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Strategies for the development and approval of COVID-19 vaccines and therapeutics in the post-pandemic period

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Signal Transduction and Targeted Therapy 2024年第1期9卷 19-35页

作者： Danyi Ao Xuemei He Jian Liu Li Xu state Key Laboratory of Biotherapy West China HospitalSichuan University610041 SichuanPeople’s Republic of China

The spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in significant casualties and put immense strain on public health systems worldwide,leading to economic recession and social *** response,various prevention and control strategies have been implemented globally,including vaccine and drug development and the promotion of preventive *** these strategies has effectively curbed the transmission of the virus,reduced infection rates,and gradually restored normal social and economic ***,the mutations of SARS-CoV-2 have led to inevitable infections and reinfections,and the number of deaths continues to ***,there is still a need to improve existing prevention and control strategies,mainly focusing on developing novel vaccines and drugs,expediting medical authorization processes,and keeping epidemic *** measures are crucial to combat the Coronavirus disease(COVID-19)pandemic and achieve sustained,long-term prevention,management,and disease ***,we summarized the characteristics of existing COVID-19 vaccines and drugs and suggested potential future directions for their ***,we discussed the COVID-19-related policies implemented over the past years and presented some strategies for the future.

关键词： prevention sustained approval

The use of fluoroscopy for detecting hypertensive lung edema due to prosthetic valve dysfunction: a case report

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World Journal of Emergency Medicine 2024年第4期15卷 313-315页

作者： Yusuf Kantar Necmi Baykan Emergency Department Akçaabat Haçkalibaba State HospitalTrabzon 61060Turkiye Emergency Department Kayseri City HospitalKayseri 38080Turkiye

Heart valve diseases affect more than one hundred million people around the world,which are a serious cause of illness and mortality.[1]Among the valve diseases,mitral valve insufficiency ranks second in the list of valve diseases requiring surgical repair in Europe.[2]Prosthetic valve replacement is the standard treatment in cases where repair is not sufficient for valve diseases.[3]Mechanical and bioprosthetic valves can be preferred for replacement,mechanical valves are more durable and require lifelong use of *** disadvantage of bioprosthetic valves is early degeneration,and infective reoperation is required due to the formation of endocarditis.[4-5]The risk of thromboembolism,lifetime anticoagulant use and complications related to anticoagulation remain disadvantages of valve surgery.[3]The most important complication requiring urgent intervention is valve dysfunction due to *** usually occurs due to inappropriate use of the anticoagulants.[6]Surgical treatment is used for severe obstructions,such as thrombi larger than 10 *** therapy can be applied in small thrombi and in cases where surgical intervention is risky.

关键词： valve disadvantage lifetime

Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

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Acta Pharmaceutica Sinica B 2024年第2期14卷 821-835页

作者： Liping Bai Jin Yang Siting Yu Zhongzheng Xiang Yuanyuan Zeng Meiling Shen Xiaorong Kou Qinjie Wu Changyang Gong Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor ***,RT-induced antitumor immunologic responses are sporadic and insufficient against cancer ***,we construct multifunctional self-sufficient nanoparticles(MARS) with dual-enzyme activity(GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic *** addition to limiting the Warburg effect to actualize starvation therapy,MARS catalyzes glucose to produce hydrogen peroxide(H_(2)O_(2)),which is then used in the Cu^(+)-mediated Fenton-like reaction and RT *** and chemodynamic therapy produce reactive oxygen species in the form of radical storms,which have a robust ICD impact on mobilizing the immune ***,when MARS is combined with RT,potent systemic antitumor immunity can be generated by activating antigen-presenting cells,promoting dendritic cells maturation,increasing the infiltration of cytotoxic T lymphocytes,and reprogramming the immuno suppre ssive tumor ***,the synergistic therapy of RT and MARS effectively suppresses local tumor growth,increases mouse longevity,and results in a 90% reduction in lung metastasis and postoperative ***,we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

关键词： Dual-enzyme activity Radiotherapy Chemodynamic therapy Fenton-likereaction Radical storms Immunogeniccell death Tumormicroenvironment Systemicimmunity

Drug delivery systems for colorectal cancer chemotherapy

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Chinese Chemical Letters 2024年第2期35卷 163-175页

作者： Wen Chen Kun Shi Yan Yu Peipei Yang Zhongwu Bei Dong Mo Liping Yuan Meng Pan Yu Chen Zhiyong Qian Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Colorectal cancer causes the third most common type of malignant tumors with high morbidity and *** is currently one of the most effective and common treatments for colorectal ***,the poor water solubility of some chemotherapeutics,untargeted drug delivery,and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer ***,drug delivery systems(DDS)based on biomaterials have been widely investigated and found to be capable of resolving those issues with good ***,the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer *** not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics,including liposomes,micelles,and nanoparticles,but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus ***,locally administered systems based on hydrogels and microspheres,which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity,were also *** provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.

关键词： Colorectal cancer Chemotherapy Drug delivery systems Solubility Targeted Local administration

Fc receptor-like 5(FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma

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Signal Transduction and Targeted Therapy 2024年第2期9卷 724-737页

作者： Zhengyu Yu Hexian Li Qizhong Lu Zongliang Zhang Aiping Tong Ting Niu Department of Hematology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Multiple myeloma(MM)remains a challenging hematologic malignancy despite advancements in chimeric antigen receptor T-cell(CAR-T)*** targets of CAR-T cells used in MM immunotherapy have limitations,with a subset of patients experiencing antigen loss resulting in ***,novel targets for enhancing CAR-T cell therapy in MM remain *** receptor-like 5(FCRL5)is a protein marker with considerably upregulated expression in MM and has emerged as a promising target for CAR-T cell therapeutic interventions,offering an alternative treatment for *** further explore this option,we designed FCRL5-directed CAR-T cells and assessed their cytotoxicity in vitro using a co-culture system and in vivo using MM cell-derived xenograft models,specifically focusing on MM with gain of chromosome *** the challenges in CAR-T therapies arising from limited T cell persistence,our approach incorporates interleukin-15(IL-15),which enhances the functionality of central memory T(TCM)cells,into the design of FCRL5-directed CAR-T cells,to improve cytotoxicity and reduce T-cell dysfunction,thereby promoting greater CAR-T cell survival and *** in vitro and xenograft models displayed that FCRL5 CAR-T cells incorporating IL-15 exhibited potent antitumor efficacy,effectively inhibiting the proliferation of MM cells and leading to remarkable tumor *** results highlight the capacity of FCRL5-specific CAR-T cells with the integration of IL-15 to improve the therapeutic potency,suggesting a potential novel immunotherapeutic strategy for MM treatment.

关键词： directed thereby offering

Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2999-3014页

作者： Yun Yang Qingya Liu Meng Wang Lang Li Yan Yu Meng Pan Danrong Hu Bingyang Chu Ying Qu Zhiyong Qian Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Cell membrane-camouflaged nanoparticles possess inherent advantages derived from their membrane structure and surface antigens,including prolonged circulation in the bloodstream,specific cell recognition and targeting capabilities,and potential for ***,we introduce a cell membrane biomimetic nanodrug platform termed MPB-3BP@CM *** microporous Prussian blue nanoparticles(MPB NPs)serving as both a photothermal sensitizer and carrier for 3-bromopyruvate(3BP),these nanoparticles are cloaked in a genetically programmable cell membrane displaying variants of signal regulatory proteinα(SIRPα)with enhanced affinity to *** a result,MPB-3BP@CM NPs inherit the characteristics of the original cell membrane,exhibiting an extended circulation time in the bloodstream and effectively targeting CD47 on the cytomembrane of colorectal cancer(CRC)***,blocking CD47 with MPB-3BP@CM NPs enhances the phagocytosis of CRC cells by ***,3BP,an inhibitor of hexokinase II(HK2),suppresses glycolysis,leading to a reduction in adenosine triphosphate(ATP)levels and lactate ***,it promotes the polarization of tumor-associated macrophages(TAMs)towards an anti-tumor M1 ***,integration with MPB NPs-mediated photothermal therapy(PTT)enhances the therapeutic efficacy against *** advantages make MPB-3BP@CM NPs an attractive platform for the future development of innovative therapeutic approaches for ***,it introduces a universal approach for engineering disease-tailored cell membranes for tumor therapy.

关键词： CD47 colorectal cancer

A non-viral gene therapy for melanoma by staphylococcal enterotoxin A

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Chinese Chemical Letters 2024年第5期35卷 325-329页

作者： Ling Yang Min Ren Jie Wang Liming He Shanshan Wu Shuai Yang Wei Zhao Hao Cheng Xiaoming Zhou Maling Gou state Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610041China state Key Laboratory of Biotherapy Department of Integrated Traditional Chinese and Western MedicineRare Diseases CenterWest China HospitalSichuan UniversityChengdu 610041China

Staphylococcal enterotoxin A(SEA)derived from Staphylococcus aureus,as a superantigen,shows potential for cancer immunotherapy,but systemic immunotoxicity restricts its clinical *** delivery of SEA to tumor site provides a promising option for reducing the systemic ***,we constructed an iRGD peptide(H-[Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys]-NH_(2))modified nanoparticle(iDPP)to deliver plasmids encoding SEA for melanoma *** iDPP/SEA nanocomplexes efficiently mediated SEA expression in B16-F10 cells in vivo and in vitro and induced the activation of lymphocytes and maturation of murine bone marrow-derived dendritic cells(BMDCs)in *** the subcutaneous B16-F10 melanoma model,the iDPP/SEA nanocomplexes could effectively enhance immune response and T lymphocytes infiltration in tumor site after intravenous administration,thereby considerably decreased melanoma ***,no obvious adverse effect was observed after intravenous administration of the iDPP/SEA nanocomplexes in *** findings demonstrated that gene therapy of SEA is a potential candidate for melanoma treatment.

关键词： Gene therapy Superantigen Melanoma Staphylococcal enterotoxins A Immunotherapyene therapy

Carcinoembryonic antigen in the diagnosis,treatment,and follow-up of focal liver lesions

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 999-1007页

作者： Osman Nuri Dilek Dilaraİrem Arslan Kahraman Gökhan Kahraman Department of Surgery İzmir Katip Celebi UniversitySchool of Medicineİzmir 35150Turkey Department of Patology Merzifon KMP State HospitalAmasya 5300Turkey Department of Radiology Suluova State HospitalAmasya 5500Turkey

In this editorial review,we comment on the article published in the recent issue of the World Journal of Gastrointestinal *** antigen(CEA)is a fetal glycoprotein and can be secreted in very small amounts from healthy adults after *** is widely used not only for diagnostic tumor markers but also importantly for the management of some gastrointestinal *** most common clinical use is surveillance for the monitoring of colorectal ***,CEA can become elevated in several malign or benign characterized *** CEA level may vary depending on the location of the lesion,whether it metastasizes or not,and its histopathological *** has been determined that cases with high preoperative CEA have a more aggressive course and the risk of metastasis to the lymph tissue and liver *** this editorial review,we focused on evaluating the role of CEA in clinical practice with a holistic approach,including the diagnostic and prognostic significance of CEA in patients with focal liver lesions,the role of CEA in follow-up after definitive surgery,and also hepatic resection for metastasis,and the management of all patients with raised CEA.

关键词： Carcinoembriyonic antigen Liver Focal liver lesions Metastasis Surgery Prognosis Surveillance

Recent Advances in Nickel Catalyzed Carbonylative Reactions via the Insertion of Carbon Monoxide

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Chinese Journal of Chemistry 2024年第2期42卷 177-189页

作者： Xinzhou Chen Gang Chen Zhong Lian Department of Dermatology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610041China

Carbonyl compounds have attracted considerable attention due to their extensive applications in drug ***,they are important synthetic intermediates for the construction of carbon-carbon and carbon-heteroatom ***-metal-catalyzed carbonylation via the insertion of co is one of the most efficient and straightforward strategies to access carbonyl ***,most of the transition-metal-catalyzed carbonylative reactions require expensive and toxic noble-metal ***,there is a growing demand for the exploration of nickel-catalyzed carbonylative reactions via the insertion of CO due to the earth abundance and low cost of *** with the well-established palladium-catalyzed carbonylative reactions,nickel-catalyzed analogous transformations have been relatively *** is primarily because CO strongly binds to nickel,often resulting in catalyst *** recent years,some research groups have focused on using CO surrogates or NN_(2) pincer nickel catalyst to circumvent the formation of Ni(CO)_(4).Nickel-catalyzed carbonylation has been applied in the construction of carbonyl-containing compounds,such as ketones,carboxylic acids,thioesters,acyl chloride and carboxamides.

关键词： Carbonylation Nickel catalysis Carbon monoxide C1 chemistry Carbonyl-containing compounds