Dear Editor Since last year,the most demanding task of the global pharmaceutical community has been focused on the development of strategies to treat coronavirus disease 2019(COVID-19).To date,several vaccines have be...Dear Editor Since last year,the most demanding task of the global pharmaceutical community has been focused on the development of strategies to treat coronavirus disease 2019(COVID-19).To date,several vaccines have been developed and already demonstrated their efficacy in reducing the incidence of COVID-19.1 However,the development of drugs treating COVID-19 is lagging far behind,and all the current treatment regimens have their limitations.展开更多
While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a f...While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a fraction of them receive the clinical benefit.There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy.Here,we carried out retrospective analyses of 1,020 formalin-fixed,paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC.We identified two proteomic subtypes:the chemo-sensitive group(CSG)and the chemo-insensitive group(CIG)in the discovery set.The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only(64.2%vs.49.6%;Cox P-value=0.002),whereas no such improvement was observed in CIG(50.0%vs.58.6%;Cox P-value=0.495).We validated these results in an independent validation set.Further,differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC.A prospective study is warranted to test these findings for future GC patient care.展开更多
Globally, SARS-CoV-2 has infected 3,113,447 people and killed 216,930 as of April 29, 2020. Identifying populations vulnerable to infection and their disease progression is critical to mitigating the negative impacts ...Globally, SARS-CoV-2 has infected 3,113,447 people and killed 216,930 as of April 29, 2020. Identifying populations vulnerable to infection and their disease progression is critical to mitigating the negative impacts on healthcare systems. Recent studies have shown that angiotensin converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 to enter human cells (Zhou et al., 2020), raising the possibility that a higher ACE2 expression level could facilitate SARS-CoV-2infection.展开更多
Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear.We analyzed 317 urine proteomes,including 86 COVID-19,55 pneumonia and 176 healthy controls,...Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear.We analyzed 317 urine proteomes,including 86 COVID-19,55 pneumonia and 176 healthy controls,and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples.Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity,metabolism and protein localization.Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease.Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients.As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA,an increase in CLYBL may lead to the depletion of itaconate,limiting its anti-inflammatory function.These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19,opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.展开更多
基金This study was supported by grants from the National Key R&D Program of China(2018YFA0507600 and 2018YFA0801405)the National Natural Science Foundation of China(81970690).
文摘Dear Editor Since last year,the most demanding task of the global pharmaceutical community has been focused on the development of strategies to treat coronavirus disease 2019(COVID-19).To date,several vaccines have been developed and already demonstrated their efficacy in reducing the incidence of COVID-19.1 However,the development of drugs treating COVID-19 is lagging far behind,and all the current treatment regimens have their limitations.
基金supported by the National Key Research and Development Program of China(2017YFC1308900,2017YFC0908404,2018YFA0507503,2017YFA0505103)Beijing Municipal Government Key Research and Development Program(Z181100001918020,Z161100002616036)+4 种基金the National Natural Science Foundation of China(31870828,81972790,81672319)the Guangdong Provincial Key R&D Programmes(2019B020229002)the Science and Technology Program of Guangzhou(201902020009)the National Key Basic Research Program of China(2014CBA02002)the National Key Technology Support Program(2015BAI13B07).
文摘While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a fraction of them receive the clinical benefit.There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy.Here,we carried out retrospective analyses of 1,020 formalin-fixed,paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC.We identified two proteomic subtypes:the chemo-sensitive group(CSG)and the chemo-insensitive group(CIG)in the discovery set.The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only(64.2%vs.49.6%;Cox P-value=0.002),whereas no such improvement was observed in CIG(50.0%vs.58.6%;Cox P-value=0.495).We validated these results in an independent validation set.Further,differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC.A prospective study is warranted to test these findings for future GC patient care.
基金supported by the National Key R&D Program of China (2018YFA0507503)。
文摘Globally, SARS-CoV-2 has infected 3,113,447 people and killed 216,930 as of April 29, 2020. Identifying populations vulnerable to infection and their disease progression is critical to mitigating the negative impacts on healthcare systems. Recent studies have shown that angiotensin converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 to enter human cells (Zhou et al., 2020), raising the possibility that a higher ACE2 expression level could facilitate SARS-CoV-2infection.
基金This work was supported by the National Key Research and Development Program of China(2017YFA0505102,2017YFA0505103,2017YFA0505104,2017YFC0908404,2018YFA0507503,2020YFA0708001)the National Natural Science Foundation of China(81874237,31870828)+4 种基金Major National Science and technology projects(2017ZX10305501-006)National Administration of Traditional Chinese Medicine:2019 Project of Building Evidence Based Practice Capacity for TCM(2019XZZX-LG003)Guangdong Key-Area Research and Development Program(2019B020229002,2020B1111300005)Guangzhou Science and Technology Program(201902020009)Guangdong Provincial Key Laboratory of Research on Emergency in TCM(2017B030314176).
文摘Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear.We analyzed 317 urine proteomes,including 86 COVID-19,55 pneumonia and 176 healthy controls,and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples.Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity,metabolism and protein localization.Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease.Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients.As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA,an increase in CLYBL may lead to the depletion of itaconate,limiting its anti-inflammatory function.These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19,opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.