|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Pseudomonas aeruginosa:pathogenesis,virulence factors,antibiotic resistance,interaction with host,technology advances and emerging therapeutics显示文摘Pseudomonas aeruginosa(P.aeruginosa)is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis,burn wounds,immunodeficiency,chronic obstructive pulmonary disorder(COPD),cancer,and severe infection requiring ventilation,such as COVID-19.P.aeruginosa is also a widely-used model bacterium for all biological areas.In addition to continued,intense efforts in understanding bacterial pathogenesis of P.aeruginosa including virulence factors(LPS,quorum sensing,two-component systems,6 type secretion systems,outer membrane vesicles(OMVs),CRISPR-Cas and their regulation),rapid progress has been made in further studying host-pathogen interaction,particularly host immune networks involving autophagy,inflammasome,noncoding RNAs,cGAS,etc.Furthermore,numerous technologic advances,such as bioinformatics,metabolomics,scRNA-seq,nanoparticles,drug screening,and phage therapy,have been used to improve our understanding of P.aeruginosa pathogenesis and host defense.Nevertheless,much remains to be uncovered about interactions between P.aeruginosa and host immune responses,including mechanisms of drug resistance by known or unannotated bacterial virulence factors as well as mammalian cell signaling pathways.The widespread use of antibiotics and the slow development of effective antimicrobials present daunting challenges and necessitate new theoretical and practical platforms to screen and develop mechanism-tested novel drugs to treat intractable infections,especially those caused by multi-drug resistance strains.Benefited from has advancing in research tools and technology,dissecting this pathogen’s feature has entered into molecular and mechanistic details as well as dynamic and holistic views.Herein,we comprehensively review the progress and discuss the current status of P.aeruginosa biophysical traits,behaviors,virulence factors,invasive regulators,and host defense patterns against its infection,which point out new directions for future investigation and add to the design of novel and/or alternative therapeutics to combat this clinically significant pathogen. | Shugang Qin Wen Xiao Chuanmin Zhou Qinqin Pu Xin Deng Lefu Lan Haihua Liang Xiangrong Song Min Wu | 2022 | Signal Transduction and Targeted Therapy2022，7，7： | 5 |
| 2 | Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection显示文摘Bitter receptors function primarily in sensing taste,but may also have other functions,such as detecting pathogenic organisms due to their agile response to foreign objects.The mouse taste receptor type-2 member 138(TAS2R138)is a member of the G-protein-coupled bitter receptor family,which is not only found in the tongue and nasal cavity,but also widely distributed in other organs,such as the respiratory tract,gut,and lungs.Despite its diverse functions,the role of TAS2R138 in host defense against bacterial infection is largely unknown.Here,we show that TAS2R138 facilitates the degradation of lipid droplets(LDs)in neutrophils during Pseudomonas aeruginosa infection through competitive binding with PPARG(peroxisome proliferator-activated receptor gamma)antagonist:A/-(3-oxododecanoyl)-L-homoserine lactone(AHL-12),which coincidently is a virulence-bound signal produced by this bacterium(P.aeruginosa).The released PPARG then migrates from nuclei to the cytoplasm to accelerate the degradation of LDs by binding PLIN2(perilipin-2).Subsequently,the TAS2R138-AHL-12 complex targets LDs to augment their degradation,and thereby facilitating the clearance of AHL-12 in neutrophils to maintain homeostasis in the local environment.These findings reveal a crucial role for TAS2R138 in neutrophil-mediated host immunity against P.aeruginosa infection. | Qinqin Pu Kai Guo Ping Lin Zhihan Wang Shugang Qin Pan Gao Colin Combs Nadeem Khan Zhenwei Xia Min Wu | 2021 | Signal Transduction and Targeted Therapy2021，6，7： | 2 |
| 3 | A novel heterologous receptor-binding domain dodecamer universal mRNA vaccine against SARS-CoV-2 variants显示文摘There are currently approximately 4000 mutations in the SARS-CoV-2 S protein gene and emerging SARS-CoV-2 variants continue to spread rapidly worldwide.Universal vaccines with high efficacy and safety urgently need to be developed to prevent SARS-CoV-2 variants pandemic.Here,we described a novel self-assembling universal mRNA vaccine containing a heterologous receptorbinding domain(HRBD)-based dodecamer(HRBD^(dodecamer))against SARS-CoV-2 variants,including Alpha(B.1.1.7),Beta(B.1.351),Gamma(B.1.1.28.1),Delta(B.1.617.2)and Omicron(B.1.1.529).HRBD containing four heterologous RBD(Delta,Beta,Gamma,and Wild-type)can form a stable dodecameric conformation under T4 trimerization tag(Flodon,FD).The HRBD^(dodecamer)-encoding mRNA was then encapsulated into the newly-constructed LNPs consisting of a novel ionizable lipid(4N4T).The obtained universal mRNA vaccine(4N4T-HRBD^(dodecamer))presented higher efficiency in mRNA transfection and expression than the approved ALC-0315 LNPs,initiating potent immune protection against the immune escape of SARS-CoV-2 caused by evolutionary mutation.These findings demonstrated the first evidence that structure-based antigen design and mRNA delivery carrier optimization may facilitate the development of effective universal mRNA vaccines to tackle SARS-CoV-2 variants pandemic. | Shugang Qin Hai Huang Wen Xiao Kepan Chen Xi He Xiaoshan Tang Zhiying Huang Yupei Zhang Xing Duan Na Fan Qian Zheng Min Wu Guangwen Lu Yuquan Wei Xiawei Wei Xiangrong Song | 2023 | Acta Pharmaceutica Sinica B2023，13，10： | 1 |
| 4 | Interaction among inflammasome,autophagy and non-coding RNAs:new horizons for drug显示文摘Autophagy and inflammasomes are shown to interact in various situations including infectious disease,cancer,diabetes and neurodegeneration.Since multiple layers of molecular regulators contribute to the interplay between autophagy and inflammasome activation,the detail of such interplay remains largely unknown.Non-coding RNAs(ncRNAs),which have been implicated in regulating an expanding list of cellular processes including immune defense against pathogens and inflammatory response in cancer and metabolic diseases,may join in the crosstalk between inflammasomes and autophagy in physiological or disease conditions.In this review,we summarize the latest research on the interlink among ncRNAs,inflammasomes and autophagy and discuss the emerging role of these three in multiple signaling transduction pathways involved in clinical conditions.By analyzing these intriguing interconnections,we hope to unveil the mechanism inter-regulating these multiple processes and ultimately discover potential drug targets for some refractory diseases. | Qinqin Pu Ping Lin Zhihan Wang Pan Gao Shugang Qin Luqing Cui Min Wu | 2019 | Precision Clinical Medicine2019，2，3： | 1 |
| 5 | Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine显示文摘The extraordinary advantages associated with mRNA vaccines,including their high efficiency,relatively low severity of side effects,and ease of manufacture,have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers.Nevertheless,most mRNA delivery carriers have many disadvantages,such as high toxicity,poor biocompatibility,and low efficiency in vivo,which have hindered the widespread use of mRNA vaccines.To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier,a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate(SA).Intriguingly,the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA,which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA.In addition,we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting.Finally,we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E.G7-OVA tumor-bearing mice,dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect.Therefore,we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects. | Xing Duan Yi Zhang Mengran Guo Na Fan Kepan Chen Shugang Qin Wen Xiao Qian Zheng Hai Huang Xiawei Wei Yuquan Wei Xiangrong Song | 2023 | Acta Pharmaceutica Sinica B2023，13，3： | 1 |
| 6 | Oral nanoparticles containing naringenin suppress atherosclerotic progression by targeting delivery to plaque macrophages显示文摘Atherosclerosis is the main cause of ischemic stroke and myocardial infarction diseases.Nanoparticles have shown unique benefits for atherosclerosis treatment by targeting the lesional macrophages of plaques.However,most of the nanocarriers are administered intravenously,which is inconvenient and may cause complications.Herein,we developed an oral lipid-polymer based nanoparticles(FA-LNPs)decorated with folic acid,which can not only effectively overcome intestinal mucosal-epithelial barrier by increasing the transmembrane transport through intestinal epithelial and the accumulation in Peyer’s patches but also actively target to the aortic plaque sites and accumulate in lesional macrophages.Subsequently,naringenin(Nrg),one of the antiinflammation drugs,was designed to be the oral nanomedicine(FA-LNPs/Nrg)for the first time via the encapsulation of FALNPs.FA-LNPs/Nrg presented highly anti-atherosclerotic efficacy.After the atherosclerotic ApoE−/−mice were treated by FALNPs/Nrg via oral administration for three months,the aortic lesion area,plaque area,and necrotic core area of the aortic root were significantly decreased.Meanwhile,the lipid-related blood parameters recovered to normal levels.Our study provides a promising approach to atherosclerosis treatment based on the novel oral targeting delivery system. | Mengran Guo Zhongshan He Zhaohui Jin Lingjing Huang Jingmei Yuan Shugang Qin Xinchun Wang Lili Cao Xiangrong Song | 2023 | Nano Research2023，16，1： | 0 |
| 7 | mRNA-based therapeutics:powerful and versatile tools to combat diseases显示文摘The therapeutic use of messenger RNA(mRNA)has fueled great hope to combat a wide range of incurable diseases.Recent rapid advances in biotechnology and molecular medicine have enabled the production of almost any functional protein/peptide in the human body by introducing mRNA as a vaccine or therapeutic agent.This represents a rising precision medicine field with great promise for preventing and treating many intractable or genetic diseases.In addition,in vitro transcribed mRNA has achieved programmed production,which is more effective,faster in design and production,as well as more flexible and cost-effective than conventional approaches that may offer.Based on these extraordinary advantages,mRNA vaccines have the characteristics of the swiftest response to large-scale outbreaks of infectious diseases,such as the currently devastating pandemic COVID-19.It has always been the scientists’desire to improve the stability,immunogenicity,translation efficiency,and delivery system to achieve efficient and safe delivery of mRNA.Excitingly,these scientific dreams have gradually been realized with the rapid,amazing achievements of molecular biology,RNA technology,vaccinology,and nanotechnology.In this review,we comprehensively describe mRNA-based therapeutics,including their principles,manufacture,application,effects,and shortcomings.We also highlight the importance of mRNA optimization and delivery systems in successful mRNA therapeutics and discuss the key challenges and opportunities in developing these tools into powerful and versatile tools to combat many genetic,infectious,cancer,and other refractory diseases. | Shugang Qin Xiaoshan Tang Yuting Chen Kepan Chen Na Fan Wen Xiao Qian Zheng Guohong Li Yuqing Teng Min Wu Xiangrong Song | 2022 | Signal Transduction and Targeted Therapy2022，7，6： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员