Type 2 diabetes is a risk factor for Alzheimer’s disease and Parkinson’s disease. Insulin signaling in the brains of people with Alzheimer’s disease or Parkinson’s disease is impaired. Preclinical studies of growt...Type 2 diabetes is a risk factor for Alzheimer’s disease and Parkinson’s disease. Insulin signaling in the brains of people with Alzheimer’s disease or Parkinson’s disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alz-heimer’s disease and Parkinson’s disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer’s disease and Parkinson’s disease. On the basis of these promising ifndings, several clinical trials are ongoing with the ifrst encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer’s disease and Parkinson’s disease that are currently unavailable.展开更多
Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain inclu...Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.展开更多
OBJECTIVE： To investigate the neuroprotective mechanism of combination extract of Renshen （Ponax Ginseng）, Yinyanghuo （Herba Epimedii Brevi-comus）, Yuanzhi （Radix Palygalae） and Jianghuang （Rhizoma Curcumae Lo...OBJECTIVE： To investigate the neuroprotective mechanism of combination extract of Renshen （Ponax Ginseng）, Yinyanghuo （Herba Epimedii Brevi-comus）, Yuanzhi （Radix Palygalae） and Jianghuang （Rhizoma Curcumae Longae） （GEPT） in treating AI- zheimer＇s disease on the target of glycogen syn- thase kinase 3β（GSK-3β）. METHODS： Three-month-old APPV7171 transgenic mice were randomly divided into ten groups （n=12 per group） and intragastrically administrated vehi- cle or medicines： APP group was given 0.5% CMC, donepezil group was given donepezil （APP ＋ D group） （0.92 mg/kg-1. day-1）, and GEPT groups were given small dose of GEPT （APP＋Gs group） （0.075 g/ kg-1. day-1）, medium dose （APP＋Gm group） （0.15 g/ kg-1. day-1）, and large dose （APP＋GI group） （0.30 g/ kg-1. day-1） for 4 or 8 months, respectively. Three-month-old C57BL/6J mice as vehicle controls （n=12） were given 0.5% CMC for 4 or 8 months as well. The GSK-3β expression in the cortex of 7- and 11-month-old APPV7171 transgenic mice with and without GEPT or donepezil treatment and normal C57BL/6J mice were measured via Western blotting and Immunohistochemistry. RESULTS： Immunohistochemistry analysis showed significant increase of GSK-3β in the cerebral cortex of 7-month-old APP group （compare to control group P=0.003）, while the GSK-313 expression of donepezil or OEPT group were all significantly de-creased （Donepezil vs APP： P=0.041; GI vs APP： P=0.049, Gm vs APP： P=0.029, Gh vs APP： P=0.036）. Western blot analysis showed similar results. The densitometric measures of GSK-3β in APP mice in- creased significantly as compared with the control group （P=0.008）. And the GSK-3β expression indonepezil and GEPT groups were all decreased. There was significant difference between Gh group or donepezil group and the control group （P=0.05）. Similar findings were shown in the 11-month-old mice in each group, except for greater decrease of GSK-3β in the GEPT group. CONCLUSION： GEPT can effectively decrease the level of GSK-3β expression in the brain cortex of AP- PV7171 transgenic mice, and such effect is more sig- nificant in 11-month-old mice. This partially ex- plains the neuroprotecting mechanism of GEPT in preventing and treating of AD.展开更多
The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activati...The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.展开更多
We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subs...We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subsequent reorganization of extracellular matrix assembly correlates to the restoration of impaired vestibular function. The tenascin-R has repelling effect on pathfinding during axonal growth/regrowth, and thus inhibits neural circuit repair. By using immunohistochemical method, we studied the modification of tenascin-R expression in the superior, medial, lateral, and descending vestibular nuclei of the rat following unilateral labyrin- thectomy. On postoperative day 1, tenascin-R reaction in the perineuronal nets disappeared on the side of labyrinthectomy in the superior, lateral, medial, and rostral part of the descending vestibular nuclei. On survival day 3, the staining intensity of tenascin-R reaction in perineuronal nets recovered on the operated side of the medial vestibular nucleus, whereas it was restored by the time of postoperative day 7 in the superior, lateral and rostral part of the descending vestib- ular nuclei. The staining intensity of tenascin-R reaction remained unchanged in the caudal part of the descending vestibular nucleus bilaterally. Regional differences in the modification of tena- scin-R expression presented here may be associated with different roles of individual vestibular nuclei in the compensatory processes. The decreased expression of the tenascin-R may suggest the extracellular facilitation of plastic modifications in the vestibular neural circuit after lesion of the labyrinthine receptors.展开更多
Damage to the vestibular sense organs evokes static and dynamic deficits in the eye movements,posture and vegetative functions.After a shorter or longer period of time,the vestibular function is partially or completel...Damage to the vestibular sense organs evokes static and dynamic deficits in the eye movements,posture and vegetative functions.After a shorter or longer period of time,the vestibular function is partially or completely restored via a series of processes such as modification in the efficacy of synaptic inputs.As the plasticity of adult central nervous system is associated with the alteration of extracellular matrix,including its condensed form,the perineuronal net,we studied the changes of brevican expression in the perineuronal nets of the superior vestibular nucleus after unilateral labyrinth lesion.Our results demonstrated that the unilateral labyrinth lesion and subsequent compensation are accompanied by the changing of brevican staining pattern in the perineuronal nets of superior vestibular nucleus of the rat.The reduction of brevican in the perineuronal nets of superior vestibular nucleus may contribute to the vestibular plasticity by suspending the non-permissive role of brevican in the restoration of perineuronal net assembly.After a transitory decrease,the brevican expression restored to the control level parallel to the partial restoration of impaired vestibular function.The bilateral changing in the brevican expression supports the involvement of commissural vestibular fibers in the vestibular compensation.All experimental procedures were approved by the 'University of Debrecen–Committee of Animal Welfare'(approval No.6/2017/DEMAB) and the 'Scientific Ethics Committee of Animal Experimentation'(approval No.HB/06/éLB/2270-10/2017;approved on June 6,2017).展开更多
AIM: To determine real life clinical outcomes in poorly responsive and treatment-nave neovascular age-related macular degeneration(nv AMD) patients using bimonthly fixed dosing aflibercept regimen.METHODS: This was a ...AIM: To determine real life clinical outcomes in poorly responsive and treatment-nave neovascular age-related macular degeneration(nv AMD) patients using bimonthly fixed dosing aflibercept regimen.METHODS: This was a retrospective study of 165 eyes with nv AMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata(PRN) ranibizumab/bevacizumab due to poor response(107 eyes), or treatment- nave( 58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity(BCVA) and central retinal thickness(CRT)from baseline were assessed using the Wilcoxon signedrank test. The proportion of patients maintaining BCVA(<15 letters loss) at 12 mo was also evaluated.RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and nave aflibercept groups respectively(P <0.01). BCVA was maintained in 95.3% of switched and 96.6% of nave patients. CRT at month 12 showed a decrease of -6.16 μm in the switched group and -35.36 μm in the nave group(P <0.01).Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6 mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections(nave group), 7.5 injections(switched group) and 4 clinic visits per year.CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-nave and poorly responsive nv AMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.展开更多
A nonlinear autoregressive approach with exogenous input is used as a novel method for statistical forecasting of the disturbance storm time index, a measure of space weather related to the ring current which surround...A nonlinear autoregressive approach with exogenous input is used as a novel method for statistical forecasting of the disturbance storm time index, a measure of space weather related to the ring current which surrounds the Earth, and fluctuations in disturbance storm time field strength as a result of incoming solar particles. This ring current produces a magnetic field which opposes the planetary geomagnetic field. Given the occurrence of solar activity hours or days before subsequent geomagnetic fluctuations and the potential effects that geomagnetic storms have on terrestrial systems, it would be useful to be able to predict geophysical parameters in advance using both historical disturbance storm time indices and external input of solar winds and the interplanetary magnetic field. By assessing various statistical techniques it is determined that artificial neural networks may be ideal for the prediction of disturbance storm time index values which may in turn be used to forecast geomagnetic storms. Furthermore, it is found that a Bayesian regularization neural network algorithm may be the most accurate model compared to both other forms of artificial neural network used and the linear models employing regression analyses.展开更多
AIM:To provide an epidemiological characterization of ocular cicatricial pemphigoid(OCP)in Colombia.METHODS:We conducted a cross-sectional study using SISPRO.We applied the specific code of the International Classific...AIM:To provide an epidemiological characterization of ocular cicatricial pemphigoid(OCP)in Colombia.METHODS:We conducted a cross-sectional study using SISPRO.We applied the specific code of the International Classification of Diseases for Ocular Pemphigoid,from 2009-2019 to estimate prevalence,incidence,and the demographic status of the disease in Colombia.RESULTS:The estimated average prevalence was 0.22 per 1000000 inhabitants,and the estimated average incidence was 0.24 per 1000000 inhabitants.With a female predominance of 62.5%,and a male/female ratio of 1:1.6.The group of patients diagnosed with the disease after the age of 80 presented the highest prevalence.The departments with the highest prevalence were Antioquia,Bogotá,and Santander.CONCLUSION:There are important differences between worldwide and Colombian prevalence and incidence data,which may be related to genetic and epigenetic factors,and the possible underdiagnosis of the disease.According to the results,OCP is an extremely rare disease in Colombia.Nevertheless,it is important to encourage awareness of the disease due to its devastating consequences.展开更多
Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). I...Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). In recent decades, several studies have come to the understanding that genetic factors play a major role in the risk for a large number of NPDs. However, few neuropsychiatric genetics studies have been published from LMICs. In this Editorial, we discuss important issues impinging on advances in neuropsychiatric genetics research in LMICs. It is essential that scientists educate policymakers and officials of funding agencies on the importance of providing adequate funding for research in these areas. Development of local well-supported research programs focused on NPD genetics should be an important asset to develop; it would facilitate the establishment of sustainable research efforts that could lead to appropriate diagnosis and specific, affordable and feasible interventions in LMICs. It is important to point out that research into the biological basis of human NPDs is not only an academic effort reserved for a few elite institutions in economically developed countries, but it is vitally important for the mental health of people around the world.展开更多
Until recently, the synaptic transmission and excitatory amino acid transporters activation of neurons are very well discussed in the previous studies and are considered to be the two distinct features of Synapse. It ...Until recently, the synaptic transmission and excitatory amino acid transporters activation of neurons are very well discussed in the previous studies and are considered to be the two distinct features of Synapse. It is also found that a large number of interactions take place in the domain of ionic exchanges and protein interactions in synapses. It is evolutionary to have destined to release of Neurotransmitters to conduct an impulse to the other consecutive neurons, which forms the most important characteristic of synapse. From the popular perspective, it has been identified that detailed theoretical closer correlation of data produced through various studies about synapse can unravel many mysteries related to functions of synapse. Hence, this research paper tries to concentrate on a selected group of prominent characteristics and properties of synapse and also highlights some noteworthy discoveries, emphasizing the influential capabilities of them in the thought process and improving the knowledge of the field. It also highlights the expressive properties and forms of synapse brought out through the evidences available in sparse to dense data in a correlational way.展开更多
Background: Antiparkinsonian pharmacotherapy represents one of the most important expenses related to Parkinson’s disease. The application of generic drugs may help to reduce the economic burden of the disease;howeve...Background: Antiparkinsonian pharmacotherapy represents one of the most important expenses related to Parkinson’s disease. The application of generic drugs may help to reduce the economic burden of the disease;however, efficacy and safety of these products have been less studied. Objective: To investigate the efficacy and safety of generic rasagiline (Ralago?) from a clinical perspective. Methods: The Clinical Global Impression of Severity scale was used to rate the most important motor and non-motor symptoms at baseline and 12 weeks after the initiation of Ralago?. Patients also identified symptoms which were the main sources of their disability and distress in everyday life. Results: A total of 499 patients were enrolled (231 females, mean age: 73.2 ± 9.1 years, mean duration of disease: 3.6 ± 3.7 years). Of them, 486 patients completed the study protocol. Both motor and non-motor symptoms showed improvement during 12-week Ralago? treatment. Adverse events were rare, and the majority of them were not considered as serious. Conclusions: The generic rasagiline (Ralago?) is an effective and safe generic product.展开更多
Magnetic resonance imaging(MRI)has become the gold standard for the diagnosis of many pathologies.Using MRI in patients with auditory implants can however raise concerns due to mutual interactions between the implant ...Magnetic resonance imaging(MRI)has become the gold standard for the diagnosis of many pathologies.Using MRI in patients with auditory implants can however raise concerns due to mutual interactions between the implant and imaging device,resulting in potential patient risks.Several implant manufacturers have been working towards more MRI safe devices.Older devices are however often labelled for more stringent conditions,possibly creating confusion with patients and professionals.With this myriad of different devices that are implanted in patients for lifetimes of at least 20 years,it is crucial that both patients and professionals have a clear understanding of the safety of their devices.This work aims at providing an exhaustive overview on the MRI safety of active auditory implants.The available industry standards that are followed by manufacturers are outlined and an overview of the latest scientific developments focusing on the last five years is provided.In addition,based on the analysis of the adverse events reported to the Food and Drug Administration(FDA)and in literature within the past ten years,a systematic review of the most commonly occurring issues for patients with auditory implants in the MRI environment is provided.Results indicate that despite the release of more MRI conditional active hearing implants on the market,adverse events still occur.An extensive overview is provided on the MRI safety of active auditory implants,aiming to increase the understanding of the topic for healthcare professionals and contribute to safer scanning conditions for patients.展开更多
Objective: To investigate the impact of possession of the -889 C/T polymorphi sm of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the int erleukin 1B gene (IL-1B) on the extent of neuroinflammation ...Objective: To investigate the impact of possession of the -889 C/T polymorphi sm of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the int erleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alz heimers disease (AD), as demonstrated by the degree of microglial cell activit y associated with each IL-1A and IL-1B genotype. Method: Microglial cell activ ity within the frontal cortex was determined in 68 patients with necropsy confir med AD by image analysis as the percentage area of tissue occupied by ferritin i mmunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracte d from frontal cortex or cerebellum. Results: The microglial cell load was 31%g reater in patients with IL-1A T allele, 62%greater with IL1A TT genotype, but 108%greater with IL-1A TT genotype in combination with APOE 4 allele. No effec ts on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone. Conclusions: Polymorphisms within IL-1A influence the degree of brain microgli al cell activation, especially in bearers of APOE 4 allele, reinforcing the impo rtance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.展开更多
Background Methylmalonic acidemia （MMA） is a multifactorial autosomal recessive inborn error of organic acid metabolism, often presenting with neurological symptoms. As neurological disorders are often related to wh...Background Methylmalonic acidemia （MMA） is a multifactorial autosomal recessive inborn error of organic acid metabolism, often presenting with neurological symptoms. As neurological disorders are often related to white matter injury, diffusion tensor imaging （DTI） is an excellent tool for assessment of white matter injury and possibly for diagnosing this disorder. Methods We retrospectively analyzed DTI images of 12 patients with MMA （7 males, 5 females, age range： 7-12 months, mean age： 9.25±1.70 months） with negative MRI findings. And another 12 age-matched and gender-matched infants were enrolled as control subjects. Fractional anisotropy （FA） of different white matter tracts of the brain was measured in both groups. Results For patients with negative MRI findings, compared with healthy infants, a statistically significant reduction in DTI FA value of the frontal white matter, temporal white matter, and occipital white matter was observed （P〈0.01）. Conclusions In addition to conventional TlW and T2W MR Image, Brain DTI presents a useful, sensitive and complementary tool for the assessment of brain damage in patients with MMA.展开更多
Memory impairment in children is an ongoing issue worldwide related to a learning disability. This neurobiological condition has been suggested to associate with bisphenol A (BPA) exposure during pregnancy. BPA is an ...Memory impairment in children is an ongoing issue worldwide related to a learning disability. This neurobiological condition has been suggested to associate with bisphenol A (BPA) exposure during pregnancy. BPA is an inorganic compound used to produce polycarbonate plastics and epoxy resins. We conduct this study to investigate the effects of prenatal BPA exposure on the level of the N-methyl-D-aspartate (NMDA) receptor subunits, synaptic markers of the hippocampus and neurobehavioral outcomes in rats. The pregnant rats were given a daily dose of 5 mg/kg and 50 mg/kg of BPA with 0.5% Tween 80 orally from gestation day 2 until 21 (GD21). The level of GluN2A, GluN2B, PSD-95 and synapsin I in the hippocampus and its neurobehaviour outcomes were quantified and evaluated in the male foetus and adolescent rat. Prenatal BPA exposure reduced GluN2A, GluN2B, synapsin I and PSD-95 (Postsynaptic Density-95) in the male foetus and adolescent rat hippocampus compared to the control group. The prenatal BPA exposed rats demonstrated anxiety-related behaviour and impairment in aversive and spatial memory. The findings suggested that the impairment in neurobehavioral performance may inhibit the signalling pathway in the NMDA receptor subunits in the male foetus rat hippocampus leading to learning and memory deficits when reaching adolescence.展开更多
文摘Type 2 diabetes is a risk factor for Alzheimer’s disease and Parkinson’s disease. Insulin signaling in the brains of people with Alzheimer’s disease or Parkinson’s disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alz-heimer’s disease and Parkinson’s disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer’s disease and Parkinson’s disease. On the basis of these promising ifndings, several clinical trials are ongoing with the ifrst encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer’s disease and Parkinson’s disease that are currently unavailable.
文摘Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.
基金Supported by Grant from the Innovative Research Team for Alzheimer's Disease's Prevention and Treatment of Ministry of Education of China (No. IRT-08-010)the Project on Absorption of Intellects by Institutions of Higher Education for Academic Disciplinary Innovations (the "111 Project") (No.B08006)+5 种基金the National Natural Science Foundation of China(No. 30973738)the National Key Technology R & D Program(No. 2009BA177B09)the Technological Platform of Clinical Evaluation and Research for New Herbal Medicinal Products(No. 2011ZX09302-006-01)the Innovative Research Team in Beijing University of Chinese Medicine (No. 2011-CXTD-21)Research Fund of Capital Medical Development (No.SF-2009-Ⅲ-11)the Study of Secondary Prevention with Chinese Herbal Medicine for Chronic Diseases (No.Z111107056811043)
文摘OBJECTIVE： To investigate the neuroprotective mechanism of combination extract of Renshen （Ponax Ginseng）, Yinyanghuo （Herba Epimedii Brevi-comus）, Yuanzhi （Radix Palygalae） and Jianghuang （Rhizoma Curcumae Longae） （GEPT） in treating AI- zheimer＇s disease on the target of glycogen syn- thase kinase 3β（GSK-3β）. METHODS： Three-month-old APPV7171 transgenic mice were randomly divided into ten groups （n=12 per group） and intragastrically administrated vehi- cle or medicines： APP group was given 0.5% CMC, donepezil group was given donepezil （APP ＋ D group） （0.92 mg/kg-1. day-1）, and GEPT groups were given small dose of GEPT （APP＋Gs group） （0.075 g/ kg-1. day-1）, medium dose （APP＋Gm group） （0.15 g/ kg-1. day-1）, and large dose （APP＋GI group） （0.30 g/ kg-1. day-1） for 4 or 8 months, respectively. Three-month-old C57BL/6J mice as vehicle controls （n=12） were given 0.5% CMC for 4 or 8 months as well. The GSK-3β expression in the cortex of 7- and 11-month-old APPV7171 transgenic mice with and without GEPT or donepezil treatment and normal C57BL/6J mice were measured via Western blotting and Immunohistochemistry. RESULTS： Immunohistochemistry analysis showed significant increase of GSK-3β in the cerebral cortex of 7-month-old APP group （compare to control group P=0.003）, while the GSK-313 expression of donepezil or OEPT group were all significantly de-creased （Donepezil vs APP： P=0.041; GI vs APP： P=0.049, Gm vs APP： P=0.029, Gh vs APP： P=0.036）. Western blot analysis showed similar results. The densitometric measures of GSK-3β in APP mice in- creased significantly as compared with the control group （P=0.008）. And the GSK-3β expression indonepezil and GEPT groups were all decreased. There was significant difference between Gh group or donepezil group and the control group （P=0.05）. Similar findings were shown in the 11-month-old mice in each group, except for greater decrease of GSK-3β in the GEPT group. CONCLUSION： GEPT can effectively decrease the level of GSK-3β expression in the brain cortex of AP- PV7171 transgenic mice, and such effect is more sig- nificant in 11-month-old mice. This partially ex- plains the neuroprotecting mechanism of GEPT in preventing and treating of AD.
基金supported by the European Union Grant Alehoop(H2020-BBIJTI-2019-887259)And from the Xunta de Galicia(Centro singular de Investigación de Galicia accreditation 2016-2019),ED431 G/02(to FM)。
文摘The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.
基金supported by a grant from the Hungarian Academy of Sciences(MTA-TKI 11008)a grant from the European Union and the State of Hungarythe European Social Fund in the framework of TáMOP-4.2.4.A/2-11/1-2012-0001‘National Excellence Program’
文摘We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subsequent reorganization of extracellular matrix assembly correlates to the restoration of impaired vestibular function. The tenascin-R has repelling effect on pathfinding during axonal growth/regrowth, and thus inhibits neural circuit repair. By using immunohistochemical method, we studied the modification of tenascin-R expression in the superior, medial, lateral, and descending vestibular nuclei of the rat following unilateral labyrin- thectomy. On postoperative day 1, tenascin-R reaction in the perineuronal nets disappeared on the side of labyrinthectomy in the superior, lateral, medial, and rostral part of the descending vestibular nuclei. On survival day 3, the staining intensity of tenascin-R reaction in perineuronal nets recovered on the operated side of the medial vestibular nucleus, whereas it was restored by the time of postoperative day 7 in the superior, lateral and rostral part of the descending vestib- ular nuclei. The staining intensity of tenascin-R reaction remained unchanged in the caudal part of the descending vestibular nucleus bilaterally. Regional differences in the modification of tena- scin-R expression presented here may be associated with different roles of individual vestibular nuclei in the compensatory processes. The decreased expression of the tenascin-R may suggest the extracellular facilitation of plastic modifications in the vestibular neural circuit after lesion of the labyrinthine receptors.
基金supported by the Hungarian Academy of Sciences–Office for Supported Research Groups:MTA-TKI 355University of Debrecen–Medical and Health Sciences Center Bridging FundHungarian Scientific Research Fund K115471.Obtained by Clara Matesz and colleagues。
文摘Damage to the vestibular sense organs evokes static and dynamic deficits in the eye movements,posture and vegetative functions.After a shorter or longer period of time,the vestibular function is partially or completely restored via a series of processes such as modification in the efficacy of synaptic inputs.As the plasticity of adult central nervous system is associated with the alteration of extracellular matrix,including its condensed form,the perineuronal net,we studied the changes of brevican expression in the perineuronal nets of the superior vestibular nucleus after unilateral labyrinth lesion.Our results demonstrated that the unilateral labyrinth lesion and subsequent compensation are accompanied by the changing of brevican staining pattern in the perineuronal nets of superior vestibular nucleus of the rat.The reduction of brevican in the perineuronal nets of superior vestibular nucleus may contribute to the vestibular plasticity by suspending the non-permissive role of brevican in the restoration of perineuronal net assembly.After a transitory decrease,the brevican expression restored to the control level parallel to the partial restoration of impaired vestibular function.The bilateral changing in the brevican expression supports the involvement of commissural vestibular fibers in the vestibular compensation.All experimental procedures were approved by the 'University of Debrecen–Committee of Animal Welfare'(approval No.6/2017/DEMAB) and the 'Scientific Ethics Committee of Animal Experimentation'(approval No.HB/06/éLB/2270-10/2017;approved on June 6,2017).
文摘AIM: To determine real life clinical outcomes in poorly responsive and treatment-nave neovascular age-related macular degeneration(nv AMD) patients using bimonthly fixed dosing aflibercept regimen.METHODS: This was a retrospective study of 165 eyes with nv AMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata(PRN) ranibizumab/bevacizumab due to poor response(107 eyes), or treatment- nave( 58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity(BCVA) and central retinal thickness(CRT)from baseline were assessed using the Wilcoxon signedrank test. The proportion of patients maintaining BCVA(<15 letters loss) at 12 mo was also evaluated.RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and nave aflibercept groups respectively(P <0.01). BCVA was maintained in 95.3% of switched and 96.6% of nave patients. CRT at month 12 showed a decrease of -6.16 μm in the switched group and -35.36 μm in the nave group(P <0.01).Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6 mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections(nave group), 7.5 injections(switched group) and 4 clinic visits per year.CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-nave and poorly responsive nv AMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.
文摘A nonlinear autoregressive approach with exogenous input is used as a novel method for statistical forecasting of the disturbance storm time index, a measure of space weather related to the ring current which surrounds the Earth, and fluctuations in disturbance storm time field strength as a result of incoming solar particles. This ring current produces a magnetic field which opposes the planetary geomagnetic field. Given the occurrence of solar activity hours or days before subsequent geomagnetic fluctuations and the potential effects that geomagnetic storms have on terrestrial systems, it would be useful to be able to predict geophysical parameters in advance using both historical disturbance storm time indices and external input of solar winds and the interplanetary magnetic field. By assessing various statistical techniques it is determined that artificial neural networks may be ideal for the prediction of disturbance storm time index values which may in turn be used to forecast geomagnetic storms. Furthermore, it is found that a Bayesian regularization neural network algorithm may be the most accurate model compared to both other forms of artificial neural network used and the linear models employing regression analyses.
文摘AIM:To provide an epidemiological characterization of ocular cicatricial pemphigoid(OCP)in Colombia.METHODS:We conducted a cross-sectional study using SISPRO.We applied the specific code of the International Classification of Diseases for Ocular Pemphigoid,from 2009-2019 to estimate prevalence,incidence,and the demographic status of the disease in Colombia.RESULTS:The estimated average prevalence was 0.22 per 1000000 inhabitants,and the estimated average incidence was 0.24 per 1000000 inhabitants.With a female predominance of 62.5%,and a male/female ratio of 1:1.6.The group of patients diagnosed with the disease after the age of 80 presented the highest prevalence.The departments with the highest prevalence were Antioquia,Bogotá,and Santander.CONCLUSION:There are important differences between worldwide and Colombian prevalence and incidence data,which may be related to genetic and epigenetic factors,and the possible underdiagnosis of the disease.According to the results,OCP is an extremely rare disease in Colombia.Nevertheless,it is important to encourage awareness of the disease due to its devastating consequences.
基金Supported by Research grants from VCTI-UAN and Colcienciasresearch grants from Universidad del Rosario
文摘Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). In recent decades, several studies have come to the understanding that genetic factors play a major role in the risk for a large number of NPDs. However, few neuropsychiatric genetics studies have been published from LMICs. In this Editorial, we discuss important issues impinging on advances in neuropsychiatric genetics research in LMICs. It is essential that scientists educate policymakers and officials of funding agencies on the importance of providing adequate funding for research in these areas. Development of local well-supported research programs focused on NPD genetics should be an important asset to develop; it would facilitate the establishment of sustainable research efforts that could lead to appropriate diagnosis and specific, affordable and feasible interventions in LMICs. It is important to point out that research into the biological basis of human NPDs is not only an academic effort reserved for a few elite institutions in economically developed countries, but it is vitally important for the mental health of people around the world.
文摘Until recently, the synaptic transmission and excitatory amino acid transporters activation of neurons are very well discussed in the previous studies and are considered to be the two distinct features of Synapse. It is also found that a large number of interactions take place in the domain of ionic exchanges and protein interactions in synapses. It is evolutionary to have destined to release of Neurotransmitters to conduct an impulse to the other consecutive neurons, which forms the most important characteristic of synapse. From the popular perspective, it has been identified that detailed theoretical closer correlation of data produced through various studies about synapse can unravel many mysteries related to functions of synapse. Hence, this research paper tries to concentrate on a selected group of prominent characteristics and properties of synapse and also highlights some noteworthy discoveries, emphasizing the influential capabilities of them in the thought process and improving the knowledge of the field. It also highlights the expressive properties and forms of synapse brought out through the evidences available in sparse to dense data in a correlational way.
文摘Background: Antiparkinsonian pharmacotherapy represents one of the most important expenses related to Parkinson’s disease. The application of generic drugs may help to reduce the economic burden of the disease;however, efficacy and safety of these products have been less studied. Objective: To investigate the efficacy and safety of generic rasagiline (Ralago?) from a clinical perspective. Methods: The Clinical Global Impression of Severity scale was used to rate the most important motor and non-motor symptoms at baseline and 12 weeks after the initiation of Ralago?. Patients also identified symptoms which were the main sources of their disability and distress in everyday life. Results: A total of 499 patients were enrolled (231 females, mean age: 73.2 ± 9.1 years, mean duration of disease: 3.6 ± 3.7 years). Of them, 486 patients completed the study protocol. Both motor and non-motor symptoms showed improvement during 12-week Ralago? treatment. Adverse events were rare, and the majority of them were not considered as serious. Conclusions: The generic rasagiline (Ralago?) is an effective and safe generic product.
基金GF received funding from Flanders Innovation and Entrepreneurship(HBC.2018.0184)Cochlear Ltd.NV receives funding from Research Foundation Flanders(FWO 1804816N)as a senior clinical investigator.
文摘Magnetic resonance imaging(MRI)has become the gold standard for the diagnosis of many pathologies.Using MRI in patients with auditory implants can however raise concerns due to mutual interactions between the implant and imaging device,resulting in potential patient risks.Several implant manufacturers have been working towards more MRI safe devices.Older devices are however often labelled for more stringent conditions,possibly creating confusion with patients and professionals.With this myriad of different devices that are implanted in patients for lifetimes of at least 20 years,it is crucial that both patients and professionals have a clear understanding of the safety of their devices.This work aims at providing an exhaustive overview on the MRI safety of active auditory implants.The available industry standards that are followed by manufacturers are outlined and an overview of the latest scientific developments focusing on the last five years is provided.In addition,based on the analysis of the adverse events reported to the Food and Drug Administration(FDA)and in literature within the past ten years,a systematic review of the most commonly occurring issues for patients with auditory implants in the MRI environment is provided.Results indicate that despite the release of more MRI conditional active hearing implants on the market,adverse events still occur.An extensive overview is provided on the MRI safety of active auditory implants,aiming to increase the understanding of the topic for healthcare professionals and contribute to safer scanning conditions for patients.
文摘Objective: To investigate the impact of possession of the -889 C/T polymorphi sm of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the int erleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alz heimers disease (AD), as demonstrated by the degree of microglial cell activit y associated with each IL-1A and IL-1B genotype. Method: Microglial cell activ ity within the frontal cortex was determined in 68 patients with necropsy confir med AD by image analysis as the percentage area of tissue occupied by ferritin i mmunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracte d from frontal cortex or cerebellum. Results: The microglial cell load was 31%g reater in patients with IL-1A T allele, 62%greater with IL1A TT genotype, but 108%greater with IL-1A TT genotype in combination with APOE 4 allele. No effec ts on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone. Conclusions: Polymorphisms within IL-1A influence the degree of brain microgli al cell activation, especially in bearers of APOE 4 allele, reinforcing the impo rtance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.
基金This work was supported by National Science Foundation of China （No. 50537030）.
文摘Background Methylmalonic acidemia （MMA） is a multifactorial autosomal recessive inborn error of organic acid metabolism, often presenting with neurological symptoms. As neurological disorders are often related to white matter injury, diffusion tensor imaging （DTI） is an excellent tool for assessment of white matter injury and possibly for diagnosing this disorder. Methods We retrospectively analyzed DTI images of 12 patients with MMA （7 males, 5 females, age range： 7-12 months, mean age： 9.25±1.70 months） with negative MRI findings. And another 12 age-matched and gender-matched infants were enrolled as control subjects. Fractional anisotropy （FA） of different white matter tracts of the brain was measured in both groups. Results For patients with negative MRI findings, compared with healthy infants, a statistically significant reduction in DTI FA value of the frontal white matter, temporal white matter, and occipital white matter was observed （P〈0.01）. Conclusions In addition to conventional TlW and T2W MR Image, Brain DTI presents a useful, sensitive and complementary tool for the assessment of brain damage in patients with MMA.
基金funded by the Fundamental Research Grant SchemeMinistry of Higher Education+2 种基金Malaysia (Grant No. FRGS/1/2018/SKK08/UITM/02/9)Geran Penyelidikan KhasUniversiti Teknologi MARA [Grant No. 600-RMC/GPK 5/3 (191/2020)]
文摘Memory impairment in children is an ongoing issue worldwide related to a learning disability. This neurobiological condition has been suggested to associate with bisphenol A (BPA) exposure during pregnancy. BPA is an inorganic compound used to produce polycarbonate plastics and epoxy resins. We conduct this study to investigate the effects of prenatal BPA exposure on the level of the N-methyl-D-aspartate (NMDA) receptor subunits, synaptic markers of the hippocampus and neurobehavioral outcomes in rats. The pregnant rats were given a daily dose of 5 mg/kg and 50 mg/kg of BPA with 0.5% Tween 80 orally from gestation day 2 until 21 (GD21). The level of GluN2A, GluN2B, PSD-95 and synapsin I in the hippocampus and its neurobehaviour outcomes were quantified and evaluated in the male foetus and adolescent rat. Prenatal BPA exposure reduced GluN2A, GluN2B, synapsin I and PSD-95 (Postsynaptic Density-95) in the male foetus and adolescent rat hippocampus compared to the control group. The prenatal BPA exposed rats demonstrated anxiety-related behaviour and impairment in aversive and spatial memory. The findings suggested that the impairment in neurobehavioral performance may inhibit the signalling pathway in the NMDA receptor subunits in the male foetus rat hippocampus leading to learning and memory deficits when reaching adolescence.
