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ionotropic receptors mediate olfactory learning and memory in Drosophila

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insect Science 2024年第4期31卷 1249-1269页

作者： Md Zeeshan Ali Anushree Aarif Ahsan Mohammad Shamsul Ola Rizwanul Haque Jawaid Ahsan department of Biotechnology Central University of South BiharGayaBiharIndia department of Radiation oncology University of MichiganAnn ArborMichiganUSA department of Biochemistry College of ScienceKing Saud UniversityRiyadhSaudi Arabia

Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila *** acts as a potent ligand for the ionotropic receptor 84a(iR84a)in the adult fruit fly and it is detected by the iR84a/iR8a heterotetrameric *** role in the male courtship behavior through iR84a as an environmental aphrodisiac is of additional *** ***,two distinct kinds of olfactory receptors,that is,odorant receptors(ORs)and ionotropic receptors(iRs),perceive the odorant *** display unique structural,molecular,and functional characteristics in addition to having different evolutionary ***,olfactory cues detected by the ORs such as ethyl acetate,1-butanol,isoamyl acetate,1-octanol,4-methylcyclohexanol,*** as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit *** underlines the participation of OR-activated olfactory pathways in learning and memory *** study elucidates that likewise ethyl acetate(EA)(an OR-responsive odorant),PAH(an iR-responsive aromatic compound)too can form learning and memory when associated with an appetitive gustatory *** association of PAH with sucrose(PAH/SUC)led to learning and formation of the long-term memory(LTM).Additionally,the Orco^(1),ir84a^(Mi00501),and ir8a^(1)mutant flies were used to confirm the exclusive participation of the iR84a/iR8a complex in PAH/SUC olfactory associative *** results highlight the involvement of iRs via an iR-activated pathway in facilitating robust olfactory behavior.

关键词： appetitive conditioning Drosophila melanogaster ethyl acetate ionotropic receptors learning and memory phenylacetaldehyde

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

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World Journal of Gastrointestinal oncology 2024年第3期16卷 919-932页

作者： Xiao-Ting Ma Xiu Liu Kai Ou Lin Yang department of Medical oncology Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is *** use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into *** To determined the effects of differentially expressed immune-related genes(DEiRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC *** Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(iRGs)were searched from *** were extracted from the intersection of the differentially-expressed genes(DEGs)and iRGs *** enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)*** identify genes associated with prognosis,a tumor risk score model based on DEiRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox *** tumor risk score was divided into high-and lowrisk *** entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk *** infiltration of immune cells was obtained using‘CiBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was *** GC immune score data were obtained and the difference in immune scores between the two groups was *** We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 iRGs.A total of 482 DEiRGs were *** analysis showed that DEiRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and s

关键词： Differentially expressed immune-related gene immunotherapy Gastric cancer Risk score

MicroRNA (let-7b-5p)-targeted DARS2 regulates lung adenocarcinoma growth by Pi3K/AKT signaling pathway

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oncology Research 2024年第3期32卷 517-528页

作者： YUANYUAN XU XiAOKE CHEN department of oncology Surgery Shanghai Lung Cancer CenterShanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiChina

Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human *** its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain ***:initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling interactive Analysis(GEPiA)database (http:/***/)was used to analyze the prognostic relevance of DARS2 expression in ***,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were ***,we analyzed the expression levels of p-Pi3K(phosphorylated Phosphotylinosital3 kinase),Pi3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot ***:LUAD tissues showed higher DARS2 expression compared to normal *** of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior ***2 silence decreased the proliferation,migration,and invasion abilities of LUAD *** addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the Pi3K/AKT signaling ***,DARS2 silence impaired the tumonigenicity of LUAD in ***,let:7b-5p could recognize DARS2 through a complementary ***,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:in summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the Pi3K/AKT signaling pathway.

关键词： Lung adenocarcinoma Prognosis Pi3K/AKT pathway Mitochondrial asparty-tRNA synthetase MicroRNAs

The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

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oncology Research 2024年第4期32卷 785-797页

作者： MENNA AL-ADL MAGDY MYOUSSEF AHMED EL-SEBAiE SHERiF REFAAT AFAF EL-SAiD Division of Biochemistry Department of ChemistryFaculty of ScienceMansoura UniversityMansoura35511Egypt Hematology Unit Department of Clinical PathologyFaculty of MedicineMansoura UniversityMansoura35511Egypt Medical oncology Unit Oncology Center Mansoura UniversityMansoura35511Egypt department of Genetics Mansoura University Children’s HospitalMansoura35511Egypt

Cytochromes P450(CYPs)play a prominent role in catalyzing phase i xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including *** gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used *** research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide *** was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy *** presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed *** CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,pinant(GT+TT ***,OR=5.4,pide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).in conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian *** variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

关键词： B-CLL Xenobiotics Cytochromes P450 CYP2B6

Pandemic punch:SARS-CoV-2 hits pancreas

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1779-1780页

作者： Ninel Azoitei Sandra Heller Alexander Kleger institute of Molecular oncology and Stem Cell Biology Ulm UniversityUlmGermany Division of interdisciplinary Pancreatology Clinic of Internal Medicine IUniversity Hospital UlmUlmGermany

The COViD-19 pandemic has profoundly impacted global health systems,revealing the extensive repercussions of SARS-CoV-2 beyond respiratory ***,traditionally considered a respiratory virus,SARS-CoV-2’s showcased the ability to target multiple organ systems including pancreas,an organ crucial for regulating blood sugar levels and aiding digestion.

关键词： pancreas respiratory traditionally

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

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World Journal of Gastrointestinal oncology 2024年第6期16卷 2362-2379页

作者： Yi Zhou Shuang Wu Fan-Jie Qu department of oncology Affiliated Dalian Third People’s Hospital of Dalian Medical UniversityDalian 116033Liaoning ProvinceChina

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and ***,colorectal ranks third in incidence,but second in *** than half of the patients are in advanced stages at *** options are complex because of the heterogeneity of the patient population,including different molecular *** have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,*** recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

关键词： Metastatic colorectal cancer Epidermal growth factor receptor B-type RAF mutation Kirsten rat sarcoma viral oncogene wild type Kirsten rat sarcoma viral oncogene G12C mutation Human epidermal growth factor receptor 2 overexpression/amplification

Lack of evidence for germline WWP1 pathogenic variants in gastrointestinal polyposis and other phenotypes suggestive of PTEN-hamartoma-tumor syndrome

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Genes & Diseases 2024年第2期11卷 524-527页

作者： Noemi Gonzalez-Abuin Tirso Pons Teresa Fuster isabel Quintana Mariona Terradas Gemma Aiza Joan Brunet Gabriel Capellá Heather Hampel Laura Valle Hereditary Cancer Program Catalan Institute of OncologyOncobell ProgramIDIBELLHospitalet de LlobregatBarcelona 08908Spain department of immunology and oncology National Center for BiotechnologySpanish National Research Council (CNB-CSIC)Madrid 28049Spain Centro de investigación Biomédica en Red de Cáncer (CiBERONC) Madrid 28029Spain Catalan institute of oncology IDIBGiGirona 17007Spain Division of Clinical Cancer Genomics Department of Medical Oncology & Therapeutic ResearchCity of Hope National Cancer CenterDuarteCA 91010USA

Germline activating variants in WWP1,which encodes an E3 ubiquitin ligase that antagonizes PTEN tumor suppressive function,have been proposed as an alternative mechanism of PTEN inactivation in PTEN-hamartoma-tumor syndrome(PHTS)-like patients with wildtype PTEN.1 More specifically,heterozygous,potentially activating wwP1 variants were first identified by Lee et al in patients affected with gastrointestinal oligopolyposis,including adenomatous,hyperplastic/serrated,and hamartomatous polyps,and occasionally with colorectal cancer(Table 1).Subsequently,based on the PHTS phenotypic features,wWP1 mutational screening was performed in patients with thyroid nodules,2 or normocephalic autism spectrum disorder(ASD),3 where germline WWP1 variants were also identified(Table S1).

关键词： WWP1 gastrointestinal polyposis

Mutations in Ras homolog family member A in patients with peripheral T-cell lymphoma and implications for personalized medicine

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Cancer Biology & Medicine 2024年第9期21卷 754-768页

作者： Lina Hu Xuanye Zhang Shengbing Zang Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China department of Medical oncology Sun Yat-sen University Cancer CenterGuangzhou 510060China

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 ***,the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully *** 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 *** promising potential of targeting RHOA as a therapeutic modality is also *** review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.

关键词： Drug target mutation pathogenesis personalized medicine peripheral T-cell lymphoma Ras homolog family member A

Assessment of phytochemicals, antioxidant, anti-hemolytic, anti-inflammatory and anti-cancer potential of flowers, leaves and stem extracts of Rosa arvensis

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Journal of Traditional Chinese Medicine 2024年第4期44卷 804-812页

作者： Zubaria Tul Ain iram Fatima Sana Naseer Sobia Kanwal Tariq Mahmood department of Plant Sciences Quaid-i-Azam UniversityIslamabad 45320Pakistan department of Biology Allama Iqbal Open UniversityIslamabad 04403Pakistan department of Plant Sciences Faculty of Biological SciencesQuaid-i-Azam UniversityIslamabad 45320Pakistan Pakistan Academy of Sciences Islamabad 04403Pakistan

OBJECTiVE:To evaluate phytochemicals and in vitro biological potential of flowers,leaves and stem extracts of Rosa ***:Presence of twenty secondary metabolites was confirmed and then phenolic and flavonoid contents were quantified *** Transform infrared spectroscopy was conducted to ascertain functional groups and antioxidant potential was examined using 2,2-diphenyl-1-picrylhydrazyl scavenging activity,total antioxidant capacity and total reducing power *** erythrocytes were used to assess anti-hemolytic activity and five bacterial strains were examined to determine antibacterial potential of plant *** seeds were used to perform phytotoxic activity and cytotoxic potential was evaluated via brine shrimps and PC3 cell ***:Highest phenolic contents were detected in the methanolic extract of Rosa arvensis flower(RAFM)[(151.635±0.005)gallic acid equivalent mg/g]and highest flavonoid contents in the chloroform leaf extract(RALC)[(108.228±0.004)quercetin equivalent mg/g].Fourier-transform infrared spectroscopy analysis showed the presence of wide range of functional *** antioxidant assays indicated highest DPPH scavenging activity[iC50(23.5±0.6)μg/mL]in the methanolic stem extract(RASM),highest total antioxidant capacity[(265.1±0.9)μg/mL]in RAFM and highest reducing potential[(209.9±0.6)μg/mL]in leaf extract(RALM).Highest antihemolytic activity[(90.0±0.5)μg/mL]was recorded in RAFM and brine shrimp cytotoxicity potential[(52.3±0.3)μg/mL]in *** antimicrobial activity was detected highest[(21.1±0.5)mm inhibition zones]in RALM against Streptococcus *** the end,antiinflammatory and anti-cancer activity results depicted less than 50%inhibition in the methanolic ***:Our findings will be helpful in designing pharmaceutical regimens and therefore,more studies can be recommended to isolate and characterize compounds associated with the biological activities of Rosa arvensis.

关键词： anti-inflammatory agents spectroscopy,fourier transform infrared hemolysis oxidative stress PC-3 cells