Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD patt...Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.展开更多
Lung cancer is one of the most common malignancies and has the highest number of deaths among all cancers.Despite continuous advances in medical strategies,the overall survival of lung cancer patients is still low,pro...Lung cancer is one of the most common malignancies and has the highest number of deaths among all cancers.Despite continuous advances in medical strategies,the overall survival of lung cancer patients is still low,probably due to disease progression or drug resistance.Ferroptosis is an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides,and its dysregulation is implicated in cancer development.Preclinical evidence has shown that targeting the ferroptosis pathway could be a potential strategy for improving lung cancer treatment outcomes.In this review,we summarize the underlying mechanisms and regulatory networks of ferroptosis in lung cancer and highlight ferroptosis-targeting preclinical attempts to provide new insights for lung cancer treatment.展开更多
Acetylcholine(ACh)is a common neurotransmitterl)that is secreted by cholinergic neurons[2]and is found mainly in the peripheral and central nervous systems.[3]ACh transmits nerve signals from presynaptic to postsynapt...Acetylcholine(ACh)is a common neurotransmitterl)that is secreted by cholinergic neurons[2]and is found mainly in the peripheral and central nervous systems.[3]ACh transmits nerve signals from presynaptic to postsynaptic cells via synapses.展开更多
Endothelial cells(ECs)form a single cell layer that lines the inner surface of all blood and lymphatic vessels,acting as the barrier between vessels and underlying tissues.ECs are not only responsible for the flow of ...Endothelial cells(ECs)form a single cell layer that lines the inner surface of all blood and lymphatic vessels,acting as the barrier between vessels and underlying tissues.ECs are not only responsible for the flow of substances and fluid into and out of tissues but are also involved in many processes,such as coagulation,fibrinolysis,and regulation of vascular tone and inflammation.展开更多
The human microbiota,a diverse community of microorganisms living on or within their hosts,play an irreplaceable role in maintaining human health.Dysbiosis of the microbiota is associated with the pathogenesis of dive...The human microbiota,a diverse community of microorganisms living on or within their hosts,play an irreplaceable role in maintaining human health.Dysbiosis of the microbiota is associated with the pathogenesis of diverse human dis-eases.In recent years,growing evidence has been presented to support the substantial effect of human microbiota on the progression of infectious diseases.In this review,we describe the functional role of human microbiota in infec-tious diseases by highlighting their Janus-faced effects in the regulation of acute and chronic infections as well as their related co-morbidities.Thereafter,we review the latest advances elucidating the mechanisms underlying tri-directional interactions between the microbiota,hosts,and invading pathogens,with a further discussion on external environ-mental factors that shape this interconnected regulatory network.A better understanding of the regulatory functions and mechanisms of human microbiota in infectious diseases will facilitate the development of new diagnostic,preven-tive,and therapeutic approaches for infectious diseases.展开更多
Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic strategies.The metabolic reprogramming of tumor cells plays an essential role in the devel...Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic strategies.The metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely unknown.Here,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat iCCA.Methods:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome anal-ysis.Based on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was determined.Survival and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic subtypes.Cell proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA cells.Results:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were identified.These metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic alterations.The S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)mutations.Among the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)signaling.Conclusion:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing that the S2 subtype exhibited the poorest survival outcomes.We further identified DGKA as a potential target for the S2 subtype.展开更多
基金supported by the National Natural Science Foundation of China(32088101)National key Research and Development Program of China(2017YFC1700105,2021YFA1301603).
文摘Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.
基金National Natural Science Foundation of China(No.82073108)
文摘Lung cancer is one of the most common malignancies and has the highest number of deaths among all cancers.Despite continuous advances in medical strategies,the overall survival of lung cancer patients is still low,probably due to disease progression or drug resistance.Ferroptosis is an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides,and its dysregulation is implicated in cancer development.Preclinical evidence has shown that targeting the ferroptosis pathway could be a potential strategy for improving lung cancer treatment outcomes.In this review,we summarize the underlying mechanisms and regulatory networks of ferroptosis in lung cancer and highlight ferroptosis-targeting preclinical attempts to provide new insights for lung cancer treatment.
基金supported by the National Natural Science Foundation of China(No.32371505)the Innovation Fund Project of the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences(Nos.DMU-1&DICP UN202204,DICPI202110).
文摘Acetylcholine(ACh)is a common neurotransmitterl)that is secreted by cholinergic neurons[2]and is found mainly in the peripheral and central nervous systems.[3]ACh transmits nerve signals from presynaptic to postsynaptic cells via synapses.
基金This work was supported by the National Key Research and Development Program of China(2018YFA0801104 and 2021YFA1301604)the National Natural Science Foundation of China(82372721,31630093,and 82394443)Independent Research Program of the State Key Laboratory of Proteomics(SKLP-K202004).
文摘Endothelial cells(ECs)form a single cell layer that lines the inner surface of all blood and lymphatic vessels,acting as the barrier between vessels and underlying tissues.ECs are not only responsible for the flow of substances and fluid into and out of tissues but are also involved in many processes,such as coagulation,fibrinolysis,and regulation of vascular tone and inflammation.
基金supported by the National Key Research and Development Program of China(2022YFC2302900 to C.H.L.,2021YFA1300200 to C.H.L.and L.Z.,and 2022YFC2303201 to Q.C.)the National Natural Science Foundation of China(82330069,81825014,and 31830003 to C.H.L.and 82171744 to Q.C.)the State Key Laboratory of Proteomics(SKLP-K202001 to C.H.L.and L.Z.).
文摘The human microbiota,a diverse community of microorganisms living on or within their hosts,play an irreplaceable role in maintaining human health.Dysbiosis of the microbiota is associated with the pathogenesis of diverse human dis-eases.In recent years,growing evidence has been presented to support the substantial effect of human microbiota on the progression of infectious diseases.In this review,we describe the functional role of human microbiota in infec-tious diseases by highlighting their Janus-faced effects in the regulation of acute and chronic infections as well as their related co-morbidities.Thereafter,we review the latest advances elucidating the mechanisms underlying tri-directional interactions between the microbiota,hosts,and invading pathogens,with a further discussion on external environ-mental factors that shape this interconnected regulatory network.A better understanding of the regulatory functions and mechanisms of human microbiota in infectious diseases will facilitate the development of new diagnostic,preven-tive,and therapeutic approaches for infectious diseases.
基金This project was supported by grants from the National Natural Science Foundation of China(82273387,82273386,82073217,32270711,82073218 and 82003084)the National Key Research and Develop-ment Program of China(2018YFC1312100)+3 种基金Beijing Nova Program(20220484230)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)Shanghai Municipal Key Clinical Specialty,CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-058)the State Key Laboratory of Proteomics(SKLP-K202004).
文摘Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic strategies.The metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely unknown.Here,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat iCCA.Methods:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome anal-ysis.Based on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was determined.Survival and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic subtypes.Cell proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA cells.Results:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were identified.These metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic alterations.The S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)mutations.Among the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)signaling.Conclusion:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing that the S2 subtype exhibited the poorest survival outcomes.We further identified DGKA as a potential target for the S2 subtype.
