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Rare Metals 2024年第10期43卷 5152-5163页

作者： Dong-Wei Ma Jing-Sheng Lu Xiang-Xin Cao Yan-Wei Cheng Gang Wang Zi-Qian Zhang Bo-Cheng Chen Ning Lin Qing Chen College of pharmacy Guangxi Scientific Research Center of Traditional Chinese MedicineGuangxi University of Chinese Medicine Guangxi Zhuang Yao medicine center of Engineering and Technology

The rational design of a specific co-drug delivery platform that can address the unavoidable resistance, toxic side effects and low targeting efficiency of traditional cancer treatments is of great ***, Zn-based MOF-zeolitic imidazole framework-90(ZIF-90) was selected as the drug delivery carrier, with the cancer therapeutic drug mercaptopurine(6-MP) and glucose oxidase(GOD) as the drug models, hyaluronic acid(HA) was used for protection and targeted delivery, which designed and fabricated an intelligent drug delivery platform(6-MP@ZIF-90@GOD@HA). This platform aims to reduce the toxic side effects of 6-MP and enhance its efficacy while improving the targeting ability of GOD,thereby further enhancing the treatment outcome. Notably,results from both in vitro and in vivo experiments demonstrate that the targeted synergistic chemo/reactive oxygen species(ROS)-mediated/starvation therapy inhibited the cancer cell growth while reducing the chemotherapy toxicity, which provides new possibilities for the development of more precise and effective treatment strategies.

关键词： Cancer treatment Combination therapy Drug delivery Metal-organic framework Reduced toxicity

Application of nanoscale metal–organic frameworks in tumor immunotherapy

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Rare Metals 2024年第10期43卷 4867-4883页

作者： Xiao-Xuan Zeng Jing-Sheng Lu Dong-Wei Ma Yu-Ting Huang Ling Chen Gang Wang Qing Chen Ning Lin College of pharmacy Guangxi Scientific Research Center of Traditional Chinese MedicineGuangxi University of Chinese Medicine Guangxi Zhuang Yao medicine center of Engineering and Technology

Immunotherapy has attracted wide attention because it can not only kill tumor cells but also effectively prevent tumor recurrence. However, due to the poor efficacy of the monotherapy in tumor immunotherapy, combination therapies are needed to enhance their efficacy,such as chemodynamic therapy/immunotherapy, photodynamic therapy/immunotherapy, sonodynamic therapy/immunotherapy and so on. Nanoscale metal–organic frameworks(nMOFs) are widely used for drug delivery because of their rich and variable composition, high drug loading capacity and good biodegradability. Compared with other conventional drug delivery systems(DDSs),nMOFs play more advantageous role in inducing immune cell death of tumor cells and combination therapies. This article focuses on the application of n MOFs in tumor immunotherapy in terms of their use as gatekeepers, supplementary agents and drug carriers, respectively, with the aim of providing some ideas and references for the design of smart nanoscale DDS for tumor immunotherapy.

关键词： Drug delivery system Immunotherapy Metal–organic frameworks Tumor

Traditional Chinese medicine for the treatment of immune-related nephropathy:A review

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Acta Pharmaceutica Sinica B 2024年第1期14卷 38-66页

作者： Pu Jiang Changliang Yao De-an Guo School of pharmacy Nanjing University of Chinese MedicineNanjing 210023China Shanghai research center for Modernization of Traditional Chinese medicine National Engineering Research Center of TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Immune-related nephropathy(IRN)refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal *** pathogenesis of IRN is not fully understood;therefore,treatment is *** Chinese medicines(TCMs)have potent clinical effects in the treatment of the IRN conditions immunoglobulin A nephropathy,lupus nephropathy,and diabetic *** underlying mechanisms mainly include its inhibition of inflammation;improvements to renal interstitial fibrosis,oxidative stress,autophagy,apoptosis;and regulation of *** this review,we summarize the clinical symptoms of the three IRN subtypes and the use of TCM prescriptions,herbs,and bioactive compounds in treating IRN,as well as the potential mechanisms,intending to provide a reference for the future study of TCM as IRN treatments.

关键词： IgA nephropathy Diabetic nephropathy Lupus nephritis Traditional Chinese medicine Immunity Pathogenesis Mechanism Pathophysiology

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network research center Sungkyunkwan University School of MedicineSuwonKorea research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

A combined nanotherapeutic approach targeting farnesoid X receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu Pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin Wu Jiabao Zhang Chunlin Zhuang Chunquan Sheng Jiajun Xu Ying Lu Pei Wang The center for Basic research and Innovation of medicine and pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration center for Experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid X receptor(FXR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)***,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major ***,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of *** oxide(NO)is a versatile biological molecule that can degrade extracellular *** this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH *** with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ***@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota *** findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy Farnesoid X receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling

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Oncology research 2024年第2期32卷 361-371页

作者： TINGTING LI WEI ZHONG LIU YANG ZHIYU ZHAO LI WANG CONG LIU WANYUN LI HAIYAN LV SHENGYU WANG JIANGHUA YAN TING WU GANG SONG FANGHONG LUO Cancer research center School of MedicineXiamen UniversityXiamen361000China Department of pharmacy Xiamen Mental Health CenterXiamen Xianyue HospitalXiamen361000China

The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for *** study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in ***1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node ***1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC ***,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and ***,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 ***,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting *** together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.

关键词： GIPC1 PDGFR Gastric cancer Proliferation Migration

Adsorption,in vitro digestion and human gut microbiota regulation characteristics of three Poria cocos polysaccharides

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Food Science and Human Wellness 2024年第3期13卷 1685-1697页

作者： Fangming Zhang Hui Zheng Tao Zheng Pan Xu Yao Xu Yuxin Cao Fan Jia Yiqiong Zeng Yubing Fan Kai He Xinwen Dai Fengfei Hou Yong Yang College of pharmacy Hunan University of Chinese MedicineChangsha 410208China School of Pharmaceutical Science Hunan University of MedicineHuaihua 418000China Hunan Fuling Engineering Technology research center Huaihua 418100China

Poria cocos(PC)is a famous traditional Chinese medicine(TCM)and a widely used healthcare ingredient,which has antiobesity,enhancing immunity and improving sleep ***,only water-soluble poria polysaccharide(WSP)is extracted and applied for clinical application,while insoluble polysaccharide(alkali-soluble poria polysaccharide,ASP)is discarded as herb ***,the whole PC has also been historically utilized as functional herbal *** the beneficial role of dietary fiber and the traditional use of PC,ASP may also contribute substantially to the therapy function of *** to WSP,little attention has been paid to ASP and ASP modified product carboxymethyl poria polysaccharide(CMP)which has been used as an antitumor adjuvant *** this study,the oil,cholesterol,metal ions and polyphenols adsorption ability,in vitro simulated digestive and the gut microbiota fermentation characteristics of WSP,ASP and CMP were studied to evaluate the functional values of three *** polysaccharides(PCPs).The results showed that all three PCPs had good adsorption capacity on cholesterol,polyphenols and metal ions(Cd^(2+)/Zn^(2+)/Mg^(2+)),among which ASP showed the highest capacity than WSP and *** adsorption capacity of all three PCPs on heavy metal ions(Cd^(2+)/Zn^(2+))was stronger than that of non-heavy metal ions(Mg^(2+));The in vitro digestibility of all three PCPs was very low,but WSP was slightly higher than ASP and CMP;Moreover,the indigestible residue of all three PCPs could improve the richness and diversity of gut microbiota,among which ASP had the greatest *** general,ASP and CMP could significantly promote the proliferation of some probiotics and inhibit the growth of some harmful *** gut microbiota diversity of CMP was reduced,but the richness of probiotics,especially Parabacteroides distasonis was significantly enhanced compared with the ASP group,and the growth of harmful bacteria Klebsiella pneumoniae was inh

关键词： Poria cocos polysaccharides Alkali-soluble poria polysaccharide Carboxymethyl poria polysaccharide Adsorption characteristics In vitro simulated digestion In vitro simulated gut microbiota fermentation

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Advance on Chinese medicine for Hypertensive Renal Damage:Focus on the Complex Molecular Mechanisms

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Chinese Journal of Integrative medicine 2024年第10期30卷 938-948页

作者： LU Yan XIE Xue-na XIN Qi-qi YUAN Rong MIAO Yu CONG Wei-hong CHEN Ke-ji Laboratory of Cardiovascular Diseases Xiyuan Hospital of China Academy of Chinese Medical Sciences School of pharmacy Macau University of Science and Technology National Clinical research center for Chinese medicine Cardiology

Hypertensive renal damage(HRD) is a major cause of end-stage renal disease. Among the causes of end-stage renal disease, HRD accounts for nearly 34% of the total number of cases. Antihypertensive treatment is primarily drug-based, but therapeutic efficacy is less effective and can have serious side effects. Chinese medicine(CM) has significant advantages in the treatment of HRD. CM is rich in various active ingredients and has the property of targeting multiple targets and channels. Therefore, the regulatory network of CM on disease is complex. A large number of CM have been employed to treat HRD, either as single applications or as part of compound formulations. The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system, antioxidation, anti-inflammation, rescue of endothelial function, regulation of vasoactive substance secretion and obesity-related factors, etc. This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.

关键词： Chinese medicine hypertensive renal damage molecular mechanisms research progress

Rapid Simultaneous Determination of Four Ganoderic Acids in Ganoderma(Chinese Name:Lingzhi)by Direct Infusion-Multiple Reaction Monitoring Cubed

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Journal of Analysis and Testing 2024年第1期8卷 52-62页

作者： Nian Wu Bo Peng Ting Li Pengfei Tu Shengpeng Wang Bo Li Wenjing Liu Yuelin Song Modern research center for Traditional Chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Amway(China)Botanical research center Wuxi 214011China State Key Laboratory of Quality research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipa 999078China Amway(Shanghai)Innovation&Science Co. LtdShanghai 201508China School of pharmacy Henan University of Chinese MedicineZhengzhou 450046China

Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the measurement workload for a huge number of testing ***,it is urgent to pursue more efficient approaches for the quality *** of the greater selectivity of MRM cubed(MRM^(3))over MRM,there might be a chance to omit the time-intensive LC *** current study,we attempted to develop a direct infusion(DI)-MRM^(3) program,and the applicability was thereafter assessed through simultaneous determination of four ganoderic acids(GAs)in one of the most famous tonic herbal medicines namely Ganoderma(Chinese name:Lingzhi).Primary parameters such as Q1>Q3>QLIT ion transitions,collision energy(CE),and excitation energy were optimized by programming online energy-resolved mass spectrometry with authentic compounds.A single DI-MRM measurement merely costed four minutes,and in spite of the wide occurrences of isomers,satisfactory selectivity was *** validation assays demonstrated the method to be sensitive,precise,accurate,and *** quantitative results from DI-MRM^(3) were also justified by conducting LC-MRM measurements in *** differences occurred for the content patterns between the two original sources namely Ganoderma lucidum and ***,and,moreover,either cultivar or harvest time showed dramatical influence on the quantitative features of the four targeted *** importantly,DI-MRM3 is a meaningful analytical option for rapid quantitative analysis of herbal medicines,because of the comparable reliability,nonetheless,less consumptions of both measurement time and solvent,compared with LC-MRM.

关键词： Direct infusion Multiple reaction monitoring cubed High-throughput quantitative analysis Ganoderic acids Ganoderma

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Triple three-dimensional MS/MS spectrum facilitates quantitative ginsenosides-targeted sub-metabolome characterization in notoginseng

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4045-4058页

作者： Ke Zhang Jinru Jia Ting Li Wenjing Liu Pengfei Tu Jian-Bo Wan Jun Li Yuelin Song Modern research center for Traditional Chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China SCIEX China Beijing 100015China School of pharmacy Henan University of Chinese MedicineZhengzhou 450046China State Key Laboratory of Quality research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaip1Macao 999078China

Although serving as the workhorse,MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome *** more information intrinsically correlates to more structural and concentration clues,here,efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional(33D)-MS/MS ***-targeted metabolomics of notoginseng,one of the most famous edible medicinal plants,was employed as a *** authentic ginsenosides were deployed to build the correlations between 33D-MS/MS spectra and structure/concentration *** assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1st 3D spectrum,the generations of MS1 spectral signals,particularly multi-charged multimer anions,e.g.,[2Me2H]2e and[2Mt2HCOO]2e ions,relied on both concentration and the amount of sugar *** programming progressive collision energies to the front collision cell of Qtrap-MS device to gain 2nd 3D spectrum,optimal collision energy(OCE)corresponding to the glycosidic bond fission was primarily correlated with the masses of precursor and fragment ions and partially governed by the glycosidation *** quantitative relationships between OCEs and masses of precursor and fragment ions were utilized to build large-scale quantitative program for *** applying progressive exciting energies to the back collision chamber to build 3rd 3D spectrum,the fragment ion and the decomposition product anion exhibited identical dissociation trajectories when they shared the same molecular *** ginsenosides-focused quantitative metabolomics,significant differences occurred for sub-metabolome amongst different parts of *** differential ginsenosides were confirmatively identified by applying the correlations between 33D-MS/MS spectra and ***,33D-MS/MS spectrum covers all MS/MS behaviors and dramatically faci

关键词： Quantitative submetabolome characterization Ginsenosides Structural identification Notoginseng Full exciting energy ramp-MS3 spectrum