininγ2 in Extrahepatic Cholangiocarcinoma Tissues and its Influence on Tumor Invasion and Metastasis

Li, Yong,Li, Da-Jiang,Chen, Jian,Liu, Wei,Li, Jian-Wei,Jiang, Peng,Zhao, Xin,Guo, Fei,Li, Xiao-Wu,Wang, Shu-Guang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Objective: To explore the expression of $laminin{\gamma}2$ in extrahepatic cholangiocarcinoma (EHCC) tissues and its influence on tumor invasion and metastasis. Materials and Methods: Paraffin embedding samples of cancer, para-cancer, lymph node metastatic and hepatic metastatic tissues from 79 patients undergoing EHCC resection were collected. Expression of $laminin{\gamma}2$ was detected by immunohistochemistry and its relationship with clinical pathological characteristics and the prognosis of EHCC patients were analyzed. Results: $Laminin{\gamma}2$ showed negative staining in para-cancer tissues, but demonstrated a 51.9% (41/79) positive expression rate in extracellular matrix (ECM) or cytoplasm of EHCC tissues. In lymph node metastatic and distant metastatic nidi, expression of $laminin{\gamma}2$ was significantly higher than in the primary nidi (${\chi}^2=7.4173$, P=0.0065; ${\chi}^2=4.0077$, P=0.0453). The expression was in obvious association with lymph node metastasis (P<0.01), but had no relevance with age, gender, tumor location, tumor stage, differentiation and distant metastasis in ECM (P>0.05), whereas it was in marked connection with lymph node and distant metastasis (P<0.05 or P<0.01), but had no relationship with age, gender, tumor location, tumor stage and differentiation in cytoplasm (P>0.05). However, the median survival time and median recurrent period of patients with positive expression of $laminin{\gamma}2$ in both cytoplasm and ECM of tumor cells, only in ECM and only in cytoplasm, were evidently lower than with negative expression of $laminin{\gamma}2$ in RCM and cytoplasm (P<0.05 or P<0.01). Further Cox regression analysis showed that the positive expression of $laminin{\gamma}2$ and the tumor differentiation were independent risk factors influencing the prognosis of EHCC patients. Conclusions: Abnormal expression of $laminin{\gamma}2$ may be closely associated with invasion and metastasis of tumor cells, and thus a potential molecular marker for prognosis of EHCC patients.

Anti-androgen-independent Prostate Cancer Effects of Ginsenoside Metabolites In Vitro: Mechanism and Possible Structure-Activity Relationship Investigation

Wei Li,Yong Liu,Jiang-Wei Zhang,Chun-Zhi Ai,Nan Xiang,Hui-Xin Liu,Ling Yang 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.1

Treatment of androgen-independent prostate cancer (AIPC) remains unsatisfactory. In our present experiment, natural occurring ginsenosides (NOGs) and intestinal bacterial metabolites (IBMs) were employed to investigate their anti-AIPC cell growth activity using PC-3 cells. Our results showed that the IBMs exerted more portent anti-AIPC activity than NOGs, by decreasing survival rate, inhibiting proliferation, inducing apoptosis, and leading to cell cycle arrest in AIPC PC-3 cells. The increase of LogP and decrease of C-6 steric hindrance, which were caused by deglycosylation by intestinal bacteria, may be the reason for the higher anti-AIPC activity of IBMs.