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iRGD decorated liposomes:A novel actively penetrating topical ocular drug delivery strategy

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Nano Research 2020年第11期13卷 3105-3109页

作者： Hai Huang Xiaorong Yang Huili Li Hansi Lu James Oswald Yongmei Liu Jun Zeng Chaohui Jin Xingchen Peng Jiyan Liu Xiangrong Song Outpatient department Department of Critical Care MedicineNational Clinical Research Center for GeriatricsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu610041China School of Nanotechnology Engineering University of WaterlooWaterlooONN2L 3G1Canada

Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular drug administration,topical administration results in a drug bioavailability of less than 1%.iRGD modified drug delivery strategies have been developed for cancer therapy,however active targeting iRGD platforms for ocular drug delivery have yet to be ***,an iRGD modified liposomes was developed for ocular drug delivery via topical *** results indicated that iRGD modified liposomes could prolong the corneal retention time and enhance corneal permeability in an iRGD receptor mediated *** findings provided a novel strategy for topical ocular drug delivery for the treatment of posterior ocular diseases.

关键词： ocular drug delivery iRGD decorated liposomes active corneal permeability topical drops

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong department of Colorectal Cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely ***9,a key regulator of transcription,may influence the occurrence and progression of *** expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in *** normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor ***,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this *** To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and *** We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of *** also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma *** The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy *** analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal *** This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

Mechanism of cancer: Oncohistones in action

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Journal of Genetics and Genomics 2018年第5期45卷 227-236页

作者： Lei Qiu Xiaoyan Hu Qian Jing Xinyi Zeng Kui-Ming Chan Junhong Han department of Abdominal Oncology State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center department of Biomedical Sciences City University of Hong Kong

Oncohistones are histones with high-frequency point mutations that are associated with tumorigenesis. Although each histone variant is encoded by multiple genes, a single mutation in one allele of one gene seems to have a dominant effect over global histone H3 methylation level at the relevant amino acid residue. These oncohistones are highly tumor type specific. For example, H3K27M and H3G34V/R mutations occur only in pediatric brain cancers, whereas H3K36M and H3G34W/L have only been found in pediatric bone tumors. H1 mutations also seem to be exclusively linked to lymphomas. In this review, we discuss the occurrence, frequency and potential functional mechanisms of each oncohistone in tumorigenesis of its relevant cancer. We believe that further investigation into the mechanism regarding their tumor type specificity and cancer-related functions will shed new light on their application in cancer diagnosis and targeted therapy development.

关键词： Oncohistone Histone modification Tumorigenesis Pediatric cancer

Cellular mechanotransduction in health and diseases:from molecular mechanism to therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3705-3736页

作者： Xingpeng Di Xiaoshuai Gao Liao Peng Jianzhong Ai Xi Jin Shiqian Qi Hong Li Kunjie Wang Deyi Luo department of Urology and Institute of Urology National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduP.R.China State Key Laboratory of biotherapy and Cancer center West China HospitalSichuan UniversityChengduP.R.China

Cellular mechanotransduction,a critical regulator of numerous biological processes,is the conversion from mechanical signals to biochemical signals regarding cell activities and *** mechanical cues in organisms include hydrostatic pressure,fluid shear stress,tensile force,extracellular matrix stiffness or tissue elasticity,and extracellular fluid *** has been expected to trigger multiple biological processes,such as embryonic development,tissue repair and ***,prolonged excessive mechanical stimulation can result in pathological processes,such as multi-organ fibrosis,tumorigenesis,and cancer immunotherapy *** the associations between mechanical cues and normal tissue homeostasis or diseases have been identified,the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated,and no effective therapies are currently available targeting mechanical cue-related *** review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated *** key effectors responding to mechanical stimulations are listed,such as Piezo channels,integrins,Yes-associated protein(YAP)/transcriptional coactivator with PDZ-binding motif(TAZ),and transient receptor potential vanilloid 4(TRPV4).We also reviewed the key signaling pathways,therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.

关键词： diseases stimulation therapeutic

Near-infrared responsive 5-fluorouracil and indocyanine green loaded MPEG-PCL nanoparticle integrated with dissolvable microneedle for skin cancer therapy

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Bioactive Materials 2020年第3期5卷 542-552页

作者： Ying Hao YuWen Chen XinLong He Fan Yang RuXia Han ChengLi Yang Wei Li ZhiYong Qian State Key Laboratory of biotherapy and Cancer center West China HospitalSichuan Universityand Collaborative Innovation Center of BiotherapyChengdu610041PR China department of Dermatovenereology West China HospitalSichuan UniversityChengdu610041PR China

The prevalence of skin cancer is rising along with the rapid population aging in recent *** therapies,such as surgical treatment,radiotherapy,chemotherapy,photodynamic therapy,and immunotherapy,may accompany serious side effects,limiting their clinical *** to the biological characteristics of skin cancer,we have already established two kinds of synergetic systems of photothermal therapy(microneedle)and chemotherapy,containing gold nanorods(GNR).Although the microneedle system exhibited great potential for skin cancer treatment,the system could be still improved ***,we designed a near-infrared lightresponsive 5-fluorouracil(5-Fu)and indocyanine green(ICG)loaded monomethoxy-poly(ethylene glycol)-polycaprolactone(MPEG-PCL)nanoparticle(5-Fu-ICG-MPEG-PCL),and then 5-Fu-ICG-MPEG-PCL was integrated with a hyaluronic acid dissolvable microneedle system(HA MN)to get 5-Fu-ICG-MPEG-PCL loaded HA MN for treating skin cancers,including human epidermoid cancer and *** this system,hyaluronic acid,the microneedle carrier,possesses good skin penetration ability and is approved by FDA as a pharmaceutical adjuvant;5-Fu is recommended by FDA for skin cancer treatment;ICG,a photothermal agent,possesses a strong photothermal ability and is approved by FDA for its use in the human *** hypothesized that 5-Fu-ICG-MPEG-PCL could be delivered by the dissolvable microneedle through the skin,and the release behavior of the drug in the nanoparticle could be controlled by near-infrared light for achieving a single-dose cure of skin cancer,improving the cure rate of skin cancer and providing a new idea and possibility for the clinical treatment of skin cancer.

关键词： 5-Fluorouracil(5-Fu) Indocyanine green(ICG) Monomethoxy-poly(ethylene glycol)- polycaprolactone(MPEG-PCL) Hyaluronic acid dissolvable microneedle(HA MN) Skin cancer

Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer's disease:a systematic review and meta-analysis

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Translational Neurodegeneration 2021年第1期10卷 112-125页

作者： Xulong Ding Shuting Zhang Lijun Jiang Lu Wang Tao Li Peng Lei department of Neurology and State Key Laboratory of biotherapy/Collaborative Innovation center for biotherapy National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China department of Neurology West China HospitalSichuan UniversityChengdu 610041China Mental Health center and West China Brain Research center West China HospitalSichuan UniversityChengdu 610041China department of Rehabilitation Medicine West China HospitalSichuan UniversityChengdu 610041China

A lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer's disease(AD).Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral *** we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181(ptau181)using four ultrasensitive ***-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls,and that the plasma tau and ptau181 could predict AD with high-accuracy area under curve of the Receiver Operating Characteristic Therefore,plasma tau and plasma ptau181 can be considered as biomarkers for AD diagnosis.

关键词： Tau Phosphorylated tau 181 Alzheimer's disease Simoa IMR EIMAF/a-EIMAF MSD Plasma biomarker

S19W,T27W,and N33OY mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3096-3107页

作者： Fei Ye Xi Lin Zimin Che Fanli Yang Sheng Lin Jing Yang Hua Chen Honglu Sun Lingling Wang Ao Wen Xindan Zhang Yushan Dai Yu Cao Jingyun Yang Guobo Shen Li Yang Jiong Li Zhenling Wang Wei Wang Xiawei Wei Guangwen Lu West China Hospital Emergency department(WCHED) State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuanChina Disaster Medicine center West China HospitalSichuan UniversityChengduSichuanChina Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuanChina

SARS-CoV-2 recognizes,via its spike receptor-binding domain(S-RBD),human angiotensin-converting enzyme 2(ACE2)to initiate ***-domain protein of ACE2 can therefore function as a *** we show that mutations of S19W,T27W,and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding.Y330 could be synergistically combined with either W19 or W27,whereas W19 and W27 are mutually *** structures of SARS-CoV-2S-RBD bound to the ACE2 mutants reveal that the enhan ced binding is mainly con tributed by the van der Waals interactio ns mediated by the aromatic side-chai ns from W19,W27,and *** Y330 and W19/W27 are distantly located and devoid of any steric interference,W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts,explai ning their in ***,using pseudotyped SARS-CoV-2 viruses,we dem on strate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant *** together,our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W,T27W,and N330Y mutations in ACE2,paving the way for potential application of these mutants in dinical treatment of COVID-19.

关键词： ACE2 elevated RBD

The diameter factor of aligned membranes facilitates wound healing by promoting epithelialization in an immune way

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Bioactive Materials 2022年第5期7卷 206-217页

作者： Chenbing Wang Chenyu Chu Xiwen Zhao Yang Yang Chen Hu Li Liu Jidong Li Yili Qu Yi Man department of Oral Implantology&National clinical Research center for Oral Diseases&State Key Laboratory of Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Research center for Nano-Biomaterials Analytical and Testing CenterSichuan UniversityChengdu 610064China State Key Laboratory of biotherapy West China HospitalSichuan UniversityCollaborative Innovation Center for BiotherapyChengduSichuan 610041China

Topographical properties,such as pattern and diameter,of biomaterials play important roles in influencing cell activities and manipulating the related immune response during wound *** prepared aligned electrospinning membranes with different fiber diameters,including 319±100 nm(A300),588±132 nm(A600),and 1048±130 nm(A1000),by adjusting the distance from the tip to the collector,the injection rate,and the concentration of the *** A300 membranes significantly improved cell proliferation and spreading and facilitated wound healing(epithelization and vascularization)with the regeneration of immature hair follicles compared to the other *** revealed the underlying molecular mechanism that A300 could promote immune-related processes towards a pro-healing direction,significantly promoting keratinocyte migration and skin wound *** the results indicated that wound healing requires the active participation of the immune process,and that A300 was a potential candidate for guided skin regeneration applications.

关键词： Aligned membranes Diameter Wound healing Epithelialization MMP12

Immunostimulatory CKb11 gene combined with immune checkpoint PD-1/PD-L1 blockade activates immune response and simultaneously overcomes the immunosuppression of cancer

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Bioactive Materials 2024年第9期39卷 239-254页

作者： Wen Nie Yihong He Xue Mi Shi He Jing Chen Yunchu Zhang Bilan Wang Songping Zheng Zhiyong Qian Xiang Gao department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for Biotherapy610041ChengduPR China department of Pharmacy West China Second University Hospital of Sichuan University610041ChengduPR China

Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of *** study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells,resulting in high CKb11 secretion from tumor cells,successfully activating immune cells and increasing cytokine secretion to reshape the TME,and ultimately delaying tumor *** chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in *** can cause high expression of IFN-γ,which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor ***,combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense,leading to a collaborative anti-tumor ***,utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites,thereby reshaping immunosuppressive TME for cancer treatment,has great potential as an immunogene therapy in clinical applications.

关键词： Ovarian cancer Immunogene therapy CKb11 Immune checkpoint PD-1/PD-L1 Nanomedicine