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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative Medicine 2024年第4期22卷 503-514页

作者： li-hua zhu Yu-pei liang lian Yang Feng zhu li-jun Jia He-gen lia Department of Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine Cancer Institute of Traditional Chinese Medicine Longhua Hospital Shanghai University of Traditional Chinese Medicine Department of Laboratory Medicine Huadong Hospital Fudan University

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC) and elucidates the underlying molecular mechanisms.Methods:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays.Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots.Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. Genetic techniques, including small interfering RNA technology,were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model.Results:Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5?-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway.Conclusion:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

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Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data

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World Journal of Clinical Oncology 2024年第2期15卷 329-355页

作者： li-hua zhu Jun Yang Yun-Fei Zhang li Yan Wan-Rong lin Wei-Qing liu Department of Surgical Oncology The First Affiliated Hospital of Kunming Medical UniversityKunming 650032Yunnan ProvinceChina Department of Internal Medicine-Oncology The First Affiliated Hospital of Kunming Medical UniversityKunming 650032Yunnan ProvinceChina Department of Oncology The First Affiliated Hospital of Kunming Medical UniversityKunming 650032Yunnan ProvinceChina

BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.

关键词： Colorectal cancer Pyroptosis Single-cell RNA sequencing Immune infiltration Prognostic model

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Progress of photonuclear cross sections for medical radioisotope production at the SLEGS energy domain

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Nuclear Science and Techniques 2023年第12期34卷 77-92页

作者： Xuan Pang Bao‑hua Sun li‑hua zhu Guang‑Hong Lu Hong‑Bo Zhou Dong Yang School of Physics Beihang UniversityBeijing 100191China College of Physics Jilin UniversityChangchun 130012China National Basic Science Data Center Beijing 100190China

Photonuclear reactions using a laser Compton scattering(LCS)gamma source provide a new method for producing radioisotopes for medical applications.Compared with the conventional method,this method has the advantages of a high specific activity and less heat.Initiated by the Shanghai Laser Electron Gamma Source(SLEGS),we conducted a survey of potential photonuclear reactions,(γ,n),(γ,p),and(γ,γ')whose cross sections can be measured at SLEGS by summarising the experimental progress.In general,the data are rare and occasionally inconsistent.Therefore,theoretical calculations are often used to evaluate the production of medical radioisotopes.Subsequently,we verified the model uncertainties of the widely used reaction code TALYS-1.96,using the experimental data of the^(100)Mo(γ,n)^(99)Mo,^(65)Cu(γ,n)^(64)Cu,and^(68)Zn(γ,p)^(67)Cu reactions.

关键词： Medical radioisotope Photonuclear reaction LCS Cross section

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Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

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Chinese Medical Journal 2017年第7期130卷 854-858页

作者： Da-Fan Yu li-hua zhu li Jiang Department of Clinical Medcine Medical School of Southeast University Jiangsu 210009 China 2Department of Pediatrics Zhongda Hospital Southeast University Nanjing Jiangsu 210009 China

Background：Recombinant human-erythropoietin （rh-EPO） has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation.In the present study,we found that the rh-EPO was related to the promotion ofneovascularization.Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt） signaling pathway.Methods：Postnatal day 5 （PD5）,rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h.All the rat pups were randomized into five groups as follows：（1） control group;（2） hypoxia-ischemic （HI） group;（3） HI ＋ LY294002 group;（4） HI ＋ rh-EPO group;and （5） HI ＋ rh-EPO ＋ LY294002 group.The phospho-Akt protein was tested 90 min after the whole operation,and CD34,vascular endothelial growth factor receptor 2 （VEGFR2）,and vascular endothelial growth factor （VEGF） were also tested 2 days after the whole operation.Results：In the hypoxic and ischemic zone of the premature rat brain,the rh-EPO induced CD34＋ cells to immigrate to the HI brain zone （P 〈 0.05） and also upregulated the VEGFR2 protein expression （P 〈 0.05） and VEGF mRNA level （P 〈 0.05） through the PI3K/Akt （P 〈 0.05） signaling pathway when compared with other groups.Conclusions：The rh-EPO treatment augments neovascularization responses in the neonatal rat model of premature brain damage through the PI3K/Akt signaling pathway.Besides,the endogenous EPO may exist in the HI zone of rat brain and also has neovascularization function through the PI3K/Akt signaling pathway.

关键词： Erythropoietin Hypoxia-ischemia Neovascularization Premature Brain

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Integration of human papillomavirus 18 DNA in esophageal carcinoma 109 cells

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World Journal of Gastroenterology 2011年第37期17卷 4242-4246页

作者： Ke Zhang Jin-Tao li Shu-Ying li li-hua zhu ling Zhou Yi Zeng College of Basic Medicine Hebei United University Tangshan 063000 Hebei Province China College of life Science and Bio-engineering Beijing University of Technology Beijing 10024 China National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention and State Key Laboratory for Infectious Disease Prevention and Control Beijing 100052 China

AIM:To detect human papillomavirus(HPV) DNA in esophageal carcinoma(EC) 109 cells and investigate the relationship between HPV and EC.METHODS:Genomic DNA and total RNA from EC109 cells were isolated.HPV DNA was detected by polymerase chain reaction(PCR) with the general primer sets of My09/11 and GP5 +/6 + for the HPV L1 gene and type-specific primer sets for HPV18 E6 and HPV18 E6-E7.Reverse transcription(RT) of mRNA isolated from EC109 cells was performed to produce a cDNA.And then a PCR-based protocol for the amplification of papillomavirus oncogene transcripts was used to analyze HPV18 DNA and integrated transcripts of HPV18 in the chromosomes of EC109 cells.The final nested PCR products were cloned into a pMD-18T vector and sequenced to analyze the chromosomal location of HPV integration.RESULTS:HPV18 DNA was detected in EC109 cells by PCR using the general primer sets of My09/11 and GP5 +/6 + for HPV L1 and the type-specif ic primer sets for HPV18 E6 and E6-E7 to generate products of 450 bp,150 bp,335 bp and 944 bp,respectively.Approximately 600 bp of integrated HPV18-specific transcript was identified.The final nested PCR product of integrated HPV18 DNA was cloned into a pMD-18T vector and sequenced to analyze the chromosomal location of HPV integration.Sequence alignment showed that the HPV18 sequence from EC109 cells was identical to that of the encoded early protein E7-E1 of the standard HPV18 strain X05015,and another partial gene sequence was identical to a partial sequence of human chromosome 8.CONCLUSION:Integration of the HPV genome into the host cell chromosome suggests that persistent HPV infection is vital for malignant cell transformation and carcinogenesis.

关键词：乳头状瘤病毒 DNA检测细胞染色食管癌人类癌组织 PCR产物基因组DNA

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Intrinsic background radiation of LaBr3(Ce)detector via coincidence measurements and simulations

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Nuclear Science and Techniques 2020年第10期31卷 33-42页

作者： Hao Cheng Bao-hua Sun li-hua zhu Tian-Xiao li Guang-Shuai li Cong-Bo li Xiao-Guang Wu Yun Zheng School of Physics Beihang UniversityBeijing 100191China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine School of Medicine and EngineeringBeihang UniversityBeijing 100191China China Institute of Atomic Energy Beijing 102413China

The LaBr3(Ce)detector has attracted much attention in recent years because of its superior characteristics compared with other scintillating materials in terms of resolution and efficiency.However,it has a relatively high intrinsic background radiation because of the naturally occurring radioisotopes in lanthanum,actinium,and their daughter nuclei.This limits its applications in low-counting rate experiments.In this study,we identified the radioactive isotopes in theφ3"x 3"Saint-Gobain B380 detector by a coincidence measurement using a Clover detector in a low-background shielding system.Moreover,we carried out a Geant4 simulation of the experimental spectra to evaluate the activities of the main internal radiation components.The total activity of the background radiation of B380 is determined to be 1.523(34)Bq/cm^3.The main sources include 138La at 1.428(34)Bq/cm^3,207Tl at 0.0135(13)Bq/cm^3,211Bi at 0.0136(15)Bq/cm^3,215Po at 0.0135(3)Bq/cm^3,219Rn at 0.0125(12)Bq/cm^3,223Fr at 0.0019(11)Bq/cm^3,223Ra at 0.0127(10)Bq/cm^3,227Th at 0.0158(22)Bq/cm^3,and 227Ac at 0.0135(13)Bq/cm^3.Of these,the activities of 207Tl,211Po,215Po,223Fr,and 227Ac are deduced for the first time from the secular equilibrium established in the decay chain of 227Ac.

关键词： LaBr3 Coincidence measurement technique Intrinsic radiation GEANT4 simulation

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Efficient and stable PtFe alloy catalyst for electrocatalytic methanol oxidation with high resistance to CO

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Journal of Energy Chemistry 2024年第3期90卷 327-336,I0008页

作者： Qian Yang Sifan Zhang Fengshun Wu lihua zhu Guang li Mingzhi Chen An Pei Yingliang Feng Jiangxi Provincial Key Laboratory of Functional Molecular Materials Chemistry College of Chemistry and Chemical EngineeringFaculty of Materials Metallurgy and ChemistryJiangxi University of Science and TechnologyGanzhou 341000JiangxiChina College of Chemistry and Chemical Engineering Xiamen UniversityXiamen 361005FujianChina

Direct methanol fuel cells(DMFC) are widely considered to be an ideal green energy conversion device but their widespread applications are limited by the high price of the Pt-based catalysts and the instability in terms of surface CO toxicity in long-term operation.Herein,the PtFe alloy nanoparticles(NPs) with small particle size(~4.12 nm) supported on carbon black catalysts with different Pt/Fe atomic ratios(Pt_(1)Fe_(2)/C,Pt_(3)Fe_(4)/C,Pt_(1)Fe_(1)/C,and Pt_(2)Fe_(1)/C) are successfully prepared for enhanced anti-CO poisoning during methanol oxidation reaction(MOR).The optimal atomic ratio of Pt/Fe for the MOR is 1:2,and the mass activity of Pt_(1)Fe_(2)/C(5.40 A mg_(Pt)^(-1)) is 13.5 times higher than that of conventional commercial Pt/C(Pt/C-JM)(0.40 A mg_(Pt)^(-1)).The introduction of Fe into the Pt lattice forms the PtFe alloy phase,and the electron density of Pt is reduced after forming the PtFe alloy.In-situ Fourier transform infrared results indicate that the addition of oxyphilic metal Fe has reduced the adsorption of reactant molecules on Pt during the MOR.The doping of Fe atoms helps to desorb toxic intermediates and regenerate Pt active sites,promoting the cleavage of C-O bonds with good selectivity of CO_(2)(58.1%).Moreover,the Pt_(1)Fe_(2)/C catalyst exhibits higher CO tolerance,methanol electrooxidation activity,and long-term stability than other Pt_(x)Fe_(y)/C catalysts.

关键词： Alloy catalyst PtFe Methanol oxidation In-situ FTIR CO resistance

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No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19

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World Journal of Clinical Cases 2020年第22期8卷 5576-5588页

作者： Jiang-hua Zhou Bin Wu Wen-Xin Wang Fang Lei Xu Cheng Juan-Juan Qin Jing-Jing Cai Xiao-Jing Zhang Feng Zhou Ye-Mao liu Hao-Miao li li-hua zhu Zhi-Gang She Xin Zhang Juan Yang Hong-liang li Department of Cardiology Renmin Hospital of Wuhan UniversityBasic Medical SchoolWuhan UniversityWuhan 430071Hubei ProvinceChina Basic Medical School Institute of Model AnimalWuhan UniversityWuhan 430071Hubei ProvinceChina Department of Cardiology the 3rd Xiangya HospitalCentral South UniversityChangsha 410013Hunan ProvinceChina Medical Science Research Center Zhongnan Hospital of Wuhan UniversityInstitute of Model AnimalWuhan UniversityWuhan 430072Hubei ProvinceChina Department of Cardiology Renmin Hospital of Wuhan UniversityInstitute of Model Animal of Wuhan UniversityWuhan 430071Hubei ProvinceChina Institute of Model Animal Wuhan UniversityDepartment of GastroenterologyWuhan Third HospitalTongren Hospital of Wuhan UniversityWuhan 430072Hubei ProvinceChina

BACKGROUND Dipeptidyl peptidase-4(DPP4)is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects.Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),raising a promising hypothesis that DPP4 inhibitor(DPP4i)drugs might be an optimal strategy for treating coronavirus disease 2019(COVID-19)among patients with diabetes.However,there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes.AIM To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19.METHODS We conducted a multicenter,retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province,China.After excluding ineligible individuals,142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis.We performed a strict propensity score matching(PSM)analysis where age,sex,comorbidities,number of oral hypoglycemic agents,heart rate,blood pressure,pulse oxygen saturation(SpO2)lin usage were matched.Finally,111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users.Then,a linear logistic model and mixed-effect Cox model were applied to analyze the associations between inhospital DPP4i use and adverse outcomes of COVID-19.RESULTS After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model,we found that there was no significant association between in-hospital DPP4i use(DPP4i group)and 28-d allcause mortality(adjusted hazard ratio=0.44,95%CI:0.09-2.11,P=0.31).likewise,the incidences and risks of secondary outcomes,including septic shock,acute respiratory distress syndrome,or acute organ(kidney,liver,and cardiac)inj

关键词： COVID-19 SARS-CoV-2 DPP4 inhibitors Diabetes Glucose control Adverse effects

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Analysis of Health-Associated Phytochemical Compounds in Seven <i>Hypoxis</i>Species

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American Journal of Plant Sciences 2018年第4期9卷 571-583页

作者： Busie E. Nsibande Karl-Eric Gustavsson li-hua zhu Department of Plant Breeding Swedish University of Agricultural Sciences Alnarp Sweden

Some species of the genus Hypoxis within the Hypoxidaceae family are known to contain phenolic glycosides that have different clinical functions. In the African continent Hypoxis species are regarded as valuable medicinal plants that have been used for decades by traditionalists and natives to treat numerous ailments. The corms and rhizomes of the geophytes contain hypoxoside, a norlignan diglucoside, which is one of the important phytochemicals with medicinal functions found in Hypoxis. In this study corm extracts of seven species: H. acuminata, H. argentea, H. filiformis, H. gerrardii, H. hemerocallidea, H. iridifolia and H. parvifolia were analyzed for the presence of ellagic acid, total phenolic content (TPC) and hypoxoside. Extracts of H. iridifolia and H. gerardii had the highest levels of total phenolic content of 369.6 μg/g and 318.2 μg/g, respectively, compared to the rest of the species. Hypoxoside was found to be present in corm extracts of all the species in varying proportions. H. gerrardii, H. argentea and H. filiformis had the highest relative hypoxoside content of 7.1%, 6.6% and 6.6%, respectively. It is interesting to note that Hypoxis hemerocallidea, the most commonly used species for medicinal extracts contained a much lower level of hypoxoside than most of the other species. Our study included species that have not been previously analyzed for either TPC or hypoxoside presence such as H. filiformis and H. gerrardii, thus providing novel information regarding the medicinal status and biochemical compounds of these Hypoxis species.

关键词： Hypoxis Hypoxoside Medicinal Plants Total Phenolic Content

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In Vitro Regeneration of Endangered Medicinal Hypoxis Species

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American Journal of Plant Sciences 2015年第16期6卷 2585-2595页

作者： Busie E. B. Nsibande Xueyuan li Annelie Ahlman li-hua zhu Department of Plant Breeding Swedish Agricultural University Alnarp Sweden National Plant Genetic Resources Centre and Mushroom Development Unit Malkerns Swaziland

The genus Hypoxis contains some of southern Africa’s most important wild medicinal species, a situation that has placed most of them amongst endangered species facing extinction. In this study, four Hypoxis species collected from Swaziland: H. argentea, H. filiformis, H. acuminata and H. hemerocallidea, were included to assess their potential for in vitro propagation in order to efficiently conserve these species in the future. Among all types of explants tested only corm explants and seeds gave rise to shoots under the in vitro conditions. For the corm establishment, H. filiformis was the most in vitro responsive species, which had 100% shoot regeneration with high shoot number when cultured on the MS medium supplemented with 3 mg·l-1 kinetin with a piece of shoot attached, while the highest mean shoot number (17) was obtained on the same medium, but with no shoot attachment to the corm explants. H. argentea was the next most responsive species in vitro with up to 70% establishment, while the other two species had only up to 20% of in vitro establishment. For the seed explants, up to 29% seed germination was obtained for H. argentea when the seed coats were crushed before the in vitro culture. The regenerated shoots were rooted in vitro and acclimatized in the greenhouse

关键词： Corm Seed Micropropagation Plant Growth Regulators

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