Background Neurological disorders are the second leading cause of death and the leading cause of disability in the world.Thus,the development of novel disease-modifying strategies is clearly warranted.We have previous...Background Neurological disorders are the second leading cause of death and the leading cause of disability in the world.Thus,the development of novel disease-modifying strategies is clearly warranted.We have previously developed a therapeutic approach using mouse targeted rabies virus glycoprotein(RVG)extracellular vesicles(EVs)to deliver minicircles(MCs)expressing shRNA(shRNA-MCs)to induce long-termα-synuclein down-regulation.Although the previous therapy successfully reduced the pathology,the clinical translation was extremely unlikely since they were mouse extracellular vesicles.Methods To overcome this limitation,we developed a source of human RVG-EVs compatible with a personalized therapy using immature dendritic cells.Human peripheral blood monocytes were differentiated in vitro into immature dendritic cells,which were transfected to express the RVG peptide.RVG-EVs containing shRNA-MCs,loaded by electroporation,were injected intravenously in theα-synuclein performed fibril(PFF)mouse model.Level ofα-synuclein,phosphorylatedα-synuclein aggregates,dopaminergic neurons and motor function were evaluated 90 days after the treatment.To confirm that EVs derived from patients were suitable as a vehicle,proteomic analysis of EVs derived from control,initial and advanced Parkinson’s disease was performed.Results The shRNA-MCs could be successfully loaded into human RVG-EVs and downregulateα-synuclein in SHSY5Y cells.Intravenous injection of the shRNA-MC-loaded RVG-EVs induced long-term downregulation ofα-synuclein mRNA expression and protein level,decreasedα-synuclein aggregates,prevented dopaminergic cell death and ameliorated motor impairment in theα-synuclein PFF mouse model.Moreover,we confirmed that the EVs from PD patients are suitable as a personalized therapeutic vehicle.Conclusion Our study confirmed the therapeutic potential of shRNA-MCs delivered by human RVG-EVs for longterm treatment of neurodegenerative diseases.These results pave the way for clinical use of this approach.展开更多
Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor tha...Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons （OSNs）f2J. Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechelfia Ir75a gene is generally recognized as a pseudogene in OSNs.展开更多
Radar Maneuvering Targets Tracking(RMTT) in clutter is a quite challenging issue due to the errors in the models and the varying dynamics of the processes. Modern radar tracking system calls for the adaptive signal an...Radar Maneuvering Targets Tracking(RMTT) in clutter is a quite challenging issue due to the errors in the models and the varying dynamics of the processes. Modern radar tracking system calls for the adaptive signal and data processing algorithm urgently to adapt the uncertainty of the environment. The mechanism of human cognition can help persons cope with the similar diffi-culties in visual tracking. Inspired by human cognition mechanism, a comprehensive method for RMTT is proposed. In the method, the model transition probability in Interacting Multiple Model(IMM) and the validation gate can be adjusted dynamically with target maneuver;the waveform in radar transmitter can vary with the perception of the environment. Experimental results in cluttered scenes show that the proposed algorithm is more accurate for perceiving the environment and targets, and the waveform selection algorithm is better than that with fixed waveform.展开更多
Inappropriate Met-hepatocyte growth factor/scatter factor （HGF/SF） signaling is a hallmark of most types of solid tumors in humans and often correlates with poor prognosis. There are several mechanisms by which Met ...Inappropriate Met-hepatocyte growth factor/scatter factor （HGF/SF） signaling is a hallmark of most types of solid tumors in humans and often correlates with poor prognosis. There are several mechanisms by which Met signaling is deregulated including Met and/or HGF/SF overexpression, mutation, autocrine signaling, and ligand-independent activation. Because Met is an attractive therapeutic target for a multitude of cancers, extensive research towards finding Met and HGF/SF inhibitors is ongoing.？ In parallel with these efforts, several mouse models have been developed in our lab that will be valuable for preclinical testing of Met-targeted therapeutics.展开更多
During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many peopl...During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many people died before reaching adult- hood, nowadays most people survive. Hence average life ex- pectancy in 1800s was around 30-40, which was barely higher than it had been in Greek and Roman times （Finch, 2010）, but nowadays life expectancy in most modernised economies is around 75 - 80. This demographic shift, which has happened in only 200 years, has created a dramatic change in the causes of mortality. The major killers in the modern world are non- communicable diseases （NCDs）： principally cardiovascular disease, cancer and neurodegenerative disorders such as Alz- heimer＇s disease. A major factor that influences susceptibility to all these diseases is age. As we get older, our risk of developing these NCDs increases enormously. For example, the rate of breast cancer in females at age 15-19 is less than 10 per 100,000 population, but this increases to 100 at age 40-44, 275 at age 55--59 and 450 at age 85 ＋ （http：//www.cancerresearchuk.org/ cancer-info/cancerstats/types/breast/incidence/#age）. Ageing has consequently become a major medical, social and economic burden to many countries.展开更多
In April 2009, after receiving ap- proval from the State Council, the Information Office of the State Council published the NationalHuman Rights Action Plan of China （2009-2010）. It is China＇s first national plan o...In April 2009, after receiving ap- proval from the State Council, the Information Office of the State Council published the NationalHuman Rights Action Plan of China （2009-2010）. It is China＇s first national plan on the theme of human rights, and serves as a policy document of the current stage for advancing China＇s human rights in a comprehensive way. It is an important move to implement the constitutional principle of respect- ing and safeguarding human rights, and to promote sustainable development and social harmony. It is also a solemn commitment to the world made by the Chinese government on human rights.展开更多
Poverty alleviation requires knowledge support. Targeted poverty alleviation, aiming to tackle rural poverty, needs to be supported by corresponding rural human resource development. Currently, China's human resou...Poverty alleviation requires knowledge support. Targeted poverty alleviation, aiming to tackle rural poverty, needs to be supported by corresponding rural human resource development. Currently, China's human resource development in impoverished rural regions is faced with some major problems; a huge population distributed over a vast area, a lack of technological and cultural attainment, obsolete concepts, obsolete technical resources, and a significant gap between rural and urban education attainment. Rural human resource development, which is geared to targeted poverty alleviation, includes a variety of impoverished rural population-oriented trainings, such as intelligence development, skills training, modern professionalism &work attitude cultivation, physical & mental health education, as well as modern lifestyle & civilized manners guidance. Targeted poverty alleviation should be equipped with mechanisms of comprehensive layout & planning, coordinated advancement of development content and implementation, and a mechanism of organization & input. The approaches to the advancement of rural human resource development are enhancing basic education, building a system of vocational education and training, raising the social security level and improving the supporting mechanisms.展开更多
Traumatic brain injury （TBI） is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that event...Traumatic brain injury （TBI） is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as develop- ment, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma （miR-425-p, -21, -93, -191 and -499） and cerebro-spinal fluid （CSF） （miR-328, -362-3p, -451, -486a） as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TBI （e.g., miR-21, miR-23b）. MicroRNA profil- ing was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TBI （e.g., miR-21） have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in microRNA profiles in different age groups （children, adults, and elderly）.展开更多
Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human disea...Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases,展开更多
Parkinson＇s disease（PD） is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain ...Parkinson＇s disease（PD） is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons. Oxidative stress is also recognized as one of the main causes of PD, and excessive reactive oxygen species（ROS） and reactive nitrogen species can lead to dopaminergic neuron vulnerability and eventual death. Micro RNAs control a range of physiological and pathological functions, and may serve as potential targets for intervention against PD to mitigate damage to the brain. Several studies have demonstrated that micro RNAs can regulate oxidative stress and prevent ROS-mediated damage to dopaminergic neurons, suggesting that specific micro RNAs may be putative targets for novel therapeutic strategies in PD. Recent human and animal studies have identified a large number of dysregulated micro RNAs in PD brain tissue samples, many of which were downregulated. The dysregulated micro RNAs affect downstream targets such as SNCA, PARK2, LRRK2, TNFSF13 B, LTA, SLC5 A3, PSMB2, GSR, GBA, LAMP-2 A, HSC. Apart from one study, none of the studies reviewed had used agomirs or antagomirs to reverse the levels of downregulated or upregulated micro RNAs, respectively, in mouse models of PD or with isolated human or mouse dopaminergic cells. Further large-scale studies of brain tissue samples collected with short postmortem interval from human PD patients are warranted to provide more information on the micro RNA profiles in different brain regions and to test for gender differences.展开更多
Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trast...Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.展开更多
High genetic variability of human immunodeficiency virus(HIV)has been a major intractable challenge to the practical design of vaccines.But a recent pioneer study published in PNAS Xenobots,is likely to revolutionize ...High genetic variability of human immunodeficiency virus(HIV)has been a major intractable challenge to the practical design of vaccines.But a recent pioneer study published in PNAS Xenobots,is likely to revolutionize HIV prevention as it presented the world's first living robot made of cells.In the advent of this discovery,we herein discuss the possibility of using living biological cell robots to target HIV-infected T lymphocytes,and the prospects of this approach being a new HIV vaccine.We capture the current research status and trend of advances in biological cell robots'design as a new HIV vaccine.The key differences between this novel vaccine and other HIV vaccines are highlighted.展开更多
Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted th...Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancerresistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.展开更多
Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in 2008.In the advanced setting,standard ...Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in 2008.In the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong survival.Moreover,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)therapies.Trastuzumab,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy.Further,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field.Thus,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved.展开更多
基金funded by Instituto de Salud Carlos III(ISCIII)PI19/00618(LAE,MI)LAE is supported by a Miguel Servet contract(CPII20/00027)from ISCIII.
文摘Background Neurological disorders are the second leading cause of death and the leading cause of disability in the world.Thus,the development of novel disease-modifying strategies is clearly warranted.We have previously developed a therapeutic approach using mouse targeted rabies virus glycoprotein(RVG)extracellular vesicles(EVs)to deliver minicircles(MCs)expressing shRNA(shRNA-MCs)to induce long-termα-synuclein down-regulation.Although the previous therapy successfully reduced the pathology,the clinical translation was extremely unlikely since they were mouse extracellular vesicles.Methods To overcome this limitation,we developed a source of human RVG-EVs compatible with a personalized therapy using immature dendritic cells.Human peripheral blood monocytes were differentiated in vitro into immature dendritic cells,which were transfected to express the RVG peptide.RVG-EVs containing shRNA-MCs,loaded by electroporation,were injected intravenously in theα-synuclein performed fibril(PFF)mouse model.Level ofα-synuclein,phosphorylatedα-synuclein aggregates,dopaminergic neurons and motor function were evaluated 90 days after the treatment.To confirm that EVs derived from patients were suitable as a vehicle,proteomic analysis of EVs derived from control,initial and advanced Parkinson’s disease was performed.Results The shRNA-MCs could be successfully loaded into human RVG-EVs and downregulateα-synuclein in SHSY5Y cells.Intravenous injection of the shRNA-MC-loaded RVG-EVs induced long-term downregulation ofα-synuclein mRNA expression and protein level,decreasedα-synuclein aggregates,prevented dopaminergic cell death and ameliorated motor impairment in theα-synuclein PFF mouse model.Moreover,we confirmed that the EVs from PD patients are suitable as a personalized therapeutic vehicle.Conclusion Our study confirmed the therapeutic potential of shRNA-MCs delivered by human RVG-EVs for longterm treatment of neurodegenerative diseases.These results pave the way for clinical use of this approach.
基金funded by grants from the National Natural Science Foundation of China[81470434,81503074,81670265]Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study(Hunan Provincial Education Department document)[Approval number:2014-405]
文摘Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons （OSNs）f2J. Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechelfia Ir75a gene is generally recognized as a pseudogene in OSNs.
基金co-supported by the National Natural Science Foundation of China(No.61671453)the Anhui Province Natural Science Fund Project,China(No.1608085MF123)
文摘Radar Maneuvering Targets Tracking(RMTT) in clutter is a quite challenging issue due to the errors in the models and the varying dynamics of the processes. Modern radar tracking system calls for the adaptive signal and data processing algorithm urgently to adapt the uncertainty of the environment. The mechanism of human cognition can help persons cope with the similar diffi-culties in visual tracking. Inspired by human cognition mechanism, a comprehensive method for RMTT is proposed. In the method, the model transition probability in Interacting Multiple Model(IMM) and the validation gate can be adjusted dynamically with target maneuver;the waveform in radar transmitter can vary with the perception of the environment. Experimental results in cluttered scenes show that the proposed algorithm is more accurate for perceiving the environment and targets, and the waveform selection algorithm is better than that with fixed waveform.
文摘Inappropriate Met-hepatocyte growth factor/scatter factor （HGF/SF） signaling is a hallmark of most types of solid tumors in humans and often correlates with poor prognosis. There are several mechanisms by which Met signaling is deregulated including Met and/or HGF/SF overexpression, mutation, autocrine signaling, and ligand-independent activation. Because Met is an attractive therapeutic target for a multitude of cancers, extensive research towards finding Met and HGF/SF inhibitors is ongoing.？ In parallel with these efforts, several mouse models have been developed in our lab that will be valuable for preclinical testing of Met-targeted therapeutics.
文摘During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many people died before reaching adult- hood, nowadays most people survive. Hence average life ex- pectancy in 1800s was around 30-40, which was barely higher than it had been in Greek and Roman times （Finch, 2010）, but nowadays life expectancy in most modernised economies is around 75 - 80. This demographic shift, which has happened in only 200 years, has created a dramatic change in the causes of mortality. The major killers in the modern world are non- communicable diseases （NCDs）： principally cardiovascular disease, cancer and neurodegenerative disorders such as Alz- heimer＇s disease. A major factor that influences susceptibility to all these diseases is age. As we get older, our risk of developing these NCDs increases enormously. For example, the rate of breast cancer in females at age 15-19 is less than 10 per 100,000 population, but this increases to 100 at age 40-44, 275 at age 55--59 and 450 at age 85 ＋ （http：//www.cancerresearchuk.org/ cancer-info/cancerstats/types/breast/incidence/#age）. Ageing has consequently become a major medical, social and economic burden to many countries.
文摘In April 2009, after receiving ap- proval from the State Council, the Information Office of the State Council published the NationalHuman Rights Action Plan of China （2009-2010）. It is China＇s first national plan on the theme of human rights, and serves as a policy document of the current stage for advancing China＇s human rights in a comprehensive way. It is an important move to implement the constitutional principle of respect- ing and safeguarding human rights, and to promote sustainable development and social harmony. It is also a solemn commitment to the world made by the Chinese government on human rights.
基金a staged research result of"Outstanding Young Talent Development Program of Hunan Normal University"[140621]--a key program of 2016 Ministry of Education[DJA160266]under the 13th Five-Year Plan of National Education Science
文摘Poverty alleviation requires knowledge support. Targeted poverty alleviation, aiming to tackle rural poverty, needs to be supported by corresponding rural human resource development. Currently, China's human resource development in impoverished rural regions is faced with some major problems; a huge population distributed over a vast area, a lack of technological and cultural attainment, obsolete concepts, obsolete technical resources, and a significant gap between rural and urban education attainment. Rural human resource development, which is geared to targeted poverty alleviation, includes a variety of impoverished rural population-oriented trainings, such as intelligence development, skills training, modern professionalism &work attitude cultivation, physical & mental health education, as well as modern lifestyle & civilized manners guidance. Targeted poverty alleviation should be equipped with mechanisms of comprehensive layout & planning, coordinated advancement of development content and implementation, and a mechanism of organization & input. The approaches to the advancement of rural human resource development are enhancing basic education, building a system of vocational education and training, raising the social security level and improving the supporting mechanisms.
文摘Traumatic brain injury （TBI） is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as develop- ment, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma （miR-425-p, -21, -93, -191 and -499） and cerebro-spinal fluid （CSF） （miR-328, -362-3p, -451, -486a） as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TBI （e.g., miR-21, miR-23b）. MicroRNA profil- ing was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TBI （e.g., miR-21） have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in microRNA profiles in different age groups （children, adults, and elderly）.
基金supported by the grants from the National Basic Research Program of China(973 Program) awarded to N.L.(No.2011CBA01000) and L.L.(No. 2011CB944203)
文摘Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases,
文摘Parkinson＇s disease（PD） is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons. Oxidative stress is also recognized as one of the main causes of PD, and excessive reactive oxygen species（ROS） and reactive nitrogen species can lead to dopaminergic neuron vulnerability and eventual death. Micro RNAs control a range of physiological and pathological functions, and may serve as potential targets for intervention against PD to mitigate damage to the brain. Several studies have demonstrated that micro RNAs can regulate oxidative stress and prevent ROS-mediated damage to dopaminergic neurons, suggesting that specific micro RNAs may be putative targets for novel therapeutic strategies in PD. Recent human and animal studies have identified a large number of dysregulated micro RNAs in PD brain tissue samples, many of which were downregulated. The dysregulated micro RNAs affect downstream targets such as SNCA, PARK2, LRRK2, TNFSF13 B, LTA, SLC5 A3, PSMB2, GSR, GBA, LAMP-2 A, HSC. Apart from one study, none of the studies reviewed had used agomirs or antagomirs to reverse the levels of downregulated or upregulated micro RNAs, respectively, in mouse models of PD or with isolated human or mouse dopaminergic cells. Further large-scale studies of brain tissue samples collected with short postmortem interval from human PD patients are warranted to provide more information on the micro RNA profiles in different brain regions and to test for gender differences.
文摘Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.
基金AIDS Association of Inner Mongolia University for Nationalities,No.IMUN20190908.
文摘High genetic variability of human immunodeficiency virus(HIV)has been a major intractable challenge to the practical design of vaccines.But a recent pioneer study published in PNAS Xenobots,is likely to revolutionize HIV prevention as it presented the world's first living robot made of cells.In the advent of this discovery,we herein discuss the possibility of using living biological cell robots to target HIV-infected T lymphocytes,and the prospects of this approach being a new HIV vaccine.We capture the current research status and trend of advances in biological cell robots'design as a new HIV vaccine.The key differences between this novel vaccine and other HIV vaccines are highlighted.
基金KAKENHI(Grant-in-Aid for Scientific Research),No.23390329the National Cancer Center Research and Development Fund(23-A-9)
文摘Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancerresistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.
文摘Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in 2008.In the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong survival.Moreover,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)therapies.Trastuzumab,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy.Further,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field.Thus,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved.
