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Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

Oncology Research 2024年第5期32卷 877-897页

作者： KARAN WADHWA PAYAL CHAUHAN SHOBHIT KUMAR RAKESH PAHWA RAVINDER VERMA RAJAT GOYAL GOVIND SINGH ARCHANA SHARMA NEHA RAO DEEPAK KAUSHIK department of pharmaceutical Sciences Maharshi Dayanand UniversityRohtak124001India department of pharmaceutical technology Meerut Institute of Engineering and Technology(MIET)NH-58Delhi-Roorkee HighwayMeerut250005India Institute of pharmaceutical Sciences Kurukshetra UniversityKurukshetra136119India department of pharmaceutical Sciences Chaudhary Bansi Lal UniversityBhiwani127021India MM College of Pharmacy Maharishi Markandeshwar(Deemed to be University)Mullana-AmbalaHaryana133207India Delhi pharmaceutical Sciences and Research University(DIPSAR) Delhi Pharmaceutical Sciences and Research UniversityNew Delhi110017India

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive tumor.The high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the tumormass.Objective:Recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation therapy.Methods:Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several others.Conclusion:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management.Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

关键词： Glioblastoma Brain tumor Blood-brain barrier Liposomes Metallic nanoparticles Nanocarriers

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Optimization of product characteristics of porous carbon agglomerates using a design of experiments in fluidized bed agglomeration

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Particuology 2024年第6期89卷 258-269页

作者： Martin Oelofse Robert Rack Marcelle Hilden Peter Langguth department of pharmaceutical technology and Biopharmaceutics Johannes Gutenberg UniversityMainzGermany Carbon Advanced Solutions GmbH HeuchelheimGermany

Spraying parameters during particle agglomeration processes can affect the agglomeration kinetics and particle growth.This study was conducted to better understand the influence of the spraying parameters in a fluidized bed wet agglomeration process,and the influence on the stability characteristics of carbon tablets.A formulation based on fine carbon and peroxide powder,as well as carboxymethyl cellulose as a binder,was used to produce agglomerates in a first production step.Thereafter in a second production step carbon tablets with a high porosity were molded for the customer goods industry.The optimization of the compressive strength of these carbon tablets was the goal of the trials.Carbon agglomerates were produced with a laboratory scale granulator called“ProCell”and were compressed with a five-cavity mechanical press.The screening of the agglomeration process parameters and their influence on the agglomerates quality,as well as the performance characteristics of the carbon tablets,were investigated using a multilevel factorial design.The experimental runs were done by varying atomized air pressure and feed rate of the fluid.This was determined by the design model.The findings of the statistical trials showed that low atomized air pressure and a low feed rate lead to a higher tablet compressive strength.

关键词： Wet agglomeration Fluidized bed Design of experiments Carbon agglomerates and tablets

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A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent Prunus species of southeast Asia

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Journal of Traditional Chinese Medicine 2024年第3期44卷 620-628页

作者： Shikha Agrawal Adarsh Kumar Ankit Kumar Singh Harshwardhan Singh Suresh Thareja Pradeep Kumar department of pharmaceutical Sciences and Natural Products Central University of Punjab

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian subcontinent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent,it extends from the Himalayas to Sikkim, Meghalaya,Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological,microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory,hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus species from its distribution, morphological characters to phytoconstituents, and pharmacological activity.

关键词： Prunus Rosaceae antineoplastic agents distribution hypoglycemic agents phytochemistry review

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Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

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Asian Journal of pharmaceutical Sciences 2024年第2期19卷 170-187页

作者： Bao Li Haoran Niu Xiaoyun Zhao Xiaoyu Huang Yu Ding Ke Dang Tianzhi Yang Yongfeng Chen Jizhuang Ma Xiaohong Liu Keda Zhang Huichao Xie Pingtian Ding School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang pharmaceutical University Shenyang 110016 China department of Basic pharmaceutical Sciences School of Pharmacy Husson University Bangor ME 04401USA College of Pharmacy Shenzhen Technology UniversityShenzhen 518118China

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

关键词： Anti-angiogenesis Tumor apoptosis Nanoparticles VEGF siRNA Hypoxia inducible factor(HIF)-1 protein Phenethyl isothi ocyanate(PEITC)

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Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice

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Neural Regeneration Research 2024年第2期19卷 416-424页

作者： Guixiang Wang Wenjia Wang Ye Zhang Xiaoying Gou Qingqing Zhang Yanmiao Huang Kuo Zhang Haotian Zhang Jingyu Yang Yuting Li Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyangLiaoning ProvinceChina department of Pharmacology Shenyang Pharmaceutical UniversityShenyangLiaoning ProvinceChina

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

关键词： adolescence adulthood ethanol dentate gyrus EZH2 in vivo tracing lineage progression mTOR neural stem cell newborn dendritic spine newborn neurons

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Immune checkpoint inhibitors:breakthroughs in cancer treatment

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Cancer Biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of Immunology and Inflammation School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University department of Biology School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade(ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies(mAbs) are currently available as immune checkpoint inhibitors(ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4) and programmed cell death protein 1(PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response.Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1(anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains(TIGIT), mucin domain containing-3(TIM-3), lymphocyte activation gene-3(LAG-3), V-domain immunoglobulin suppressor of T cell activation(VISTA), B and T lymphocyte attenuator(BTLA), and signal-regulatory protein α(SIRPα). Functional m Abs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： CTLA-4 ICIs Immunotherapy PD-1 cancer

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Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

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Journal of Traditional Chinese Medicine 2024年第3期44卷 515-523页

作者： WANG Xiang HUANG Jianping WANG Yupeng WANG Qilong JING Yajiang ZHANG Gang PENG Liang GAO Jing WANG Hongyan YAN Yonggang department of Key Laboratory of "Qin pharmaceutical" Research and Development Shaanxi University of Traditional Chinese Medicine department of Yupeng Shaanxi Haitian pharmaceutical Co. Ltd. department of Acupuncture and Tuina Shaanxi University of Traditional Chinese Medicine

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

关键词： Dahuang () Taoren () differential metabolites kernel drug pairs metabolic networks and pathways metabolomics

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Phosphorylation-driven aggregative proteins in neurodegenerative diseases:implications and therapeutics

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Neural Regeneration Research 2024年第5期19卷 966-968页

作者： Alba Espargaró Raimon Sabate department of Pharmacy and pharmaceutical technology and Physical-Chemistry School of PharmacyUniversity of BarcelonaBarcelonaSpain Institute of Nanoscience and Nanotechnology(IN2UB) University of BarcelonaBarcelonaSpain

Protein aggregation is related to a large number of neurodegenerative disorders.Particularly in some cases,aggregation is induced by hyperphosphorylation of a given protein.This is the case of tau,TAR DNA-binding protein 43(TDP-43),amyloid-beta peptides(Aβ)and alpha-synuclein(α-syn),which play a key pathogenic role in Alzheimer’s disease(AD),Parkinson’s disease(PD)and amyotrophic lateral sclerosis,among others(Tenreiro et al.,2014;Chiti and Dobson,2017).In this perspective,we will discuss both the relationship between phosphorylation and amyloid aggregation as well as current and future therapeutic strategies aimed at inhibiting specific kinases involved in the phosphorylation step or inhibiting subsequent protein aggregation.

关键词： tau Aβ Alzheimer

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An efficient approach for the treatment of radioactive waste perfluoropolyether lubricants via a synergistic effect of thermal catalysis and immobilization

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Journal of Environmental Sciences 2024年第2期136卷 512-522页

作者： Xinhang Du Wenhua Tong Xinyu Zhou Jia Luo Yuqiu Liu Yabo Wang Panyu Li Yongkui Zhang department of pharmaceutical&Biological Engineering School of Chemical EngineeringSichuan UniversityChengdu 610065China

Perfluoropolyether(PFPE)lubricants are a kind of high-molecular polymer with many excellent properties.However,the use of PFPEs in the nuclear industry can lead to partial decomposition and carrying radionuclides,resulting in a large amount of radioactive waste PFPE lubricants annually.Moreover,radioactive waste PFPE lubricants are difficult to be effectively treated due to their high stability,the risk of possible leakage of radionuclides,and hypertoxic fluorine-containing by-products.In this study,without any precedent,a strategy of Mn O_(2)-catalyzed decomposition and Na_(2)CO_(3)-immobilized conversion was proposed for PFPE lubricant decomposition and fluorine immobilization simultaneously based on the Lewis acid-base and oxygen vacancies concept.A high fluorine conversion efficiency of 95.4%was achieved.Meanwhile,the mechanism of decomposition suggested that Mn O_(2)mainly provided Lewis acid sites and attacked the(basic)fluorine or oxygen atoms in PFPE molecules.The decomposition of PFPE chains was proceed down and volatile fluorine-containing gas was released by partial electron transfer,intramolecular disproportionation reaction,and unzipping fashion.Subsequently,gas by-products could be further oxidized and then immobilized into fluoride salts by carbonate solid absorbents.Overall,this study provides a simple,safe,and potentially practical strategy for the harmless conversion of refractory fluorinated organic wastes,especially perfluoropolymers.

关键词： Perfluoropolyether lubricants Catalyzed decomposition Fluorine-containing gas Immobilized conversion Fluoride

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Propensity score matching analysis for clinical impact of braided-type versus laser-cut-type covered self-expandable metal stents for endoscopic ultrasound-guided hepaticogastrostomy

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 181-185页

作者： Mitsuki Tomita Takeshi Ogura Akitoshi Hakoda Saori Ueno Atsushi Okuda Nobu Nishioka Yoshitaro Yamamoto Hiroki Nishikawa 2nd department of Internal Medicine Osaka Medical and Pharmaceutical UniversityOsakaJapan Endoscopy Center Osaka Medical and Pharmaceutical UniversityOsakaJapan

Background:To prevent stent migration during endoscopic ultrasound-guided hepaticogastrostomy(EUS-HGS),intra-scope channel release technique is important,but is unfamiliar to non-expert hands.The self-expandable metal stent(SEMS)is an additional factor to prevent stent migration.However,no compara-tive studies of laser-cut-type and braided-type during EUS-HGS have been reported.The aim of this study was to compare the distance between the intrahepatic bile duct and stomach wall after EUS-HGS among laser-cut-type and braided-type SEMS.Methods:To evaluate stent anchoring function,we measured the distance between the hepatic parenchyma and stomach wall before EUS-HGS,one day after EUS-HGS,and 7 days after EUS-HGS.Also,propensity score matching was performed to create a propensity score for using laser-cut-type group and braided-type group.Results:A total of 142 patients were enrolled in this study.Among them,24 patients underwent EUS-HGS using a laser-cut-type SEMS,and 118 patients underwent EUS-HGS using a braided-type SEMS.EUS-HGS using the laser-cut-type SEMS was mainly performed by non-expert endoscopists(n=21);EUS-HGS using braided-type SEMS was mainly performed by expert endoscopists(n=98).The distance after 1 day was significantly shorter in the laser-cut-type group than that in the braided-type group[2.00(1.70-3.75)vs.6.90(3.72-11.70)mm,P<0.001].In addition,this distance remained significantly shorter in the laser-cut-type group after 7 days.Although these results were similar after propensity score matching analysis,the distance between hepatic parenchyma and stomach after 7 days was increased by 4 mm compared with the distance after 1 day in the braided-type group.On the other hand,in the laser-cut-type group,the distance after 1 day and 7 days was almost the same.Conclusions:EUS-HGS using a laser-cut-type SEMS may be safe to prevent stent migration,even in non-expert hands.

关键词： Endoscopic ultrasound-guided hepaticogastrostomy Endoscopic ultrasound-guided biliary drainage Endoscopic retrograde cholangiopancreatography

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