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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

The Role of E3 Ligases in Macrophage-mediated Inflammation

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生物化学与生物物理进展 2024年第9期51卷 2037-2060页

作者： JIN Jia-Bei GE Yi-Dong JIN Xiao-Feng Zhejiang Key Laboratory of Pathophysiology Department of Biochemistry and Molecular BiologyHealth Science CenterNingbo UniversityNingbo 315211China

Macrophages,existed in almost all organs of the body,are responsible for detecting tissue injury,pathogens,playing a key role in host defense against a variety of invading pathogens triggering inflammatory *** evidence suggests that macrophage-mediated immune responses are efficiently regulated by the ubiquitination modification,which is responsible for normal immune ***,numerous studies indicates that the aberrant activation or inhibition of macrophage-mediated immune responses occurs in inflammation,mainly caused by dysregulated ubiquitination modification due to E3 ubiquitin ligases mutations or abnormal ***,E3 ubiquitin ligases,responsible for recognizing the substrates,are key enzymes in the ubiquitin proteasome system(UPS)composed of ubiquitin(Ub),ubiquitin-activating E1 enzymes,ubiquitin-conjugating E2 enzymes,E3 ubiquitin ligases,26S proteasome,and deubiquitinating ***,several E3 ubiquitin ligases are involved in the regulation of some common signal pathways in macrophage-mediated inflammation,including Toll-like receptors(TLRs),nucleotide-binding oligomerization domain(NOD)-like receptors(NLRs),RIG-I-like receptors(RLRs),C-type lectin receptors(CLRs)and the receptor for advanced glycation end products(RAGE).Herein,we summarized the physiological and pathological roles of E3 ligases in macrophage-mediated inflammation,as well as the inhibitors and agonists targeting E3 ligases in macrophage mediated inflammation,providing the new ideas for targeted therapies in macrophage-mediated inflammation caused aberrant function of E3 ligases.

关键词： E3 ligases macrophage NLRs/RLRs/TLRs targeted therapies

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

CONSTANS alters the circadian clock in Arabidopsis thaliana

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molecular Plant 2024年第8期17卷 1204-1220页

作者： Pedro de los Reyes Gloria Serrano-Bueno Francisco J.Romero-Campero He Gao Jose M.Romero Federico Valverde Plant Development Group-Institute for Plant biochemistry and Photosynthesis Consejo Superior de Investigaciones CientificasUniversidad de SevillaSevilleSpain department of Computer Science and Artificial Intelligence Universidad de SevillaSevilleSpain department of Plant Developmental biology Max Planck Institute for Plant Breeding ResearchCologneGermany department of Plant biochemistry and molecular biology Universidad de SevillaSevilleSpain

Plants are sessile organisms that have acquired highly plastic developmental strategies to adapt to the *** these processes,the floral transition is essential to ensure reproductive success and is finelyregulated by several internal andexternal genetic *** photoperiodic pathway,which controls plant response to day length,is one of the most important pathways controlling *** Arabidopsis photoperiodic flowering,CONSTANS(CO)is the central gene activating the expression of the florigen FLOWERING LOCUS T(FT)in the leaves at the end of a long *** circadian clock strongly regulates Co ***,to date,no evidence has been reported regarding a feedbackloop from the photoperiod pathway back to the circadian *** transcriptional networks,we have identified relevant network motifs regulating the interplay between the circadian clock and the photoperiod *** expression,chromatin immunoprecipitation experiments,and phenotypic analysis allowed us to elucidate the role of Co over the circadian *** with altered cO expression showed a different internal clock period,measured by daily leaf rhythmic *** showed that co upregulates the expression of key genes related to the circadian clock,such as CCA1,LHY,PRR5,and Gl,at the end of a long day by bindingto specific sites on their ***,a high numberof PRR5-repressed target genes are upregulated by CO,and this could explain the phase transition promoted by *** CO-PRR5 complex interacts with the bZiP transcriptionfactor HY5andhelps to localize the complex in the promoters of clock *** together,our results indicate that there may be a feedback loop in which co communicates back to the circadian clock,providing seasonal information to the circadian system.

关键词： CONSTANS circadian clock photoperiod