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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi Su Kun Chen Qing Wu Jiayan Ren Wenjuan Tang Yu Hu Zeren Zhu Cheng Cheng Kaihui Tu Huaizhen He Yanmin Zhang School of pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma Sorafenib

Current perspective on amyloid aggregation accelerating properties of the artificial butter flavoring,diacetyl

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Neural Regeneration Research 2024年第10期19卷 2113-2114页

作者： Ashish P.Vartak Swati S.More center for Drug Design College of PharmacyUniversity of MinnesotaMinneapolisMNUSA

The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that *** amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive *** affects critical connected structures within the brain that are responsible for memory,language,and social behavior.

关键词： amyloid Alzheimer Aβ

JW-1-283 inhibits melanoma tumor growth via stabilization of the p53 pathway

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Genes & Diseases 2024年第3期11卷 18-21页

作者： Yang Xie Ruida Hou Kelli LHartman Jianxiong Jiang Zhongzhi Wu Wei Li Drug Discovery center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN38163USA

Melanoma is a lethal skin malignancy and the fifth most diagnosed cancer in the United States.1 Currently,for unresectable melanoma,the recommended treatment options include checkpoint inhibitor immunotherapy targeting programmed cell death 1(PD-1),and inhibitors targeting the mitogen-activated protein kinase(MAPK)***,the response rate may vary among the patients,and therefore demanding the development of novel treatment *** suppressor TP53has been suggested as one of the critical regulators mediating the aggressiveness and progression of melanoma.

关键词： melanoma suppressor death

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

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

Optimization of variables and assessment of in-vitro and in-vivo antihyperlipidemic activity of Eudragit RS nanoparticles containing simvastatin

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Particuology 2024年第7期90卷 189-198页

作者： Bina Gidwani Vishal Jain Veenu Joshi Ravindra Kumar Pandey Shiv Shankar Shukla Amber Vyas Columbia Institute of pharmacy Raipur(C.G.)India University Institute of pharmacy Pt Ravishankar Shukla UniversityRaipur(C.G.)India center for Basic Science and Research Pt Ravishankar Shukla UniversityRaipur(C.G.)India

Simvastatin, a BCS class II drug, is associated with poor aqueous solubility, first-pass metabolism and short half-life. In the present work, nanoparticles were prepared and evaluated. Optimization of formulation and process parameters was done through the use of independent and dependent variables. Preliminary studies were done to determine suitable range of the concentration of Eudragit polymer (10%–30%) and the ratio of drug to polymer (1:1 to 1:5) for the formation of nanoparticles by emulsification and a solvent evaporation technique. Results revealed that the mean size of nanoparticles was affected by stirring speed from 5000 RPM, 8000 RPM, and 12000 RPM. The results of increase in association efficiency and percent yield with increase in amount of drug from 100 mg, 150 mg, and 200 mg in selected range were observed. In-vitro release studies showed that two formulations possess highest initial burst and slow sustained drug release. There was 2.93-fold decrease in total cholesterol and 3.27-fold increases in triglyceride level during in-vivo study.

关键词： Simvastatin Eudragit RS 100 Nanoparticles Hyperlipidemia

Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical Research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH

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Chinese Chemical Letters 2024年第6期35卷 392-397页

作者： Yong-Dan Zhao Yidan Wang Rongrong Wang Lina Chen Hengtong Zuo Xi Wang Jihong Qiang Geng Wang Qingxia Li Canqi Ping Shuqiu Zhang Hao Wang School of pharmacy Shanxi Medical UniversityTaiyuan 030001China National center for Nanoscience and Technology Beijing 100190China Artemisinin Research center Institute of Chinese Materia MedicaBeijing 100700China

Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination *** intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been ***,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in *** combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant *** work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.

关键词： Nanomedicines Drug delivery Artemisinins resistance Malaria Glutathione

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

Artemisia argyi extract subfraction exerts an antifungal effect against dermatophytes by disrupting mitochondrial morphology and function

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Chinese Journal of Natural Medicines 2024年第1期22卷 47-61页

作者： CHEN Le ZHU Yunyun GUO Chaowei GUO Yujie ZHAO Lu MIAO Yuhuan DU Hongzhi LIU Dahui College of pharmacy Hubei University of Chinese MedicineWuhan 430065China National Resource center for Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China College of pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Artemisia argyi(***),a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia,has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving *** its widespread use,scientific evidence validating the antifungal efficacy of *** water extract(AAWE)against dermatophytes,particularly Trichophyton rubrum,Trichophyton mentagrophytes,and Microsporum gypseum,remains *** study aimed to substantiate the scientific basis of the folkloric use of *** by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against *** results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte *** subfraction AAWE6,isolated using D101 macroporous resin,emerged as the most potent *** minimum inhibitory concentrations(MICs)of AAWE6 against ***,***,and *** were 312.5,312.5,and 625μg·mL−1,*** electron microscopy(TEM)results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of ***,creating breaches(“small holes”),and disrupt the internal mitochondrial structure(“granary”).Furthermore,transcriptome data,quantitative real-time PCR(RT-qPCR),and biochemical assays corroborated the severe disruption of mitochondrial function,evidenced by inhibited tricarboxylic acid(TCA)cycle and energy ***,chemical characterization and molecular docking analyses identified flavonoids,primarily eupatilin(131.16±4.52 mg·g^(−1))and jaceosidin(4.17±0.18 mg·g^(−1)),as the active components of *** conclusion,the subfraction AAWE6 from *** exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and *** research validates the traditional use of *** and provides scient

关键词： Artemisia argyi Dermatophyte Antifungal activity Mitochondrial structure Mitochondrial function Transcriptome analysis