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Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2748-2760页

作者： Hua-yang Fan Ming-da Zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua Liang ya-ling tang Yong Sun State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Oral Pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC progression.By analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC patients.Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p sponge.MiR-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC cells.These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression.Therefore,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC development.These findings provide a new perspective for the development of OSCC treatments.

关键词： Oral squamous cell carcinoma CircRNA MiRNA sponge Antagomir MiRNA delivery Cisplatin-based nanoparticles Drug delivery systems Tumor elimination

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Carcinosarcoma of the deep lobe of the parotid gland in the parapharyngeal region:A case report

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World Journal of Clinical Cases 2023年第31期11卷 7663-7672页

作者： Yue-yang tang Gui-Quan Zhu Zhi-Jian Zheng Li-Hong yao Zi-Xin Wan Xin-Hua Liang ya-ling tang Department of Oral Pathology West China Hospital of StomatologySichuan UniversityChengdu 610041Sichuan ProvinceChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND Salivary carcinosarcoma is an extremely rare tumor containing both malignant epithelial and mesenchymal constituents.This article reports a rare case of carcinosarcoma with salivary duct carcinoma and osteosarcoma as the tumor components.The clinicopathological characteristics,treatment,and prognosis are discussed in conjunction with the literature.CASE SUMMARY A 48-year-old man presented with a complaint of a mass in the right parotid region.Osteosarcoma was first considered for assessment by fine-needle aspiration cytology.Physical examination revealed a mass measuring approximately 4 cm×3.5 cm×3 cm.The mass,the whole lobe of the right parotid gland,and the right mandible were completely removed during surgery.Postoperative histopathology confirmed carcinosarcoma of the salivary gland.CONCLUSION A definite diagnosis of salivary gland carcinosarcoma can only be obtained after complete surgical resection.

关键词： Salivary gland tumor Carcinosarcoma Clinicopathology Fluorescence in situ hybridization Case report

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Biallelic mutations in spermatogenesis and centriole-associated 1 like(SPATC1L)cause acephalic spermatozoa syndrome and male infertility

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Asian Journal of Andrology 2022年第1期24卷 67-72页

作者： You-Zhu Li Na Li Wen-Sheng Liu yan-Wei Sha Rong-Feng Wu ya-ling tang Xing-Shen Zhu Xiao-Li Wei Xiao-ya Zhang Yi-Feng Wang Zhong-Xian Lu Fu-Xing Zhang Reproductive Medicine Center The First Affiliated Hospital of Xiamen UniversityXiamen 361003China Intensive Care Unit Fujian Medical University Xiamen Humanity HospitalXiamen 361009China Obstetrics and Gynecology Center Department of Obstetrics and GynecologyZhujiang HospitalSouthern Medical UniversityGuangzhou 510280China School of Pharmaceutical Sciences State Key Laboratory of Cellular Stress BiologyXiamen UniversityXiamen 361102China Department of Andrology United Diagnostic and Research Center for Clinical GeneticsWomen and Children’s Hospital and School of MedicineXiamen UniversityXiamen 361005China Department of Obstetrics and Gynecology First Affiliated Hospital of Xiamen UniversityXiamen 361003China Department of General Surgery First Affiliated Hospital of Xiamen UniversityXiamen 361003China

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients,and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome.Spermatogenesis and centrioleassociated 1 like(SPATC1L)is indispensable for maintaining the integrity of sperm head-to-tail connections in mice,but its roles in human sperm and early embryonic development remain largely unknown.Herein,we conducted whole-exome sequencing(WES)of 22 infertile men with acephalic spermatozoa syndrome.An in silico analysis of the candidate variants was conducted,and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility.We identified biallelic mutations in SPATC1L(c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X)from a patient whose sperm displayed complete acephalia.Both SPATC1L variants are rare and deleterious.SPATC1L is mainly expressed at the head–tail junction of elongating spermatids.Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro.Moreover,none of the patient’s four attempts at intracytoplasmic sperm injection(ICSI)resulted in a transplantable embryo,which suggests that SPATC1L defects might affect early embryonic development.In conclusion,this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome.Furthermore,WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.

关键词： acephalic spermatozoa syndrome biallelic mutations spermatogenesis and centriole-associated 1 like whole-exome sequencing

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microRNAs, an active and versatile group in cancers

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International Journal of Oral Science 2011年第4期3卷 165-175页

作者： Jeffrey Liu Min Zheng ya-ling tang Xin-hua Liang Qin yang Department of Biological Sciences University of Delaware Nowak DE 19716 USA State Key Laboratory of Oral Diseases Sichuan University Chengdu 610041 China Department of Oral and Maxillofacial Surgery West China School of Stomatology Sichuan University Chengdu 610041 China Cancer Biology Division School of Medicine Washington University St. Louis MO 63108 USA

microRNAs （miRNAs） are a class of non-coding RNAs that function as endogenous triggers of the RNA interference pathway. Studies have shown that thousands of human protein-coding genes are regulated by miRNAs, indicating that miRNAs are master regulators of many important biological processes, such as cancer development, miRNAs frequently have deregulated expression in many types of human cancers, and play critical roles in tumorigenesis, which functions either as tumor suppressors or as oncogenes. Recent studies have shown that miRNAs are highly related with cancer progression, including initiating, growth, apoptosis, invasion, and metastasis. Furthermore, miRNAs are shown to be responsible for the cancer-related inflam- mation, anti-cancer drug resistance, and regulation of cancer stem ceils. Therefore, miRNAs have generated great interest as a novel strategy in cancer diagnosis and therapy. Here we review the versatile roles of miRNAs in cancers and their potential applications for diagnosis, prognosis, and treatment as biomarkers.

关键词： microRNAs cancer epithelial-mesenchymal transition inflammation cancer stem cells drug resistance

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OXIDIZED HIGH-DENSITY LIPOPROTEIN PROMOTES MATURATION AND MIGRATION OF BONE MARROW DERIVED DENDRITIC CELLS FROM C57BL/6J MICE

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Chinese Medical Sciences Journal 2008年第4期23卷 224-229页

作者： Zeng-xiang XuYong-zong yang Da-ming Feng Shuang Wang ya-ling tang Fan He yan Xia Fang Li Department of Pathology Wannan Medical College Wuhu Anhui 241000 Institute of Cardiovascular Diseases University of South China Hengyang Hunan 421001

Objective To explore the influence of oxidized high-density lipoprotein (oxHDL) on the maturation and migration of bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice. Methods The C57BL/6J mice bone marrow cell suspension was prepared and purified. Recombinant granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant interleukin-4 (rmIL-4) were used to promote monocytes to differentiate and suppress lymphocytes. Then 50 μg/mL oxHDL was added to stimulate BMDCs, using 50 μg/mL high-density lipoprotein (HDL) as homologous protein control, PBS as negative control, and 1 μg/mL lipopolysaccharide (LPS) as positive control. The CD86 and MHCII expression rates were detected with fluorescence-activated cell sorting (FACS). Liquid scintillation counting (LSC) was used in mixed lymphocyte reactions (MLRs) to reflect the ability of BMDCs in stimulating the proliferation of homologous T cells. Levels of cytokines IL-12 and IL-10 were detected by ELISA. The cell migration was evaluated with the transwell system. Results Compared with PBS group, the expressions of CD86 and MHCII, counts per minute of MLRs, secretion of IL-12 and IL-10, and number of migrated cells in oxHDL group and LPS group significantly increased (all P < 0.05), while the increment was less in oxHDL group than LPS group. The number of migrated cells in oxHDL group was about twice of that in HDL group. Conclusion OxHDL may promote the maturation and migration of BMDCs in vitro.

关键词：树状细胞高密度脂蛋白成熟迁徙动脉粥样硬化

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The identification of AMZ2 as a candidate causative gene in a severe teratozoospermia patient characterized by vacuolated spermatozoa

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Asian Journal of Andrology 2024年第1期26卷 107-111页

作者： Liu Liu Jing yang Wen-Jing Zhang Yi-ling Zhou Gui-Jun Zhao ya Huang Shu-yan tang Obstetrics and Gynecology Hospital Fudan UniversityShanghai 200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development Department of Computational BiologySchool of Life SciencesFudan UniversityShanghai 200436China Shanghai Towako Hospital Shanghai 200131China Shanghai Institute of Medical Genetics Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200040China

Teratozoospermia with cephalic defects is one of the most severe types of sperm defects known to date.While several monogenic factors are linked to cephalic abnormalities,such as globozoospermia and macrozoospermia,the genetic cause of vacuolated spermatozoa remains inadequately described.Here,we analyzed whole-exome sequencing(WES)data for an individual from a consanguineous family with severely vacuolated spermatozoa.The analysis revealed a novel homozygous c.520A>G(p.Thr174Ala)variant in the archaelysin family metallopeptidase 2(AMZ2),a gene that encodes a zinc metalloprotease previously shown to be highly expressed in the testes and sperm.Multiple algorithms predicted this variant to be a damaging mutation.Consistent with an autosomal recessive mode of inheritance,this variant was inherited from heterozygous parental carriers.To investigate the potential pathogenicity of the identified variant,we compared the AMZ2 expression in sperm cells from the patient with the AMZ2 variant and from a healthy control.Immunoblot analysis revealed that the homozygous missense variant in AMZ2 abolished AMZ2 expression in the spermatozoa.Our findings reveal a candidate causative gene for vacuolated spermatozoa.

关键词： AMZ2 male infertility sperm quality teratozoospermia

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Recent Advances in Mechanistic Understanding of Metal-Free Carbon Thermocatalysis and Electrocatalysis with Model Molecules

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Nano-Micro Letters 2024年第7期16卷 74-97页

作者： Wei Guo Linhui Yu ling tang yan Wan yangming Lin CAS Key Laboratory of Design and Assembly of Functional Nanostructures Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002People’s Republic of China Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamen 361021People’s Republic of China State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002People’s Republic of China Institute of Urban Environment Chinese Academy of SciencesXiamen 361021People’s Republic of China

Metal-free carbon,as the most representative heterogeneous metal-free catalysts,have received considerable interests in electro-and thermo-catalytic reac-tions due to their impressive performance and sustainability.Over the past decade,well-designed carbon catalysts with tunable structures and heteroatom groups coupled with various characterization techniques have proposed numerous reaction mechanisms.However,active sites,key intermediate species,precise structure-activity relationships and dynamic evolution processes of carbon catalysts are still rife with controversies due to the monotony and limitation of used experimental methods.In this Review,we sum-marize the extensive efforts on model catalysts since the 2000s,particularly in the past decade,to overcome the influences of material and structure limitations in metal-free carbon catalysis.Using both nanomolecule model and bulk model,the real contribution of each alien species,defect and edge configuration to a series of fundamentally important reactions,such as thermocatalytic reactions,electrocatalytic reactions,were systematically studied.Combined with in situ techniques,isotope labeling and size control,the detailed reaction mechanisms,the precise 2D structure-activity relationships and the rate-determining steps were revealed at a molecular level.Furthermore,the outlook of model carbon catalysis has also been proposed in this work.

关键词： Metal-free carbon catalysts Model catalyst Electrocatalysis Active site Reaction mechanisms

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RNAi-mediated downregulation of urokinase plasminogen activator receptor inhibits proliferation, adhesion, migration and invasion in oral cancer cells

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中国口腔颌面外科杂志 2008年第B5期6卷 81-82页

作者： Xin Hua Liang Xiao Qin yang ya ling tang Hao Zhou Jia Rang Gao Zu Yi Mao Department of Oral and Maxukkifacuak Surgery West China College of Stomatology Sichuan University Chengdu 610041 Department of Oral and Maxillofaial Szzrgery State Laboratory of Oral Diseases Sichuan University Chengdu 610041 China

Purpose: To explore siRNA targeting of uPAR to downregulate the expression of uPAR in Tca8113 cells, and to investigate the inhibition of proliferation activity, adhesion, migration and invasion potential of cells by siRNA targeting of uPAR in vitro,Methods: pSIREN Vector, which contains the U6 RNA polymerase III promoter and independently expresses a Zoanthus sp。green fluorescent protein, was used for the construction of a vector expressing siRNA for uPAR (pU vector)。The levels ofuPAR mRNA and protein expression in Tca8113 cells transfected with mock (untreated/parental cells), Empty Vector, pU control vector, and pU vector were determined by quantitative real-time RT-PCR and Western blotting。Cell growth was assessed by MTT assay and adhesion assays were performed on cytometrix adhesion strips coated with human fibronectin, vitronectin, laminin, collagen I, and collagen IV, and cell migration and invasion assay was conducted with QCM-VN assay kit and QCMTM 96-well cell invasion assay kit respectively。Results: siRNA targeting of uPAR leaded to the efficient and specific inhibition of endogenous uPAR mRNA and protein expression in Tca8113 cells。Furthermore, simultaneous silencing of uPAR resulted in a dramatic reduction of tumor cell proliferation activity, adhesion, migration and invasion in pU vector group compared to the controls。Concluslon:These findings suggest that RNAi-directed targeting of uPAR can be used as a potent and specific therapeutic tool for the treatment of oral cancer, especially in inhibiting cancer cell invasion and metastasis。

关键词：口腔癌治疗方法尿激酶血纤蛋白溶解酶原

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Multi-instance partial-label learning: towards exploiting dual inexact supervision

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Science China(Information Sciences) 2024年第3期67卷 48-61页

作者： Wei tang Weijia ZHANG Min-ling ZHANG School of Computer Science and Engineering Southeast University Key Laboratory of Computer Network and Information Integration (Southeast University) Ministry of Education School of Information and Physical Sciences The University of Newcastle

Weakly supervised machine learning algorithms are able to learn from ambiguous samples or labels, e.g., multi-instance learning or partial-label learning. However, in some real-world tasks, each training sample is associated with not only multiple instances but also a candidate label set that contains one groundtruth label and some false positive labels. Specifically, at least one instance pertains to the ground-truth label while no instance belongs to the false positive labels. In this paper, we formalize such problems as multi-instance partial-label learning(MIPL). Existing multi-instance learning algorithms and partial-label learning algorithms are suboptimal for solving MIPL problems since the former fails to disambiguate a candidate label set, and the latter cannot handle a multi-instance bag. To address these issues, a tailored algorithm named MIPLGP, i.e., multi-instance partial-label learning with Gaussian processes, is proposed.MIPLGP first assigns each instance with a candidate label set in an augmented label space, then transforms the candidate label set into a logarithmic space to yield the disambiguated and continuous labels via an exclusive disambiguation strategy, and last induces a model based on the Gaussian processes. Experimental results on various datasets validate that MIPLGP is superior to well-established multi-instance learning and partial-label learning algorithms for solving MIPL problems.

关键词： machine learning multi-instance partial-label learning multi-instance learning partial-label learning Gaussian processes

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Promoting effect of FeOx addition on the mechanochemically prepared vanadium-based catalyst for real PCDD/Fs removal and mechanism insight

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Journal of Environmental Sciences 2024年第3期137卷 478-487页

作者： Minghui tang ling Wang Hongxian Li Xinlei Huang Cuicui Du Shengyong Lu State Key Laboratory for Clean Energy Utilization Institute for Thermal Power EngineeringZhejiang UniversityHangzhou 310027China

Industrial-use VOx-based catalysts usually have a higher active temperature window (>250-300℃),which becomes a“bottleneck”for the practical application of PCDD/Fs catalytic degradation technology.In this work,VO_(x)-FeO_(x)/TiO_(2) catalyst prepared via mechanochemically method was investigated for the catalytic removal of PCDD/Fs.The removal efficiency of 1,2-DCBz,pure PCDD/Fs gas generated in the lab,PCDD/Fs from actual fue gas,long-term were studied,and the degradation mechanism was explored using FTIR and TOFMS.The degradation efficiency of 1,2-DCBz and PCDD/Fs on VO_(x)-FeO_(x)/TiO_(2) were higher than that of VO_(x)/TiO_(2)catalyst,and the optimal FeOx addition ratio was 3 wt.%.The characterization results show that the addition of FeOx can effectively improve the pore structure,surface acidity,and VOx dispersion of the catalyst,thus contributing to increasing the V^(5+)content and surface-active oxygen,which is conducive to the improvement of adsorption and redox performance of the catalyst.Under the actual MSWI (municipal solid waste incineration)fue gas,the PCDD/Fs removal efficiency over VTi-3Fe-MC maintained long-term stability,higher than 85%for 240 min.This result was not significantly reduced compared with the data obtained in the laboratory.According to the analysis results of intermediate products by FTIR and GC-TOFMS,it can be inferred that the epoxidation fracture of benzene ring is the rate-limiting step of dioxin catalytic degradation reaction.This work gives an in-depth view into the PCDD/Fs removal over VO_(x)-FeO_(x)/TiO_(2) catalysts and could provide guidelines for the rational design of reliable catalysts for industrial applications.

关键词： PCDD/F removal MSWI fue gas VO_(x)-FeO_(x)/TiO_(2) Mechanochemical GC-TOFMS

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