1.Exercise Ameliorates Chronic Restraint Stress-induced Anxiety via PVN CRH Neurons
Jing CHEN ; Cong-Cong CHEN ; Kai-Na ZHANG ; Yu-Lin LAI ; Yang ZOU
Progress in Biochemistry and Biophysics 2025;52(2):501-512
		                        		
		                        			
		                        			ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders. 
		                        		
		                        		
		                        		
		                        	
2.Isoliquiritigenin alleviates abnormal endoplasmic reticulum stress induced by type 2 diabetes mellitus
Kai-yi LAI ; Wen-wen DING ; Jia-yu ZHANG ; Xiao-xue YANG ; Wen-bo GAO ; Yao XIAO ; Ying LIU
Acta Pharmaceutica Sinica 2025;60(1):130-140
		                        		
		                        			
		                        			 Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. 
		                        		
		                        	
3.Construction of Chinese Herbal Medicine Traceability System Based on Influencing Factors of Chinese Herbal Medicine Quality
Kunyang LAI ; Jiancai XIAO ; Binbin YAN ; Xiufu WAN ; Jian YANG ; Guangxing MENG ; Chuanzhi KANG ; Kai SUN ; Yan ZHANG ; Lanping GUO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):215-224
		                        		
		                        			
		                        			As a Chinese saying goes, "good Chinese medicinal material makes good medicine", the quality of Chinese herbal medicines is related to the development prospect of Chinese medicine industry in China. With the rapid development of new technologies such as traceability methods and monitoring instruments, it is imperative to integrate and innovate traditional Chinese herbal medicines with new-generation information technology in view of the quality problems existing in the current production and circulation of Chinese herbal medicines, and it is of great significance for the construction of traceability system to ensure the quality and safety of Chinese herbal medicines and to promote the industry of Chinese herbal medicines to move towards high-quality development. This paper reviews the development history of the traceability system of Chinese herbal medicines in China, takes the influencing factors of the quality of Chinese herbal medicines as the entry point, and proposes that the construction of the traceability system should satisfy the traceability requirements of the characteristics of Chinese herbal medicines and their traditional medication experience. By analyzing the influencing factors of the quality of Chinese herbal medicines, it is pointed out that focusing on the influencing factors to build a traceability system is of great significance for targeting the problematic links at a later stage and exploring the interrelationship between environmental factors and the quality of Chinese herbal medicines. Based on the previous explorations, the author summarizes the system framework, functional modules and practical applications of the traceability system of Chinese herbal medicines, and looks forward to the development of a traceability system with risk early warning function and expert decision-making function in its functional development. Finally, based on the factors affecting the quality of Chinese herbal medicines, the author puts forward several thoughts on construction of the traceability system, and makes an in-depth analysis and puts forward a solution for the current situation that a unified, standardized and universal traceability system has not yet been built, with a view to providing ideas and references for the construction of traceability system of Chinese herbal medicines. 
		                        		
		                        		
		                        		
		                        	
4.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
		                        		
		                        			
		                        			Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
		                        		
		                        		
		                        		
		                        	
5.Sentinel surveillance data of influenza in Hunan Province from 2014 to 2023
Xiao-Lei WANG ; Chao-Yang HUANG ; Qian-Lai SUN ; Zhi-Hong DENG ; Yi-Wei HUANG ; Shan-Lu ZHAO ; Kai-Wei LUO ; Xiang REN ; Sheng-Bao CHEN ; Zhi-Hui DAI
Chinese Journal of Infection Control 2024;23(11):1413-1420
		                        		
		                        			
		                        			Objective To understand the prevalence characteristics of influenza and changes of influenza virus strains,and provide reference for the prevention and control of influenza in the province.Methods Surveillance da-ta about influenza in Hunan Province from 2014 to 2023 were exported from China Influenza Surveillance Informa-tion System.Differences in the percentage of influenza-like illness(ILI)cases(percentage of influenza-like cases[ILI%]in outpatient and emergency department visits)among different years and different populations,as well as the positive rate of influenza virus in ILI specimens were compared.Results From 2014 to 2023,over 2.65 million cases of ILI were reported,with an ILI%of 4.70%.ILI%among different years presented statistically significant differences(P<0.001).People aged 0-14 years old were the main population with ILI,accounting for 82.90%.The positive rate of influenza virus in ILI specimens was 14.14%,the positive rate of influenza virus among diffe-rent years and age groups were both significantly different(both P<0.001).The main prevalent influenza strains from 2014 to 2023 included types A(H1N1),A(H3N2),B(Victoria),and B(Yamagata),alternating among di-fferent years.However,type B(Yamagata)strains were not detected from 2020 to 2023.There were basically two influenza prevalence seasons every year,namely winter-spring and summer.Conclusion People<15 years old are the main population of influenza,and the prevalence peaks are in winter-spring and summer.From 2021 to 2023,the prevalence alternates mainly among 3 types:A(H1N1),A(H3N2),and B(Victoria).
		                        		
		                        		
		                        		
		                        	
6.Paying attention to the epidemic of group A Streptococcus infections in multiple European and American countries.
Kai-Hu YAO ; Meng-Yang GUO ; Yun LAI ; Jiang-Hong DENG
Chinese Journal of Contemporary Pediatrics 2023;25(4):333-338
		                        		
		                        			
		                        			At the end of 2022, the World Health Organization reported an increase in group A Streptococcus (GAS) infections, such as scarlet fever, in multiple countries. The outbreak primarily affected children under 10 years old, and the number of deaths was higher than anticipated, causing international concern. This paper reviews the current state of the GAS disease outbreak, its causes, and response measures. The authors aim to draw attention from clinical workers in China and increase their awareness and vigilance regarding this epidemic. Healthcare workers should be aware of the potential epidemiological changes in infectious diseases that may arise after the optimization of control measures for coronavirus disease 2019 to ensure children's health.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Streptococcus pyogenes
		                        			;
		                        		
		                        			COVID-19/epidemiology*
		                        			;
		                        		
		                        			Streptococcal Infections/epidemiology*
		                        			;
		                        		
		                        			Scarlet Fever/epidemiology*
		                        			;
		                        		
		                        			Epidemics
		                        			;
		                        		
		                        			Disease Outbreaks
		                        			
		                        		
		                        	
7.Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF underwent coronary artery bypass graft.
Yao LU ; Jian CAO ; En Jun ZHU ; Ming Xin GAO ; Tian Tian MOU ; Ying ZHANG ; Xiao Fen XIE ; Yi TIAN ; Ming Kai YUN ; Jing Jing MENG ; Xiu Bin YANG ; Yong Qiang LAI ; Ran DONG ; Xiao Li ZHANG
Chinese Journal of Cardiology 2023;51(4):384-392
		                        		
		                        			
		                        			Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Stroke Volume
		                        			;
		                        		
		                        			Heart Failure
		                        			;
		                        		
		                        			Fluorodeoxyglucose F18
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Reproducibility of Results
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Coronary Artery Bypass
		                        			;
		                        		
		                        			Ventricular Dysfunction, Left
		                        			;
		                        		
		                        			Tomography, Emission-Computed, Single-Photon
		                        			;
		                        		
		                        			Perfusion
		                        			;
		                        		
		                        			Myocardium
		                        			
		                        		
		                        	
8.The correlation between FCER2 gene polymorphism and the efficacy of inhaled corticosteroids in patients with chronic rhinosinusitis.
Shuangxi LIU ; Na CHE ; Ling JIN ; Yang WANG ; Kai FAN ; Ju LAI ; Shaoqing YU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(11):856-863
		                        		
		                        			
		                        			Objective:To investigate the correlation between FCER2(2206A>G) gene polymorphism and the efficacy of inhaled corticosteroids(ICS) in patients with chronic rhinosinusitis(CRS). Methods:A total of 208 CRS patients were routinely treated with functional endonasal sinus surgery and postoperative ICS. DNA extraction, PCR amplification and gene sequencing were performed to observe the FCER2(2206A>G) gene polymorphism and calculate the allele frequency. The visual analog scale(VAS) score, Lund-Kennedy score, and computed tomography(CT) Lund-Mackay score were determined 6 months after surgery among patients with different genotypes. Moreover, the polymorphism frequency was compared among different subgroups(chronic rhinosinusitis with nasal polyps versus chronic rhinosinusitis without nasal polyps, eosinophilic chronic rhinosinusitis versus non-eosinophilic chronic rhinosinusitis). Results:There were FCER2(2206A>G) gene polymorphism in patients with CRS, and the phenotypes included 3 genotypes, AA, AG and GG, with distribution frequencies of 68(32.7%), 116(55.8%) and 24(11.5%) cases, respectively. No significant differences were found in age, VAS score, nasal endoscopic Lund-Kennedy score and CT imaging Lund-Mackay score among patients with CRS of each genotype before surgery. In patients with the AA genotype, the changes in VAS score(5.74±1.10), Lund Kennedy score(5.92 ± 1.14), and CT imaging Lund-Mackay score(13.26±4.26) were significantly higher than in patients with the AG(4.37±0.86, 5.37±1.24, 10.82±3.77) and GG(4.26±0.80, 5.18±1.56, 10.10±3.53) genotype(P<0.05). However, there were no marked difference between patients with the AG genotype and those with the GG genotype(P>0.05). Compared with patients with non-eosinophilic sinusitis, Among them, the differences between the GG genotype and AG /AA genes were more significant in eosinophilic sinusitis compared to non-eosinophilic sinusitis(P<0.01). Conclusion:The FCER2(2206A>G) gene in patients with CRS has genetic polymorphism and is associated with the recovery of CRS patients after surgery, individual corticosteroid sensitivity, and subgroup variability.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Nasal Polyps/complications*
		                        			;
		                        		
		                        			Rhinitis/complications*
		                        			;
		                        		
		                        			Sinusitis/complications*
		                        			;
		                        		
		                        			Adrenal Cortex Hormones/therapeutic use*
		                        			;
		                        		
		                        			Polymorphism, Genetic
		                        			;
		                        		
		                        			Endoscopy/methods*
		                        			;
		                        		
		                        			Chronic Disease
		                        			;
		                        		
		                        			Receptors, IgE
		                        			;
		                        		
		                        			Lectins, C-Type
		                        			
		                        		
		                        	
9. Apoptotic and cytostatic actions of maslinic acid in colorectal cancer cells through possible IKK-β inhibition
Kai Xin OOI ; Menaga SUBRAMANIAM ; Yang Mooi LIM ; Lai Yen FONG ; Yang Mooi LIM ; Hoe Han GOH ; Soo Beng Alan KHOO
Asian Pacific Journal of Tropical Biomedicine 2021;11(3):122-131
		                        		
		                        			
		                        			 Objective: To explore the anti-cancer activity of maslinic acid against colorectal cancer (CRC) cell lines and its possible mechanism. Methods: The inhibitory effect of maslinic acid was screened against five CRC cell lines (HT-29, HCT 116, SW480, SW48, and LS 174T) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle analyses were carried out using annexin V-FITC/propidium iodide staining and propidium iodide staining, respectively and subjected to fluorescence-activated cell sorting analysis. Protein expression studies of inhibitor of κB kinase-β (IKK-β), checkpoint kinase 1 (Chk1) and cyclin D1 were conducted using the JESS system. Results: Maslinic acid exhibited growth inhibitory effect in a doseand time-dependent manner in HT-29 and HCT 116 cell lines. A more prominent apoptosis induced by maslinic acid was observed in HCT 116 cell line. However, in HT-29 cell line, maslinic acid induced cell cycle arrest by inhibiting the G1-S transition, which was accompanied by the downregulation of cyclin D1. The expression of unphosphorylated IKK-β protein was increased in both (HT-29 and HCT 116) cell lines after maslinic acid treatment. Conclusions: Maslinic acid inhibits the growth of HT-29 and HCT 116 cells in a different manner, induces cell cycle arrest in HT-29 cells and causes apoptosis in HCT 116 cells partially via NF-κB pathway inhibition. 
		                        		
		                        		
		                        		
		                        	
10.Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae
Shun-Kai YANG ; Khatijah YUSOFF ; Mokrish AJAT ; Wai-Sum YAP ; Erin-Swee-Hua LIM ; Kok-Song LAI
Journal of Pharmaceutical Analysis 2021;11(2):210-219
		                        		
		                        			
		                        			Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance.This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate(LNA)against carbapenemase-producing Klebsiella pneumoniae(KPC-KP).LNA alone exhibited bacteri-cidal activity at 2.5%(V/V),and in combination with meropenem(MPM)at 1.25%(V/V).Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins,indicating membrane damage in LNA-treated KPC-KP cells.Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress.Zeta po-tential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability.Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells,inferring membrane damage.Furthermore,intracel-lular leakage of nucleic acid and proteins was detected upon LNA treatment.Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular ma-terials.LNA was found to induce oxidative stress by generating reactive oxygen species(ROS)that initiate lipid peroxidation and damage the bacterial membrane.In conclusion,LNA generates ROS,initiates lipid peroxidation,and damages the bacterial membrane,resulting in intracellular leakage and eventually killing the KPC-KP cells.
		                        		
		                        		
		                        		
		                        	
            
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