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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

SIRT2 as a potential new therapeutic target for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 124-131页

作者： Noemi Sola-Sevilla Elena Puerta department of Pharmacology and Toxicology Faculty of PharmacyUniversity of NavarraNavarra Institute for Health Research(IdiSNA)PamplonaSpain

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective *** this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative *** review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative *** role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's ***,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific *** studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological *** will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.

关键词： Alzheimer's disease amyloid autophagy memory neurodegenerative diseases neuroinflammation sirtuin 2 tau

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Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

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Oncology Research 2024年第4期32卷 769-784页

作者： HUAN GAO JIE ZHANG TONY GKLEIJN ZHAOYONG WU BING LIU YUJIN MA BAOYUE DING DONGFENG YIN Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics Department of PharmaceuticsCollege of MedicineJiaxing UniversityJiaxing314001China department of pharmacy The General Hospital of Xinjiang Military RegionUrumqi830000China department of Pathology and Medical biology University Medical Center GroningenUniversity of GroningenGroningen9713 GZThe Netherlands department of Pathology Laboratory of Experimental OncologyErasmus MCRotterdam3015 GDThe Netherlands department of pharmacy Jiaxing Maternal and Child Health Care HospitalAffiliated Hospital of Jiaxing UniversityJiaxing314001China Qinghai Enlu Biotechnology Co. Ltd.Haidong810700China

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and *** treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic *** improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone ***(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size *** in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX *** micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated *** binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis *** vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic *** conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

关键词： Pluronic micelles Targeted nanotherapeutics Nanoparticulate drug delivery system Breast cancer with bone metastasis Therapeutic efficacy

Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges

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World Journal of Diabetes 2024年第5期15卷 853-866页

作者： Md Abdul Alim Al-Bari Nicholas Peake Nabil Eid department of pharmacy University of RajshahiRajshahi 6205Bangladesh Biosciences and Chemistry and Biomolecular Research Centre Sheffield Hallam UniversitySheffield S11WBUnited Kingdom department of Anatomy Division of Human BiologySchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia

Tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor *** infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of chronic illnesses such as diabetes mellitus(DM)greatly aggravate TB morbidity and ***[particularly type 2 DM(T2DM)]and TB have converged making their control even more *** contemporary global epidemics,TB-DM behaves like a syndemic,a synergistic confluence of two highly prevalent diseases.T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive *** a bidirectional relationship exists between TB and DM,it is necessary to concurrently treat both,and promote recommendations for the joint management of both *** are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure,and *** addition,autophagy may play a role in these ***,the TB-DM comorbidities present several health challenges,requiring a focus on multidisciplinary collaboration and integrated strategies,to effectively deal with this double *** effectively manage the comorbidity,further screening in affected countries,more suitable drugs,and better treatment strategies are required.

关键词： Diabetes mellitus Tuberculosis Coinfections Comorbidity Drug-drug interactions Autophagy Treatment challenges

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)

Modern approaches for detection of volatile organic compounds in metabolic studies focusing on pathogenic bacteria:Current state of the art

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Journal of Pharmaceutical Analysis 2024年第4期14卷 483-505页

作者： Karolina Zuchowska Wojciech Filipiak department of Pharmacodynamics and Molecular Pharmacology Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Torun85-089 BydgoszczPoland

Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted ***,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these ***,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are *** this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical *** also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.

关键词： Volatile organic compounds Pathogenic bacteria metabolites Metabolomics Microextraction techniques Gas chromatography-mass spectrometry In vivo breath analysis In vitro model

Survival effects of antibiotic exposure during the larval and adult stages in the West Nile virus vector Culex pipiens

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Insect Science 2024年第2期31卷 542-550页

作者： Marta Garrigos Mario Garrido Manuel Morales-Yuste JosuéMartinez-de la Puente Jesus Veiga Faculty of pharmacy Department of ParasitologyUniversity of GranadaGranadaSpain CIBER de Epidemiologia y Salud Publica(CIBERESP) MadridSpain

The ability of mosquitoes to transmit a pathogen is affected,among other factors,by their survival rate,which is partly modulated by their *** microbiota is acquired during the larval phase and modified during their development and adult feeding behavior,being highly dependent on environmental *** residues including antibiotics are widespread pollutants potentially being present in mosquito breeding waters likely affecting their ***,we used Culex pipiens mosquitoes to assess the impact of antibiotic exposure during the larval and adult stages on the survival rate of adult ***-collected larvae were randomly assigned to two treatments:larvae maintained in water supplemented with antibiotics and control *** adults were subsequently assigned to each of two treatments,fed with sugar solution with antibiotics and fed only with sugar solution(controls).Larval exposure to antibiotics significantly increased the survival rate of adult females that received a control *** addition,the effect of adult exposure to antibiotics on the survival rate of both male and female mosquitoes depended on the number of days that larvae fed ad libitum in the laboratory before *** particular,shorter larval ad libitum feeding periods reduced the survival rate of antibiotic-treated adult mosquitoes compared with those that emerged after a longer larval feeding *** differences were not found in control adult *** results extend the current understanding of the impact of antibiotic exposure of mosquitoes on a key component of vectorial capacity,that is the vector survival rate.

关键词： antibiotics avian malaria microbiota mosquitoes vector competence vector survival

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham department of Pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is en

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

Bacterial microcompartment-mimicking Pickering emulsion droplets for detoxification of chemical threats under sweet conditions

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Science China Chemistry 2024年第9期67卷 3039-3049页

作者： Xiao Xu Wenqi Xie Ting Wu Chen Chen Xiaoning Chen Yuheng Yang Hao Lian Hao Chen Xiaofeng Cheng Zhitong Chen Guojun Chen Chaoqun Liu Lanlan Chen Yu He Zhaowei Chen Bernard P.Binks Huanghao Yang New Cornerstone Science Laboratory MOE Key Laboratory for Analytical Science of Food Safety and Biology College of ChemistryFuzhou University Institute of Biomedical and Health Engineering Shenzhen Institute of Advanced Technology Chinese Academy of Sciences department of Biomedical Engineering and the Rosalind & Morris Goodman Cancer Research Institute Mc Gill University School of pharmacy Henan University department of Chemistry University of Hull

Chemical warfare agents represent a severe threat to mankind and their efficient decontamination is a global necessity. However,traditional disposal strategies have limitations, including high energy consumption, use of aggressive reagents and generation of toxic byproducts. Here, inspired by the compartmentalized architecture and detoxification mechanism of bacterial microcompartments, we constructed oil-in-water Pickering emulsion droplets stabilized by hydrogen-bonded organic framework immobilized cascade enzymes for decontaminating mustard gas simulant(2-chloroethyl ethyl sulfide, CEES) under sweet conditions. Two exemplified droplet systems were developed with two-enzyme(glucose oxidase/chloroperoxidase) and threeenzyme(invertase/glucose oxidase/chloroperoxidase) cascades, both achieving over 6-fold enhancement in decontamination efficiency compared with free enzymes and >99% selectivity towards non-toxic sulfoxide. We found that the favored mass transfer of sugars and CEES from their respective phases to approach the cascade enzymes located at the droplet surface and the facilitated substrate channeling between proximally immobilized enzymes were key factors in augmenting the decontamination efficacy. More importantly, the robustness of immobilized enzymes enabled easy reproduction of both the droplet formation and detoxification performance over 10 cycles, following long-term storage and in far-field locations.

关键词： Pickering emulsion biomimetics chemical warfare agent bacterial microcompartment biocatalysis

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