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Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1787-1800页

作者： Yupeng Wang Lina Wang Tao Li Min Ouyang Hejian Xiong Dongfang Zhou Department of Ultrasonic Diagnosis Zhujiang HospitalKey Laboratory of Mental Health of the Ministry of EducationNMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Testing and Analysis Center Hebei Normal UniversityShijiazhuang 050024China Department of Mechanical Engineering The University of Texas at DallasRichardsonTX 75080USA

Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant *** particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent ***-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of ***,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust *** OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor *** cascade reactions of the released metallic drugs can sensitize RT by inducing dna damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune *** a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal ***,a long-term immunological memory effect to protect mice from tumor rechal-lenging is ***,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.

关键词： Bimetallic nanoparticles Radio-immunotherapy Cascade sensitizing amplifier,Oxaliplatin Fenton-typeHaber-Weiss reaction Radiosensitization Immunogenic cell death Radio-resistance

Mitophagy and cGAS-STING crosstalk in neuroinflammation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3327-3361页

作者： Xiaogang Zhou Jing Wang Lu Yu Gan Qiao Dalian Qin Betty Yuen-Kwan Law Fang Ren Jianming Wu Anguo Wu Sichuan Key Medical laboratory of New Drug Discovery and Drugability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou 646000China State Key laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao SAR 999078China Chongqing Key laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

Mitophagy,essential for mitochondrial health,selectively degrades damaged *** is intricately linked to the cGAS-STING pathway,which is crucial for innate *** pathway responds to mitochondrial dna and is associated with cellular stress *** review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING *** critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions,primarily through the accumulation of damaged mitochondria,which activates the cGAS-STING *** activation prompts the production of pro-inflammatory cytokines,exacerbating *** review emphasizes the interaction between mitophagy and the cGAS-STING *** mitophagy may suppress the cGAS-STING pathway,offering protection against ***,impaired mitophagy may activate the cGAS-STING pathway,leading to chronic ***,we explored how this interaction influences neurodegenerative disorders,suggesting a common mechanism underlying these *** conclusion,there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in *** review highlights potential therapies targeting these pathways,potentially leading to new treatments for neuroinflammatory and neurodegenerative *** synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

关键词： Neuroinflammation Mitophagy cGAS-STING Innate immunity Mitochondrial dna Crosstalk Therapeutic avenues Neurodegenerative diseases

Fangchinoline induces antiviral response by suppressing STING degradation

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Journal of Pharmaceutical Analysis 2024年第6期14卷 902-913页

作者： Jinyong Wang Fang Xie Xin Jia Xuejiao Wang Lingdong Kong Yiying Li b Xue Liang Meiqi Zhang Yuting He Wandi Feng Tong Luo Yao Wang Anlong Xu School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing100029China School of Life Science Beijing University of Chinese MedicineBeijing100029China Beijing Key laboratory of Drug Target Identification and New Drug screening Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China

The stimulator of interferon genes(STING),an integral adaptor protein in the dna-sensing pathway,plays a pivotal role in the innate immune response against ***,it presents a valuable therapeutic target for infectious diseases and *** observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1N1),and herpes simplex virus-1(HSV-1)in *** treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse ***,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(IFN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in ***,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral ***,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degradation,as a promising candidate for antiviral therapy.

关键词： Fangchinoline Virus Type I interferons Stimulator of interferon genes Protein degradation

Human circBOULE RNAs as potential biomarkers for sperm quality and male infertility

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The Journal of Biomedical Research 2024年第05期 473-484+397-402页

作者： Liping Cheng He Jin Tianheng Xiao Xiaoyu Yang Tingting Zhao Eugene Yujun Xu State Key laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Center for Clinical Reproduction the First Affiliated Hospital with Nanjing Medical University & Jiangsu Province Hospital Cellular screening Center the University of Chicago

Reliable molecular biomarkers to predict fertility remain scarce. The current study investigated the potential of testis-specific circBOULE RNAs as biomarkers for male infertility and sperm quality. Using reverse transcription-PCR and real-time reverse transcription-PCR assays, we identified seven circular RNAs from the human BOULE gene in human sperm. We observed that the expression level of circEx3-6 was significantly reduced in asthenozoospermia, while the expression levels of both circEx2-6 and circEx2-7 were decreased in teratozoospermia, compared with the controls. Furthermore, we demonstrated that the expression level of circEx2-6 was negatively correlated with the sperm dna fragmentation index, and the expression level of circEx2-7 was correlated with both fertilization and cleavage rates in those treated with the assisted reproductive *** functional analyses in a transgenic fly model supported the roles of circBOULE RNAs in sperm development and human male fertility. Collectively, our findings support that sperm circBOULE RNAs may serve as diagnostic biomarkers for assessing sperm motility and dna quality. Therefore, clinical application and significance of sperm circBOULE RNAs in the assisted reproductive technologies warrant further investigation.

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COX-2 blocking therapy in cisplatin chemosensitization of ovarian cancer:An allicin-based nanomedicine approach

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Chinese Chemical Letters 2024年第8期35卷 449-454页

作者： Huijiao Fu Peiqin Liang Qianwen Chen Yan Wang Guang Li Xuzi Cai Shengtao Wang Kun Chen Shengying Shi Zhiqiang Yu Xuefeng Wang Department of Obstetrics and Gynecology The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China Department of Obstetrics and Gynecology Huizhou Central People’s HospitalHuizhou 516001China Affiliated Foshan Maternity&Child Healthcare Hospital Southern Medical University(Foshan Maternity&Child Healthcare Hospital)Foshan 528000China Guangdong Key laboratory of New Drug screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Nursing Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of laboratory Medicine Dongguan Institute of Clinical Cancer ResearchThe Tenth Affiliated Hospital of Southern Medical University(Dongguan People’s Hospital)Dongguan 523018China

Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably ***,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting ***,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive *** one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP ***,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting dna *** essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.

关键词： COX-2 blocking therapy CDDP Chemosensitization Allicin Ovarian cancer

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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-Yang Liu Song Dong Xue-Ning Yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji Yang Qing Zhou Hong-Rui Li Ke Liu Wendy Wu Si-Yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key laboratory of Advanced Technology for Cancer screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor dna(ctdna)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctdna negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctdna–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctdna negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

Recent advances in the culture-independent discovery of natural products using metagenomic approaches

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Chinese Journal of Natural Medicines 2024年第2期22卷 100-111页

作者： SHEN Yiping LIU Nan WANG Zongqiang laboratory of Microbial Drug Discovery China Pharmaceutical UniversityNanjing 211198China

Natural products derived from bacterial sources have long been pivotal in the discovery of drug ***,the cultivation of only about 1%of bacteria in laboratory settings has left a significant portion of biosynthetic diversity hidden within the genomes of uncultured *** in sequencing technologies now enable the exploration of genetic material from these metagenomes through culture-independent *** approach involves extracting genetic sequences from environmental dna and applying a hybrid methodology that combines functional screening,sequence tag-based homology screening,and bioinformatic-assisted chemical *** this process,numerous valuable natural products have been identified and synthesized from previously uncharted metagenomic *** paper provides an overview of the recent advancements in the utilization of culture-independent techniques for the discovery of novel biosynthetic gene clusters and bioactive small molecules within metagenomic libraries.

关键词： Metagenomics Culture-independent approach Natural product Functional screening Sequence tag-based homology screening Syn-BNP

RNA interference in insects:the link between antiviral defense and pest control

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Insect Science 2024年第1期31卷 2-12页

作者： Jinzhi Niu Ruoyu Chen Jin-Jun Wang Key laboratory of Entomology and Pest Control Engineering College of Plant ProtectionSouthwest UniversityChongqingChina Key laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River(Ministry of Education) Southwest UniversityChongqingChina

RNA interference(RNAi)is a form of gene silencing triggered by double-stranded RNA(dsRNA)that operates in all eukaryotic *** has been widely investigated in insects to determine the underlying molecular mechanism,to investigate its role in systemic antiviral defense,and to develop strategies for pest *** insect cells are infected by viruses,viral dsRNA signatures trigger a local RNAi response to block viral replication and generate virus-derived dna that confers systemic ***-based insect pest control involves the application of exogenous dsRNA targeting genes essential for insect development or survival,but the efficacy of this approach has limited potency in many pests through a combination of rapid dsRNA degradation,inefficient dsRNA uptake/processing,and ineffective RNAi *** could be addressed by dsRNA screening and evaluation,focusing on dsRNA design and off-target management,as well as dsRNA production and *** review summarizes recent progress to determine the role of RNAi in antiviral defense and as a pest control strategy in insects,addressing gaps between our fundamental understanding of the RNAi mechanism and the exploitation of RNAi-based pest control strategies.

关键词： RNAi response systemic RNAi insecticidal dsRNA biological control off-targets

Coupling WO_(3-x) dots-encapsulated metal-organic frameworks and template-free branched polymerization for dual signal-amplified electrochemiluminescence biosensing

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Chinese Chemical Letters 2024年第4期35卷 469-474页

作者： Fei Yin Erli Yang Xue Ge Qian Sun Fan Mo Guoqiu Wu Yanfei Shen Medical School Southeast UniversityNanjing 210009China Center of Clinical laboratory Medicine Zhongda HospitalSoutheast UniversityNanjing 210009China Jiangsu Provincial Key laboratory of Critical Care Medicine Southeast UniversityNanjing 210009China

Developing accurate and sensitive dna methyltransferase(MTase) analysis methods is essential for early clinical diagnosis and development of antimicrobial drug targets. In this work, by coupling WO_(3-x) dotsencapsulated metal-organic frameworks(MOFs) as co-reactants and terminal deoxynucleotidyl transferase(Td T)-mediated template-free branched polymerization, a dual signal-amplified electrochemiluminescent(ECL) biosensor was constructed to detect dna adenine methylation(Dam) MTase. The employment of WO_(3-x) dots-encapsulated MOFs(i.e., NH_(2)-UIO66@WO_(3-x) ) was not only beneficial for biomolecule conjugation because of the abundant amino groups but also led to a 7-fold enhanced ECL response due to the increased loading of WO_(3-x). Moreover, Td T-mediated template-free branched polymerization promoted the capture of ECL emitters on the electrode surface, achieving 20-fold enhanced signal amplification. The presented ECL biosensor demonstrated a low detection limit of 2.4 × 10^(-4)U/m L, and displayed high reliability for the detection of Dam MTase in both spiked human serum and E. coli cell samples, and for the screening of potential inhibitors. This study opens a new avenue for designing a dual signal amplificationbased ECL bioassay for Dam MTase and screening inhibitors in the fields of clinical diagnosis and drug development.

关键词： Dual signal-amplified electrochemiluminescence WO_(3-x)dots MOFs Template-free branched polymerization dna methyltransferase

维普期刊数据库