Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we i...Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.展开更多
We measured serum level of cortisol and lactate, the stiffness of trapezius, skin blood flow and VAS before and after the back massages of 25 senior college students, who had sent stressful days for 11 months starting...We measured serum level of cortisol and lactate, the stiffness of trapezius, skin blood flow and VAS before and after the back massages of 25 senior college students, who had sent stressful days for 11 months starting from April, preparing for the national license examination. These students usually had complaints of stiffness of shoulder and/or lumber. Back massages significantly reduced the level of serum cortisol from 8.85 ± 0.78 to 5.95 ± 0.68 μg/dl, without affecting that of lactate. The treatment also improved the stiffness of the trapezius of students with complaints from 63.24 ± 0.78 to 59.12 ± 0.78 after the treatment without affecting skin blood flow (SKBF). In addition, back massages reduced the VAS value at the same time. These results indicate that back massages of the student are effective to improve the physical and psychological conditions of the students.展开更多
The accumulation of amyloid β peptide 1 - 42 (Aβ1-42) in the brain of Alzheimer’s disease (AD) patients is known to be associated with neurodegeneration and memory impairment. More recently, we reported that madeca...The accumulation of amyloid β peptide 1 - 42 (Aβ1-42) in the brain of Alzheimer’s disease (AD) patients is known to be associated with neurodegeneration and memory impairment. More recently, we reported that madecassoside, an active component of Centella asiatica, improved memory impairment in an Aβ1-42 infusion rat model of AD, ameliorated neurotoxicity in SH-SY5Y cells, and inhibited in vitro Aβ1-42 fibril formation. In the present study, we investigated the utility of in silico analyses in corroborating observed in vivo and in vitro effects of madecassoside in AD to further assess the therapeutic benefits of madecassoside. The 3D structure of Aβ1-42 was downloaded from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). The binding of madecassoside to Aβ1-42 was assessed by molecular docking. The chemical structure of madecassoside was modeled and converted to the PDB format. Madecassoside was found to successfully dock with Aβ1-42. Computational demonstration of the binding of madecassoside to Aβ1-42 further corroborated the inhibitory effect of madecassoside on Aβ1-42 fibrillogenesis which was demonstrated in our previous study. These data showed the potential utility of madecassoside as a preventive medication in Aβ1-42-induced neurodegenerative diseases such as AD.展开更多
The accumulation of amyloid β peptide<sub>1-42</sub> (Aβ<sub>1-42</sub>) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We ha...The accumulation of amyloid β peptide<sub>1-42</sub> (Aβ<sub>1-42</sub>) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ<sub>1-42</sub> curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ<sub>1-42</sub> were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ<sub>1-42</sub>. Computational analyses of the binding of DHA to Aβ<sub>1-42</sub>, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ<sub>1-42</sub> fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.展开更多
Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common ...Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.展开更多
Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e....Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.展开更多
This article reviews the effectiveness of intratympanic corticosteroids for vertigo control in Meniere's disease at 2-years follow-up according to the guidelines expressed by the American Academy of Otolaryngology...This article reviews the effectiveness of intratympanic corticosteroids for vertigo control in Meniere's disease at 2-years follow-up according to the guidelines expressed by the American Academy of Otolaryngology-Head & Neck Surgery. Despite the increased use of intratympanic corticosteroids for vertigo control in Meniere's disease there is debate as to their effectiveness, particularly compared to gentamicin. Even so,after just a single course of injections, corticosteroids can reliably provide complete vertigo control(Class A) at 2-years in about 50% of cases as indicated in a recent double-blind randomized controlled clinical trial(Patel et al., 2016). But the effectiveness of intratympanic corticosteroids truly increases when treatment is provided 'as-needed', whereby complete vertigo control is established in up to 91% of cases. On the basis of available literature, there is good evidence to recommend the use of intratympanic steroid treatment for vertigo control in Meniere's disease, but patients must be monitored for non-response. The rationale for treating patients as-needed and the possible reasons for corticosteroid nonresponse are discussed.展开更多
Huntington's disease(HD) is a progressive and fatal neurodegenerative disorder caused by an expanded tri-nucleotide CAG sequence in huntingtin gene(HTT) on chromosome 4. HD manifests with chorea, cognitive and psy...Huntington's disease(HD) is a progressive and fatal neurodegenerative disorder caused by an expanded tri-nucleotide CAG sequence in huntingtin gene(HTT) on chromosome 4. HD manifests with chorea, cognitive and psychiatric symptoms. Although advances in genetics allow identification of individuals carrying the HD gene, much is still unknown about the mechanisms underly-ing the development of overt clinical symptoms and the transitional period between premanifestation and mani-festation of the disease. HD has no cure and patients rely only in symptomatic treatment. There is an urgent need to identify biomarkers that are able to monitor disease progression and assess the development and efficacy of novel disease modifying drugs. Over the past years, neuroimaging techniques such as magnetic resonance imaging(MRI) and positron emission tomog-raphy(PET) have provided important advances in our understanding of HD. MRI provides information about structural and functional organization of the brain, while PET can detect molecular changes in the brain. MRI and PET are able to detect changes in the brains of HD gene carriers years ahead of the manifestation of the dis-ease and have also proved to be powerful in assessingdisease progression. However, no single technique hasbeen validated as an optimal biomarker. An integrativemultimodal imaging approach, which combines differ-ent MRI and PET techniques, could be recommendedfor monitoring potential neuroprotective and preventivetherapies in HD. In this article we review the currentneuroimaging literature in HD.展开更多
In an attempt to study the relationship between sleep postures and sleep parameters assessed by actigraphy, we applied the newly developed Activity Monitoring and Evaluation System (A-MES) and actigraphy at the same t...In an attempt to study the relationship between sleep postures and sleep parameters assessed by actigraphy, we applied the newly developed Activity Monitoring and Evaluation System (A-MES) and actigraphy at the same time to younger and senior Japanese volunteer groups. It was found that sleep postures and diurnal activity determines, to some extent, sleep parameters including activity mean score (AMS), activity index (ACTX), waking episodes (WEP) and sleep fragmentation index (SFX). It was also found that sleep properties are different in younger and senior Japanese. For example, increase in the proportion of time in the supine position resulted in enhancement and deterioration of the sleep in the younger and senior groups, respectively. Furthermore, there were correlations between supine posture and AMS, ACTX, SFX, total minutes scored as awake (TMSA) and WEP obtained by actigraphy in the younger group, but only AMS and ACTX in senior group. In addition, we also assessed sleep parameters by use of questionnaires, and found that objective sleep quality was rather poor but subjective sleep quality was better in the senior group. In the younger group, in contrast, objective sleep quality was better but subjective sleep quality was poor. On the other hand, there was no correlation between sleep parameters assessed by actigraphy and self-report at all. The present study with A-MES and actigraphy provides the first evidence that sleep posture affects sleep quality and is a convenient, inexpensive and home-based method for studying sleep.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81871024 (to HN),82301957 (to XW),82001382 (to LL),62127810 (to HN)the Natural Science Foundation of Jiangsu Province of China,No.SBK2020040785 (to LL)。
文摘Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.
文摘We measured serum level of cortisol and lactate, the stiffness of trapezius, skin blood flow and VAS before and after the back massages of 25 senior college students, who had sent stressful days for 11 months starting from April, preparing for the national license examination. These students usually had complaints of stiffness of shoulder and/or lumber. Back massages significantly reduced the level of serum cortisol from 8.85 ± 0.78 to 5.95 ± 0.68 μg/dl, without affecting that of lactate. The treatment also improved the stiffness of the trapezius of students with complaints from 63.24 ± 0.78 to 59.12 ± 0.78 after the treatment without affecting skin blood flow (SKBF). In addition, back massages reduced the VAS value at the same time. These results indicate that back massages of the student are effective to improve the physical and psychological conditions of the students.
文摘The accumulation of amyloid β peptide 1 - 42 (Aβ1-42) in the brain of Alzheimer’s disease (AD) patients is known to be associated with neurodegeneration and memory impairment. More recently, we reported that madecassoside, an active component of Centella asiatica, improved memory impairment in an Aβ1-42 infusion rat model of AD, ameliorated neurotoxicity in SH-SY5Y cells, and inhibited in vitro Aβ1-42 fibril formation. In the present study, we investigated the utility of in silico analyses in corroborating observed in vivo and in vitro effects of madecassoside in AD to further assess the therapeutic benefits of madecassoside. The 3D structure of Aβ1-42 was downloaded from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). The binding of madecassoside to Aβ1-42 was assessed by molecular docking. The chemical structure of madecassoside was modeled and converted to the PDB format. Madecassoside was found to successfully dock with Aβ1-42. Computational demonstration of the binding of madecassoside to Aβ1-42 further corroborated the inhibitory effect of madecassoside on Aβ1-42 fibrillogenesis which was demonstrated in our previous study. These data showed the potential utility of madecassoside as a preventive medication in Aβ1-42-induced neurodegenerative diseases such as AD.
文摘The accumulation of amyloid β peptide<sub>1-42</sub> (Aβ<sub>1-42</sub>) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ<sub>1-42</sub> curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ<sub>1-42</sub> were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ<sub>1-42</sub>. Computational analyses of the binding of DHA to Aβ<sub>1-42</sub>, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ<sub>1-42</sub> fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.
基金funded by Ministry of Education,University and Research(MIUR)ex-60% research fund University of Brescia,Italy
文摘Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.
基金funded by Ministry of Education,University and Research(MIUR)ex-60%research fund University of Brescia,Italy.Emilio Merlo Pich is employee of Takeda Pharmaceutical International AG
文摘Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.
基金supported by the National Institute for Health Research(NIHR)Imperial Biomedical Research Centre
文摘This article reviews the effectiveness of intratympanic corticosteroids for vertigo control in Meniere's disease at 2-years follow-up according to the guidelines expressed by the American Academy of Otolaryngology-Head & Neck Surgery. Despite the increased use of intratympanic corticosteroids for vertigo control in Meniere's disease there is debate as to their effectiveness, particularly compared to gentamicin. Even so,after just a single course of injections, corticosteroids can reliably provide complete vertigo control(Class A) at 2-years in about 50% of cases as indicated in a recent double-blind randomized controlled clinical trial(Patel et al., 2016). But the effectiveness of intratympanic corticosteroids truly increases when treatment is provided 'as-needed', whereby complete vertigo control is established in up to 91% of cases. On the basis of available literature, there is good evidence to recommend the use of intratympanic steroid treatment for vertigo control in Meniere's disease, but patients must be monitored for non-response. The rationale for treating patients as-needed and the possible reasons for corticosteroid nonresponse are discussed.
文摘Huntington's disease(HD) is a progressive and fatal neurodegenerative disorder caused by an expanded tri-nucleotide CAG sequence in huntingtin gene(HTT) on chromosome 4. HD manifests with chorea, cognitive and psychiatric symptoms. Although advances in genetics allow identification of individuals carrying the HD gene, much is still unknown about the mechanisms underly-ing the development of overt clinical symptoms and the transitional period between premanifestation and mani-festation of the disease. HD has no cure and patients rely only in symptomatic treatment. There is an urgent need to identify biomarkers that are able to monitor disease progression and assess the development and efficacy of novel disease modifying drugs. Over the past years, neuroimaging techniques such as magnetic resonance imaging(MRI) and positron emission tomog-raphy(PET) have provided important advances in our understanding of HD. MRI provides information about structural and functional organization of the brain, while PET can detect molecular changes in the brain. MRI and PET are able to detect changes in the brains of HD gene carriers years ahead of the manifestation of the dis-ease and have also proved to be powerful in assessingdisease progression. However, no single technique hasbeen validated as an optimal biomarker. An integrativemultimodal imaging approach, which combines differ-ent MRI and PET techniques, could be recommendedfor monitoring potential neuroprotective and preventivetherapies in HD. In this article we review the currentneuroimaging literature in HD.
文摘In an attempt to study the relationship between sleep postures and sleep parameters assessed by actigraphy, we applied the newly developed Activity Monitoring and Evaluation System (A-MES) and actigraphy at the same time to younger and senior Japanese volunteer groups. It was found that sleep postures and diurnal activity determines, to some extent, sleep parameters including activity mean score (AMS), activity index (ACTX), waking episodes (WEP) and sleep fragmentation index (SFX). It was also found that sleep properties are different in younger and senior Japanese. For example, increase in the proportion of time in the supine position resulted in enhancement and deterioration of the sleep in the younger and senior groups, respectively. Furthermore, there were correlations between supine posture and AMS, ACTX, SFX, total minutes scored as awake (TMSA) and WEP obtained by actigraphy in the younger group, but only AMS and ACTX in senior group. In addition, we also assessed sleep parameters by use of questionnaires, and found that objective sleep quality was rather poor but subjective sleep quality was better in the senior group. In the younger group, in contrast, objective sleep quality was better but subjective sleep quality was poor. On the other hand, there was no correlation between sleep parameters assessed by actigraphy and self-report at all. The present study with A-MES and actigraphy provides the first evidence that sleep posture affects sleep quality and is a convenient, inexpensive and home-based method for studying sleep.
