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Combination losartan with hyaluronic acid modified diethyldithiocarbamate loaded hollow copper sulfide nanoparticles for the treatment of breast cancer and metastasis

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Chinese Chemical Letters 2024年第3期35卷 406-414页

作者： Haili Hu Weiwei Zhang Lei Lei Fan Tong Huilin Zhang Yiwei Zhang Wenqin Yang Yilu Tang Ruyi Lin Xue Xia Jiamei Li Shiyong Song Huile Gao Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China school of pharmacy Henan UniversityKaifeng 475004China Department of Public Health Chengdu Medical CollegeChengdu 610500China

The application of photothermal therapy(PTT)is greatly limited by the low accumulation of photothermal agents,uneven photothermal distribution,and heat endurance of cancer *** still,despite PTT enhances immunogenicity,the anti-tumor immune efficacy is still unsatisfactory due to the inefficient immunogenic cell death(ICD)induction and poor infiltration of immune *** solve the above problems of PTT,we developed hyaluronic acid(HA)modified hollow copper sulfide nanoparticles encapsulating diethyldithiocarbamate(DDTC)to construct a breast tumor targeting and near infrared(NIR)photo-responsive drug delivery system(D-HCuS@HA),which further combined with losartan to improve the accumulation and penetration in the tumor *** irradiation,D-HCuS@HA realized enhanced PTT and released cytotoxic Cu(DDTC)_(2)to eliminate heat endurance tumor cells,thereby enhancing antitumor effect and inducing effective ***,the combination with losartan could remodel the tumor microenvironment,allowing more T cells to infiltrate into the tumor,and significantly inhibiting the occurrence and development of metastatic *** vitro/vivo results revealed the great potential of D-HCuS@HA combined with losartan,which provides a new paradigm for anti-tumor and anti-metastases.

关键词： Targeted drug delivery system Hollow copper sulfide nanoparticles Photothermal therapy Hyaluronic acid Breast cancer Anti-metastasis

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Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units

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Neural Regeneration Research 2024年第4期19卷 887-894页

作者： Yifang Wu Jun Sun Qi Lin Dapeng Wang Jian Hai Department of Neurosurgery Tongji HospitalSchool of MedicineTongji University Department of pharmacy Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective ***,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently *** this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning *** found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 *** 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose ***,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved ***,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

关键词： brain ischemia brain microvascular endothelial cell nanofiber membrane neurovascular unit

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Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1380-1399页

作者： Yixian Li Peng Yang Ran Meng Shuting Xu Lingling Zhou Kang Qian Pengzhen Wang Yunlong Cheng Dongyu Sheng Minjun Xu Tianying Wang Jing Wu Jinxu Cao Qizhi Zhang Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China

Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal *** the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological ***,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD ***,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside *** by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected *** nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ ***,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic *** research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.

关键词： Autophagy-lysosome pathway Alzheimer’s disease Proteostasis Neuroinflammation Multi-target therapy Rapamycin Gypenoside XVII Cascade dual-targeting

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Preparation of baicalin colon-targeted granules and its intervention effect on ulcerative colitis in rats

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Particuology 2024年第2期85卷 13-21页

作者： Yongqing Huang Yuxin Zhou Yao Shen Jin Wang Liangliang Zhou Zhenhua Chen Jiangxi Provincial Key Laboratory of Drug Design and Evaluation School of PharmacyJiangxi Science and Technology Normal UniversityNanchang330013China

Baicalin(BA)is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi with excellent antioxidant and anti-inflammatory biological *** this study,Eudragit S100 was used as the colonic target material to prepare BA colonic targeting granules(EBCGs)based on plasticizer dry powder coating technology to improve the targeting transportation performance of *** vitro studies showed that EBCGs with pH-sensitive properties were successfully prepared by plasticizer dry powder coating,and in vivo animal imaging studies showed that EBCGs could deliver BA to the colon and inhibit the release of BA in the upper gastrointestinal tract(GIT).In vivo studies showed that EBCGs had good therapeutic effects in colitis,which reduced expression levels of tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)and increased superoxide dismutase(SOD)activities in the colonic tissues of rats with *** conclusion,Eudragit S100 could be used for the preparation of multi-unit oral colon-targeted formulations by plasticizer dry powder coating technology,and our prepared EBCGs had good colon-targeting properties,which could improve the therapeutic effect and provide a potential application for ulcerative colitis(UC).

关键词： Plasticizer dry powder coating Colon-targeted granulesIn vivo imaging Ulcerative colitis

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Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of Clinical Pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1

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Contemporary strategies and approaches for characterizing composition and enhancing biofilm penetration targeting bacterial extracellular polymeric substances

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Journal of Pharmaceutical Analysis 2024年第4期14卷 506-524页

作者： Lan Lu Yuting Zhao Mingxing Li Xiaobo Wang Jie Zhu Li Liao Jingya Wang Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department Sichuan Industrial Institute of AntibioticsSchool of PharmacyChengdu UniversityChengdu610000China Meishan Pharmaceutical Vocational College School of PharmacyMeishanSichuan620200China Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhouSichuan646000China Hepatobiliary Surgery Langzhong People's HospitalLangzhongSichuan646000China

Extracellular polymeric substances(EPS)constitutes crucial elements within bacterial biofilms,facili-tating accelerated antimicrobial resistance and conferring defense against the host's immune *** precise and effective antibiofilm approaches and strategies,tailored to the specific charac-teristics of EPS composition,can offer valuable insights for the creation of novel antimicrobial ***,in turn,holds the potential to mitigate the alarming issue of bacterial drug *** analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias,which is likely due to the selection of a standard compound and the cross-interference of various EPS *** the pivotal role of EPS in biofilm functionality,it is imperative for EPS research to delve deeper into the analysis of intricate compositions,moving beyond the current focus on polymeric *** ne-cessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical *** this study,we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS ***,novel strategies aimed at targeting EPS to enhance biofilm penetration were explored,with a specific focus on high-lighting the limitations associated with colorimetric ***,we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these *** review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS,thereby inhibiting biofilm *** insight opens up a new avenue for exploration within this research domain.

关键词： Analytic strategies and approaches Composition characterization Extracellular polymeric substances(EPS) Promoting biofilm penetration

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Effects of small molecules on neurogenesis:Neuronal proliferation and differentiation

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Acta Pharmaceutica Sinica B 2024年第1期14卷 20-37页

作者： MichałK Jastrze˛bski Piotr Wo´jcik Piotr Ste˛pnicki Agnieszka A.Kaczor Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory Medical University of LublinFaculty of PharmacyLublin PL-20093Poland school of pharmacy University of Eastern FinlandKuopio FI-70211Finland

Neurons are believed to be non-proliferating ***,neuronal stem cells are still present in certain areas of the adult brain,although their proliferation diminishes with *** as with other cells,their proliferation and differentiation are modulated by various *** mechanisms are foundational to the strategies developed to induce neuronal proliferation and differentiation,with potential therapeutic applications for neurodegenerative *** most common among these diseases are Parkinson's disease and Alzheimer's disease,associated with the formation ofβ-amyloid(Aβ)aggregates which cause a reduction in the number of *** such as LiCl,4-aminothiazoles,Pregnenolone,ACEA,harmine,D2AAK1,methyl 3,4-dihydroxybenzoate,and shikonin may induce neuronal proliferation/differentiation through the activation of pathways:MAPK ERK,PI3K/AKT,NFκB,Wnt,BDNF,and ***,combinations of these compounds can potentially transform somatic cells into *** transformation process involves the activation of neuron-specific transcription factors such as NEUROD1,NGN2,ASCL1,and SOX2,which subsequently leads to the transcription of downstream genes,culminating in the transformation of somatic cells into *** diseases are not the only conditions where inducing neuronal proliferation could be ***,the impact of pro-proliferative compounds on neurons has also been researched in mouse models of Alzheimer's disease.

关键词： Neurogenesis Proliferation Differentiation Maturation Small-molecules Drug coctail Alzheimer’s disease Parkinson’s disease

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of Clinical pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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Beyond 1,4-addition of in-situ generated(aza-)quinone methides and indole imine methides

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Chinese Chemical Letters 2024年第7期35卷 35-53页

作者： Yan-Li Li Zhi-Ming Li Kai-Kai Wang Xiao-Long He Medical College Xinxiang UniversityXinxiang 453000China school of pharmacy Xinxiang UniversityXinxiang 453000China school of Food and Bioengineering Xihua UniversityChengdu 610039China

The conjugate addition of in-situ generated(aza-)quinone methides(QMs)and indole imine methides(IIMs)emerged as a powerful protocol to access densely functionalized benzenes and *** alcohols,aminobenzhydryl alcohols,and varied indolylmethanols served as most effective precursors for the in-situ generation of such reactive species under acid *** relevant propargylic alcohol has proven to be an elegant precursor to generate the propargylic-QMs and-IIMs via the acid promoted dehydration process,thus enabling diverse challenging remote activation to proceed conjugate1,6-and 1,***,the heteroarene has proven to be workable to transfer the LUMO of the p-QMs and 2-IIMs,thus inducing the remote nucleophilic dearomative *** conjugate additions of(aza-)p-QMs and varied IIMs has made significant contribution in the field of remote activation chemistry in past *** review summarizes the latest advances of the remote conjugate additions of the in-situ generated QMs and IIMs.

关键词： Conjugate addition QMs IIMs LUMO Remote activation Dearomative addition

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Stereospecific Assembly of Trisubstituted Alkenes via Photoinduced Nitrogen-Centered Radical-Triggered C—C Bond Cleavage/Functionalization of Oxime Esters

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Chinese Journal of Chemistry 2024年第12期42卷 1399-1406页

作者： Yu Bao Zhi-Jie Song Jin-Long Dai Shenghu Yan Yue Zhang Jia-Yin Wang Guigen Li school of pharmacy Changzhou UniversityChangzhouJiangsu 213164China Department of Chemistry and Biochemistry Texas Tech University79409USA

Comprehensive Summary A general and convenient photoredox-catalyzed acylation and alkylcyanation of MBH acetates has been established,enabling the assembly of the C(sp2)–C(sp3)bond by a nitrogen-centered radical strategy for the synthesis of trisubstituted alkenes in moderate to excellent chemical yields(48 examples in total).The reaction of MBH acetates with acyl(indanone)oxime esters afforded trisubstituted alkenes containing 1,4-dicarbonyl ***,the use of Eosin Y as a photocatalyst in the catalytic system resulted in the formation of distal cyano group-anchored trisubstituted alkenes via deconstructive functionalization of cycloketone oxime ***,these resulting 1,4-dicarbonyl compounds could be applied to late-stage transformations,providing important methods for the synthesis of dihydropyridazin-3(2H)-one.

关键词： Photocatalysis Radical reactions MBH acetates Oxime esters Stereoselectivity Acylation Alkylation Green chemistry

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