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Antibacterial activity of bacillomycin D-like compounds isolated from Bacillus amyloliquefaciens HAB-2 against Burkholderia pseudomallei

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Asian Pacific Journal of tropical Biomedicine 2020年第4期10卷 183-188页

作者： Mamy Jayne Nelly Rajaofera Xun Kang Peng-Fei Jin Xin Chen Chen-Chu Li Li Yin Lin Liu Qing-Hui Sun Nan Zhang Chui-Zhe Chen Na He Qian-Feng Xia Wei-Guo Miao Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of tropical medicine and laboratory medicine Hainan Medical UniversityHaikouHainanChina key laboratory of Green Prevention and Control of tropical Plant Diseases and Pests(Hainan University) Ministry of EducationHaikou 570228HainanChina

Objective:To investigate the inhibitory effect on Burkholderia pseudomallei(B.pseudomallei)strain HNBP001 of a bacillomycin D-like cyclic lipopeptide compound named bacillomycin DC isolated from Bacillus amyloliquefaciens HAB-2.Methods:The antibacterial effect of bacillomycin DC on B.pseudomallei was determined using the disk diffusion method.The minimum inhibitory concentrations were evaluated by microdilution assay.In addition,transmission electron microscopy was performed and quantitative real-time polymerase chain reaction assay was carried out to determine the expression of Mex B,Opr D2,and qnr S genes.Results:Bacillomycin DC produced an inhibition zone against B.pseudomallei with minimum inhibitory concentration values of 12.5μg/mL 24 h after treatment and 50μg/mL at 48 and 72 h.Transmission electron microscopy showed that bacillomycin DC resulted in roughening cell surface and cell membrane damage.Quantitative real-time polymerase chain reaction analysis showed low expression of Mex B,Opr D2 and qnr S genes.Conclusions:Bacillomycin DC inhibits the growth of B.pseudomallei and can be a new candidate for antimicrobial agents of B.pseudomallei.

关键词： Bacillomycin DC Bioactive compound Burkholderia pseudomallei

Lomatogonium rotatum extract alleviates diabetes mellitus induced by a high-fat,high-sugar diet and streptozotocin in rats

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World Journal of Diabetes 2023年第6期14卷 846-861页

作者： Li-Li Dai Sung-Bo Cho Hui-Fang Li Li-Sha A Xiao-Ping Ji Sirigunqiqige Pan Ming-Lan Bao Laxinamujila Bai Gen-Na Ba Ming-Hai Fu NMPA key laboratory of Quality Control of Traditional Chinese medicine(Mongolian medicine) Inner Mongolia Minzu UniversityTongliao 028000Inner Mongolia Autonomous RegionChina Key Laboratory of Tropical Translational Medicine of Ministry of Education Hainan Provincial Key Laboratory for Research and Development of Tropical HerbsHainan Medical UniversityHaikou 571199Hainan ProvinceChina Key Laboratory of Tropical Translational Medicine of Ministry of Education Hainan Provincial Key Laboratory for Research and Development of Tropical HerbsSchool of PharmacyHainan Medical UniversityHaikou 571199Hainan ProvinceChina

BACKGROUND Lomatogonium rotatum(LR)is traditionally used in Mongolian folk medicine as a hypoglycemic agent,but its evidence-based pharmacological effects and mechanisms of action have not been fully elucidated.AIM To emphasize the hypoglycemic action mechanism of LR in a type 2 diabetic rat model and examine potential biomarkers to obtain mechanistic understanding regarding serum metabolite modifications.METHODS A high-fat,high-sugar diet and streptozotocin injection-induced type 2 diabetic rat model was established.The chemical composition of the LR was identified by high performance liquid chromatography.LR extract administrated as oral gavage at 0.5 g/kg,2.5 g/kg,and 5 g/kg for 4 wk.Anti-diabetic effects of LR extract were evaluated based on histopathological examination as well as the measurement of blood glucose,insulin,glucagon-like peptide 1(GLP-1),and lipid levels.Serum metabolites were analyzed using an untargeted metabolomics approach.RESULTS According to a chemical analysis,swertiamarin,sweroside,hesperetin,coumarin,1.7-dihydroxy-3,8-dimethoxyl xanthone,and 1-hydroxy-2,3,5 trimethoxanone are the principal active ingredients in LR.An anti-diabetic experiment revealed that the LR treatment significantly increased plasma insulin and GLP-1 levels while effectively lowering blood glucose,total cholesterol,triglycerides,low-density lipoprotein cholesterol,and oral glucose tolerance test compared to the model group.Furthermore,untargeted metabolomic analysis of serum samples detected 236 metabolites,among which 86 were differentially expressed between the model and the LR group.It was also found that LR considerably altered the levels of metabolites such as vitamin B6,mevalonate-5P,Dproline,L-lysine,and taurine,which are involved in the regulation of the vitamin B6 metabolic pathway,selenium amino acid metabolic pathway,pyrimidine metabolic pathway,and arginine and proline metabolic pathways.CONCLUSION These findings indicated that LR may have a hypoglycemic impact and that its role may be related to changes

关键词： Mongolian medicine Lomatogonium rotatum Type 2 diabetes Metabolomics Swertiamarin Streptozotocin

Metabolomics investigation on antiobesity effects of Corydalis bungeana on high-fat high-sugar diet-induced obese rats

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Chinese Herbal medicines 2022年第3期14卷 414-421页

作者： Minghai Fu Terigele Bao Hongzhen Yu LiSha A. HuiFang Li Genna Ba Sungbo Cho Key Laboratory of Tropical Translational Medicine of Ministry of Education Hainan Key Laboratory for Research and Development of Tropical HerbsSchool of PharmacyHainan Medical UniversityHaikou 571199China NMPA key laboratory of Quality Control of Traditional Chinese medicine(Mongolian medicine) Inner Mongolia Minzu UniversityTongliao 028000China

Objective:Corydalis bungeana(CB)is a well-used medicinal herb in Mongolian folk medicine and has been traditionally applied as an antiobesity agent.However,the evidence-based pharmacological effects of CB and its specific metabolic alterations in the obese model are not entirely understood.This study aimed to utilize untargeted metabolomic techniques to identify biomarkers and gain mechanistic insight into the serum metabolite alterations associated with weight loss and lipid metabolism in obese rats.Methods:A high-fat high-sugar(HFHS)diet was used to induce obese models in rats.CB extract was orally gavaged at 0.18,0.9 and 1.8 g/kg doses for six weeks,and feed intake,body weight,fat pad weight,and blood indexes were measured.Blood serum metabolites were evaluated by gas chromatography/quadrupole time-of-fight tandem mass spectrometry(GC-TOF/MS).Results:The results showed that compared with the obese group,the administration of CB extract caused significant decreases in body weight(P<0.05),feed intake,Lee’s index,and perirenal,mesenteric,epididymal fat weight.CB extract also reduced blood triglyceride and total cholesterol levels(P<0.05)of obese rats.Metabolomic findings showed that nine differential metabolites,including pyruvic acid,D-glucuronic acid,malic acid,dimethylglycine,oxoglutaric acid,pantothenic acid,sorbitol acid,fumaric acid and glucose 6-phosphate were identified under CB treatment and altered metabolic pathways such as TCA cycle,pantothenate and CoA biosynthesis,and glycolysis/gluconeogenesis.Conclusion:This study demonstrated weight loss and lipid lowering effects of CB on HFHS diet-induced obese rats and identified nine metabolites as potential biomarkers for evaluating the favorable therapeutic mechanism of CB via regulation of lipid and glucose metabolism.

关键词： Corydalis bungeana Turcz. GC-TOF/MS metabolomics Mongolian medicine obesity

A novel lytic phage potentially effective for phage therapy against Burkholderia pseudomallei in the tropics

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Infectious Diseases of Poverty 2022年第4期11卷 98-98页

作者： Yanshuang Wang Xuemiao Li David A.B.Dance Han Xia Chen Chen Nini Luo Anyang Li Yanmei Li Qiao Zhu Qinghui Sun Xingyong Wu Yingfei Zeng Lin Chen Shen Tian Qianfeng Xia Key Laboratory of Tropical Translational Medicine of Ministry of Education NHC Key Laboratory of Tropical Disease ControlSchool of Tropical Medicine and The Second Affliated HospitalHainan Medical UniversityHaikouHainanChina 不详

Background:Burkholderia pseudomallei is a tropical pathogen that causes melioidosis.Its intrinsic drug-resistance is a leading cause of treatment failure,and the few available antibiotics require prolonged use to be effective.This study aimed to assess the clinical potential of B.pseudomallei phages isolated from Hainan,China.Methods:Burkholderia pseudomallei strain(HNBPoo1)was used as the isolation host,and phages were recovered from domestic environmental sources,which were submitted to the host range determination,lytic property assays,and stability tests.The best candidate was examined via the transmission electron microscope for classification.With its genome sequenced and analyzed,its protective efficacy against B.pseudomallei infection in A549 cells and Caenorhabditis elegans was evaluated,in which cell viability and survival rates were compared using the one-way ANOVA method and the log-rank test.Results:A phage able to lyse 24/25 clinical isolates was recovered.It was classified in the Podoviridae family and was found to be amenable to propagation.Under the optimal multiplicity of infection(MOl)of o.1,an eclipse period of around 20 min and a high titer(io12 PFU/ml)produced within 1 h were demonstrated.This phage was found stabile at a wide range of temperatures(24,37,40,50,and 60 C)and pH values(3-12).After being designated as vB_BpP_HN01,it was fully sequenced,and the 71,398 bp linear genome,containing 93 open reading frames and a tRNA-Asn,displayed a low sequence similarity with known viruses.Additionally,protective effects of applications of vB_BpP_HNo1(MOl=0.1 and MOl=1)alone or in combination with antibiotics were found to improve viability of infected cells(70.6±6.8%,85.8±5.7%,91.9±1.8%,and 96.8±1.8%,respectively).A significantly reduced mortality(10%)and a decreased pathogen load were demonstrated in infected C.elegans following the addition of this phage.Conclusions:As the frst B.pseudomallei phage was isolated in Hainan,China,phage vB_BpP_HNO1 was characterized by promising lytic property,stabil

关键词： classification. protective stability

Herb-drug interaction in the protective effect of Alpinia officinarum against gastric injury induced by indomethacin based on pharmacokinetic, tissue distribution and excretion studies in rats

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Journal of Pharmaceutical Analysis 2021年第2期11卷 200-209页

作者： Xuguang Zhang Zhenrui Xie Xun Chen Junqiang Qiu Yinfeng Tan Xiaoliang Li Hailong Li Junqing Zhang key laboratory of tropical Translation medicine of ministry of education Hainan Provincial Key Laboratory for Research and Development of Tropical HerbsSchool of PharmacyHainan Medical UniversityHaikou571199China

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis, abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects. However, the role of herb-drug interaction between indomethacin and A. officinarum based on pharmacokinetic, tissue distribution and excretion still remains unknown. In this study, an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS) method was developed for simultaneous determination of indomethacin and its three metabolites, O-desmethylindomethacin(ODI), deschlorobenzoylindomethacin(NDI) and indomethacin acyl-b-D-glucuronide(IDAbG) by oral administration of indomethacin solution with and without the ethanolic extract of A. officinarum and applied to comparative pharmacokinetic, tissue distribution and excretion studies. Our results clarified that oral administration of A. officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin and A. officinarum reduced the systemic exposure of indomethacin and increased its elimination. Tissue distribution results demonstrated that co-administration of A. Officinarum could not reduce the accumulation of indomethacin in the target tissue of the stomach, but could accelerate the excretions of indomethacin and its three metabolites including ODI, NDI and IDAb G in the bile and feces of rats in the excretion study.Therefore, A. Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

关键词： Alpinia officinarum Hance Indomethacin Herb-drug interaction Pharmacokinetics Tissue distribution Excretion

Seedless synthesis of gold nanorods with tunable plasmonic peaks beyond 1300 nm

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Chinese Chemical Letters 2022年第5期33卷 2491-2495页

作者： Liangxi Zhu Zhuoxuan Lu Liming Zhang Nongyue He State key laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China key laboratory of tropical Disease and translational medicine of the ministry of education&Hainan Provincial key laboratory of tropical medicine Hainan Medical CollegeHaikou 571101China Hunan key laboratory of Biomedical Nanomaterials and Devices Hunan University of TechnologyZhuzhou 412007China

Gold nanorods(AuNRs),as relatively common materials used in biomedical areas,have been synthesized by means of many methods.However,the conventional seed-mediated method is limited by complex operations and low yield.Besides,for further applications of AuNRs,well monodispersed AuNRs and tun-able longitudinal surface plasmon resonance(LSPR)remain to be improved.Herein,we report a one-pot method for synthesizing AuNRs without seeding agents.In this method,we use phenols as reducing agents and hydrochloric acid and nitric acid are used to regulate the pH of the growth solution.AuNRs with the longest LSPR peak position reaching 1340 nm are prepared.Furthermore,by systematically op-timizing concentrations of the reagents involved in the growth solution,different aspect ratios of AuNRs are synthesized.The facile synthesis,controllability aspect ratio,and long LSPR peak make our method promising for wider applications of AuNRs.

关键词： Gold nanorods Seedless method Hydroquinone Acid Aspect ratio

A novel therapeutic vaccine based on graphene oxide nanocomposite for tumor immunotherapy

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Chinese Chemical Letters 2022年第8期33卷 4089-4095页

作者： Liming Zhang Lingfeng Xu Yi Wang Jieyu Liu Guanghong Tan Fengying Huang Nongyue He Zhuoxuan Lu Key Laboratory of Tropical Translational Medicine of Ministry of Education&Hainan Provincial key laboratory of tropical medicine Hainan Medical UniversityHaikou 571199China State key laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Department of Clinical laboratory HwaMei HospitalUniversity of Chinese Academy of SciencesNingbo 315000China

With an intensive understanding of the mechanism of immune system,developing a therapeutic tumor vaccine is one of the most perspective strategy of cancer immunotherapy.In this study,we report a facile approach to prepare graphene oxide(GO)-based therapeutic cancer-nanovaccine.The model antigen(ovalbumin,OVA)and adjuvant(CpG ODN),are conjugated with GO-PEI nanosheet through electrostatic interaction.The addition of PEG can improve biocompatibility and prevent nanoparticle aggregation.The prepared GO-based nanovaccine,GO-PEI-OVA-PEG-CpG,exhibits good biocompatibility and low toxicity both in vivo and in vitro.More importantly,it can efficiently induce the maturation of dendritic cells(DCs),the enhancement of antigen cross-presentation ability,and the amplification of cytokine production of immune cells.Impressively,this nanovaccine shows a remarkable therapeutic effect against preestablished B16-OVA-melanoma tumors,which can significantly inhibit tumor growth and prolong the survival time of the OVA-expressed tumor-bearing mice.Moreover,combining GO-PEI-OVA-PEG-CpG with NLG919,an IDO-1(indoleamine-2,3-dioxygenase)inhibitor which can regulate the tumor microenvironment,displays a synergistic therapeutic effect.These findings indicate the GO-PEI-OVA-PEG-CpG nanovaccine actively induces an antigen-specific antitumor immune response and it combined with NLG919 could achieve better therapeutic outcomes.

关键词： Nanovaccine Graphene Oxide Adjuvant Tumor-specific antigen NLG919

Pathological BBB Crossing Melanin-Like Nanoparticles as Metal-Ion Chelators and Neuroinflammation Regulators against Alzheimer’s Disease

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Research 2024年第1期6卷 687-706页

作者： Qianqian Huang Chaoqing Jiang Xue Xia Yufan Wang Chenxing Yan Xiaorong Wang Ting Lei Xiaotong Yang Wenqin Yang Guo Cheng Huile Gao key laboratory of Drug-Targeting and Drug Delivery System of the education ministry West China School of PharmacySichuan UniversityChengdu 610041P.R.China laboratory of Molecular translational medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationDepartment of PediatricsWest China Second University HospitalSichuan UniversityChengdu 610041P.R.China

Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD progression.Herein,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of AD.In this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβhitchhiking.In vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB crossing.The engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.

关键词： oxidative aggregation chelating

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

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Chinese Journal of Cancer Research 2022年第4期34卷 383-394页

作者： Changlong Li Zhen Guan Yi Zhao Tingting Sun Zhongwu Li Weihu Wang Zhexuan Li Lin Wang Aiwen Wu key laboratory of Carcinogenesis and translational Research(ministry of education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China key laboratory of Carcinogenesis and translational Research(ministry of education/Beijing) Department of RadiologyPeking University Cancer Hospital&InstituteBeijing 100142China key laboratory of Carcinogenesis and translational Research(ministry of education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China key laboratory of Carcinogenesis and translational Research(ministry of education/Beijing) Department of Radiation OncologyPeking University Cancer Hospital&InstituteBeijing 100142China key laboratory of Carcinogenesis and translational Research(ministry of education/Beijing) Department of Cancer EpidemiologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains challenging.Few studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after treatment.This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital.Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant predictors.Results:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had ypCR.Univariate and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive consistency.The follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 months.The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT.Endoscopic mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

关键词： Rectal cancer preoperative chemoradiotherapy tumor regression grade flat mucosal lesions pathologic complete response