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Epigenetic memory of drug exposure history controls neural stem cell quiescence in the adult brain

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Neural Regeneration Research 2024年第4期19卷 711-712页

作者： Masakazu Iwamoto Taito Matsuda Department of Stem Cell Biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous *** adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in the hippocampus and ventricular subventricular zone lining the lateral ventricle(Olpe and Jessberger,2022).Adult NSCs in rodents are preserved throughout life and continuously produce new neurons that integrate into the pre-existing neuronal network.

关键词： neural integrate continuously

Pathogenic contribution of cholesteryl ester accumulation in the brain to neurodegenerative disorders

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Neural Regeneration Research 2024年第10期19卷 2099-2100页

作者： Michiko Shirane Department of Molecular Biology Graduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan

Cholesteryl esters(CEs) have been increasingly implicated in neurodegenerative disorders such as Alzheimer's disease(AD).Alois Alzheimer noted three prominent neuropathologic features in his original analysis of the AD brain:senile plaques,neurofibrillary tangles,and lipid granule *** plaques,which are aggregates of amyloid-beta(Aβ),and neurofibrillary tangles,which are aggregates of phosphorylated tau,have been regarded as more consistent characteristics of the AD brain compared with lipid granule accumulation and thus have been studied more intensively(Foley,2010).

关键词： esters ester cholesteryl

Drug-induced mucosal alterations observed during esophagogastroduodenoscopy

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World Journal of Gastroenterology 2024年第16期30卷 2220-2232页

作者： Masaya Iwamuro Seiji Kawano Motoyuki Otsuka Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama 700-8558Japan

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract,i.e.,the esophagus,stomach,and *** include pill-induced esophagitis,desquamative esophagitis,worsening of gastroesophageal reflux,chemotherapy-induced esophagitis,proton pump inhibitor-induced gastric mucosal changes,medication-induced gastric erosions and ulcers,pseudomelanosis of the stomach,olmesartan-related gastric mucosal inflammation,lanthanum deposition in the stomach,zinc acetate hydrate tabletinduced gastric ulcer,immune-related adverse event gastritis,olmesartan-associated sprue-like enteropathy,pseudomelanosis of the duodenum,and lanthanum deposition in the *** endoscopists,acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other *** minireview aims to provide essential information on druginduced mucosal alterations observed on esophagogastroduodenoscopy,along with representative endoscopic images.

关键词： Diagnosis Esophagogastroduodenoscopy Non-neoplastic lesions Esophageal lesions Gastric lesions Duodenal lesions

1,3-Dipolar Cycloaddition of Polycyclic Aromatic Azomethine Ylides and Alkynylbenziodoxoles for Synthesis of Functional Dibenzoullazines

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Chinese Journal of Chemistry 2024年第10期42卷 1079-1083页

作者： Hui Han Glen Wee Zhuan Goh Yongxin Li Naohiko Yoshikai Shingo Ito schoolof Chemistry ChemicalEngineering and BiotechnologyNanyang Technoogical University21 Nanyang LinkSingapore 637371Singapore graduate school of pharmaceutical sciences Tohoku UniversitySendai 980-8578Japan

A new family of dibenzoullazine derivatives was synthesized through 1,3-dipolar cycloaddition of polycyclic aromatic azomethine ylides with alkynylbenziodoxoles followed by *** benziodoxole moiety in the resulting products was used as a versatile linchpin for the synthesis of structurally diverse functional dibenzoullazines that are difficult to access by other synthetic methods.

关键词： Cycloaddition Nitrogen heterocycles Azomethine ylides Hypervalent compounds Dibenzoullazine

Thermally activated delayed fluorescence carbazole-triazine dendrimer with bulky substituents

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Aggregate

Aggregate 2024年第1期5卷 236-243页

作者： Hiroki Ikebe Kohei Nakao Eri Hisamura Minori Furukori Yasuo Nakayama Takuya Hosokai Minlang Yang Guanting Liu Takuma Yasuda Ken Albrecht Interdisciplinary graduate school of Engineering sciences Kyushu UniversityFukuokaJapan Institute for Materials Chemistry and Engineering Kyushu UniversityKasugaJapan Department of Pure and Applied Chemistry Graduate School of Science and TechnologyTokyo University of ScienceNodaChibaJapan National Metrology Institute of Japan(NMIJ) National Institute of Advanced Industrial Science and Technology(AIST)TsukubaIbarakiJapan Institute for Advanced Study Kyushu UniversityNishi-kuFukuokaJapan

Carbazole-triazine dendrimers with a bulky terminal substituent were synthesized,and the thermally activated delayed fluorescence(TADF)property was *** to unsubstituted carbazole dendrimers,dendrimers with bulky terminal substituents showed comparable to better photoluminescence quantum yields(PLQY)in neat ***(PF)-substituted dendrimers showed the highest PLQY of 81%,a smallΔEst of 0.06 eV,and the fastest reverse intersystem crossing(RISC)rate of∼1×10^(5 )s^(−1) compared to other *** measurements of dendrimers and dendrons(fragments)indicate that the close proximity of the triplet energy of phenylfluorene-substituted carbazole dendrons(^(3)LE)to that of phenylfluorene-substituted dendrimers(^(1)CT,^(3)CT)contributes to RISC promotion and improves TADF *** modification fine-tunes the energy level and suppresses intermolecular interactions,and this study provides a guideline for designing efficient solution-processable and non-doped TADF materials.

关键词： dendrimer OLED TADF 1 INTRODUCTION Thermally activated delayed fluorescence(TADF)materials which are inexpensive and highly efficient alternatives to fluorescent

Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation

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Chinese Journal of Natural Medicines 2024年第5期22卷 387-401页

作者： FENG Qianwen SUN Lu Muhammad Jibran Sualeh ZHAO Qingli ZHAO Songji CUI Zhengguo INADERA Hidekuni Department of Public Health Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Department of Pediatric Cardiology Heart CenterGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510000China Department of Basic Medical sciences College of MedicineUniversity of SharjahSharjah 57545United Arab Emirates Department of Radiology Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Advanced Clinical Research Center Fukushima Global Medical Science CenterFukushima Medical UniversityFukushima CityFukushima 960-8074Japan Department of Environmental Health School of Medical SciencesUniversity of FukuiFukui 910-8580Japan

Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal *** its notable properties,the anti-cancer effects of Her have remained largely *** this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis ***,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 *** findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy ***,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter ***,we determined that Her did not prevent the fusion of autophagosomes and ***,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal *** use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome *** application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell *** observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell *** study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell *** insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic st

关键词： Hernandezine Apoptosis Mitophagy Autophagic flux Lysosome Noncanonical autophagy

Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song Suah Yang Jinseong Kim Yujeong Moon Nayeon Shim Hong Yeol Yoon Sehoon Kim Man Kyu Shim Kwangmeyung Kim KU-KIST graduate school of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

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Journal of pharmaceutical Analysis 2024年第6期14卷 889-901页

作者： Shaowei Huang Xueqian Xie Bo Xu Zengfeng Pan Junjie Liang Meiling Zhang Simin Pan Xiaojing Wang Meng Zhao Qing Wang Jinyan Chen Yanyang Li Lian Zhou Xia Luo school of pharmaceutical sciences Guangzhou University of Chinese Medicine510006China school of Basic Medicine Guangzhou University of Chinese Medicine510006China First Clinical Medical College Guangzhou University of Chinese Medicine510000China

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains *** this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG *** detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,***,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for *** results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal ***,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune *** additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via *** conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

关键词： Paeoniflorin Ulcerative colitis Intestinal mucosal barrier DR3 signaling pathway Group 3 innate lymphoid cells

Photocatalytic vinyl radical-mediated multicomponent 1,4-/1,8-carboimination across alkynes and olefins/(hetero)arenes

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Science China Chemistry 2024年第2期67卷 558-567页

作者： Shan-Shan Li Yu-Shi Jiang Xue-Ling Luo Xuming Ran Yuqiang Li Dong Wu Cheng-Xue Pan Peng-Ju Xia school of Chemistry and pharmaceutical sciences Guangxi Normal UniversityGuilin541004China Shanghai Artificial Intelligence Laboratory Shanghai200433China The Institute for Advanced Studies Wuhan UniversityWuhan430064China

We developed a highly selective and efficient multicomponent transformation by utilizing alkynes and olefins/(hetero)arenes through photoinduced energy-transfer *** reaction involves the formation of three distinct chemical bonds,namely C(sp~3)–C(sp~2),C(sp~2)–C(sp~3),and C(sp~3)–N,in a single coordinated *** strategy used a vinyl radical-mediated radical relay approach under mild conditions,exhibiting a broad substrate scope(>70 examples),excellent functional-group tolerance,and remarkable regio-and *** the utilization of a combination of experimental techniques and density functional theory(DFT),we delved deeper into the mechanistic intricacies of this distinctive *** revealed that the selective radical addition to electron-deficient alkynes,rather than olefins,was governed by the inherent reactivity of alkyl *** discovery presented a highly effective approach for the synthesis of stereodefined multisubstituted alkenes.

关键词： alkyne-olefin coupling DFT studies regio-and anti-stereoselectivity multisubstituted alkenes