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Remodeling the tumor microenvironment by vascular normalization and GSH-depletion for augmenting tumor immunotherapy

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Chinese Chemical Letters 2024年第2期35卷 329-334页

作者： Jin Wang Qingqing Zhang Yanchen Li Xiaoyan Pan Yuanyuan Shan Jie Zhang school of pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an 710061China Department of pharmacy The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061China

Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and *** of tumor vasculature as well as depletion of glutathione(GSH)can improve the ***,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated *** which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic *** addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron *** may also lead to endoplasmic stress and release of calmodulin,which activates the immune ***,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific *** summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.

关键词： Vascular normalization Tumor microenvironment GSH depletion Ferroptosis Activated immune

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

Curcumin inhibits colorectal cancer development by blocking the YAP/TAZ signaling axis

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BIOCELL 2024年第3期48卷 443-451页

作者： FEI SHA DAISHAN XIN JUN XU ZHIWEI ZHENG WENXIN LIN XIAORUI CAI FEI LIN MINGHAO ZHENG JIAOLING CHEN Department of pharmacy Affiliated Cancer Hospital of Shantou University School of MedicineShantouChina Department of pharmacy Shantou University Mental Health CenterShantouChina Static Distribution Center Affiliated Cancer Hospital of Shantou University School of MedicineShantouChina

Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits ***:HT29 and SW480 cells were treated with curcumin or/and Doxycycline(DOX),and cell viability,colony forming ability,migration and invasion were conﬁrmed by cell counting kit-8(CCK-8),colony forming,Transwell *** Yes-associated protein 1(YAP)and PDZ-binding motif(TAZ)signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR),western blot,and immunoﬂuorescence *** nude mice xenograft tumor model was constructed,YAP and Ki67 expressions were tested by immunohistochemistry(IHC)***:In our study,we proved that curcumin signiﬁcantly inhibited the CRC cell viability,cell migration,and cell invasion *** addition,curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC ***,in the nude mice model,curcumin treatment signiﬁcantly decreased the size and weight of xenotransplant ***:Therefore,curcumin signiﬁcantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis.

关键词： Curcumin Colorectal cancer YAP/TAZ signaling axis

Spinal intradural electrodes: opportunities, challenges and translation to the clinic

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Neural Regeneration Research 2024年第3期19卷 503-504页

作者： Bruce Harland Chien Yew Kow Darren Svirskis school of pharmacy University of AucklandAucklandNew Zealand Department of Neurosurgery Auckland City HospitalAucklandNew Zealand

Damage to the spinal cord disrupts the electrically active nerve cells which normally transmit afferent and efferent signals,resulting in loss of motor,sensory,and autonomic *** treatments for spinal cord injury utilizing implanted spinal electrodes can be broadly classified into three different *** first of these approaches is“spinal stimulation”where electrodes,usually positioned above the level of injury,provide electrical stimulation to target and disrupt pain signals before they reach the *** second approach uses“activity-dependent neuro-technologies”,in which electrodes positioned below the level of injury initiate a complex spatiotemporal pattern of stimulation at the lumbar spinal cord to generate a walking gait in the limbs(Minev et al.,2015;Wagner et al.,2018).

关键词： stimulation electrodes utilizing

Difluoromethyl phenoxathiinium salt: A new general and versatile difluoromethylating reagent with divergent ·CF_(2)H, CF_(2)H^(+), and :CF_(2) reactivities

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Science China Chemistry 2024年第3期67卷 953-962页

作者： Yuan-Qing Gu Hong-Xin Long Dan-Dan Zhang Mei-Feng Ruan Guo-Kai Liu school of pharmacy Shenzhen University Medical SchoolShenzhen UniversityShenzhen 518055China

Development of practical and versatile electrophilic difluoromethylating reagent is still a grand challenge so far due to its inherent instability or low ***,we report the design and synthesis of difluoromethyl phenoxathiinium tetrafluoroborate(PT-CF_(2)H^(+)BF_(4)^(-)) as a novel difluoromethylating reagent,which proves to be a bench-stable,general,powerful and versatile reagent with divergent·CF_(2)H,CF_(2)H^(+),and:CF_(2) *** use of this reagent,we demonstrated a vast array of difluoromethyl radical transfer reactions via diverse pathways involving photocatalyst-free visible-light induction,visible-light photoredox catalysis and visible-light mediation single electron transfer of EDA ***,the green and highly effective CF_(2)H^(+) and:CF_(2) transfer reactions were also readily accomplished.

关键词： difluoromethyl phenoxathiinium salt versatile difluoromethylating reagent difluoromethyl radical difluoromthyl cation difluorocarbene

Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 100-115页

作者： Jianjian Chu Weicong Zhang Yan Liu Baofeng Gong Wenbo Ji Tong Yin Chao Gao Danqi Liangwen Mengqi Hao Cuimin Chen Jianhua Zhuang Jie Gao You Yin Department of Neurology Second Affiliated Hospital(Shanghai Changzheng Hospital)of Naval Medical UniversityShanghaiChina school of pharmacy University College LondonLondonUK Department of Clinical pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineClinical Pharmacy Innovation InstituteShanghai Jiao Tong University School of MedicineShanghaiChina school of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease *** re,there is an urgent need for new effective *** underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease *** inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's *** review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's *** review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

关键词： Alzheimer's disease anti-inflammation blood-brain barrier drug delivery microglia nanoparticles neuroinflammation plant extracts

Divergent defluorocarboxylation of α-CF_(3) alkenes with formate via photocatalyzed selective mono-or triple C-F bond cleavage

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Science China Chemistry 2024年第1期67卷 368-373页

作者： Xing-Yu Wang Pei Xu Wen-Wen Liu Hao-Qiang Jiang Song-Lei Zhu Dong Guo Xu Zhu Jiangsu Key Laboratory of New Drug Research and Clinical pharmacy School of PharmacyXuzhou Medical UniversityXuzhou 22100China

Unprecedented divergent synthesis of gem-difluorovinylacetic acid and glutaric acid derivatives fromα-CF_(3)alkenes with formate as the carbonyl source was *** reaction can undergo selective mono-or triple C-F bond cleavage by simply switching the photocatalyst and hydrogen atom transfer(HAT)catalyst under visible-light-induced conditions at room *** acts as both the C1 source and the reductant through the generation of CO_(2)^(·-)species,which underwent Giese radical addition to electron-deficient alkenes to trigger the consecutive C-F bond cleavage and carboxylation process.

关键词： C-F bond activation defluorocarboxylation carbon dioxide radical anion visible light

Advanced nano drug delivery systems for neuroprotection against ischemic stroke

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Chinese Chemical Letters 2024年第2期35卷 151-162页

作者： Chenchen Xie Jun Liao Ning Zhang Yuhan Sun Yi Li Liyan Xiong Yingnan Zhang Xiaoyan Liu Wei Su Heming Chen Ping Zeng Xiaoqing Zhang Ying Lu Tingfang Wang Chuan Zhang Shanghai Engineering Research Center of Organ Repair School of MedicineShanghai UniversityShanghai 200444China Department of Pharmaceutical Science School of PharmacyNaval Medical UniversityShanghai 200433China Department of pharmacy the International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China school of pharmacy Shanghai Jiao Tong UniversityShanghai 200040China

Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability *** efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited ***,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug *** review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of *** examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery *** these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.

关键词： Target Blood-brain barrier Ischemic stroke Nano drug delivery Neuroprotection

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

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Neural Regeneration Research 2024年第3期19卷 642-649页

作者： Xiuling Tang Tao Yan Saiying Wang Qingqing Liu Qi Yang Yongqiang Zhang Yujiao Li Yumei Wu Shuibing Liu Yulong Ma Le Yang Precision pharmacy&Drug Development Center Department of PharmacyTangdu HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Clinical pharmacy Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu ProvinceChina Department of Pharmacology School of PharmacyAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Anesthesiology The First Medical Center of Chinese PLA General HospitalBeijingChina Department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreAir Force Medical UniversityXi’anShaanxi ProvinceChina

β-Sitosterol is a type of phytosterol that occurs naturally in *** studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic *** we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced *** investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic *** addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its *** conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

关键词： apoptosis blood-brain barrier β-sitosterol cerebral ischemia/reperfusion injury cholesterol overload cholesterol transport endoplasmic reticulum stress ischemic stroke molecular docking NPC1L1