Major depressive disorder(MDD) is a common psychiatric disorder with an estimated lifetime prevalence rate in the range of 13% to 16% in the United States population. Patients with MDD often have symptoms such as depr...Major depressive disorder(MDD) is a common psychiatric disorder with an estimated lifetime prevalence rate in the range of 13% to 16% in the United States population. Patients with MDD often have symptoms such as depressed mood, loss of interest or pleasure in usual activities, changes in eating or sleeping patterns, fatigue, difficulty concentrating and thoughts of suicide. Although many pharmacotherapy treatment options are available for MDD, antidepressants can oftencause adverse effects that could affect adherence to the medication. Additionally, it is estimated that MDD is unremitting in 15% of patients and 35% can have recurrent episodes. Given the high rate of recurrence and the adverse effects associated with existing medications, new treatment options for depression are needed. Both levomilnacipran and vortioxetine are new antidepressants that were approved by the food and drug administration in 2013 for the treatment of MDD in adults. Levomilnacipran is a serotonin norepinephrine reuptake inhibitor that was effective in several short term studies and sustained efficacy and tolerability was demonstrated in a 48-wk extension study. Vortioxetine is a multi-modal antidepressant and it is thought to work via inhibition of the serotonin(5-HT) transporter, 5-HT3 A, 5-HT7 and 5-HT1 D antagonist, a 5-HT1 B partial agonist, and a 5-HT1 A agonist. Vortioxetine was effective in the treatment of MDD in both short-term trials as well as in the prevention of relapse in a 24-36 wk trial. Sustained efficacy and tolerability was demonstrated in several long-term open-label trials. Further studies comparing levomilnacipran and vortioxetine to other currently available antidepressants are needed to establish its place in therapy.展开更多
AIM: To predict the HLA-A2-restricted CTL epitopes of tumor antigens associated with hepatocellular carcinoma (HCC).METHODS: MAGE-1, MAGE-3, MAGE-8, P53 and AFP were selected as objective antigens in this study for th...AIM: To predict the HLA-A2-restricted CTL epitopes of tumor antigens associated with hepatocellular carcinoma (HCC).METHODS: MAGE-1, MAGE-3, MAGE-8, P53 and AFP were selected as objective antigens in this study for the close association with HCC. The HLA-A*0201 restricted CTL epitopes of objective tumor antigens were predicted by SYFPEITHI prediction method combined with the polynomial quantitative motifs method. The threshold of polynomial scores was set to -24.RESULTS: The SYFPEITHI prediction values of all possible nonamers of a given protein sequence were added together and the ten high-scoring peptides of each protein were chosen for further analysis in primary prediction. Thirtyfive candidates of CTL epitopes (nonamers) derived from the primary prediction results were selected by analyzing with the polynomial method and compared with reported CTL epitopes.CONCLUSION: The combination of SYFPEITHI prediction method and polynomial method can improve the prediction efficiency and accuracy. These nonamers may be useful in the design of therapeutic peptide vaccine for HCC and as immunotherapeutic strategies against HCC after identified by immunology experiment.展开更多
The basic consideration in the feld of antidepressants is that tests to model depression do not exist, as de-pression etiopathology is unknown. So far, any kind of proposed model for depression needs to satisfy constr...The basic consideration in the feld of antidepressants is that tests to model depression do not exist, as de-pression etiopathology is unknown. So far, any kind of proposed model for depression needs to satisfy construct, face and predictive validities. In the present editorial, this idea is challenged, based on the fact that “old” methods can only reveal therapeutical “me-too” drugs and that there is no longer a need of therapeu-tical “me-too” drugs in the field of antidepressants. Since reduction in the number of antidepressant non-responders is a real medical need, the predictive valid-ity of animal models will be challenged in the future, as the new methods should be based on antidepressant-insensitive animals. Moreover, antidepressants exert similar effects in depressed and non-depressed sub-jects, but mood normalization is only induced in de-pressed patients. This implies that the use of normal cells and animals only involves pharmacological rather than therapeutical actions of drugs. Therefore, the use of environmental-induced changes, in the hope that these can evidence antidepressant-insensitive animals, will predominantly be used in the future. In the choice of experimental settings, other factors need to be taken into consideration： （1） gender of animals, as de-pression affects females more than males, （2） natural rhythmicity in drug effects; （3） pharmacokinetics; and （4） possible biomarker（s） to be measured. There are no golden recipes to discover new antidepressants but the experimental long-term strategy should very clearly be declared before starting the experiments.展开更多
文摘Major depressive disorder(MDD) is a common psychiatric disorder with an estimated lifetime prevalence rate in the range of 13% to 16% in the United States population. Patients with MDD often have symptoms such as depressed mood, loss of interest or pleasure in usual activities, changes in eating or sleeping patterns, fatigue, difficulty concentrating and thoughts of suicide. Although many pharmacotherapy treatment options are available for MDD, antidepressants can oftencause adverse effects that could affect adherence to the medication. Additionally, it is estimated that MDD is unremitting in 15% of patients and 35% can have recurrent episodes. Given the high rate of recurrence and the adverse effects associated with existing medications, new treatment options for depression are needed. Both levomilnacipran and vortioxetine are new antidepressants that were approved by the food and drug administration in 2013 for the treatment of MDD in adults. Levomilnacipran is a serotonin norepinephrine reuptake inhibitor that was effective in several short term studies and sustained efficacy and tolerability was demonstrated in a 48-wk extension study. Vortioxetine is a multi-modal antidepressant and it is thought to work via inhibition of the serotonin(5-HT) transporter, 5-HT3 A, 5-HT7 and 5-HT1 D antagonist, a 5-HT1 B partial agonist, and a 5-HT1 A agonist. Vortioxetine was effective in the treatment of MDD in both short-term trials as well as in the prevention of relapse in a 24-36 wk trial. Sustained efficacy and tolerability was demonstrated in several long-term open-label trials. Further studies comparing levomilnacipran and vortioxetine to other currently available antidepressants are needed to establish its place in therapy.
基金Supported by Natural Scientific Foundation of China, No. 39830420
文摘AIM: To predict the HLA-A2-restricted CTL epitopes of tumor antigens associated with hepatocellular carcinoma (HCC).METHODS: MAGE-1, MAGE-3, MAGE-8, P53 and AFP were selected as objective antigens in this study for the close association with HCC. The HLA-A*0201 restricted CTL epitopes of objective tumor antigens were predicted by SYFPEITHI prediction method combined with the polynomial quantitative motifs method. The threshold of polynomial scores was set to -24.RESULTS: The SYFPEITHI prediction values of all possible nonamers of a given protein sequence were added together and the ten high-scoring peptides of each protein were chosen for further analysis in primary prediction. Thirtyfive candidates of CTL epitopes (nonamers) derived from the primary prediction results were selected by analyzing with the polynomial method and compared with reported CTL epitopes.CONCLUSION: The combination of SYFPEITHI prediction method and polynomial method can improve the prediction efficiency and accuracy. These nonamers may be useful in the design of therapeutic peptide vaccine for HCC and as immunotherapeutic strategies against HCC after identified by immunology experiment.
文摘The basic consideration in the feld of antidepressants is that tests to model depression do not exist, as de-pression etiopathology is unknown. So far, any kind of proposed model for depression needs to satisfy construct, face and predictive validities. In the present editorial, this idea is challenged, based on the fact that “old” methods can only reveal therapeutical “me-too” drugs and that there is no longer a need of therapeu-tical “me-too” drugs in the field of antidepressants. Since reduction in the number of antidepressant non-responders is a real medical need, the predictive valid-ity of animal models will be challenged in the future, as the new methods should be based on antidepressant-insensitive animals. Moreover, antidepressants exert similar effects in depressed and non-depressed sub-jects, but mood normalization is only induced in de-pressed patients. This implies that the use of normal cells and animals only involves pharmacological rather than therapeutical actions of drugs. Therefore, the use of environmental-induced changes, in the hope that these can evidence antidepressant-insensitive animals, will predominantly be used in the future. In the choice of experimental settings, other factors need to be taken into consideration： （1） gender of animals, as de-pression affects females more than males, （2） natural rhythmicity in drug effects; （3） pharmacokinetics; and （4） possible biomarker（s） to be measured. There are no golden recipes to discover new antidepressants but the experimental long-term strategy should very clearly be declared before starting the experiments.
