OBJECTIVES To investigate the prevalence of potentially inappropriate prescribing(PIP)for cardiovascular system(CVS)and antiplatelet/anticoagulant(AP/AC)drugs among Korean elderly patients,using the Screening Tool of ...OBJECTIVES To investigate the prevalence of potentially inappropriate prescribing(PIP)for cardiovascular system(CVS)and antiplatelet/anticoagulant(AP/AC)drugs among Korean elderly patients,using the Screening Tool of Older Persons’Prescriptions(STOPP)criteria version 2 and to identify the risk factors related to PIP.METHODS The 2016 National Aged Patient Sample data,comprising National Health Insurance claim records for a random sample of 20%of patients aged≥65 years,were used to calculate PIP prevalence of outpatient prescriptions.For criteria including drugdisease interactions,PIP prevalence per indication was estimated.RESULTS Among 1,274,148 elderly patients and 27,062,307 outpatient prescription claims,100,085 patients(7.85%)and 341,664 claims(1.27%)had one or more PIP.The most frequent PIP was“nonsteroidal antiinflammatory drug with concurrent antiplatelet agent(s)without protonpump inhibitor prophylaxis”in the claimlevel(0.97%)and patientlevel(6.33%)analyses.“Betablocker with bradycardia”(16.47%of claims)and“angiotensin receptor blockers in patients with hyperkalaemia”(23.89%of claims)showed the highest PIP prevalence per indication.Logistic regression analysis revealed that,among the patient and health care provider characteristics,female,older age,more severe comorbidities,polypharmacy,higher level of healthcare organization,and specialty of prescriber were significantly associated with a higher risk of PIP.CONCLUSIONS Our findings of a high prevalence of PIP for CVS and AP/AC drugs among the elderly suggest that an effective strategy is urgently needed to improve the prescription practices of these drugs.展开更多
Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are cur...Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called "isoprenoids") are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed.展开更多
The myocardium adapts to ischemic insults in a variety of ways.One adaptation is the phenomenon of acute preconditioning,which can greatly ameliorate ischemic damage.However,this effect wanes within a few hours and do...The myocardium adapts to ischemic insults in a variety of ways.One adaptation is the phenomenon of acute preconditioning,which can greatly ameliorate ischemic damage.However,this effect wanes within a few hours and does not confer chronic protection.A more chronic adaptation is the so-called second window of preconditioning,which enables protection for a few days.The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart,angiogenesis and arteriogenesis (collateral growth),which prevent the development of ischemia by enabling flow to a jeopardized region of the heart.This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart.The concept of a redox window,which is an optimal redox state for vascular growth,is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion.Finally,the review discusses of some of the pathologies,especially the metabolic syndrome,that negatively affect collateral growth through the corruption of redox signaling processes.展开更多
Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus(TA26-46)with a histone deacetylation modifier(100μmol L^(−1) nicotinamide),resulting in the isolation of a new 14-membe...Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus(TA26-46)with a histone deacetylation modifier(100μmol L^(−1) nicotinamide),resulting in the isolation of a new 14-membered resorcylic acid lactone named 7′(Z)-zeaenol(1),together with six known analogues(2−7)from the treated broth.The planar structure of 1 was determined by comprehensive NMR spectroscopy and HRESIMS data.The absolute configuration of 1 was elucidated by ECD spectrum,^(13)C NMR shift calculations,and on the basis of biogenetic considerations.Compound 5 exhibited cytotoxic activity against the human tumor cell lines A549,HCT-116,HT-29,Hela,MCF-7,and K562 with the IC_(50) values ranging from 2.54 to 7.44μmolL^(−1).展开更多
Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels,a process called cross-talk.The N-methyl-D-aspartate receptor (NMDA r...Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels,a process called cross-talk.The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system,respectively.Currently,cross-talk between the NMDA receptor and the GABAA receptor,particularly in the central auditory system,is not well understood.In the present study,we investigated functional interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus,which is an important nucleus in the central auditory system.We found that the currents induced by aspartate at 100 μmol L-1 were suppressed by the pre-perfusion of GABA at 100 μmol L-1,indicating cross-inhibition of NMDA receptors by activation of GABAA receptors.Moreover,we found that the currents induced by GABA at 100 μmol L-1 (IGABA) were not suppressed by the pre-perfusion of 100 μmol L-1 aspartate,but those induced by GABA at 3 μmol L-1 were suppressed,indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors.In addition,inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+,however,CdCl2 effectively attenuated the inhibition of IGABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L-1 BAPTA,a membrane-permeable Ca2+ chelator,suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors,rather than voltage-dependent Ca2+ channels.Finally,KN-62,a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII),reduced the inhibition of IGABA by aspartate,indicating the involvement of CaMKII in this cross-inhibition.Our study demonstrates a functional interaction between NMDA and GABAA receptors in the inferior colliculus of rats.The presence of cross-talk between these receptors suggests that the mechanisms underlying information processing in the central auditory system may be more complex than previously believed.展开更多
In the United States,there is currently an exponential growth for the COVID-19 cases.The US president’s coronavirus guidelines for America“30 Days to Slow The Spread”are necessary.To effectively curb the rapid spre...In the United States,there is currently an exponential growth for the COVID-19 cases.The US president’s coronavirus guidelines for America“30 Days to Slow The Spread”are necessary.To effectively curb the rapid spread of SARS-CoV-2,two more control measures facemasks and thermometers are strongly suggested to be included in the Guidelines.展开更多
To the editor,Sir,the problem of hemoglobin Constant Spring(Hb Constant Spring)is still a big problem in tropical Indochina.The high prevalence can be seen in this area.According to a recent study by Nguyen VH et al.,...To the editor,Sir,the problem of hemoglobin Constant Spring(Hb Constant Spring)is still a big problem in tropical Indochina.The high prevalence can be seen in this area.According to a recent study by Nguyen VH et al.,the very prevalence on Hb Constant Spring can be seen in the minorities in remote villages of Nam Dong in Central Vietnam^([1]).The observed rate is about 26.2%^([1]),which is significant higher than previous reports among other populations in Indochina^([2,3]).展开更多
Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness,high recurrence,and poor prognosis.Currently,surgical resection is the main treatment for fibrosarcoma.However,due to the lack of specific...Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness,high recurrence,and poor prognosis.Currently,surgical resection is the main treatment for fibrosarcoma.However,due to the lack of specific biomarkers,the inability to accurately diagnose fibrosarcoma can lead to sub-optimal surgical outcomes and decreased survival.Here,we seek to address this translational barrier and we show that DNA aptamer S11e was able to recognize fibrosarcoma cells(HT1080)but not human embryonic lung fibroblast cells with Kd values in the nanomolar range.In addition,we found that S11e discerned tumors in HT1080 xenograft mouse models and tumor tissues from fibrosarcoma patients.Furthermore,we demonstrated that S11e internalized into HT1080 cells independent of the lysosome pathway and located in mitochondria.Moreover,we revealed that S11e promoted the apoptosis of HT1080 cells and inhibited HT1080 cell migration.Finally,we investigated the biologically functional cellular target of S11e using a mass spectrometry approach,and identified that Diablo/SMAC protein is a cellular binding protein of S11e,by interacting to which S11e inhibited HT1080 cell migration and invasion.Taken together,these results provide the evidence that S11e may be useful for early diagnosis,targeted therapy,and prognostication of fibrosarcoma.展开更多
文摘OBJECTIVES To investigate the prevalence of potentially inappropriate prescribing(PIP)for cardiovascular system(CVS)and antiplatelet/anticoagulant(AP/AC)drugs among Korean elderly patients,using the Screening Tool of Older Persons’Prescriptions(STOPP)criteria version 2 and to identify the risk factors related to PIP.METHODS The 2016 National Aged Patient Sample data,comprising National Health Insurance claim records for a random sample of 20%of patients aged≥65 years,were used to calculate PIP prevalence of outpatient prescriptions.For criteria including drugdisease interactions,PIP prevalence per indication was estimated.RESULTS Among 1,274,148 elderly patients and 27,062,307 outpatient prescription claims,100,085 patients(7.85%)and 341,664 claims(1.27%)had one or more PIP.The most frequent PIP was“nonsteroidal antiinflammatory drug with concurrent antiplatelet agent(s)without protonpump inhibitor prophylaxis”in the claimlevel(0.97%)and patientlevel(6.33%)analyses.“Betablocker with bradycardia”(16.47%of claims)and“angiotensin receptor blockers in patients with hyperkalaemia”(23.89%of claims)showed the highest PIP prevalence per indication.Logistic regression analysis revealed that,among the patient and health care provider characteristics,female,older age,more severe comorbidities,polypharmacy,higher level of healthcare organization,and specialty of prescriber were significantly associated with a higher risk of PIP.CONCLUSIONS Our findings of a high prevalence of PIP for CVS and AP/AC drugs among the elderly suggest that an effective strategy is urgently needed to improve the prescription practices of these drugs.
文摘Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called "isoprenoids") are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed.
基金Supported by National Institute of Health Grants No.HL32788, R01 83366,RC1HL100828(to Chilian WM)an American Heart Association Post-doctoral Fellowship,No.09POST2290021 (to Pung YF)
文摘The myocardium adapts to ischemic insults in a variety of ways.One adaptation is the phenomenon of acute preconditioning,which can greatly ameliorate ischemic damage.However,this effect wanes within a few hours and does not confer chronic protection.A more chronic adaptation is the so-called second window of preconditioning,which enables protection for a few days.The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart,angiogenesis and arteriogenesis (collateral growth),which prevent the development of ischemia by enabling flow to a jeopardized region of the heart.This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart.The concept of a redox window,which is an optimal redox state for vascular growth,is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion.Finally,the review discusses of some of the pathologies,especially the metabolic syndrome,that negatively affect collateral growth through the corruption of redox signaling processes.
基金supported by the National Natural Science Foundation of China(Nos.81673350,81703411,41776156)the National Science and Technology Major Project for Significant New Drugs Development,China(No.2018ZX09735-004)+1 种基金the Fundamental Research Funds for the Central Universities of China(No.201962002)the Taishan Scholars Program,China.
文摘Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus(TA26-46)with a histone deacetylation modifier(100μmol L^(−1) nicotinamide),resulting in the isolation of a new 14-membered resorcylic acid lactone named 7′(Z)-zeaenol(1),together with six known analogues(2−7)from the treated broth.The planar structure of 1 was determined by comprehensive NMR spectroscopy and HRESIMS data.The absolute configuration of 1 was elucidated by ECD spectrum,^(13)C NMR shift calculations,and on the basis of biogenetic considerations.Compound 5 exhibited cytotoxic activity against the human tumor cell lines A549,HCT-116,HT-29,Hela,MCF-7,and K562 with the IC_(50) values ranging from 2.54 to 7.44μmolL^(−1).
基金supported by the National Basic Research Program of China (Grant Nos. 2011CB504506 and 2007CB512306)the National Natural Science Foundation of China (Grant Nos. 30970977 and 30730041)the Knowledge Innovation Project of the Chinese Academy of Sciences (Grant No. KSCX1-YW-R-36)
文摘Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels,a process called cross-talk.The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system,respectively.Currently,cross-talk between the NMDA receptor and the GABAA receptor,particularly in the central auditory system,is not well understood.In the present study,we investigated functional interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus,which is an important nucleus in the central auditory system.We found that the currents induced by aspartate at 100 μmol L-1 were suppressed by the pre-perfusion of GABA at 100 μmol L-1,indicating cross-inhibition of NMDA receptors by activation of GABAA receptors.Moreover,we found that the currents induced by GABA at 100 μmol L-1 (IGABA) were not suppressed by the pre-perfusion of 100 μmol L-1 aspartate,but those induced by GABA at 3 μmol L-1 were suppressed,indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors.In addition,inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+,however,CdCl2 effectively attenuated the inhibition of IGABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L-1 BAPTA,a membrane-permeable Ca2+ chelator,suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors,rather than voltage-dependent Ca2+ channels.Finally,KN-62,a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII),reduced the inhibition of IGABA by aspartate,indicating the involvement of CaMKII in this cross-inhibition.Our study demonstrates a functional interaction between NMDA and GABAA receptors in the inferior colliculus of rats.The presence of cross-talk between these receptors suggests that the mechanisms underlying information processing in the central auditory system may be more complex than previously believed.
文摘In the United States,there is currently an exponential growth for the COVID-19 cases.The US president’s coronavirus guidelines for America“30 Days to Slow The Spread”are necessary.To effectively curb the rapid spread of SARS-CoV-2,two more control measures facemasks and thermometers are strongly suggested to be included in the Guidelines.
文摘To the editor,Sir,the problem of hemoglobin Constant Spring(Hb Constant Spring)is still a big problem in tropical Indochina.The high prevalence can be seen in this area.According to a recent study by Nguyen VH et al.,the very prevalence on Hb Constant Spring can be seen in the minorities in remote villages of Nam Dong in Central Vietnam^([1]).The observed rate is about 26.2%^([1]),which is significant higher than previous reports among other populations in Indochina^([2,3]).
基金supported by the National Natural Science Foundation of China(No.31701249,31970692,81803068,91953000,21827811)Changsha Science and Technology Plan(kq2004009)+3 种基金Corbett Estate Fund for Cancer Researchthe Hunan Provincial Key Area R&D Program(2019SK2201)Hunan Science and Technology Creative Program(2017XK2103)the National Key R&D Program of China(2020YFA0909000).
文摘Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness,high recurrence,and poor prognosis.Currently,surgical resection is the main treatment for fibrosarcoma.However,due to the lack of specific biomarkers,the inability to accurately diagnose fibrosarcoma can lead to sub-optimal surgical outcomes and decreased survival.Here,we seek to address this translational barrier and we show that DNA aptamer S11e was able to recognize fibrosarcoma cells(HT1080)but not human embryonic lung fibroblast cells with Kd values in the nanomolar range.In addition,we found that S11e discerned tumors in HT1080 xenograft mouse models and tumor tissues from fibrosarcoma patients.Furthermore,we demonstrated that S11e internalized into HT1080 cells independent of the lysosome pathway and located in mitochondria.Moreover,we revealed that S11e promoted the apoptosis of HT1080 cells and inhibited HT1080 cell migration.Finally,we investigated the biologically functional cellular target of S11e using a mass spectrometry approach,and identified that Diablo/SMAC protein is a cellular binding protein of S11e,by interacting to which S11e inhibited HT1080 cell migration and invasion.Taken together,these results provide the evidence that S11e may be useful for early diagnosis,targeted therapy,and prognostication of fibrosarcoma.