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A multi-parameter-induced activation of gas therapeutic platform to remarkably amplify photodynamic therapy efficacy

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Science China Chemistry 2024年第7期67卷 2403-2411页

作者： Jie Sun Ziwen Zhang Hongyu Wu Xuemei Dong Chengjun Dong Lixin Sun Zhiqian Guo Yingchao Liu Xianfeng Gu Chunchang Zhao Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center Institute of Fine ChemicalsSchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China shandong provincial hospital affiliated to shandong first medical university Shandong First Medical University&Shandong Academy of Medical ScienceJinan 250021China

Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT *** uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological ***,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT *** nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)*** importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor *** H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT *** expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic *** multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.

关键词： gas therapy precision gas release hydrogen sulfide depletion photodynamic therapy multimodal synergistic therapy

Regulation of protein thermal stability and its potential application in the development of thermo-attenuated vaccines

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Engineering Microbiology 2024年第3期4卷 16-21页

作者： Maofeng Wang Cancan Wu Nan Liu Xiaoqiong Jiang Hongjie Dong Shubao Zhao Chaonan Li Sujuan Xu Lichuan Gu State Key Laboratory of Microbial Technology Shandong UniversityQingdao 266237China Research Center of Translational Medicine Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013China Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China shandong Institute of Parasitic Diseases Shandong First Medical University&Shandong Academy of Medical SciencesJining 272033China

The coronavirus disease 2019(COVID-19)pandemic has highlighted the importance of developing novel *** ideal vaccine should trigger an intense immune reaction without causing significant side *** this study we found that substitution of tryptophan located in the cores of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)protein structures with certain smaller amino acids resulted in variants with melting temperatures of 33-37℃.An enzyme activity assay indicated that the proteolytic activity of the main proteinase(3CLpro)decreased sharply when the environmental temperature exceeded the melting temperature,implying that other protein variants may lose most of their functions under the same *** finding suggests that a virus variant containing engineered proteins with melting temperatures of 33-37℃ may only be functional in the upper respiratory tract where the temperature is about 33℃,but will be unable to invade internal organs,which maintain temperatures above 37℃,thus making it possible to construct temperature-sensitive attenuated vaccines.

关键词： Protein melting temperature Enzyme activity SARS-CoV-2 N protein 3CL^(pro) Temperature sensitive attenuated vaccines

Pleural effusion,ascites,colon ulcers and hematochezia:What we can learn from the diagnostic process of a patient with plasma cell myeloma:A case report

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World Journal of Clinical Cases 2024年第22期12卷 5196-5207页

作者： Ming-Xian Yan Department of Gastroenterology The First Affiliated Hospital of Shandong First Medical UniversityShandong Provincial Qianfoshan HospitalJinan 250014Shandong ProvinceChina

BACKGROUND Plasma cell myeloma(PCM)is characterized by hypercalcemia,renal impairment,anemia,and bone *** pleural effusion,ascites,abdominal pain,and bloody stool are common manifestations of lung disease or gastrointestinal disorders,they are rarely observed in patients with *** SUMMARY A 66-year-old woman presented with complaints of recurrent chest tightness,wheezing,and abdominal bloating accompanied by bloody *** tomography revealed pleural effusion and *** effusion tests showed inflammation,but the T-cell spot test and carcinoembryonic antigen were *** showed colonic mucosal edema with ulcer formation and local intestinal lumen *** revealed enlarged atria and reduced left ventricular systolic *** diagnosis remained *** testing revealed elevated blood light chain lambda and urine immunoglobulin *** immunofixation electrophoresis was positive for immunoglobulin G lambda *** cytology of the bone marrow showed a high proportion of plasma cells,accounting for about 4.5%.Histopathological examination of the bone marrow suggested *** cytometry showed abnormal plasma cells with strong expression of CD38,CD138,cLambda,CD28,CD200,and *** in situ hybridization gene testing of the bone marrow suggested 1q21 gene amplification,but cytogenetic testing showed no clonal *** mucosa and bone marrow biopsy tissues were negative for Highman Congo red *** patient was finally diagnosed with *** A diagnosis of PCM should be considered in older patients with pleural effusion,ascites,and multi-organ injury.

关键词： Plasma cell myeloma Pleural effusion Ascites Hematochezia Colon ulcers Bone marrow aspirate Case report

Sirt5 desuccinylates Cdc42 to mediate osteoclastogenesis and bone remodeling in mice

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Genes & Diseases 2024年第3期11卷 75-78页

作者： Yuang Zhanngg Jing Wang Jing Luan Chuanju Liu Yazhou Cui Jinxiang Han Department of Orthopedics The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalJi'nanShandong 250014China Biomedical Sciences College&shandong Medicinal Biotechnology Centre Shandong First Medical University&Shandong Academy of Medical SciencesJi'nanShandong 250117China NHC Key Laboratory of Biotechnology Drugs(shandong Academy of medical Sciences) Ji'nanShandong 250117China Key Lab for Rare&Uncommon Diseases of shandong Province Ji'nanShandong250117China Department of Orthopaedic Surgery New York University Grossman School of MedicineNew YorkNY 10003USA Department of Cell Biology New York University Grossman School of MedicineNewYorkNY10016USA

Post-translational modifications(PTMs)play a critical role in bone remodeling,with phosphorylation and acetylation being particularly well ***,succinylation,a relatively uncommon PTM on lysine,has received considerable research attention for its influence on several physiological and pathological processes and conditions.1 Several substrates involved in mitochondrial pathways have been validated as substrates for the desuccinylase sirtuin 5(Sirt5),a key regulator of succinylation.2 Bone is one of the most metabolically active organs,but the role of succinylation during bone remodeling is not well characterized.

关键词： remodeling organs media

Complement factor H in molecular regulation of angiogenesis

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medical Review 2024年第5期4卷 452-466页

作者： Jiang Li Kaili Wang Maria N.Starodubtseva Eldar Nadyrov Carolyn M.Kapron Josephine Hoh Ju Liu Laboratory of Translational Medicine in Microvascular Regulation Institute of Microvascular MedicineMedical Research CenterThe First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalJinanShandong Province250014China shandong provincial Key medical and Health Laboratory of Translational Medicine in Microvascular Aging JinanShandong ProvinceChina medical Research Center Shandong Provincial Qianfoshan HospitalShandong UniversityJinanShandong Province 250014China Gomel State medical university GomelBelarus Institute of Radiobiology of NAS of Belarus GomelBelarus Department of Biology Trent UniversityPeterboroughONCanada Department of Ophthalmology Yale School of MedicineNew HavenCTUSA

Angiogenesis,the process of formation of new capillaries from existing blood vessels,is required for multiple physiological and pathological *** factorH(CFH)is a plasma protein that inhibits the alternative pathway of the complement *** of CFH enhances the alternative pathway and increases complement activation fragments with pro-angiogenic capacity,including complement 3a,complement 5a,and membrane attack *** protein contains binding sites for C-reactive protein,malondialdehyde,and endothelial heparan *** of CFH prevents its interaction with these molecules and initiates pro-angiogenic *** in the CFH gene have been found in patients with age-related macular degeneration characterized by choroidal *** Cfh-deficient mice show an increase in angiogenesis,which is decreased by administration of recombinant CFH pro*** this review,we summarize the molecular mechanisms of the anti-angiogenic effects of CFH and the regulatory mechanisms of CFH *** therapeutic potential of recombinant CFH protein in angiogenesisrelated diseases has also been discussed.

关键词： complement factor H angiogenesis mechanical properties therapeutic target

Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

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Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu Department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China shandong provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease Jinan 250033China Department of Pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China Department of Pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is ***: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance

关键词： Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

Injectable“cocktail”hydrogel with dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic effect

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SmartMat 2024年第2期5卷 43-53页

作者： Li Zhao Jiawen Xu Yao Tong Pengyu Gong Fucheng Gao Hui Li Yanyan Jiang Key Laboratory for Liquid-Solid Structural Evolution&Processing of Materials(Ministry of Education) School of Materials Science and EngineeringShandong UniversityJinanChina Department of Pathology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanChina Department of Clinical Laboratory The Second HospitalCheeloo College of MedicineShandong UniversityJinanChina

The combination of the first-line standard chemotherapeutic drug doxorubicin hydrochloride(DOX)and the molecular-targeted drug Herceptin(HCT)has emerged as a promising strategy for human epidermal growth receptor 2(HER-2)overexpressing breast cancer ***,insufficient drug accumulation and severe cardiotoxicity are two major challenges that limit its clinical ***,an in situ forming gold nanorods(AuNRs)-sodium alginate(ALG)hybrid hydrogel encapsulating DOX and HCT was engineered for tumor synergistic therapy involving injectable,dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic *** photothermal agent AuNRs,anticancer drug DOX,and anticancer antibody HCT were mixed in ALG solution,and after injection,the soluble ALG was quickly transformed into a hydrogel in the presence of Ca^(2+)in the ***,the hybrid hydrogel exhibits an extremely high photothermal conversion efficiency of 70%under 808 nm laser *** thermal effect can also provide photothermal stimulation to trigger the drug release from the gel *** addition,the drug release rate and the releasing degree are also sensitive to the *** vitro studies demonstrated that the PEI-AuNR/DOX/HCT/ALG hydrogel has facilitated the therapeutic efficiency of each payload and demonstrated a strong synergistic killing effect on SK-BR-3 *** vivo imaging results showed that the local drug delivery system can effectively reduce the nonspecific distribution in normal tissues and increase drug concentration at tumor *** proposed hydrogel system shows significant clinical implications by easily introducing a sustainable photothermal therapy and a potential universal carrier for the local delivery of multiple drugs to overcome the challenges faced in HER-2 overexpressing cancer therapy.

关键词： dual-stimuli-responsive drug release HER-2 overexpressing breast cancer injectable hydrogel photothermal therapy synergistic effect

Nomogram predicting the cardiovascular disease mortality for older patients with colorectal cancer:A real-world population-based study

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World Journal of Cardiology 2024年第8期16卷 458-468页

作者： Jia-Yu Tan Shuo-Hao Shen Department of medical Ultrasound The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalJinan 250000Shandong ProvinceChina Department of General Surgery Qilu Hospital of Shandong UniversityJinan 250000Shandong ProvinceChina

BACKGROUND Cardio-oncology has received increasing attention especially among older patients with colorectal cancer(CRC).Cardiovascular disease(CVD)-specific mortality is the second-most frequent cause of *** risk factors for CVDspecific mortality among older patients with CRC are still poorly *** To identify the prognostic factors and construct a nomogram-based model to predict the CVD-specific mortality among older patients with *** The data on older patients diagnosed with CRC were retrieved from The Surveillance,Epidemiology,and End Results database from 2004 to *** prognostic factors and a nomogram-based model predicting the CVD-specific mortality were assessed using least absolute shrinkage and selection operator and Cox *** A total of 141251 eligible patients with CRC were enrolled,of which 41459 patients died of CRC and 12651 patients died of *** age at diagnosis,sex,marital status,year of diagnosis,surgery,and chemotherapy were independent prognostic factors associated with CVD-specific mortality among older patients with *** used these variables to develop a model to predict CVD-specific *** calibration curves for CVD-specific mortality probabilities showed that the model was in good agreement with actual *** C-index value of the model in the training cohort and testing cohort for predicting CVD-specific mortality was 0.728 and 0.734,*** The proposed nomogram-based model for CVD-specific mortality can be used for accurate prognostic prediction among older patients with *** model is a potentially useful tool for clinicians to identify high-risk patients and develop personalized treatment plans.

关键词： Older patients Colorectal cancer Cardio-oncology Nomogram Outcome

Characterization of humoral immune responses against SARS-CoV-2 accessory proteins in infected patients and mouse model

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Virologica Sinica 2024年第3期39卷 414-421页

作者： Yuming Li Yanhong Tang Xiaoqian Wang Airu Zhu Dongdong Liu Yiyun He Hu Guo Jie Zheng Xinzhuo Liu Fengyu Chi Yanqun Wang Zhen Zhuang Zhaoyong Zhang Donglan Liu Zhao Chen Fang Li Wei Ran Kuai Yu Dong Wang Liyan Wen Jianfen Zhuo Yanjun Zhang Yin Xi Jingxian Zhao Jincun Zhao Jing Sun School of Public Health Shandong First Medical University&Shandong Academy of Medical SciencesJi'nan250117China Key Laboratory of Emerging Infectious Diseases in Universities of shandong Shandong First Medical University&Shandong Academy of Medical SciencesJi'nan250117China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong510182China Hunan provincial People's hospital The First Affiliated Hospital of Hunan Normal UniversityHunan Normal UniversityChangsha410005China Guangzhou National Laboratory GuangzhouGuangdong510005China Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghai Tech UniversityShanghai201210China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalThe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen518005China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of COVID-19,encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune ***,their expressions in infected cells and immunogenicity in infected humans and mice are still not fully *** study utilized various techniques such as luciferase immunoprecipitation system(LIPS),immunofluorescence assay(IFA),and western blot(WB)to detect accessory protein-specific antibodies in sera of COVID-19 *** antibodies to proteins 3a,3b,7b,8 and 9c can be detected by LIPS,but only protein 3a antibody was detected by IFA or *** against proteins 3a and 7b were only detected in ICU patients,which may serve as a marker for predicting disease ***,we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a,6,7a,8,and *** also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a,6,7a,8,9b and 9c were able to induce measurable antibody productions,but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 *** findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response,providing a basis for protein detection assays and their role in pathogenesis.

关键词： SARS-CoV-2 Accessory protein Humoral immune responses COVID-19 Mouse model