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Science China Chemistry 2025年

作者： Shunfei Cui Yiyao Pan Chenzhe Ma Bin Qi Qingqiang Min Ming Li Huabing Chen Hengte Ke Xingyue Ji Jiangsu Province Engineering Research Center of precision Diagnostics and therapeutics Development College of Pharmaceutical ScienceSoochow University

Carbon monoxide（CO） has recently been well-established as a promising therapeutic modality against cancer. The development of transition-metal-free and tumor-targeted delivery platforms for CO is highly demanded but remains very sporadic. Herein, we developed a polyprodrug system for the co-delivery of CO and a chemotherapeutic agent combretastin A-4（CA-4） to the tumor site based on a chemiexcitation mechanism. Such a poly-prodrug successfully achieved the co-activation of CO and CA-4 in response to H2O2at the tumor site both in vitro and in vivo. Importantly, a synergist effect between CO and CA-4 was observed in suppressing tumor growth in a mouse tumor model. It is anticipated that such a poly-prodrug system could be potentially adapted for the co-delivery of CO and another drug payload for combinational therapy for other indications.

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Role of copper chelating agents: between old applications and new perspectives in neuroscience

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Neural Regeneration Research 2025年第3期20卷 751-762页

作者： Rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella Nikola Puvača Luca Piemontese department of Pharmacy-Pharmaceutical Science University of Bari Aldo MoroBariItaly department of precision and Regenerative medicine and Jonian Area(DiMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly department of Engineering Management in Biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

Gut microbiota in cancer initiation,development and therapy

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Science China Life Sciences 2025年

作者： Ruyi Zhang Xiang Zhang Harry Cheuk Hay Lau Jun Yu Institute of Digestive Disease and department of medicine and therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong Kong

Cancer has long been associated with genetic and environmental factors,but recent studies reveal the important role of gut microbiota in its initiation and *** 13%of cancers are linked to infectious agents,highlighting the need to identify the specific microorganisms *** microbiota can either promote or inhibit cancer growth by influencing oncogenic signaling pathways and altering immune *** can lead to cancer,while certain probiotics and their metabolites may help reestablish microecological balance and improve anti-tumor immune *** into targeted approaches that enhance therapy with probiotics is ***,the effects of probiotics in humans are complex and not yet fully ***,methods to counteract harmful bacteria are still in *** clinical trials also indicate that modifying gut microbiota may help manage side effects of cancer *** research is crucial to understand better how gut microbiota can be used to improve cancer prevention and treatment outcomes.

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University department of Oncology Shanghai Medical CollegeFudan University department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for precision medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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Breast cancer stem cells: The role of sex steroid receptors

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World Journal of Stem Cells 2019年第9期11卷 594-603页

作者： Pia Giovannelli Marzia Di Donato Giovanni Galasso Erika Di Zazzo Nicola Medici Antonio Bilancio Antimo Migliaccio Gabriella Castoria department of precision medicine University of Campania "L.Vanvitelli"

Breast cancer(BC)is the most common cancer among women,and current available therapies often have high success ***,BC might acquire drug resistance and sometimes *** knowledge about the most aggressive forms of BC points to the role of specific cells with stem properties located within BC,the so-called“BC stem cells”(BCSCs).The role of BCSCs in cancer formation,growth,invasiveness,therapy resistance and tumor recurrence is becoming increasingly *** growth and metastatic properties of BCSCs are regulated by different pathways,which are only partially *** steroid receptors(SSRs),which are involved in BC etiology and progression,promote BCSC proliferation,dedifferentiation and ***,in the literature,there is incomplete information about their ***,there are contrasting conclusions about the expression and role of the classical BC hormonal biomarkers,such as estrogen receptor alpha(ERα),together with scant,albeit promising information concerning ER beta(ERβ)and androgen receptor(AR)properties that control different transduction pathways in *** this review,we will discuss the role that SRs expressed in BCSCs play to BC progression and recurrence and how these findings have opened new therapeutic possibilities.

关键词： Breast cancer Steroids Sex steroid receptors Cancer stem cells Therapeutic implications

Emerging new therapeutic antibody derivatives for cancer treatment

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Signal Transduction and Targeted Therapy 2022年第3期7卷 638-665页

作者： Shijie Jin Yanping Sun Xiao Liang Xinyu Gu Jiangtao Ning Yingchun Xu Shuqing Chen Liqiang Pan Institute of Drug Metabolism and Pharmaceutical Analysis College of Pharmaceutical SciencesZhejiang University310058 HangzhouChina department of precision medicine on tumor therapeutics ZJU-Hangzhou Global Scientific and Technological Innovation Center311200 HangzhouChina The First Affiliated Hospital Zhejiang University School of Medicine310003 HangzhouChina Key Laboratory of Pancreatic Disease of Zhejiang Province 310003 HangzhouChina

Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer *** successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies,such as antibody fragments,bispecific antibodies,and antibody derivatives(e.g.,antibody-drug conjugates and immunocytokines).

关键词： therapeutic cancer antibodies

Novel multimodal analgesia regimen improves post-TACE pain in patients with hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 510-516页

作者： Jian-Guo Guo Lu-Ping Zhao Yue-Feng Rao Yin-Ping Gao Xue-Jiao Guo Tan-Yang Zhou Zhi-Ying Feng Jun-Hui Sun Xiao-Yang Lu department of Pain medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of precision Diagnosis and Treatment for Hepatobiliary and Pancreatic tumor of Zhejiang Province Hangzhou 310003China department of Pharmacy Dongyang People’s HospitalDongyang 322100China

Backgroud: Transarterial chemoembolization(TACE) is the primary palliative treatment for patients with unresectable hepatocellular carcinoma(HCC). However, it is often accompanied by postoperative pain which hinder patient recovery. This study was to examine whether preemptive parecoxib and sufentanilbased patient controlled analgesia(PCA) could improve the pain management in patients receiving TACE for inoperable HCC. Methods: From June to December 2016, 84 HCC patients undergoing TACE procedure were enrolled. Because of the willingness of the individuals, it is difficult to randomize the patients to different groups. We matched the patients’ age, gender and pain scores, and divided the patients into the multimodal group( n = 42) and control group( n = 42). Patients in the multimodal group received 40 mg of parecoxib, 30 min before TACE, followed by 48 h of sufentanil-based PCA. Patients in the control group received a routine analgesic regimen, i.e., 5 mg of dezocine during operation, and 100 mg of tramadol or equivalent intravenous opioid according to patient’s complaints and pain intensity. Postoperative pain intensity, percentage of patients as per the pain category, adverse reaction, duration of hospital stay, cost-effectiveness, and patient’s satisfaction were all taken into consideration when evaluated. Results: Compared to the control group, the visual analogue scale scores for pain intensity was significantly lower at 2, 4, 6, and 12 h(all P < 0.05) in the multimodal group and a noticeably lower prevalence of post-operative nausea and vomiting in the multimodal group(31.0% vs. 59.5%). Patient’s satisfaction in the multimodal group was also significantly higher than that in the control group(95.2% vs. 69.0%). No significant difference was observed in the duration of hospital stay between the two groups. Conclusion: Preemptive parecoxib and sufentanil-based multimodal analgesia regime is a safe, efficient and cost-effective regimen for postoperative pain con

关键词： Multimodal analgesia Transarterial chemoembolization Parecoxib Pain management

Olfactomedin-4 in digestive diseases: A mini-review

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World Journal of Gastroenterology 2018年第17期24卷 1881-1887页

作者： Xin-Yu Wang Sheng-Hui Chen Ya-Nan Zhang Cheng-Fu Xu department of Gastro-enterology the First Affiliated Hospital College of Medicine Zhejiang University department of Geriatrics Zhejiang Provincial People’s Hospital department of Gastroenterology Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province the First Affiliated Hospital College of Medicine Zhejiang University

Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori(H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Downregulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advancedstage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.

关键词： Olfactomedin-4 Inflammation Cancer Helicobacter pylori infection

Crown aldoxime ethers:Their synthesis,structure,acid-catalyzed/photo-induced isomerization and adjustable guest binding

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Chinese Chemical Letters 2024年第11期35卷 318-322页

作者： Yulin Mao Jingyu Ma Jiecheng Ji Yuliang Wang Wanhua Wu Cheng Yang Key Laboratory of Green Chemistry&Technology of Ministry of Education College of ChemistrySichuan UniversityChengdu 610065China Laboratory of precision Cancer therapeutics Precision Medicine Research CenterWest China HospitalSichuan UniversityChengdu 610041China

A series of novel crown aldoxime ethers were synthesized,demonstrating notable thermal and hydrolysis *** showcased acid-catalyzed and photo-induced cis/trans isomerization,which enables orthogonal control over both guest complexation and the chiroptical effects of these crown aldoxime ethers,manifesting a regulation of complexation through isomerization at binding heteroatoms.

关键词： Crown aldoxime ether Cis/trans isomerization Photoisomerization Chiroptical induction Orthogonal control