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Subcellular Distribution and Chemical Forms of Cadmium in the Medicine Food Homology Plant Platycodon grandiflorum(Jacq.)A.DC.
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作者 Jia An Xiang Wang +7 位作者 Yajiang Jing Jianping Huang Qilong Wang Gang Zhang Jing Gao Liang Peng Wenli Huang Yonggang Yan 《Phyton-International Journal of Experimental Botany》 SCIE 2023年第5期1405-1420,共16页
Although Platycodon grandiflorum(Jacq.)A.DC.is a renowned medicine food homology plant,reports of excessive cadmium(Cd)levels are common,which affects its safety for clinical use and food consumption.To enable its Cd ... Although Platycodon grandiflorum(Jacq.)A.DC.is a renowned medicine food homology plant,reports of excessive cadmium(Cd)levels are common,which affects its safety for clinical use and food consumption.To enable its Cd levels to be regulated or reduced,it is necessary to first elucidate the mechanism of Cd uptake and accumulation in the plant,in addition to its detoxification mechanisms.This present study used inductively couple plasma-mass-spectrometry to analyze the subcellular distribution and chemical forms of Cd in different tissues of P.grandiflorum.The experimental results showed that Cd was mainly accumulated in the roots[predominantly in the cell wall(50.96%-61.42%)],and it was found primarily in hypomobile and hypotoxic forms.The proportion of Cd in the soluble fraction increased after Cd exposure,and the proportion of insoluble phosphate Cd and oxalate Cd increased in roots and leaves,with a higher increase in oxalate Cd.Therefore,it is likely that root retention mechanisms,cell wall deposition,vacuole sequestration,and the formation of low mobility and low toxicity forms are tolerance strategies for Cd detoxification used by P.grandiflorum.The results of this study provide a theoretical grounding for the study of Cd accumulation and detoxification mechanisms in P.grandiflorum,and they can be used as a reference for developing Cd limits and standards for other medicine food homology plants. 展开更多
关键词 CADMIUM Platycodon grandiflorum inductively coupled plasma-mass-spectrometry subcellular distribution chemical forms heavy metal tolerance medicine food homology
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Deep Learning Algorithm for Detection of Protein Remote Homology
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作者 Fahriye Gemci Turgay Ibrikci Ulus Cevik 《Computer Systems Science & Engineering》 SCIE EI 2023年第9期3703-3713,共11页
The study aims to find a successful solution by using computer algorithms to detect remote homologous proteins,which is a significant problem in the bioinformatics field.In this experimental study,structural classific... The study aims to find a successful solution by using computer algorithms to detect remote homologous proteins,which is a significant problem in the bioinformatics field.In this experimental study,structural classification of proteins(SCOP)1.53,SCOP benchmark,and the newly created SCOP protein database from the structural classification of proteins—extended(SCOPe)2.07 were used to detect remote homolog proteins.N-gram method and then Term Frequency-Inverse Document Frequency(TF-IDF)weighting were performed to extract features of the protein sequences taken from these databases.Next,a smoothing process on the obtained features was performed to avoid misclassification.Finally,the proteins with balanced features were classified into remote homologs using the built deep learning architecture.As a result,remote homologous proteins have been detected with novel deep learning architecture using both negative and positive protein instances with a mean accuracy of 89.13%and a mean relative operating characteristic(ROC)score of 88.39%.This experiment demonstrated the following:1)The successful outcome of this study in detecting remote homology is auspicious in discovering new proteins and thus in drug discovery in medicine.2)Natural language processing(NLP)techniques were used successfully in bioinformatics,3)the importance of choosing the correct n-value in the n-gram process,4)the necessity of using not only positive but negative instances in a classification problem,and 5)how effective the processes,such as smoothing,are in the classification accuracy in an imbalanced dataset.6)The deep learning architecture gives better results than the support vector machine(SVM)model on the smoothed data to detect proteins’remote homology. 展开更多
关键词 Bioinformatics deep learning N-GRAM remote homolog protein text classification TF-IDF weighting
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Polycystic Ovary Syndrome-Related Infertility Based on the Theory of“Liver and Kidney Homology”
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作者 Meng Dong Hongli Zhu 《Journal of Clinical and Nursing Research》 2023年第1期1-6,共6页
Polycystic ovary syndrome(PCOS)is an endocrine disorder caused by hypothalamic-pituitary-ovarian(HPO)axis dysfunction.In the field of gynecology and reproduction,PCOS has emerged as both a research hot spot and a chal... Polycystic ovary syndrome(PCOS)is an endocrine disorder caused by hypothalamic-pituitary-ovarian(HPO)axis dysfunction.In the field of gynecology and reproduction,PCOS has emerged as both a research hot spot and a challenging area of study.According to Chinese medicine,this disease is related to kidney deficiency,phlegm and dampness obstruction,blood stasis and interconnection,Chong pulse impassability,the lack of Ren pulse,and the loss of uterine nourishment,all of which affect the normal development and maturation of eggs as well as the duration at which menstrual blood stores.In this paper,based on the theoretical basis of“liver collects blood,regulates the flow of qi,and is the master of drainage,”we explore the rationality of the treatment of this disease from the perspective of“liver and kidney have the same origin”and the development of PCOS-related infertility in relation to dysfunctional internal organs.We also explore the feasibility of treatment from the perspective of“liver and kidney homology,”expand the ideas for treatment,as well as develop and innovate the application of organ identification in PCOS in relation to infertility. 展开更多
关键词 Polycystic ovary syndrome INFERTILITY Liver and kidney homology Dialectical treatment
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Bioinformatics Analysis and Homology Modeling Study of Protein Disulfide Isomerase(mPDI) from Medicago sativa L. 被引量:3
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作者 王海波 施晓东 +1 位作者 张梅芬 郭俊云 《Agricultural Science & Technology》 CAS 2009年第5期59-64,共6页
pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase( mPDI ), has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical p... pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase( mPDI ), has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical properties, hydrophilicity/hydrophobicity, signal peptide, secondary structure, coiled coil, transmembrane domains, O-glycogylation site, active site, subcellular localization, functional structural domains and three-dimensional structure were analyzed by a series of bioinformatics software. The results showed that mPDI was a hydrophobic and stable protein with 3 coiled coils, 30-glycogylation sites, 2 structural domains of thioredoxin, 2 active sites of thioredoxin, and located in rough endoplasmic reticulum. It has 512 amino acids, the theoretical pl is 4.98, and signal peptide located in 1-24AA. In the secondary structure, a-helix, random coil, extended chain is 26.37%, 53.32%, 20.31% respectively. The validation of modeling accords with the stereochemistry. 展开更多
关键词 Medicago sativa L. Protein disulfide isomerase homology modeling
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Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism 被引量:3
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作者 Xiao-Li Mei Shu-Yi Wu +4 位作者 Si-Lan Wu Xiao-Lin Luo Si-Xing Huang Rui Liu Zhe Qiang 《World Journal of Hepatology》 2024年第7期1051-1066,共16页
BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence ... BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH. 展开更多
关键词 Hepatic steatosis INFLAMMATION Sex hormone metabolism Male hormone Phosphatase and tensin homolog deleted on chromosome ten
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The Tianma 65 m radio telescope antenna 被引量:1
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作者 Biao Du Yuanpeng Zheng +8 位作者 Guoxi Liu Yifan Zhang Wancai Zhang Lijun Zhang Shunyou Qin Zhiqiang Shen Qinghui Liu Bin Li Jinqing Wang 《Astronomical Techniques and Instruments》 CSCD 2024年第5期247-259,共13页
The Tianma 65 m radio telescope(TMRT)at Shanghai is a fully steerable single-dish radio telescope in China,operating at centimeter to millimeter wavelengths(1.25 GHz to 50 GHz).This paper presents details on the main ... The Tianma 65 m radio telescope(TMRT)at Shanghai is a fully steerable single-dish radio telescope in China,operating at centimeter to millimeter wavelengths(1.25 GHz to 50 GHz).This paper presents details on the main specifications,design,performance analysis,testing,and construction of the telescope antenna.The measured total efficiency is better than 50%over the whole elevation angle range,first sidelobe levels are less than−20 dB,antenna system noise temperatures are less than 70 K at 30°elevation angle,and pointing accuracy is less than 3″.The measured and calculated results are in good agreement,verifying the effectiveness of the design and analysis. 展开更多
关键词 Radio telescope Reflector antenna High sensitivity homology design High pointing accuracy
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Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model
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作者 Xintian Ding Chun Chen +6 位作者 Heng Zhao Bin Dai Lei Ye Tao Song Shuai Huang Jia Wang Tao You 《Neural Regeneration Research》 SCIE CAS 2025年第3期858-872,共15页
Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PT... Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury. 展开更多
关键词 apoptosis GLYCOLYSIS inflammatory response MICROGLIA neurons POLARIZATION spinal cord injury Src homology 2-containing protein tyrosine phosphatase 2
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Gedunin attenuates streptozotocin-induced diabetic hepatopathy in rats
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作者 Suchismita Mazumdar Thankamani M Marar Jyoti M Patki 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2024年第7期288-297,共10页
Objective:To examine the hepatoprotective effects of gedunin in streptozotocin(STZ)-induced diabetic rats.Methods:Rats were divided into 4 groups:control,STZ,gedunin,and STZ+gedunin.Biochemical parameters for liver fu... Objective:To examine the hepatoprotective effects of gedunin in streptozotocin(STZ)-induced diabetic rats.Methods:Rats were divided into 4 groups:control,STZ,gedunin,and STZ+gedunin.Biochemical parameters for liver function and liver histology were studied.The molecular interaction of gedunin with the liver glucose transporters GLUT2 and SGLT1 was examined using AutoDock Vina.Results:Gedunin attenuated STZ-induced increase in the levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,lactate dehydrogenase and gamma-glutamyl transferase in the serum and liver tissue,reduced lipid peroxidation,and enhanced antioxidant activity.Histopathological studies showed considerable restoration of liver architecture in gedunin-treated diabetic rats.In silico studies revealed stable binding of gedunin with GLUT2 and SGLT1.Conclusions:Gedunin exerts hepatoprotective effects in STZ-induced diabetic rats by reducing liver enzymatic activities and oxidative stress.Further studies are warranted to verify the mechanism of its hepatoprotective action. 展开更多
关键词 Gedunin GLUT2 SGLT1 Diabetic hepatopathy DOCKING HISTOLOGY homology modelling
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Preparation and interaction mechanism analysis of single‑chain fragment variables against phenylethanolamine A
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作者 Long Li Ren Hou +4 位作者 Huaming Li Shiyun Han Jixiang Liang Yu Si Dapeng Peng 《Animal Diseases》 CAS 2024年第2期127-137,共11页
This is the first report on the screening,expression,and recognition mechanism analysis of single-chain fragment variable(scFv)against phenylethanolamine A(PEAA),a newly emergedβ-adrenergic agonist illegally used as ... This is the first report on the screening,expression,and recognition mechanism analysis of single-chain fragment variable(scFv)against phenylethanolamine A(PEAA),a newly emergedβ-adrenergic agonist illegally used as a feed additive for growth promotion.The PEAA-specific scFv scFv,called scFv-32,was screened from hybridoma cell lines by phage display and was found to be optimally expressed in the E.coli system.The ic-ELISA results revealed an IC_(50)value of 10.34μg/L for scFv-32 and no cross-reactivity with otherβ-adrenergic agonists.Homology modeling and molecular docking revealed the key binding sites VAL178,TYP228,and ASP229.One hydrogen bond,two pisigma bonds,and one pi-pi bond maintain the formation of the antibody‒drug complex.Alanine scanning mutagenesis of the three predicted key binding sites showed that the mutants completely lost their recognition activity,which confirmed the accuracy of the theoretical analysis.These results are valuable for the preparation of scFvs and the analysis of the molecular recognition mechanism of antigen-antibodies. 展开更多
关键词 Phenylethanolamine A SCFV Recognition mechanism homology modeling Molecular docking
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Dependence of impact regime boundaries on the initial temperatures of projectiles and targets
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作者 Stefano Signetti Andreas Heine 《Defence Technology(防务技术)》 SCIE EI CAS CSCD 2024年第1期49-57,共9页
Towards higher impact velocities,ballistic events are increasingly determined by the material temperatures.Related effects might range from moderate thermal softening to full phase transition.In particular,it is of gr... Towards higher impact velocities,ballistic events are increasingly determined by the material temperatures.Related effects might range from moderate thermal softening to full phase transition.In particular,it is of great interest to quantify the conditions for incipient or full melting of metals during impact interactions,which result in a transition from still strength-affected to hydrodynamic material behavior.In this work,we investigate to which extent the respective melting thresholds are also dependent on the initial,and generally elevated,temperatures of projectiles and targets before impact.This is studied through the application of a model developed recently by the authors to characterize the transition regime between high-velocity and hypervelocity impact,for which the melting thresholds of materials were used as the defining quantities.The obtained results are expected to be of general interest for ballistic application cases where projectiles or targets are preheated.Such conditions might result,for example,from aerodynamic forces acting onto a projectile during atmospheric flight,explosive shapedcharge-jet formation or armor exposure to environmental conditions.The performed analyses also broaden the scientific understanding of the relevance of temperature in penetration events,generally known since the 1960s,but often not considered thoroughly in impact studies. 展开更多
关键词 Ballistic impact Thermal effects Metallic targets Energy partitioning Homologous temperature
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Mutations in Ras homolog family member A in patients with peripheral T-cell lymphoma and implications for personalized medicine
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作者 Lina Hu Xuanye Zhang Shengbing Zang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第9期754-768,共15页
Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discr... Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type,thereby leading to different functional and biological properties,which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors.However,the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated.Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways.The promising potential of targeting RHOA as a therapeutic modality is also outlined.This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients. 展开更多
关键词 Drug target MUTATION PATHOGENESIS personalized medicine peripheral T-cell lymphoma Ras homolog family member A
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B7 homolog 3 in pancreatic cancer
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作者 Dijana Perovic Marija Dusanovic Pjevic +5 位作者 Vladimir Perovic Milka Grk Milica Rasic Maja Milickovic Tanja Mijovic Petar Rasic 《World Journal of Gastroenterology》 SCIE CAS 2024年第31期3654-3667,共14页
Despite advances in cancer treatment,pancreatic cancer(PC)remains a disease with high mortality rates and poor survival outcomes.The B7 homolog 3(B7-H3)checkpoint molecule is overexpressed among many malignant tumors,... Despite advances in cancer treatment,pancreatic cancer(PC)remains a disease with high mortality rates and poor survival outcomes.The B7 homolog 3(B7-H3)checkpoint molecule is overexpressed among many malignant tumors,including PC,with low or absent expression in healthy tissues.By modulating various immunological and nonimmunological molecular mechanisms,B7-H3 may influence the progression of PC.However,the impact of B7-H3 on the survival of patients with PC remains a subject of debate.Still,most available scientific data recognize this molecule as a suppressive factor to antitumor immunity in PC.Furthermore,it has been demonstrated that B7-H3 stimulates the migration,invasion,and metastasis of PC cells,and enhances resistance to chemotherapy.In preclinical models of PC,B7-H3-targeting monoclonal antibodies have exerted profound antitumor effects by increasing natural killer cell-mediated antibodydependent cellular cytotoxicity and delivering radioisotopes and cytotoxic drugs to the tumor site.Finally,PC treatment with B7-H3-targeting antibody-drug conjugates and chimeric antigen receptor T cells is being tested in clinical studies.This review provides a comprehensive analysis of all PC-related studies in the context of B7-H3 and points to deficiencies in the current data that should be overcome by future research. 展开更多
关键词 B7 homolog 3 Pancreatic cancer PROGNOSIS Signaling pathways IMMUNOTHERAPY
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Histological Assessment of Bone Regeneration in the Maxilla with Homologous Bone Graft:A Feasible Option for Maxillary Bone Reconstruction
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作者 Sergio Henrique Gonçalves Motta Ana Paula Ramos Soares +1 位作者 Juliana Campos Hasse Fernandes Gustavo Vicentis Oliveira Fernandes 《Journal of Renewable Materials》 EI CAS 2024年第1期131-148,共18页
Bone biomaterials have been increasingly used to reconstruct maxillary atrophic ridges.Thus,the aim of this study was to evaluate bone reconstruction in the maxilla using a homologous cortico-cancellous FFB(lyophilize... Bone biomaterials have been increasingly used to reconstruct maxillary atrophic ridges.Thus,the aim of this study was to evaluate bone reconstruction in the maxilla using a homologous cortico-cancellous FFB(lyophilized)graft and verify its reliability.Eight individuals were included from 2014 to 2018.The first surgery was performed to install homologous bone blocks in the maxilla.The period of the second intervention varied between 5 months and 15 days to 11 months(≈7.93 months).The biopsies were taken from the central region of the matured graft during the surgery for implant placement.All patients presented clinical and radiographic conditions for the installation of dental implants.There was a 100%of survival rate.The histological assessment showed that the homologous block bone graft was an osteoconductive biomaterial,with connective tissue present,and newly formed bone juxtaposed on its surface.There were bone trabeculae with osteocytes and active osteoblasts with connective tissue in the mineralization process;the remodeling process can be found through the reverse lines.A limited focus of necrosis with fibrosis was detected,with small resorption and areas of inflammatory infiltrate,but without clinical significance.The homologous block bone graft can be considered a feasible option to substitute the autogenous bone graft(gold standard),with predictable clinical and favorable histological results.The patients had a shorter surgical period,low morbidity,and an unlimited amount of biomaterial available at an accessible cost. 展开更多
关键词 Regeneration bone graft HISTOLOGY HOMOLOGOUS allogenous AUTOGENOUS
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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis
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作者 Yifei Wang Yidan Ma +14 位作者 Lei He Jun Du Xiaoguang Li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou Li Yang Jing Di Changbin Zhu Liming Xu Tianlin Sun Lin Li Dongge Liu Zheng Wang 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2024年第3期282-297,共16页
Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not ... Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients. 展开更多
关键词 Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment PROGNOSIS
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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention
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作者 Ju Zheng Yixin Li +8 位作者 Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao 《Neural Regeneration Research》 SCIE CAS 2025年第5期1455-1466,共12页
Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb... Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury. 展开更多
关键词 apoptosis ATF4 AUTOPHAGY C/EBP homologous protein cerebral ischemia/reperfusion injury EIF2Α endoplasmic reticulum stress PERK
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Modeling Rice rgMT as a Plant Metallothionein-Like Protein by the Distance Geometry and Homology Methods
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作者 吕暾 刘进元 +1 位作者 张日清 赵南明 《Acta Botanica Sinica》 CSCD 2003年第11期1297-1306,共10页
Rice metallothionein-like protein (rgMT) shows characteristics of a three-section pattern composed of two highly conserved cysteine rich (CR) domains in the terminals and a spacer without cysteine (cys) residues in th... Rice metallothionein-like protein (rgMT) shows characteristics of a three-section pattern composed of two highly conserved cysteine rich (CR) domains in the terminals and a spacer without cysteine (cys) residues in the center of the molecule. In this paper, the two CR domains and the spacer region were modeled by the distance geometry and homology methods separately. For the CR domains, twenty random models were generated for each cys combination based on the constraint conditions of CXC (C represents cys, X represents any amino acid other than cys), and CXXC motifs and a metal-sulfur chelating cluster. Four models for the N-terminal and two for C-terminal CR domain containing metal chelating structures formed by different combinations of cys were selected from 900 possible conformations. The GOR method was used to predict the secondary structure of the spacer region and its model was built by the homology method. After three parts of the protein were modeled, they were connected to form a three-dimensional structure model of rgMT. The whole conformation showed that rgMT could form two independent metal-sulfur chelating structures connected by a spacer peptide, without a structural or energy barrier for them to form two independent metal-chelating clusters just as mammalian metallothionein (MT) proteins. As all plant metallothionein-like (MT-L) proteins have the same primary structural characteristic, two CR domains connected by a spacer region, and many have the same cys arrangement pattern as rgMT, the three-dimensional structure model of rgMT will provide an important reference for the structural study of other plant MT-L proteins. 展开更多
关键词 distance geometry homology method rice metallothionein-like protein structural modeling
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Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury
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作者 Yan Wang Dai Li +12 位作者 Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第9期2010-2018,共9页
We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repet... We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury. 展开更多
关键词 apoptosis C/EBP homologous protein endoplasmic reticulum stress EXOSOME inositol-requiring enzyme MICROGLIA miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1
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Mitochondrial carrier homolog 2 increases malignant phenotype of human gastric epithelial cells and promotes proliferation,invasion,and migration of gastric cancer cells
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作者 Jing-Wen Zhang Ling-Yan Huang +3 位作者 Ya-Ning Li Ying Tian Jia Yu Xiao-Fei Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第3期991-1005,共15页
BACKGROUND The precise role of mitochondrial carrier homolog 2(MTCH2)in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated.AIM To determi... BACKGROUND The precise role of mitochondrial carrier homolog 2(MTCH2)in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated.AIM To determine the role of MTCH2 in gastric cancer.METHODS We collected 65 samples of poorly differentiated gastric cancer tissue and adjacent tissues,constructed MTCH2-overexpressing and MTCH2-knockdown cell models,and evaluated the proliferation,migration,and invasion of human gastric epithelial cells(GES-1)and human gastric cancer cells(AGS)cells.The mito-chondrial membrane potential(MMP),mitochondrial permeability transformation pore(mPTP)and ATP fluorescence probe were used to detect mitochondrial function.Mitochondrial function and ATP synthase protein levels were detected via Western blotting.RESULTS The expression of MTCH2 and ATP2A2 in gastric cancer tissues was significantly greater than that in adjacent tissues.Overexpression of MTCH2 promoted colony formation,invasion,migration,MMP expression and ATP production in GES-1 and AGS cells while upregulating ATP2A2 expression and inhibiting cell apoptosis;knockdown of MTCH2 had the opposite effect,promoting overactivation of the mPTP and promoting apoptosis.CONCLUSION MTCH2 can increase the malignant phenotype of GES-1 cells and promote the proliferation,invasion,and migration of gastric cancer cells by regulating mitochondrial function,providing a basis for targeted therapy for gastric cancer cells. 展开更多
关键词 Gastric cancer Mitochondrial carrier homolog 2 ATP synthase ATP2A2 Mitochondrial permeability transformation pore
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Low testing rates and high BRCA prevalence: Poly (ADP-ribose) polymerase inhibitor use in Middle East BRCA/homologous recombination deficiency-positive cancer patients
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作者 Naveed Syed Ashish Vittalrao Chintakuntlawar +6 位作者 Deepti Vilasini Aisha Mohamed Al Salami Riad Al Hasan Imrana Afrooz Kanishka Uttam Chandani Ashok Uttam Chandani Aref Chehal 《World Journal of Clinical Oncology》 2024年第7期848-858,共11页
BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breas... BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients. 展开更多
关键词 Homologous recombination repair BRCA1 BRCA2 Homologous recombination deficiency Ovarian cancer Breast cancer Poly(ADP-ribose)polymerase inhibitors OLAPARIB DNA double-strand breaks
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Suppression of hepatic steatosis in non-alcoholic steatohepatitis model by modified Xiaoyao San formula:Evidence,mechanisms and perspective
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作者 Nabil Eid Payal Bhatnagar +1 位作者 Li-Li Chan Marina Garcia-Macia 《World Journal of Hepatology》 2024年第10期1208-1212,共5页
In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic... In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases. 展开更多
关键词 STEATOSIS Liver Xiaoyao San Inflammation ANDROGEN Adenosine 5’-monophosphate-activated protein kinase Phosphatase and tensin homolog Autophagy Lipophagy Alpha smooth muscle actin
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