A New Quorum-Sensing Inhibitor Attenuates Virulence and Decreases Antibiotic Resistance in Pseudomonas aeruginosa

Yu-Xiang Yang,Zhen-Hua Xu,Yu-Qian Zhang,Jing Tian,Li-Xing Weng,Lian-Hui Wang 한국미생물학회 2012 The journal of microbiology Vol.50 No.6

Quorum sensing (QS) has been a novel target for the treatment of infectious diseases. Here structural analogs of Pseudomonas aeruginosa autoinducer N-acyl homoserine lactone (AHL) were investigated for QS inhibitor (QSI) activity and a novel QSI was discovered, N-decanoyl-L-homoserine benzyl ester (C2). Virulence assays showed that C2 downregulated total protease and elastase activities, as well as the production of rhamnolipid, that are controlled by QS in P.aeruginosa wild-type strain PAO1 without affecting growth. C2 was also shown to inhibit swarming motility of PAO1. Using a microdilution checkerboard method, we identified synergistic interactions between C2 and several antibiotics, tobramycin, gentamycin, cefepime, and meropenem. Data from real-time RT-PCR suggested that C2 inhibited the expression of lasR (29.67%), lasI (21.57%), rhlR (28.20%), and rhlI (29.03%).

RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer

Tian-Hao Weng,Min-Ya Yao,Xiang-Ming Xu,Chen-Yu Hu,Shu-Hao Yao,Yi-Zhi Liu,Zhi-Gang Wu,Tao-Ming Tang,Pei-Fen Fu,Ming-Hai Wang,Hang-Ping Yao 대한암학회 2020 Cancer Research and Treatment Vol.52 No.3

Purpose Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. Materials and Methods We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. Results Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. Conclusion RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.

Systematic Evaluation and Meta-Analysis of the Effect of Gynostemma pentaphyllum on Clinical Indexes of Hyperlipidemia

Hao-Tian Luo,Man-Yu Xiao,Wen-Jing Pei,Kang-Le Bi,Peng Xie,Yu-Long Gu,Xiang-Lan Piao 한국생약학회 2023 Natural Product Sciences Vol.29 No.4

Near-Ultraviolet Lateral Photovoltaic Effect of Epitaxial Nb:SrTiO3 Films on Si Substrate Using TiN as a Buffer Layer

Fang Wang,Yu Liu,Tian Yu,Cai,Wenfeng Xiang 대한금속·재료학회 2024 ELECTRONIC MATERIALS LETTERS Vol.20 No.3

In recent years, signifi cant attention has been directed toward exploring heterojunctions based on perovskite materials forultraviolet photodetectors. This study focuses on the fabrication of high-quality single-crystal Nb:SrTiO 3 (NSTO) fi lms onSi substrates, achieved through the utilization of a TiN thin fi lm as a buff er layer. The investigation delves into the lateralphotovoltaic effect exhibited by the fi lm. Characterization using X-ray diff raction and high-resolution transmission electronmicroscopy confi rms the exceptional quality of the NSTO fi lm. Notably, the observed position sensitivity attains an impressivevalue of 43.9 mV mm−1. Analysis of the lateral photovoltaic effect reveals response and relaxation times of approximately105.6 ns and 4.49 μs, respectively. Intriguingly, fi tting results for the relaxation time indicate minimal defects withinthe NSTO/TiN/Si heterostructures. These fi ndings underscore the signifi cant potential of NSTO/TiN/Si heterojunctions,presenting a promising avenue for their widespread application in the realm of position change technology.

Blood lipids and all-cause mortality among old people: the Chinese Longitudinal Healthy Longevity Survey 2008-2018

Wang Rongxi,Yu Xiaoyue,Wang Zhiqiang,Liu Yujie,Chen Hui,Liu Shangbin,XU CHENG,Chen Yingjie,Xia Danni,Ge Xin,Chang Ruijie,Xu Gang,Xiang Mi,Wang Ying,Shen Tian,Hu Fan,Cai Yong 한국역학회 2022 Epidemiology and Health Vol.44 No.-

OBJECTIVES: Proper blood lipid levels are essential for survival in older adults, but inconsistent relationships have been reported between blood lipids and all-cause mortality in the elderly. METHODS: This retrospective longitudinal study analyzed data from 1,067 Chinese older adults enrolled in the Chinese Longitudinal Healthy Longevity Survey collected in 2008 and followed up until death or December 31, 2018. The outcome was allcause mortality. Multivariate Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with stratification by age (60-80, 80-100, or ≥ 100 years) for further analysis. The survival probability according to lipid profile quartiles was calculated using Kaplan-Meier curves and the log-rank test. RESULTS: The participants’ mean age was 84.84 years, and 57.0% were female. In total, 578 individuals died, and 277 were lost to follow-up. The mean total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were higher among those who died than among those who survived. Participants in the second HDL-C quartile and the highest LDL-C and triglyceride (TG) quartiles had 28% higher, 23% lower, and 49% lower risks of all-cause mortality, respectively. After further adjustment, the associations remained except for HDL-C, and additional associations were observed between all-cause mortality and the third TC and LDL-C quartiles and the second TG quartile (HR, 1.44; 95% CI, 1.01 to 2.06; HR, 0.68; 95% CI, 0.49 to 0.94; HR, 0.79; 95% CI, 0.62 to 0.99, respectively). CONCLUSIONS: Older adults should maintain an LDL-C level of 1.91-2.47 mmol/L and a TG level of no less than 1.66 mmol/L.

CDK2 is Required for the DNA Damage Response during Porcine Early Embryonic Development

HaiYang Wang,Yu-Jin Jo,Tian-Yi Sun,Suk Namgoong,Xiang-Shun Cui,Jeong Su Oh,Nam-Hyung Kim 한국동물생명공학회(구 한국동물번식학회) 2016 발생공학 국제심포지엄 및 학술대회 Vol.2016 No.10

CDK2 is Required for the DNA Damage Response during Porcine Early Embryonic Development

HaiYang Wang,Yu-Jin Jo,Tian-Yi Sun,Suk Namgoong,Xiang-Shun Cui,Jeong Su Oh,Nam-Hyung Kim 한국수정란이식학회 2016 한국수정란이식학회 학술대회 Vol.2016 No.10

CDK2 inhibition plays a central role in DNA damage–induced cell cycle arrest and DNA repair. However, whether CDK2 also influences early porcine embryo development is unknown. In this study, we examined whether CDK2 is involved in the regulation of oocyte meiosis and early embryonic development of porcine. We found that disrupting CDK2 activity with RNAi or an inhibitor did not affect meiotic resumption or MII arrest. However, CDK2 inhibitor-treated embryos showed delayed cleavage and ceased development before the blastocyst stage. Disrupting CDK2 activity is able to induce sustained DNA damage as demonstrated by the formation of distinct γH2AX foci in nuclei of day 3- and day 5-embryos. Inhibiting CDK2 triggers a DNA damage checkpoint by activating of the ATM-P53-P21 pathway. However, the mRNA expression of genes involved in non-homologous end-joining (NHEJ) or homologous recombination (HR) pathways for double strand break (DSB) repair reduced after administering CDK2 inhibitor to 5-day-old embryos. Furthermore, CDK2 inhibition caused apoptosis in day 7 blastocysts. Thus, our results indicate that an ATM-P53-P21 DNA damage checkpoint is intact in the absence of CDK2; however, CDK2 is important for proper repair of the damaged DNA by either directly or indirectly influencing DNA repair-related gene expression.

Pemetrexed as a Component of First-, Second- and Third-line Chemotherapy in Treating Patients with Metastatic Lung Adenocarcinoma

Huang, Xin-En,Tian, Guang-Yu,Cao, Jie,Xu, Xia,Lu, Yan-Yan,Wu, Xue-Yan,Liu, Jin,Shi, Lin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Purpose: The current research was conducted to investigate the efficacy and safety of pemetrexed given continuously as a basement agent for first-, second- to third line chemotherapy of patients with metastatic lung adenocarcinoma. Patients and Methods: Patients with metastatic lung adenocarcinoma who were diagnosed in Jiangsu Cancer Hospital and Research Insitute, were enrolled. All received pemetrexed 500 $mg/m^2$ (intravenous; on day 1), and another chemotherapieutic agent every 3 weeks until disease progression, or intolerable toxicity. Then the patients were changed to a second line chemotherapy that was still based on pemetrexed 500 $mg/m^2$ and another chemotherapeutic agent differing from the first line example, until disease progression, or intolerable toxicity. When third line chemotherapy was needed, pemetrexed 500 $mg/m^2$ and another new chemotherapeutic agent were combined until disease progression. Evaluation of efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to NCI Criteria for Adverse Events version 3.0. Results: From January 2010 to September 2013, 15 patients were enrolled. Their median age was 56 years (range 43 to 77 years). Eight patients were male and 7 female. Five patients (33.3%) achieved PR, while 6 patients (40.0%) remained stable, no CR on first line; and 1 PR (7.7%), 5 stable (38.5%) were recorded when pemetrexed was ordered in second line; 5 patients (41.7%) were stable after pemetrexed was combined in third line; no complete response was observed. Main side effects were grade 1 to 2 neutrophil suppression and thrombocytopenia. Other toxicities included elevated transaminase and oral mucositis, but no treatment related death occurred. Conclusions: Pemetrexed continuously as a basement agent from first-, second- to third line chemotherapy is mildly effective in treating patients with metastatic lung adenocarcinoma with tolerable toxicity.

Efficacy and Safety Profile of Combining Sorafenib with Chemotherapy in Patients with HER2-Negative Advanced Breast Cancer: A Meta-analysis

Jie Chen,Chun-Xiang Tian,Miao Yu,Qing Lv,Nan-Sheng Cheng,Zu Wang,Xi Wu 한국유방암학회 2014 Journal of breast cancer Vol.17 No.1

Purpose: The aim of the study was to evaluate the efficacy andsafety of combining sorafenib with chemotherapy in patients withhuman epidermal growth factor receptor 2 (HER2)-negative advancedbreast cancer. Methods: MEDLINE, EMBASE, CochraneCentral Register of Controlled Trials, American Society for ClinicalOncology abstracts, and European Society for Medical Oncologyabstracts were searched. Randomized clinical trials that comparedthe efficacy and safety of sorafenib plus chemotherapy inpatients with HER2-negative advanced breast cancer with placeboplus chemotherapy were eligible. The endpoints were progression-free survival (PFS), overall survival (OS), time to progression(TTP), duration of response (DOR), overall response rate(ORR), clinical benefits, and adverse effects. The meta-analysiswas performed using Review Manager 5.2.6 (The Nordic CochraneCentre), and the fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneitywas found (p<0.1), further analysis (subgroup analysis, sensitivityanalysis, or random-effect model) was performed to identifythe potential cause. The results are expressed as hazard ratios orrisk ratios, with their corresponding 95% confidence intervals. Results: The final analysis included four trials comprising 844 patients. The results revealed longer PFS and TTP, and higher ORRand clinical benefit rates in patients receiving sorafenib combinedwith chemotherapy compared to those receiving chemotherapyand placebo. OS and DOR were similar in the two groups. Meanwhile,the incidence of some adverse effects, including hand-footskin reaction/hand-foot syndrome, diarrhea, rash, and hypertension,were significantly higher in the sorafenib arm. Conclusion:Sorafenib combined with chemotherapy may prolong PFS andTTP. This treatment was associated with manageable toxicities,but frequent dose interruptions and reductions were required.

Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Cerebral Venous Thrombosis : A Meta-Analysis

Lv, Bin,Jing, Feng,Tian, Cheng-lin,Liu, Jian-chao,Wang, Jun,Cao, Xiang-yu,Liu, Xin-feng,Yu, Sheng-yuan The Korean Neurosurgical Society 2021 Journal of Korean neurosurgical society Vol.64 No.3

Objective : A role of diffusion-weighted imaging (DWI) in the diagnosis of cerebral venous thrombosis (CVT) is not well-understood. This study evaluates the effectiveness of DWI in the diagnosis of CVT. Methods : Literature search was conducted in electronic databases for the identification of studies which reported the outcomes of patients subjected to DWI for CVT diagnosis. Random-effects meta-analyses were performed to achieve overall estimates of important diagnostic efficiency indices including hyperintense signal rate, the sensitivity and specificity of DWI in diagnosing CVT, and the apparent diffusion coefficient (ADC) of DWI signal areas and surrounding tissue. Results : Nineteen studies (443 patients with 856 CVTs; age 40 years [95% confidence interval (CI), 33 to 43]; 28% males [95% CI, 18 to 38]; symptom onset to DWI time 4.6 days [95% CI, 2.3 to 6.9]) were included. Hyperintense signals on DWI were detected in 40% (95% CI, 26 to 55) of the cases. The sensitivity of DWI for detecting CVT was 22% (95% CI, 11 to 34) but specificity was 98% (95% CI, 95 to 100). ADC values were quite heterogenous in DWI signal areas. However, generally the ADC values were lower in DWI signal areas than in surrounding normal areas (mean difference-0.33×10-3 ㎟/s [95% CI, -0.44 to -0.23]; p<0.00001). Conclusion : DWI has a low sensitivity in detecting CVT and thus has a high risk of missing many CVT cases. However, because of its high specificity, it may have supporting and exploratory roles in CVT diagnosis.