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Self-assembly of tau fragments as a key pathologic event in tauopathies

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Neural Regeneration Research 2024年第12期19卷 2565-2566页

作者： Ly Thi Huong Luu Le Jung Hoon Lee Min Jae Lee department of biochemistry and molecular biology Seoul National University College of MedicineSeoulKorea

Tau protein is encoded by the microtubuleassociated protein tau(MAPT)gene and stabilizes microtubules in the *** has unique biophysical properties that make it both highly water-soluble and positively *** tau is an intrinsically disordered protein lacking defined secondary structures,it can acquire highly organized-sheet structures and stack into a filamentous inclusion such as a paired helical filament(PHF).

关键词： tau pathologic assembly

Targeted nanopore sequencing for the identification of novel PRMT1 circRNAs unveils a diverse transcriptional profile of this gene in breast cancer cells

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Genes & Diseases 2024年第2期11卷 589-592页

作者： Maria Papatsirou Andreas Scorilas Diamantis C.Sideris Christos K.Kontos department of biochemistry and molecular biology National and Kapodistrian University of AthensPanepistimiopolisAthens GR 15701Greece

Long-read sequencing with nanopore technology has been widely utilized for the identification of the full-length sequence of RNA molecules."It is especially suitable for the identification of circular RNAs(circRNAs),which are regulatory molecules that are regarded as promising non-invasive biomarkers for various human malignancies,including breast cancer.2 The impact of circRNAs derived from the protein arginine methyltransferase 1(PRMT1)gene has not been clarified yet,even though the effect of PRMT1-mediated methylation on breast cancer cell characteristics has been well established.

关键词： PRMT1 breast cancer

Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreaticβ-cell Dysfunction

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Current Medical Science 2024年第2期44卷 346-354页

作者： Kai-yuan WANG Shi-mei WU Zheng-jian YAO Yun-xia ZHU Xiao HAN Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing 211166China

Objective:While the reduction of transient receptor potential channel subfamily M member 5(TRPM5)has been reported in islet cells from type 2 diabetic(T2D)mouse models,its role in lipotoxicity-induced pancreaticβ-cell dysfunction remains *** study aims to study its ***:Pancreas slices were prepared from mice subjected to a high-fat-diet(HFD)at different time points,and TRPM5 expression in the pancreaticβcells was examined using immunofluorescence ***-stimulated insulin secretion(GSIS)defects caused by lipotoxicity were mimicked by saturated fatty acid palmitate(Palm).Primary mouse islets and mouse insulinoma MIN6 cells were treated with Palm,and the TRPM5 expression was detected using qRT-PCR and Western ***-induced GSIS defects were measured following siRNA-based Trpm5 *** detrimental effects of Palm on primary mouse islets were also assessed after overexpressing Trpm5 via an adenovirus-derived Trpm5(Ad-Trpm5).Results:HFD feeding decreased the mRNA levels and protein expression of TRPM5 in mouse pancreatic *** reduced TRPM5 protein expression in a time-and dose-dependent manner in MIN6 *** also inhibited TRPM5 expression in primary mouse *** of Trpm5 inhibited insulin secretion upon high glucose stimulation but had little effect on insulin *** of Trpm5 reversed Palm-induced GSIS defects and the production of functional maturation molecules unique toβ***:Our findings suggest that lipotoxicity inhibits TRPM5 expression in pancreaticβcells both in vivo and in vitro and,in turn,drivesβ-cell dysfunction.

关键词： type 2 diabetes β-cell dysfunction lipotoxicity TRPM5

N-glycosylation of Wnt3 regulates the progression of hepatocellular carcinoma by affecting Wnt/β-catenin signal pathway

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2769-2780页

作者： Xin-Zhan Zhang Xiao-Chuan Mo Zhu-Ting Wang Rong Sun Da-Quan Sun department of biochemistry and molecular biology&Research Center for Basic Medical Sciences Guizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina

BACKGROUND Wnt/FZD-mediated signaling pathways are activated in more than 90%of hepatocellular carcinoma(HCC)cell *** a well-known secretory glycoprotein,Wnt3 can interact with FZD receptors on the cell surface,thereby activating the Wnt/β-catenin signaling ***,the N-glycosylation modification site of Wnt3 and the effect of this modification on the biological function of the protein are still *** To investigate the effect of Wnt3 N-glycosylation on the biological function of HCC *** Site-directed mutagenesis was used to verify the Wnt3 N-glycosylation sites,actinomycin D treatment was used to detect the stability of Wnt3 after site-directed mutation,the binding of the N-glycosylation site-directed mutant Wnt3 to FZD7 was observed by laser confocal microscopy,and the effects of the N-glycosylation site-directed mutation of Wnt3 on the Wnt/β-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function *** Wnt3 has two N-glycosylation-modified sites(Asn90 and Asn301);when a single site at amino acid 301 is mutated,the stability of Wnt3 is weakened;the binding ability of Wnt3 to FZD7 decreases when both sites are mutated simultaneously;and the level of proteins related to the Wnt/β-catenin signaling pathway is *** proliferation,migration and invasion are also weakened in the case of single 301 site and double-site *** These results indicate that by inhibiting the N-glycosylation of Wnt3,the proliferation,migration,invasion and colony formation abilities of liver cancer cells can be weakened,which might provide new therapeutic strategies for clinical liver cancer in the future.

关键词： Wnt3 N-glycosylation Hepatocellular carcinoma Liver cancer Wnt/β-catenin FZD7

Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

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Oncology Research 2024年第3期32卷 577-584页

作者： MONA SA BDELLATEIF NAGLAA MHASSAN MAHMOUD MKAMEL YOMNA MEL-MELIGUI department of Cancer biology Medical Biochemistry and Molecular BiologyNational Cancer InstituteCairo UniversityCairo11976Egypt department of Cinical Pathology National Cancer InstituteCairo UniversityCairo11976Egypt

Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still *** current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML ***:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using *** data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)***:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].*** relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML ***:miR-34a could be a beneficial diagnostic biomarker for AML *** addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity.

关键词： AML miR 34a microRNA Leukemia

BFP1:One of 700 Arabidopsis F-box proteins mediates degradation of JA oxidases to promote plant immunity

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molecular Plant 2024年第3期17卷 375-376页

作者： Claus Wasternack Bettina Hause department of molecular Signal Processing Leibniz Institute of Plant Biochemistry7 Weinberg 306120 Halle(Saale)Germany department of Cell and Metabolic biology Leibniz Institute of Plant Biochemistry06120 Halle(Saale)Germany

A switch off in jasmonate(JA)signaling by hydroxylation upon wounding was described in 2008(Miersch et al.,2008).This initiated the cloning of CYP450 enzymes involved in hydroxylation and carboxylation of JA and its amino acid conjugate JA-le,the most active form of JA compounds(reviewed by Wasternack and Feussner[2018]and Heitz et al.[2019]).Due to the central role of JA and JA-lle in plant stress responses and development(Wasternack and Hause,2013),catabolism of JA and its derivatives is an essential component in the sustainment of homeostasis of active JA compounds(Howe et al.,2018;Heitz et al.,2019).Catabolism of JA and JAIle takes place by JA-induced oxygenases(JOXs),also named JA-oxidases(JAOs),and by hydroxylation(CYP94B3/B1)followed by carboxylation(CYP94C1),respectively(Heitz et al.,2019).Another reaction performed by IAR3/ILL6 results in the deconjugation of JA-lle and 12-OH-JA-le to JA and 12-OH-JA,respectively(Heitz et al.,2019;Wasternack and Feussner,2018).

关键词： conjugate initiated media

Cellular preconditioning and mesenchymal stem cell ferroptosis

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World Journal of Stem Cells 2024年第2期16卷 64-69页

作者： Doaa Hussein Zineldeen Mazhar Mushtaq Khawaja Husnain Haider Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia department of Medical biochemistry and molecular biology Faculty of MedicineTanta UniversityTanta 6632110Egypt

In this editorial,we comment on the article published in the recent issue of the World Journal of Stem *** focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary *** stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured *** also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell ***,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to *** lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular *** these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related *** editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis *** presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic *** research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.

关键词： Cell survival Cell therapy Hydrogen sulfide Ferroptosis Preconditioning Stem cells Umbilical cord

Sciadopitysin exerts anticancer effects on HepG2 hepatocellular carcinoma cells by regulating reactive oxygen species-mediated signaling pathways

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BIOCELL 2024年第7期48卷 1055-1069页

作者： YAN-NAN LI YUN-HONG XIU YAN-JUN TANG JING-LONG CAO WEN-SHUANG HOU AN-QI WANG TIAN-ZHU LI CHENG-HAO JIN department of biochemistry and molecular biology Heilongjiang Bayi Agricultural UniversityDaqingChina Hemodialysis Center Daqing Oilfield General HospitalDaqingChina department of Food Science and Engineering Heilongjiang Bayi Agricultural UniversityDaqingChina department of molecular biology Chifeng UniversityChifengChina National Coarse Cereals Engineering Research Center DaqingChina

Objectives:Sciadopitysin(SP)is aﬂavonoid in Ginkgo biloba that exhibits various pharmacological *** study aimed to investigate its antitumor effects and the underlying molecular mechanism of SP in hepatocellular carcinoma(HCC)***:Network pharmacology was used for target prediction *** Counting Kit-8(CCK-8)assay was used to test the cell *** cytometry was used to test the cell cycle distribution,apoptosis status,and reactive oxygen species(ROS)*** and wound-healing assay was used to test the migration effect of SP on HepG2 *** Blot assay was used to test the expression levels of ***:Network pharmacology analysis results showed that the mitogen-activated protein kinase(MAPK)and other signaling pathways are involved in the SP anti-HCC biological ***-8 assay results demonstrated that SP showed an obvious killing effect on three types of HCC cells and low cytotoxic effect on normal *** Blot andﬂow cytometry results showed that SP regulated MAPK/signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa-B(NF-κB)signaling pathway to induce mitochondrion-dependent apoptosis in HepG2 ***,SP can arrest the G0/G1 phase cell cycle via the protein kinase B(AKT)/p21/p27/cyclin-dependent kinase(CDK)/Cyclin signaling *** healing and transwell assays showed that SP inhibited cell motility and invasion through the AKT/glycogen synthase kinase3β(GSK-3β)/vimentin/β-catenin signaling ***:Theseﬁndings demonstrated that SP induced mitochondrion-dependent apoptosis,arrested cell cycle in the G0/G1 phase,and inhibited cell migration by regulating the ROS-mediated signaling pathway in HepG2 ***,SP could serve as a therapeutic agent for the treatment of human HCC.

关键词： Sciadopitysin Hepatocellular carcinoma Apoptosis Cell cycle Cell migration

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome

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Journal of Pharmaceutical Analysis 2024年第1期14卷 152-155页

作者： Shuyu Zheng Yanlin Xin Jiamin Lin Zejuan Xie Keyu Cheng Shanshan Wang Wenli Lu Hao Yang Tianming Lu Jun Li Ruogu Qi Yuanyuan Guo department of biochemistry and molecular biology School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing210023China department of Neurosurgery The Second Affiliated HospitalZhejiang UniversityHangzhou310009China

The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget *** a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(***)and is used as an expectorant for pulmonary disease in Asia[2].

关键词： NSCLC eIF4E treatment