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The increasing demand for artificially intelligent smartphone cradles has prompted the need for real-time moving object detection. Real-time moving object tracking requires the development of algorithms for instant tracking analysis without delays. In particular, developing a system for smartphones should consider different operating systems and software development environments. Issues in current real-time moving object tracking systems arise when small and large objects coexist, causing the algorithm to prioritize larger objects or struggle with consistent tracking across varying scales. Fast object motion further complicates accurate tracking and leads to potential errors and misidentification. To address these issues, we propose a deep learning-based real-time moving object tracking system which provides an accuracy priority mode and a speed priority mode. The accuracy priority mode achieves a balance between the high accuracy and speed required in the smartphone environment. The speed priority mode optimizes the speed of inference to track fast-moving objects. The accuracy priority mode incorporates CSPNet with ResNet to maintain high accuracy, whereas the speed priority mode simplifies the complexity of the convolutional layer while maintaining accuracy. In our experiments, we evaluated both modes in terms of accuracy and speed.
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Migraine, especially chronic migraine, is highly debilitating and still lacks effective treatment. The persistent headache arises from activation and sensitization of primary afferent neurons in the trigeminovascular pathway, but the underlying mechanisms remain incompletely understood. Animal studies indicate that signalling through chemokine C-C motif ligand 2 (CCL2) and C-C motif chemokine receptor 2 (CCR2) mediates the development of chronic pain after tissue or nerve injury. Some migraine patients had elevated CCL2 levels in CSF or cranial periosteum. However, whether the CCL2-CCR2 signalling pathway contributes to chronic migraine is not clear. Here, we modelled chronic headache with repeated administration of nitroglycerin (NTG, a reliable migraine trigger in migraineurs) and found that both Ccl2 and Ccr2 mRNA were upregulated in dura and trigeminal ganglion (TG) tissues that are implicated in migraine pathophysiology. In Ccl2 and Ccr2 global knockout mice, repeated NTG administration did not evoke acute or persistent facial skin hypersensitivity as in wild-type mice. Intraperitoneal injection of CCL2 neutralizing antibodies inhibited chronic headache-related behaviours induced by repeated NTG administration and repetitive restraint stress, suggesting that the peripheral CCL2-CCR2 signalling mediates headache chronification. We found that CCL2 was mainly expressed in TG neurons and cells associated with dura blood vessels, whereas CCR2 was expressed in subsets of macrophages and T cells in TG and dura but not in TG neurons under both control and disease states. Deletion of Ccr2 gene in primary afferent neurons did not alter NTG-induced sensitization, but eliminating CCR2 expression in either T cells or myeloid cells abolished NTG-induced behaviours, indicating that both CCL2-CCR2 signalling in T cells and macrophages are required to establish chronic headache-related sensitization. At cellular level, repeated NTG administration increased the number of TG neurons that responded to calcitonin-gene-related peptide (CGRP) and pituitary adenylate cyclase activating polypeptide (PACAP) as well as the production of CGRP in wild-type but not Ccr2 global knockout mice. Lastly, co-administration of CCL2 and CGRP neutralizing antibodies was more effective in reversing NTG-induced behaviours than individual antibodies. Taken together, these results suggest that migraine triggers activate CCL2-CCR2 signalling in macrophages and T cells. This consequently enhances both CGRP and PACAP signalling in TG neurons, ultimately leading to persistent neuronal sensitization underlying chronic headache. Our work not only identifies the peripheral CCL2 and CCR2 as potential targets for chronic migraine therapy, but also provides proof-of-concept that inhibition of both peripheral CGRP and CCL2-CCR2 signalling is more effective than targeting either pathway alone.
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Quimiocina CCL2 , Transtornos de Enxaqueca , Receptores CCR2 , Animais , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Cefaleia , Camundongos Knockout , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Receptores de QuimiocinasRESUMO
OBJECTIVE: To evaluate the risk of stroke associated with intravitreal ranibizumab in age-related macular degeneration (AMD). METHODS: A nationwide retrospective case-crossover study was performed using data from the Korean National Health Insurance Service (KNHIS) database, which included patients with exudative AMD in South Korea (n = 41,860). The index date was the date of hospitalization for stroke. We defined the case period as 60 days and four control periods before the index date. A pharmacy prescription database was searched for ranibizumab use during the case and control periods. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with a conditional logistic regression model. RESULTS: A total of 865 patients with AMD and incident stroke were included. Of all the patients, 12.02% had been treated during the preceding 60-day case period, compared with 9.25-10.29% during control periods. The adjusted OR of stroke associated with intravitreal ranibizumab during the case period was 1.285 (95% CI 0.979-1.686) (p = 0.07). In the subgroup analysis, the risk of hemorrhagic stroke had an OR of 2.252 (95% CI 1.068-4.749, p = 0.033). Further analyses based on patient gender, age, and different risk periods of 15 and 30 days yielded no increase in the risk of stroke associated with intravitreal ranibizumab. CONCLUSIONS: This case-crossover analysis revealed no evidence of increased risk of hospitalization for stroke within 60 days of intravitreal ranibizumab injection in AMD patients. A secondary analysis indicated the possibility of an increased risk of hemorrhagic stroke, with borderline significance. Further research is needed regarding the underlying biological mechanisms and drug safety.
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Degeneração Macular , Acidente Vascular Cerebral , Degeneração Macular Exsudativa , Inibidores da Angiogênese/efeitos adversos , Estudos Cross-Over , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Ranibizumab/efeitos adversos , República da Coreia/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/epidemiologiaRESUMO
BACKGROUND: Ischemia/reperfusion (IR) injury is 1 of the major problems in liver surgery. This study aims to evaluate the histologic and biochemical effects of dexmedetomidine on ischemia/reperfusion injury in the liver of rats. METHODS: Twenty-two Sprague-Dawley male rats were separated into 3 groups: group sham, IR (IR injury), and IR-D (IR with dexmedetomidine). Ischemia was induced for 45 minutes with portal clampage and the reperfusion period was 120 minutes. Group IR-D received 3 µg/kg of dexmedetomidine with loading for 10 minutes and then 3 µg/kg/h of dexmedetomidine was continuously injected intravenously 30 minutes before portal clampage. Biochemical factors (alanine aminotransferase and aspartate aminotransferase), variable cytokines (B cell lymphoma-2 (Bcl-2), Bax, caspase 3, caspase 8, nuclear factor-kappa B, interleukin (IL)-1ß, IL-6, IL-10, mixed lineage kinase domain-like protein, and receptor-interacting protein kinase-3), and histologic findings were investigated. RESULTS: Dexmedetomidine preconditioning significantly suppressed the histologic damage. In the IR-D group, the expression of IL-6 was decreased and the Bcl-2 was increased when compared with the IR group. CONCLUSION: Dexmedetomidine suppresses hepatic IR injury and the protective mechanism appears to involve the decrease of IL-6 and upregulation of Bcl-2 expression, which result in the attenuation of inflammatory response and the inhibition of apoptosis.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Fígado/patologia , Traumatismo por Reperfusão/patologia , Animais , Apoptose/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Propofol is widely used in general anesthesia, and it has been reported to protect various organs against ischemia-reperfusion injury (IRI), including liver. To evaluate the hepatoprotective effects of ischemic preconditioning (IP) under propofol anesthesia, we investigated the possible underlying mechanisms in rats. METHODS: Male Sprague-Dawley rats were randomly assigned to 3 groups: sham group (n = 5), non-IP group (n = 9; 45 minutes of hepatic ischemia followed by 2 hours of reperfusion), and IP group (n = 9; IP applied as 10 minutes of hepatic ischemia followed by 15 minutes of reperfusion before 45 minutes of ischemia). Anesthesia was maintained with intravenous (IV) infusion of propofol (800 µg/kg/min). Liver enzymes, histopathological changes, and cytokine expression were examined. RESULTS: The IP group showed significantly lower liver enzyme levels (aspartate aminotransferase, P = .045; alanine aminotransferase, P = .006) and reduced the histologic grades of hepatic injury 2 hours after reperfusion (P = .004) compared to the non-IP group. Lactate dehydrogenase activity (P < .001) and interleukin-6 mRNA levels were significantly higher in the non-IP group than in the sham and IP groups (P = .002, both groups). CONCLUSIONS: Our results demonstrate that IP under propofol anesthesia significantly attenuated hepatic IRI. The principal mechanism of the protective effects appeared to involve reduced expression of the IL-6 pro-inflammatory cytokine and subsequent reduction of the degree of necrosis.
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Anestésicos Intravenosos/farmacologia , Precondicionamento Isquêmico/métodos , Fígado , Propofol/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/cirurgia , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologiaRESUMO
PURPOSE: This study aimed to evaluate the risk of acute myocardial infarction (AMI) associated with intravitreal ranibizumab in age-related macular degeneration (AMD). METHODS: This nationwide retrospective case-crossover study using data from the Korean National Health Insurance Service database included patients diagnosed with exudative AMD using the registration code for exudative AMD (V201) from 2009 to 2014. We identified all incident AMI cases among these exudative AMD cases from inpatient claims and defined the index date as the date of hospitalization. For each patient, we defined the case period as one to 60 days and four control periods as 121 to 180, 181 to 240, 241 to 300, and 301 to 361 days, respectively, before the index date. A prescription of ranibizumab was searched for during the case and control periods. We calculated the adjusted odds ratios and their 95% confidence intervals using a conditional logistic regression model. RESULTS: From a cohort of patients with exudative AMD (n = 41,860), a total of 181 AMI patients with exudative AMD were included. Among all the patients, 11.05% were treated during the 2 months preceding the index date as compared with 8.29% to 9.39% treated during control periods. The adjusted odds ratio of AMI associated with intravitreal ranibizumab during the preceding 2 months was 1.22 (95% confidence interval, 0.673-2.213; p = 0.5124). Analyses based on case periods of 15 days and 1 month yielded similar results. CONCLUSIONS: Intravitreal ranibizumab injection does not appear to increase the risk of hospitalization for AMI within 60 days in exudative AMD patients.
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Degeneração Macular/tratamento farmacológico , Infarto do Miocárdio/etiologia , Ranibizumab/administração & dosagem , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Estudos Cross-Over , Feminino , Humanos , Incidência , Injeções Intravítreas , Degeneração Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Neurogenesis in the adult hippocampus plays a major role in cognitive ability of animals including learning and memory. Korean red ginseng (KRG) has long been known as a medicinal herb with the potential to improve learning and memory; however, the mechanisms are still elusive. Therefore, we evaluated whether KRG can promote cognitive function and enhance neurogenesis in the hippocampus. Eight-week-old male C57BL/6 mice received 50 mg/kg of 5-bromo-2'-deoxyuridine (BrdU) intraperitoneally and 100 mg/kg of KRG or vehicle orally once a day for 14 days. Pole, Rotarod and Morris water maze tests were performed and the brains were collected after the last behavioral test. Changes in the numbers of BrdU- and BrdU/doublecortin (DCX; a marker for neuronal precursor cells and immature neurons)-positive cells in the dentate gyrus and the gene expression of proliferating cell nuclear antigen (a marker for cell differentiation), cerebral dopamine neurotrophic factor and ciliary neurotrophic factor in the hippocampus were then investigated. KRG-treated mice came down the pole significantly faster and stood on the rotarod longer than vehicle-treated mice. The Morris water maze test showed that KRG administration enhanced the learning and memory abilities significantly. KRG also significantly increased BrdU- and BrdU/DCX-positive cells in the dentate gyrus as well as the proliferating cell nuclear antigen, cerebral dopamine neurotrophic factor and ciliary neurotrophic factor mRNA expression levels in the hippocampus compared to vehicle. Administration of KRG promotes learning and memory abilities, possibly by enhancing hippocampal neurogenesis. This study was approved by the Pusan National University Institutional Animal Care and Use Committee (approval No. PNU-2016-1071) on January 19, 2016.
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IMPORTANCE: Detailed incidence data for cataract surgery in the general population are limited, yet important for determining the surgical needs of the community and formulation of healthcare policies. BACKGROUND: To report incidence rates of cataract surgery in South Korea. DESIGN: Nationwide, retrospective population-based study. PARTICIPANTS: This study involved the entire population of South Korea (n = 47 990 761); 2 236 107 eyes of 1 591 176 patients confirmed as having cataract surgery from 1 January 2011 to 31 December 2015 were included. METHODS: Data for all patients who underwent primary cataract surgery in South Korea were retrieved using Korean Electronic Data Interchange and Korean Standard Classification of Diseases-7 codes. Annual incidence rates were calculated and adjusted to the national population data for the corresponding year. MAIN OUTCOME MEASURES: The average incidence of cataract surgery during the 5-year study period was estimated using population data from the 2010 Korean census. RESULTS: The incidence of cataract surgery increased from 8.54/1000 person-years in 2011 to 9.67/1000 person-years in 2015. The probability of second-eye surgery within 12 months after the first-eye surgery increased from 42.98% in 2011 to 48.01% in 2015. In total, 85.72% of surgeries were performed in non-rural areas: 43.18% in individuals with a higher household income and 76.65% in primary healthcare centres. The rate of vitrectomy for posterior capsular rupture was 0.72%. CONCLUSIONS AND RELEVANCE: The incidence of cataract surgery in South Korea is increasing over time. Our findings are expected to aid in the formulation of future healthcare policies concerning cataract surgery in South Korea.
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Extração de Catarata , Catarata , Extração de Catarata/estatística & dados numéricos , Humanos , Incidência , República da Coreia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Purpose: To compare the changes in human tear proteome and clinical effects following topical cyclosporine A (CsA) 0.05% or diquafosol tetrasodium (DQS) 3% treatment of dry eye disease (DED), and to identify biomarkers for determining disease severity and treatment effectiveness in DED. Methods: A total of 18 patients were diagnosed with non-Sjögren DED. Nine patients in each group were treated with topical CsA 0.05% or DQS 3% for 4 weeks. Tear samples were collected after evaluation of tear breakup time, corneal and conjunctival erosion staining, and results of Schirmer's test 1 before and after treatment. Proteomes were characterized using liquid chromatography mass spectrometry, and proteins exhibiting a fold change >1.5 or <0.67 (P < 0.05) were considered differentially expressed (DEP). Results: A total of 794 proteins were identified, with no significant difference observed between pretreatment and posttreatment conditions. Proteomic analysis identified 54 and 106 DEPs between treatment groups (CsA and DQS, respectively), with gene ontology analysis indicating that both treatments enhanced innate and adaptive immune responses and cellular detoxification. Protein-network analysis showed that inflammation associated with the immune response was primarily responsible for the therapeutic process in both groups. Conclusions: These results provide insight into the broad scope of changes at the ocular surface in DED and indicated that although both drugs improved the clinical parameters, the activated tear-specific biomarkers differed significantly between treatments. Our findings suggest that the DEPs identified here and those correlated with the clinical parameters might represent candidate biomarkers for DED.
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Ciclosporina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Polifosfatos/administração & dosagem , Proteoma/metabolismo , Lágrimas/metabolismo , Nucleotídeos de Uracila/administração & dosagem , Administração Tópica , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Córnea/metabolismo , Córnea/patologia , Relação Dose-Resposta a Droga , Síndromes do Olho Seco/metabolismo , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Estudos Prospectivos , Método Simples-Cego , Lágrimas/efeitos dos fármacos , Resultado do TratamentoRESUMO
Adipose-derived mesenchymal stem cells (AdMSCs) have been reported to ameliorate neurological deficits after acute ischemic stroke. As neuregulin 1 (NRG1, or heregulin 1), a growth factor with versatile functions in the central nervous system, has demonstrated protective effects against ischemic brain injuries, we have generated NRG1-overexpressing AdMSCs in order to investigate whether NRG1-AdMSCs could enhance therapeutic benefits of AdMSCs in ischemic stroke. After AdMSCs were infected with adenoviral NRG1, increased NRG1 secretion in NRG1-AdMSCs was confirmed with ELISA. At 1 d after ischemic stroke that was induced by the occlusion of middle cerebral artery (MCAo) for 60 min in Sprague Dawley (SD) rats, adenoviral NRG1, AdMSCs, NRG1-AdMSCs, or PBS were injected into the striatum and serial neurologic examinations were performed. Administration of NRG1-AdMSCs resulted in significant improvement of functional outcome following stroke compared to AdMSCs- or adenoviral NRG1-treated group, in addition to the reduction in the infarct size evaluated by hematoxylin and eosin staining. When NRG1 expression in the brain was examined by double immunofluorescence to human nuclei (HuNu)/NRG1 and ELISA, NRG1-AdMSCs demonstrated marked increase in NRG1 expression. Moreover, western blot analysis further showed that transplantation of NRG1-AdMSCs significantly increased both endogenous and adenoviral NRG1 expression compared to AdMSCs-treated group. To elucidate molecular mechanisms, NRG1-associated downstream molecules were evaluated by western blot analysis. Expression of ErbB4, a receptor for NRG1, was markedly increased by NRG1-AdMSCs administration, in addition to pMAPK and pAkt, crucial molecules of NRG1-ErbB4 signaling. Taken together, our data suggest that NRG1-AdMSCs can provide excellent therapeutic potential in ischemic stroke by activating NRG1-ErbB4 signaling network.
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Tecido Adiposo/citologia , Isquemia Encefálica/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Neuregulina-1/uso terapêutico , Acidente Vascular Cerebral/terapia , Animais , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Neuregulina-1/administração & dosagem , Neuregulina-1/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: To evaluate the incidence and risk factors for retinal detachment (RD) after cataract surgery in the years 2011 to 2015 in Korea. METHODS: A nationwide retrospective cohort study was performed using health claim data from the Korean National Health Insurance Service (KNHIS) database. Patients over 40 years of age who underwent cataract surgery from 2011 and 2015 in Korea were retrospectively identified using Korean Electronic Data Interchange (KEDI) code and Korean Classification of Diseases (KCD)-7 code. RESULTS: A total of 2,191,510 eyes in 1,455,968 patients (58.63% female; mean age, 69.19 ± 9.82 years) underwent cataract surgery from 2011 to 2015 in Korea and 17,351 patients experienced RD (45.4% female; mean age, 60.89 ± 10.21 years). The 5-year cumulative risk of RD after cataract surgery was 1.19%, and 80.9% of RD occurred within 1 year after cataract surgery. In multivariate analysis, adjusted hazard ratio (HR) of RD was 1.335 [95% confidence interval (CI), 1.293-1.378] for male gender, 1.422 [95% CI, 1.371-1.475] for preoperative myopia, and 2.596 [95% CI, 2.367-2.849] for anterior vitrectomy during cataract surgery. Younger age was one of the factors highly associated with RD after cataract surgery, with HR [95% CI], 5.873 [5.527-6.240] in 40 to 54 years of age, 4.037 [3.811-4.277] in 55 to 64 years, and 2.026 [1.911-2.147] in 65 to 74 years. Adjusted HR of RD for surgery in secondary and primary healthcare centers were 0.495 [95% CI, 0.477-0.513] and 0.108 [95% CI, 0.104-0.113], respectively. Residence in non-metropolitan area and lower household income was associated with higher risk of RD. CONCLUSIONS: Younger age, anterior vitrectomy for posterior capsule rupture, preoperative myopia, male gender, surgery in tertiary referral centers, residence in non-metropolitan area, and lower household income were associated with an increased risk of RD after cataract surgery. The optimal timing of cataract surgery should be determined considering patient's risk factors, and appropriate pre- and postoperative evaluation is needed to prevent RD in patients with higher risks.
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Extração de Catarata/efeitos adversos , Vigilância da População/métodos , Descolamento Retiniano/epidemiologia , Medição de Risco/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Descolamento Retiniano/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Mapping enhancers to genes is a fundamental goal of modern biology. We have developed an innovative strategy that maps enhancers to genes in a principled manner. We illustrate its power by applying it to Myrf. Despite being a master regulator of oligodendrocytes, oligodendrocyte enhancers governing Myrf expression remain elusive. Since chromatin conformation capture studies have shown that a gene and its enhancer tend to be found in the same topologically associating domain (TAD), we started with the delineation of the Myrf TAD. A genome-wide map of putative oligodendrocyte enhancers uncovered 6 putative oligodendrocyte enhancers in the Myrf TAD, narrowing down the search space for Myrf enhancers from the entire genome to 6 loci in a principled manner. Epigenome editing experiments revealed that two of them govern Myrf expression for oligodendrocyte development. Our new method is simple, principled, and powerful, providing a systematic way to find enhancers that regulate the expression of a gene of interest. Since it can be applied to most cell types, it would greatly facilitate our effort to unravel transcriptional regulatory networks of diverse cell types.
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Elementos Facilitadores Genéticos , Loci Gênicos , Análise de Sequência de DNA/métodos , Fatores de Transcrição/genética , Animais , Células Cultivadas , Montagem e Desmontagem da Cromatina , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Oligodendroglia/citologia , Oligodendroglia/metabolismoRESUMO
Regulation of adult neurogenesis plays an important role in therapeutic strategies for various neurodegenerative diseases. Recent studies have suggested that the enhancement of adult neurogenesis can be helpful in the treatment of Parkinson's disease (PD). In this study, we investigated whether Korean red ginseng (KRG) can enhance neurogenesis in the subventricular zone (SVZ) of a PD mouse model. To accomplish this, male 8-week-old C57BL/6 mice were injected with vehicle or 20 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) four times at 2 h intervals. After the final injection, they were administered water or 100 mg/kg of KRG extract and injected intraperitoneally with 50 mg/kg of 5'-bromo-2'-deoxyuridine-monophosphate (BrdU) once a day for 14 consecutive days. After the last pole test, dopaminergic neuronal survival in the striatum and the substantia nigra (SN), cell proliferation in the SVZ and mRNA expression of neurotrophic factors and dopamine receptors in the striatum were evaluated. KRG administration suppressed dopaminergic neuronal death induced by MPTP in the striatum as well as the SN, augmented the number of BrdU- and BrdU/doublecortin (Dcx)-positive cells in the SVZ and enhanced the expression of proliferation cell nuclear antigen, brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), ciliary neurotrophic factor (CNTF), dopamine receptor D3 (DRD3) and D5 mRNAs. These results suggest that KRG administration augments neurogenesis in the SVZ of the PD mouse model.
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BACKGROUND: Recent studies have shown that Korean Red Ginseng (KRG) successfully protects against dopaminergic neuronal death in the nigrostriatal pathway of a Parkinson's disease (PD) mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration; however, the mechanism has yet to be identified. Therefore, in this study we used two-dimensional electrophoresis to investigate the effects of KRG on the changes in protein expression in the substantia nigra (SN) of MPTP-treated mice. METHODS: Male C57BL/6 mice (9 wk old) were intraperitoneally administered MPTP (20 mg/kg) four times at 2-h intervals, after which KRG (100 mg/kg) was orally administered once a day for 5 d. Two hours after the fifth KRG administration, a pole test was conducted to evaluate motor function, after which the brains were immediately collected. Survival of dopaminergic neurons was measured by immunohistochemistry, and protein expression was measured by two-dimensional electrophoresis and Western blotting. RESULTS: KRG alleviated MPTP-induced behavioral dysfunction and neuronal toxicity in the SN. Additionally, the expression of eight proteins related to neuronal formation and energy metabolism for survival were shown to have changed significantly in response to MPTP treatment or KRG administration. KRG alleviated the downregulated protein expression following MPTP administration, indicating that it may enhance neuronal development and survival in the SN of MPTP-treated mice. CONCLUSION: These findings indicate that KRG may have therapeutic potential for the treatment of patients with PD.
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BACKGROUND AND PURPOSE: Prospective memory (PM) has a known relationship with frontal function, and PM decline has been observed in amnestic mild cognitive impairment (aMCI). Cerebral small vessel disease, as evidenced by white matter hyperintensities (WMHs), is linked to frontal dysfunction. This study was undertaken to evaluate the relationship between PM decline and WMHs in patients with aMCI. METHODS: Of 74 enrollees with aMCI, 69 completed this prospective study. We compared total scores and sub-scores of the Prospective and Retrospective Memory Questionnaire (PRMQ) administered at baseline and 3 months later, stratifying patients by degree of WMHs. RESULTS: A significant decline was seen in PRMQ total scores and PM scores at the 3-month mark in patients with moderate (vs. mild) degrees of WMHs (-2.8±7.2 vs. 0.2±7.1; p=0.032). In addition, patients with moderate (vs. mild) degrees of deep WMHs (DWMHs) showed greater PM decline, whereas PM loss in patients with mild, moderate, or severe degrees of periventricular WMHs (PVWMHs) did not differ significantly. CONCLUSIONS: Findings of this study indicate that the burden of WMHs is consistently implicated in PM deterioration experienced by patients with aMCI, and signifies greater PM decline, especially in instances of extensive DWMHs. Greater attention to the change of PM is therefore needed in aMCI patients with WMHs.
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Versatile biological activities of Hericium erinaceus (HE) have been reported in many brain diseases. However, roles of HE in major psychiatric disorders such as depression and anxiety remain to be investigated. Therefore, we evaluated whether HE could reduce anxiety and depressive behaviors in the adult mouse and its underlying mechanisms. Male C57BL/6 mice were administered HE (20 or 60 mg/kg, p.o.) or saline once a day for 4 weeks. Open field and tail suspension tests were performed 30 min after the last administration of HE, followed by forced swim test 2 days later. We found that chronic administration of HE showed anxiolytic and antidepressant-like effects. To elucidate possible mechanisms, proliferative activity of the hippocampal progenitor cells was assessed by immunohistochemistry of proliferating cell nuclear antigen (PCNA) and Ki67. Moreover, to evaluate neuronal survival in the dentate gyrus, 5-bromo-2'-deoxyuridine (BrdU) (120 mg/kg, i.p.) was given at the first day of HE administration, followed by isolation of the brains 4 weeks later. HE (60 mg/kg) increased the number of PCNA- and Ki67-positive cells in the subgranular zone of the hippocampus, indicating increased proliferation of hippocampal progenitors. In addition, BrdU- and BrdU/NeuN-positive cells in the dentate gyrus were significantly increased when treated with HE (60 mg/kg) compared with the saline-treated group, demonstrating enhanced neurogenesis by HE treatment. Taken together, the results indicate that chronic HE administration can exert anxiolytic and antidepressant-like effects, possibly by enhancing adult hippocampal neurogenesis.
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Ansiolíticos/administração & dosagem , Antidepressivos/administração & dosagem , Ansiedade/tratamento farmacológico , Basidiomycota/química , Depressão/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Animais , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Depressão/psicologia , Hipocampo/citologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/efeitos dos fármacosRESUMO
Recent studies have suggested that increased oxidative stress is a potential etiology in Parkinson's disease (PD). In this study, we investigated whether acupuncture regulates antioxidants in the striatum (ST) of a PD mouse model. Male C57BL/6 mice were administered 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally once a day for 5 days and given acupuncture stimulation at SI3 or GB34 (Yanglingquan) was for 12 consecutive days. Dopaminergic neuronal survival in the nigrostriatal pathway and DJ-1 expression in the ST was evaluated by immunostaining, and the activities of superoxide dismutase (SOD) and catalase (CAT) in the ST was by enzyme-linked immunosorbent assay. MPTP administration induced dopaminergic neuronal death in the nigrostriatal pathway, which was suppressed by acupuncture stimulation at GB34. MPTP administration also suppressed DJ-1 expression and SOD and CAT activities in the ST, which were restored by acupuncture stimulation at GB34. These results indicate that the neuroprotective effect of acupuncture stimulation is due to regulation of the antioxidants.
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Terapia por Acupuntura , Corpo Estriado/metabolismo , Intoxicação por MPTP/metabolismo , Estresse Oxidativo/fisiologia , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Phanerochaete chrysosporium (ATCC 20696) has a catabolic ability to degrade lignin. Here, we report whole-genome sequencing used to identify genes related to lignin modification. We determined the 39-Mb draft genome sequence of this fungus, comprising 13,560 predicted gene models. Gene annotation provided crucial information about the location and function of protein-encoding genes.
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Polyporus brumalis is able to synthesize several sesquiterpenes during fungal growth. Using a single-molecule real-time sequencing platform, we present the 53-Mb draft genome of P. brumalis, which contains 6,231 protein-coding genes. Gene annotation and isolation support genetic information, which can increase the understanding of sesquiterpene metabolism in P. brumalis.