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Alternative splicing and related RNA binding proteins in human health and disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 839-871页

作者： Yining Tao Qi Zhang Haoyu Wang Xiyu Yang Haoran Mu Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of Medicine200000 ShanghaiChina Shanghai Bone tumor Institution 200000 ShanghaiChina Department of Biochemistry and molecular Cell biology Shanghai Key Laboratory for Tumor Microenvironment and InflammationShanghai Jiao Tong University School of Medicine200000 ShanghaiChina

Alternative splicing(AS)serves as a pivotal mechanism in transcriptional regulation,engendering transcript diversity,and modifications in protein structure and *** varying tissues,developmental stages,or under specific conditions,AS gives rise to distinct splice *** implies that these isoforms possess unique temporal and spatial roles,thereby associating AS with standard biological activities and *** these,AS-related RNA-binding proteins(RBPs)play an instrumental role in regulating alternative splicing *** physiological conditions,the diversity of proteins mediated by AS influences the structure,function,interaction,and localization of proteins,thereby participating in the differentiation and development of an array of tissues and *** pathological conditions,alterations in AS are linked with various diseases,particularly *** changes can lead to modifications in gene splicing patterns,culminating in changes or loss of protein *** instance,in cancer,abnormalities in AS and RBPs may result in aberrant expression of cancer-associated genes,thereby promoting the onset and progression of *** and RBPs are also associated with numerous neurodegenerative diseases and autoimmune ***,the study of AS across different tissues holds significant *** review provides a detailed account of the recent advancements in the study of alternative splicing and AS-related RNA-binding proteins in tissue development and diseases,which aids in deepening the understanding of gene expression complexity and offers new insights and methodologies for precision medicine.

关键词： organs alterations thereby

Enzymatically controlled DNA tetrahedron nanoprobes for specific imaging of ATP in tumor

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Chinese Chemical Letters 2024年第8期35卷 221-224页

作者： Xiaohong Wen Mei Yang Lie Li Mingmin Huang Wei Cui Suping Li Haiyan Chen Chen Li Qiuping Guo College of biology State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringKey Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan ProvinceHunan UniversityChangsha 410082China

Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer ***,the conventional ATP biosensing strat-egy is often limited by the undesired on-target off-tumor ***,we reported a novel strategy to design enzymatically controlled DNA tetrahedron nanoprobes(En-DT)for biosensing and imaging ATP in tumor *** En-DT was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on the DNA *** En-DT could be catalytically activated by apurinic/apyrimidinic endonuclease 1(APE1)in cancer cells,but they did not respond to ATP in normal cells,thereby enabling cancer-specific ATP biosensing and imaging in vitro and in vivo with improved tumor *** strategy would facilitate the precise detection of a broad range of biomarker in tumors and may promote the development of smart probes for cancer diagnosis.

关键词： Enzyme-controlled APE1 DNA tetrahedron Cancer-specific ATP biosensing

Exploring treatment options in cancer: tumor treatment strategies

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3337-3380页

作者： Beilei Liu Hongyu Zhou Licheng Tan Kin To Hugo Siu Xin-Yuan Guan Department of Clinical Oncology The University of Hong Kong-Shenzhen HospitalShenzhenChina Department of Clinical Oncology The University of Hong KongHong KongChina state key laboratory for Liver Research The University of Hong KongHong KongChina Advanced Energy Science and Technology Guangdong laboratory HuizhouChina MOE key laboratory of tumor molecular biology Jinan UniversityGuangzhouChina

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical and psychological ***,the landscape of tumor treatment has undergone a comprehensive and remarkable *** as fervently pursued modalities are small molecule targeted agents,antibody-drug conjugates(ADCs),cell-based therapies,and gene *** cutting-edge treatment modalities not only afford personalized and precise tumor targeting,but also provide patients with enhanced therapeutic comfort and the potential to impede disease ***,it is acknowledged that these therapeutic strategies still harbour untapped potential for further *** a comprehensive understanding of the merits and limitations of these treatment modalities holds the promise of offering novel perspectives for clinical practice and foundational research *** this review,we discussed the different treatment modalities,including small molecule targeted drugs,peptide drugs,antibody drugs,cell therapy,and gene *** will provide a detailed explanation of each method,addressing their status of development,clinical challenges,and potential *** aim is to assist clinicians and researchers in gaining a deeper understanding of these diverse treatment options,enabling them to carry out effective treatment and advance their research more effciently.

关键词： drugs treatment holds

Defect spinel oxides for electrocatalytic reduction reactions

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Nano Research 2024年第5期17卷 3547-3570页

作者： Zhijuan Liu Jinyu Guo Lu-yu Liu Fen Wang Zhijie Kong Yanyong Wang Henan key laboratory of Crystalline molecular Functional Materials Henan International Joint Laboratory of Tumor Theranostical Cluster MaterialsKey Laboratory of Special Environmental Functional Materials(Zhengzhou University)Ministry of EducationGreen Catalysis Centerand College of ChemistryZhengzhou UniversityZhengzhou 450001China State key laboratory of Chem/Bio-sensing and Chemometrics College of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China

Electrocatalytic reduction reactions play a crucial role in electrochemical energy conversion and storage technology,which are emerging technologies to ameliorate environmental *** oxides are widely explored in electrocatalytic oxidation reactions but have a poor intrinsic ability to reduction reactions,making their electrocatalytic ability less *** improve this,defect engineering is a valuable method for regulating the electronic structure and coordination ***,this manuscript discusses the use of defect spinel oxides in electrocatalytic reduction reactions,including the different types of defects,construction methods,and characterization *** also outlines the various applications of defect spinel oxides in different electrocatalytic reduction ***,it goes over the challenges and future outlooks for defect *** review aims to thoroughly explain how defect spinels work in electrocatalytic reduction reactions and serve as a helpful guide for creating effective electrocatalysts.

关键词： defect spinel oxides electrochemical reduction reactions electrocatalytic mechanism dynamic evolution

Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

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Food Science and Human Wellness 2024年第4期13卷 2327-2345页

作者： Chenghao Fu Zhehao Liang Zemiao Niu Ning Chen Yuemin Li Zhenhua Liang Yanwei Huo Hao Xi Rong Wang Yonghuan Yan Xiaoruo Gan Mengtian Wang Yun Huang Yan Zhang Mingming Gao Pin Lü Postdoctoral Station for Basic Medicine Cardiovascular Medical Science CenterDepartment of Cell BiologyKey Laboratory of Neural and Vascular Biology of Ministry of EducationHebei Medical UniversityShijiazhuang 050017China Hebei key laboratory of Forensic Medicine College of Forensic MedicineHebei Medical UniversityShijiazhuang 050017China Hebei Food Safety key laboratory Hebei Food Inspection and Research InstituteShijiazhuang 050091China laboratory of Lipid Metabolism Department of Biochemistry and Molecular BiologyKey Laboratory of Medical Biotechnology of Hebei ProvinceShijiazhuang 050017China

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or ***,it is still uncertain how to select immunotherapy drugs to combine with intermittent *** we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast *** this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor ***,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic *** investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of *** the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)*** summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.

关键词： Intermittent fasting Ly6G^(low)myeloid-derived suppressor cell apoptosis Extramedullary hematopoiesis Colony stimulating factor Glucose metabolism restriction

The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells

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Science China(Life Sciences) 2024年第9期67卷 1867-1880页

作者： Weixiao Yan Xiaotong Wang Wenjing Wang Qi Guo Na Huang Hao Chen Xing-Jie Liang Yu Han Dandan Liu Jinchao Zhang State key laboratory of New Pharmaceutical Preparations and Excipients/key laboratory of Medicinal Chemistry and molecular Diagnosis of the Ministry of Education/College of Chemistry and Materials Science Chemical Biology Key Laboratory of Hebei ProvinceHebei UniversityBaoding 071002China CAS key laboratory for Biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Cancer stem cells(CSCs)play an important role in metastasis development,tumor recurrence,and treatment resistance,and are essential for the eradication of ***,therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape,which leads to enhanced aggressive behaviors compared with CSCs that have never been ***,the underlying mechanisms regulating the therapeutic escape remain *** this end,we established a model to isolate the therapeutic escaped CSCs(TSCSCs)from breast CSCs and performed the transcription profile to reveal the ***,we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway,resulting in TSCSCs exhibiting enhanced motility and ***,blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo,which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition(EMT)-related proteins vimentin and *** obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

关键词： therapeutic escape breast cancer stem cells motility p38/MAPK signaling pathway molecular mechanism

The combined detection of carcinoembryonic antigen,carcinogenic antigen 125,and carcinogenic antigen 19-9 in colorectal cancer patients

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2073-2079页

作者： Ling-Zhen Gong Qian-Wen Wang Jie-Wen Zhu Department of Clinical laboratory Huangshi Central Hospital(Affiliated Hospital of Hubei Polytechnic University)Hubei Key Laboratory of Kidney Disease Pathogenesis and InterventionHuangshi Tumor Molecular Diagnosis and Treatment Key LaboratoryHuangshi 435000Hubei ProvinceChina

BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)*** predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is *** To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of *** The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January *** CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver *** addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic *** The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone ***,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL *** 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL *** addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(Ptumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.

关键词： Colorectal cancer Liver metastasis Serum markers Carcinoembryonic antigen Cancer antigen 125 Cancer antigen 19-9 Receiver operating characteristic analysis

Integrating Homogeneous and Heterogeneous Catalysis in a Copper Nanocluster with Lewis Acid–Base Sites for Chemical Conversion of CO_(2) and Propargylamine

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CCS Chemistry 2024年第9期6卷 2131-2141页

作者： Wan-Zhen Qiao Yu-Jue Wang Si Li Rui Wang Jie Wu Shuang-Quan Zang Henan key laboratory of Crystalline molecular Functional Materials Henan International Joint Laboratory of Tumor Theranostical Cluster MaterialsGreen Catalysis and College of ChemistryZhengzhou UniversityZhengzhou 450001

It remains a significant challenge to develop a catalyst that merges the advantages of homogeneous and heterogeneous catalysis with high reactivity and great ***,an atomically precise Cu_(6)-NH_(2) nanocluster with distorted octahedral Cu_(6) core and NH_(2)-functionalized ligands has been developed as the first homo/heterogeneous catalyst to catalyze the cyclization reaction of propargylic amines with carbon dioxide(CO_(2))under mild *** a homogeneous catalyst,Cu_(6)-NH_(2) shows excellent catalytic activity with high turnover frequency due to highly accessible active *** definite coordination geometry and homogeneity nature of active centers make it convenient to investigate the structure–activity relationship at the atomic level through experiments and theory *** addition,the nanocluster exhibits excellent stability,great recrystallizability,and reusability in five catalytic cycles,in which its catalytic performance has no obvious ***,Cu_(6)-NH_(2) incorporates Lewis acid and base sites in metal and ligand,respectively,which can promote catalytic efficiency in a synergistic effect in the absence of any ***,Cu_(6)-NH_(2) can realize direct conversion of CO_(2) in simulated flue gas into oxazolidinones with high *** metal-ligand cooperative effect and integrated advantages of homogeneous and heterogeneous catalysis would provide new perspectives to achieve advanced metal nanocluster catalysts for CO_(2) conversion.

关键词： copper nanocluster atomically precise structure Lewis acid-base sites CO_(2)cyclization reaction cocatalyst-free

MnO_(2)-coated nanodiamond-driven photodynamic therapy for enhanced antitumor effect by addressing hypoxia and glutathione depletion

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Particuology 2024年第9期92卷 305-315页

作者： Jicheng Cui Dongmei Zhang Hui Qiao Zeyu Yan Wenxia Zhang Yingqi Li key laboratory of Chemical biology and molecular Engineering of Ministry of Education Institute of Molecular ScienceShanxi UniversityTaiyuan030006China Taiyuan Central Hospital Taiyuan030009China School of Chemistry and Chemical Engineering Shanxi UniversityTaiyuan030006China

The generation of reactive oxygen species(ROS)at the tumor site to induce destruction is emerging as a novel strategy for cancer treatment,which involves photodynamic therapy(PDT).Nevertheless,tumors typically create a hypoxic environment and are equipped with an endogenous antioxidant defense system that could potentially impede the efficiency of the therapeutic *** overcome these drawbacks,herein,a tumor microenvironment-responsive the ND-PAA-CD-Ce6@MnO_(2)(NPCC@M)delivery system was fabricated by disulfide bond coupling chlorin e6(Ce6)to nanodiamond(ND)and further wrapped by MnO_(2)nanosheets to facilitate *** use of disulfide bond not only stabilizes Ce6 in the blood circulation to prevent premature leakage,but also destroys the antioxidant barrier of overexpressed glutathione(GSH)in tumor ***,the outer MnO_(2)was rapidly degraded by the endogenous hydrogen peroxide(H_(2)O_(2))in the acidic pH and GSH within the tumor cells,which leads to an abundance of O_(2)and while increases the level of 1O_(2)under laser *** results eventually broke the redox homeostasis and attenuate hypoxia,thereby inducing apoptosis and necrosis of tumor *** in vitro and in vivo biological effect has revealed a good biosafety profile and a high tumor suppression *** a novel ND-based system with tumor microenvironment-modulating capability to elevate oxygen content and promote GSH consumption in tumor cells opens new opportunities for enhanced ROS treatment paradigms.

关键词： Nanodiamond Photodynamic Chlorin e6 MnO_(2) tumor suppression