On Aug 14,2024,the World Health Organization(WHO)declared the second public health emergency of international concern(PHEIC)on mpox spread,considering the upsurge of mpox in the Democratic Republic of the Congo and a ...On Aug 14,2024,the World Health Organization(WHO)declared the second public health emergency of international concern(PHEIC)on mpox spread,considering the upsurge of mpox in the Democratic Republic of the Congo and a growing number of countries in Africa[1].Mpox has been mainly confinedwithin Africa since its first isolation in Denmark inmonkeys kept for research in 1958 and the first reported human mpox case of an infant boy in the Democratic Republic of the Congo in 1970[2].The spillover spread outside of Africa to America in 2003 caused approximately 70 infections[3].Fortunately,the endemic caused no deaths but alerted society to the potential threat of mpox.In Jul 2022,WHO once declared the first PHEIC on mpox since quickly reported mpox-infected cases in Europe,America,and Asia.The rapid increase of mpox in 2024 calls for urgent collaborative efforts to address the disease’s evolving epidemiology and transmission dynamics[4],emphasizing the potential threat from mpox and the need for caution and preparedness.展开更多
Objective:Acute lung injury(ALI)is a life-threatening respiratory disorder and a major concern in modern medical research.Clinical research has shown that Qingfei Liyan Decoction(QFLYT),a formula based on Yin Qiao San...Objective:Acute lung injury(ALI)is a life-threatening respiratory disorder and a major concern in modern medical research.Clinical research has shown that Qingfei Liyan Decoction(QFLYT),a formula based on Yin Qiao San,is used to treat lung-associated inflammatory diseases.However,the mechanism through which QFLYT exerts its therapeutic effects remains unclear.The purpose of this study was to evaluate the effects of QFLYT on lipopolysaccharide(LPS)-induced ALI and investigate the underlying molecular mechanisms.Materials and Methods:We established an ALI model by administering LPS drops into the trachea of mice.Bronchoalveolar lavage fluid(BALF)and lung tissue were collected to determine inflammatory indices.The effects of QFLYT and its single herbs on the cyclic GMP-AMP synthase-stimulator of interferon gene(cGAS-STING)pathway and inflammasomes were studied in vitro.Relevant proteins and factors were detected using the enzyme linked immunosorbent assay,real-time quantitative polymerase chain reaction,and Western blotting.Results:QFLYT reduced the secretion of inflammatory factors in BALF and lung tissue,and attenuated pathological damage to the latter.In addition,QFLYT inhibited multiple stimuli-induced cGAS-STING pathway and inflammasomes activation in vitro.Further investigation revealed that the herbs in QFLYT had no combined effects on the activation of the two pathways at their formulated doses.However,Forsythiae fructus,Lonicerae japonicae flos,and Licorice inhibited the activation of both pathways at higher concentrations.Conclusions:Our findings show that QFLYT ameliorates LPS-induced ALI by inhibiting the cGAS-STING pathway and inflammasomes.展开更多
Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievi...Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievirus B5(CVB5)infection remain unknown.Here,we identified a novel cytoplasmic lncRNA,LINC1392,which was highly inducible in CVB5 infected RD cells in a time-and dose-dependent manner,and also can be induced by the viral RNA and IFN-β.Further investigation showed that LINC1392 promoted several important interferon-stimulated genes(ISGs)expression,including IFIT1,IFIT2,and IFITM3 by activating MDA5,thereby inhibiting the replication of CVB5 in vitro.Mechanistically,LINC1392 bound to ELAV like RNA binding protein 1(ELAVL1)and blocked ELAVL1 interaction with MDA5.Functional study revealed that the 245–835 nt locus of LINC1392 exerted the antiviral effect and was also an important site for ELAVL1 binding.In mice,LINC1392 could inhibit CVB5 replication and alleviated the histopathological lesions of intestinal and brain tissues induced by viral infection.Our findings collectively reveal that the novel LINC1392 acts as a positive regulator in the IFN-I signaling pathway against CVB5 infection.Elucidating the underlying mechanisms on how lncRNA regulats the host innate immunity response towards CVB5 infection will lay the foundation for antiviral drug research.展开更多
The stimulator of interferon genes(STING)pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy.Despite promising preclinical studies,clinical trials of STING agonist...The stimulator of interferon genes(STING)pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy.Despite promising preclinical studies,clinical trials of STING agonists have largely failed to deliver durable efficacy,with no agents progressing to phase III trials.This review examines the biological,pharmacological,and clinical barriers limiting STING pathway activation in cancer treatment.展开更多
In a recent article published in Cell,He and colleagues reported that vitamin C(VitC)modifies lysine residues in proteins and peptides,thereby forming vitcyl-lysine,a process they have called vitcylation.They show tha...In a recent article published in Cell,He and colleagues reported that vitamin C(VitC)modifies lysine residues in proteins and peptides,thereby forming vitcyl-lysine,a process they have called vitcylation.They show that vitcylation of signal transducer and activator of transcription-1(STAT1)increases its phosphorylation and thereby promotes interferon pathway activation in cancer cells and anti-tumor immunity.展开更多
DDX58(DExD/H-box helicase 58)encodes retinoic acid-inducible gene I(RIG-I),a crucial cytosolic dsRNA sensor that recognizes dsRNA from infected viruses and activates the type I interferon(IFN-I)pathway[1].
Although cancer immunotherapy has made great strides in the clinic,it is still hindered by the tumor immunosuppressive microenvironment(TIME).The stimulator of interferon genes(STING)pathway which can modulate TIME ef...Although cancer immunotherapy has made great strides in the clinic,it is still hindered by the tumor immunosuppressive microenvironment(TIME).The stimulator of interferon genes(STING)pathway which can modulate TIME effectively has emerged as a promising therapeutic recently.However,the delivery of most STING agonists,specifically cyclic dinucleotides(CDNs),is performed intratumorally due to their insufficient pharmacological properties,such as weak permeability across cell membranes and vulnerability to nuclease degradation.To expand the clinical applicability of CDNs,a novel pH-sensitive polycationic polymer-modified lipid nanoparticle(LNP-B)system was developed for intravenous delivery of CDNs.LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor,spleen,and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages.These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models.In addition,due to the acid-sensitive property of the polycationic polymer,the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP(LNP-D).These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.展开更多
Infectious bronchitis virus(IBV)can cause respiratory infections in animals that often lead to heavy losses for breeding industry.Ban-Qin-Fei-Re-Qing oral liquid(BQ),a Chinese herbal compound,has been used to treat in...Infectious bronchitis virus(IBV)can cause respiratory infections in animals that often lead to heavy losses for breeding industry.Ban-Qin-Fei-Re-Qing oral liquid(BQ),a Chinese herbal compound,has been used to treat infectious bronchi-tis(IB).This research aimed to assess the antiviral effect of BQ against IBV and elucidate the underlying mechanisms through bioinformatics analysis.The experiments designed in this study investigated how BQ inhibits IBV propagation in chicken embryos and enhances protective effects on chicken embryos.The findings indicated that,in compari-son to the model group(untreated),the BQ-treated groups exhibited a significant protective effect on IBV-infected chicken embryos.Moreover,the groups administered medium or high doses of BQ demonstrated a superior protec-tive effect compared to the group treated with a lower dose.In addition,even at a low dose(2.5 mL/L),BQ success-fully treated IB in chickens.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that the differentially expressed genes were enriched in antiviral pathways,such as the JAK/STAT and typeⅠinterferon signaling pathways.In conclusion,the current study demonstrated that BQ has antiviral activity and plays an antiviral role through the combined action of multiple antiviral pathways.These findings could lead to future research on identifying drugs to prevent and treat IB.展开更多
基金approved by the Institutional Animal Ethics Committee of Guangzhou Eighth People’s Hospital,Guangzhou Medical University(IACUC-LF-2024-05).
文摘On Aug 14,2024,the World Health Organization(WHO)declared the second public health emergency of international concern(PHEIC)on mpox spread,considering the upsurge of mpox in the Democratic Republic of the Congo and a growing number of countries in Africa[1].Mpox has been mainly confinedwithin Africa since its first isolation in Denmark inmonkeys kept for research in 1958 and the first reported human mpox case of an infant boy in the Democratic Republic of the Congo in 1970[2].The spillover spread outside of Africa to America in 2003 caused approximately 70 infections[3].Fortunately,the endemic caused no deaths but alerted society to the potential threat of mpox.In Jul 2022,WHO once declared the first PHEIC on mpox since quickly reported mpox-infected cases in Europe,America,and Asia.The rapid increase of mpox in 2024 calls for urgent collaborative efforts to address the disease’s evolving epidemiology and transmission dynamics[4],emphasizing the potential threat from mpox and the need for caution and preparedness.
基金by the National Key R and D Program of China(2023YFC2308200)the Natural Science Foundation of Beijing,China(7232321)+1 种基金the National Natural Science Foundation of China(U23A20519,81930110,82230118)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(2060302)。
文摘Objective:Acute lung injury(ALI)is a life-threatening respiratory disorder and a major concern in modern medical research.Clinical research has shown that Qingfei Liyan Decoction(QFLYT),a formula based on Yin Qiao San,is used to treat lung-associated inflammatory diseases.However,the mechanism through which QFLYT exerts its therapeutic effects remains unclear.The purpose of this study was to evaluate the effects of QFLYT on lipopolysaccharide(LPS)-induced ALI and investigate the underlying molecular mechanisms.Materials and Methods:We established an ALI model by administering LPS drops into the trachea of mice.Bronchoalveolar lavage fluid(BALF)and lung tissue were collected to determine inflammatory indices.The effects of QFLYT and its single herbs on the cyclic GMP-AMP synthase-stimulator of interferon gene(cGAS-STING)pathway and inflammasomes were studied in vitro.Relevant proteins and factors were detected using the enzyme linked immunosorbent assay,real-time quantitative polymerase chain reaction,and Western blotting.Results:QFLYT reduced the secretion of inflammatory factors in BALF and lung tissue,and attenuated pathological damage to the latter.In addition,QFLYT inhibited multiple stimuli-induced cGAS-STING pathway and inflammasomes activation in vitro.Further investigation revealed that the herbs in QFLYT had no combined effects on the activation of the two pathways at their formulated doses.However,Forsythiae fructus,Lonicerae japonicae flos,and Licorice inhibited the activation of both pathways at higher concentrations.Conclusions:Our findings show that QFLYT ameliorates LPS-induced ALI by inhibiting the cGAS-STING pathway and inflammasomes.
基金This work was supported by the National Natural Science Foundation of China(No.81860357)the Young Talents Support Program of Yunnan Province,China(Ten Thousand People Plan,YNWR-QNBJ-2019-178).
文摘Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievirus B5(CVB5)infection remain unknown.Here,we identified a novel cytoplasmic lncRNA,LINC1392,which was highly inducible in CVB5 infected RD cells in a time-and dose-dependent manner,and also can be induced by the viral RNA and IFN-β.Further investigation showed that LINC1392 promoted several important interferon-stimulated genes(ISGs)expression,including IFIT1,IFIT2,and IFITM3 by activating MDA5,thereby inhibiting the replication of CVB5 in vitro.Mechanistically,LINC1392 bound to ELAV like RNA binding protein 1(ELAVL1)and blocked ELAVL1 interaction with MDA5.Functional study revealed that the 245–835 nt locus of LINC1392 exerted the antiviral effect and was also an important site for ELAVL1 binding.In mice,LINC1392 could inhibit CVB5 replication and alleviated the histopathological lesions of intestinal and brain tissues induced by viral infection.Our findings collectively reveal that the novel LINC1392 acts as a positive regulator in the IFN-I signaling pathway against CVB5 infection.Elucidating the underlying mechanisms on how lncRNA regulats the host innate immunity response towards CVB5 infection will lay the foundation for antiviral drug research.
基金supported by the National Natural Science Foundation of China(grant 82373323 to T.Z.,82405119 to J.S.,U24A20724 and 82273364 to X.L.)the National Key Research and Development Program of China(grant 2023YFC3504600 to T.Z.)+3 种基金the Heilongjiang Provincial Natural Science Foundation of China(grant YQ2024H022 to J.S.)the Research fees of Heilongjiang Provincial Research Institutes(CZKYF2025-1-4012 to T.Z.)the Heilongjiang Province New Era Longjiang Outstanding Doctoral Dissertation Project(grant LJYXL2022-068 to J.S.)the Hai Yan Key Research Fund Project of Harbin Medical University Cancer Hospital(grant JJZD2024-21 to J.S.).
文摘The stimulator of interferon genes(STING)pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy.Despite promising preclinical studies,clinical trials of STING agonists have largely failed to deliver durable efficacy,with no agents progressing to phase III trials.This review examines the biological,pharmacological,and clinical barriers limiting STING pathway activation in cancer treatment.
基金supported by Deutsche Forschungsgemeinschaft grant Ka502/19-3 to D.K.
文摘In a recent article published in Cell,He and colleagues reported that vitamin C(VitC)modifies lysine residues in proteins and peptides,thereby forming vitcyl-lysine,a process they have called vitcylation.They show that vitcylation of signal transducer and activator of transcription-1(STAT1)increases its phosphorylation and thereby promotes interferon pathway activation in cancer cells and anti-tumor immunity.
文摘DDX58(DExD/H-box helicase 58)encodes retinoic acid-inducible gene I(RIG-I),a crucial cytosolic dsRNA sensor that recognizes dsRNA from infected viruses and activates the type I interferon(IFN-I)pathway[1].
基金supported by the National Science Foundation of China(8217070298,81773283)the Guangdong Basic and Applied Basic Research Foundation(2021A1515220011,China).
文摘Although cancer immunotherapy has made great strides in the clinic,it is still hindered by the tumor immunosuppressive microenvironment(TIME).The stimulator of interferon genes(STING)pathway which can modulate TIME effectively has emerged as a promising therapeutic recently.However,the delivery of most STING agonists,specifically cyclic dinucleotides(CDNs),is performed intratumorally due to their insufficient pharmacological properties,such as weak permeability across cell membranes and vulnerability to nuclease degradation.To expand the clinical applicability of CDNs,a novel pH-sensitive polycationic polymer-modified lipid nanoparticle(LNP-B)system was developed for intravenous delivery of CDNs.LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor,spleen,and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages.These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models.In addition,due to the acid-sensitive property of the polycationic polymer,the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP(LNP-D).These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.
基金Beijing Municipal Commission of Science and Technology(project numbers Z191100001619001).
文摘Infectious bronchitis virus(IBV)can cause respiratory infections in animals that often lead to heavy losses for breeding industry.Ban-Qin-Fei-Re-Qing oral liquid(BQ),a Chinese herbal compound,has been used to treat infectious bronchi-tis(IB).This research aimed to assess the antiviral effect of BQ against IBV and elucidate the underlying mechanisms through bioinformatics analysis.The experiments designed in this study investigated how BQ inhibits IBV propagation in chicken embryos and enhances protective effects on chicken embryos.The findings indicated that,in compari-son to the model group(untreated),the BQ-treated groups exhibited a significant protective effect on IBV-infected chicken embryos.Moreover,the groups administered medium or high doses of BQ demonstrated a superior protec-tive effect compared to the group treated with a lower dose.In addition,even at a low dose(2.5 mL/L),BQ success-fully treated IB in chickens.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that the differentially expressed genes were enriched in antiviral pathways,such as the JAK/STAT and typeⅠinterferon signaling pathways.In conclusion,the current study demonstrated that BQ has antiviral activity and plays an antiviral role through the combined action of multiple antiviral pathways.These findings could lead to future research on identifying drugs to prevent and treat IB.
