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1.
Sensors (Basel) ; 21(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34372214

RESUMO

This paper proposes a method to embed and extract a watermark on a digital hologram using a deep neural network. The entire algorithm for watermarking digital holograms consists of three sub-networks. For the robustness of watermarking, an attack simulation is inserted inside the deep neural network. By including attack simulation and holographic reconstruction in the network, the deep neural network for watermarking can simultaneously train invisibility and robustness. We propose a network training method using hologram and reconstruction. After training the proposed network, we analyze the robustness of each attack and perform re-training according to this result to propose a method to improve the robustness. We quantitatively evaluate the results of robustness against various attacks and show the reliability of the proposed technique.


Assuntos
Segurança Computacional , Interpretação de Imagem Assistida por Computador , Algoritmos , Redes Neurais de Computação , Reprodutibilidade dos Testes
2.
Neurochem Res ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34403064

RESUMO

p27Kip1 (p27) regulates the cell cycle by inhibiting G1 progression in cells. Several studies have shown conflicting results on the effects of p27 against cell death in various insults. In the present study, we examined the neuroprotective effects of p27 against H2O2-induced oxidative stress in NSC34 cells and against spinal cord ischemia-induced neuronal damage in rabbits. To promote delivery into NSC34 cells and motor neurons in the spinal cord, Tat-p27 fusion protein and its control protein (Control-p27) were synthesized with or without Tat peptide, respectively. Tat-p27, but not Control-27, was efficiently introduced into NSC34 cells in a concentration- and time-dependent manner, and the protein was detected in the cytoplasm. Tat-p27 showed neuroprotective effects against oxidative stress induced by H2O2 treatment and reduced the formation of reactive oxygen species, DNA fragmentation, and lipid peroxidation in NSC34 cells. Tat-p27, but not Control-p27, ameliorated ischemia-induced neurological deficits and cell damage in the rabbit spinal cord. In addition, Tat-p27 treatment reduced the expression of α-synuclein, activation of microglia, and release of pro-inflammatory cytokines such as interleukin-1ß and tumor necrosis factor-α in the spinal cord. Taken together, these results suggest that Tat-p27 inhibits neuronal damage by decreasing oxidative stress, α-synuclein expression, and inflammatory responses after ischemia.

3.
Viruses ; 13(8)2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34452517

RESUMO

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, suffer from respiratory and non-respiratory symptoms. Among these symptoms, the loss of smell has attracted considerable attention. The objectives of this study were to determine which cells are infected, what happens in the olfactory system after viral infection, and how these pathologic changes contribute to olfactory loss. For this purpose, Syrian golden hamsters were used. First, we verified the olfactory structures in the nasal cavity of Syrian golden hamsters, namely the main olfactory epithelium, the vomeronasal organ, and their cellular components. Second, we found angiotensin-converting enzyme 2 expression, a receptor protein of SARS-CoV-2, in both structures and infections of supporting, microvillar, and solitary chemosensory cells. Third, we observed pathological changes in the infected epithelium, including reduced thickness of the mucus layer, detached epithelia, indistinct layers of epithelia, infiltration of inflammatory cells, and apoptotic cells in the overall layers. We concluded that a structurally and functionally altered microenvironment influences olfactory function. We observed the regeneration of the damaged epithelium, and found multilayers of basal cells, indicating that they were activated and proliferating to reconstitute the injured epithelium.


Assuntos
COVID-19/virologia , Células Quimiorreceptoras/virologia , Mucosa Olfatória/virologia , SARS-CoV-2 , Órgão Vomeronasal/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/patologia , Células Quimiorreceptoras/patologia , Masculino , Mesocricetus , Cavidade Nasal/patologia , Cavidade Nasal/virologia , Mucosa Olfatória/metabolismo , Mucosa Olfatória/patologia , Neurônios Receptores Olfatórios/metabolismo , Neurônios Receptores Olfatórios/patologia , Neurônios Receptores Olfatórios/virologia , Receptores de Coronavírus/metabolismo , Regeneração , SARS-CoV-2/isolamento & purificação , Órgão Vomeronasal/metabolismo , Órgão Vomeronasal/patologia
4.
Nutrients ; 13(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072678

RESUMO

The incidence of metabolic and chronic diseases including cancer, obesity, inflammation-related diseases sharply increased in the 21st century. Major underlying causes for these diseases are inflammation and oxidative stress. Accordingly, natural products and their bioactive components are obvious therapeutic agents for these diseases, given their antioxidant and anti-inflammatory properties. Research in this area has been significantly expanded to include chemical identification of these compounds using advanced analytical techniques, determining their mechanism of action, food fortification and supplement development, and enhancing their bioavailability and bioactivity using nanotechnology. These timely topics were discussed at the 20th Frontier Scientists Workshop sponsored by the Korean Academy of Science and Technology, held at the University of Hawaii at Manoa on 23 November 2019. Scientists from South Korea and the U.S. shared their recent research under the overarching theme of Bioactive Compounds, Nanoparticles, and Disease Prevention. This review summarizes presentations at the workshop to provide current knowledge of the role of natural products in the prevention and treatment of metabolic diseases.


Assuntos
Anti-Inflamatórios , Antioxidantes , Produtos Biológicos , Doenças Metabólicas , Animais , Suplementos Nutricionais , Humanos , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Camundongos , Nanopartículas , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos
5.
Cells ; 10(2)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572372

RESUMO

The present study explored the effects of endophilin A1 (SH3GL2) against oxidative damage brought about by H2O2 in HT22 cells and ischemic damage induced upon transient forebrain ischemia in gerbils. Tat-SH3GL2 and its control protein (Control-SH3GL2) were synthesized to deliver it to the cells by penetrating the cell membrane and blood-brain barrier. Tat-SH3GL2, but not Control-SH3GL2, could be delivered into HT22 cells in a concentration- and time-dependent manner and the hippocampus 8 h after treatment in gerbils. Tat-SH3GL2 was stably present in HT22 cells and degraded with time, by 36 h post treatment. Pre-incubation with Tat-SH3GL2, but not Control-SH3GL2, significantly ameliorated H2O2-induced cell death, DNA fragmentation, and reactive oxygen species formation. SH3GL2 immunoreactivity was decreased in the gerbil hippocampal CA1 region with time after ischemia, but it was maintained in the other regions after ischemia. Tat-SH3GL2 treatment in gerbils appreciably improved ischemia-induced hyperactivity 1 day after ischemia and the percentage of NeuN-immunoreactive surviving cells increased 4 days after ischemia. In addition, Tat-SH3GL2 treatment in gerbils alleviated the increase in lipid peroxidation as assessed by the levels of malondialdehyde and 8-iso-prostaglandin F2α and in pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß, and interleukin-6; while the reduction of protein levels in markers for synaptic plasticity, such as postsynaptic density 95, synaptophysin, and synaptosome associated protein 25 after transient forebrain ischemia was also observed. These results suggest that Tat-SH3GL2 protects neurons from oxidative and ischemic damage by reducing lipid peroxidation and inflammation and improving synaptic plasticity after ischemia.

6.
Ann Plast Surg ; 86(4): 412-420, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33559995

RESUMO

PURPOSE: Although the pronator quadratus (PQ) preservation approach for volar plating of distal radius fracture has been commonly used recently, its superiority to the conventional PQ dissection approach, especially for comminuted intra-articular distal radius fractures, has not been well established. The purpose of this study was to assess the efficacy of PQ preservation for comminuted intra-articular fractures and to evaluate the healed PQ during hardware removal surgery. MATERIALS AND METHODS: From January 2014 to March 2019, 86 patients who underwent both volar plating for AO Foundation/Orthopedic Trauma Association classification type C2 or C3 distal radius fractures and subsequent hardware removal were assessed in this study. Radiographic measurements, clinical outcomes at each follow-up, and the integrity of healed PQ during hardware removal were compared between the PQ dissection (group D) and PQ preservation (group P) groups. RESULTS: Complete union with acceptable reduction on radiographic measurements was achieved in both groups. Group P showed a statistically significant earlier recovery of clinical outcomes at 2 weeks and 1 month postoperatively and improved anatomical restoration of PQ muscle covering the plate, which was identified during hardware removal surgery. Flexor tendon rupture was identified in 2 patients (5%) and tenosynovitis in 6 patients (14%) in group D; no patient had flexor tendon rupture (0%), and 2 patients (5%) had tenosynovitis in group P. CONCLUSIONS: Pronator quadratus preservation approach for volar plating is easily applicable and useful even for comminuted intra-articular distal radius fractures and is helpful for earlier restoration of wrist function and in preventing flexor tendon problems in the latter postoperative period.


Assuntos
Fraturas Cominutivas , Fraturas do Rádio , Placas Ósseas , Dissecação , Fixação Interna de Fraturas , Fraturas Cominutivas/diagnóstico por imagem , Fraturas Cominutivas/cirurgia , Humanos , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgia
7.
Nutrients ; 13(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33435613

RESUMO

Gynura procumbens has been used in Southeast Asia for the treatment of hypertension, hyperglycemia, and skin problems induced by ultraviolet irradiation. Although considerable studies have reported the biological properties of Gynura procumbens root extract (GPE-R), there are no studies on the effects of GPE-R in brain damages, for example following brain ischemia. In the present study, we screened the neuroprotective effects of GPE-R against ischemic damage and neuroinflammation in the hippocampus based on behavioral, morphological, and biological approaches. Gerbils received oral administration of GPE-R (30 and 300 mg/kg) every day for three weeks and 2 h after the last administration, ischemic surgery was done by occlusion of both common carotid arteries for 5 min. Administration of 300 mg/kg GPE-R significantly reduced ischemia-induced locomotor hyperactivity 1 day after ischemia. Significantly more NeuN-positive neurons were observed in the hippocampal CA1 regions of 300 mg/kg GPE-R-treated animals compared to those in the vehicle-treated group 4 days after ischemia. Administration of GPE-R significantly reduced levels of pro-inflammatory cytokines such as interleukin-1ß, -6, and tumor necrosis factor-α 6 h after ischemia/reperfusion. In addition, activated microglia were significantly decreased in the 300 mg/kg GPE-R-treated group four days after ischemia/reperfusion compared to the vehicle-treated group. These results suggest that GPE-R may be one of the possible agents to protect neurons from ischemic damage by reducing inflammatory responses.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Região CA1 Hipocampal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Animais , Peso Corporal , Isquemia Encefálica/patologia , Isquemia Encefálica/cirurgia , Região CA1 Hipocampal/patologia , Citocinas , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Gerbillinae , Hipocampo/efeitos dos fármacos , Masculino , Microglia , Traumatismo por Reperfusão/patologia
8.
Mar Drugs ; 18(12)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255381

RESUMO

Laminaria japonica is widely cultivated in East Asia, including South Korea. Fucoidan, a main component of L. japonica, protects neurons from neurological disorders such as ischemia and traumatic brain injury. In the present study, we examined the effects of extract from fermented L. japonica on the reduction of proliferating cells and neuroblasts in mice that were physically (with electric food shock) or psychologically (with visual, auditory and olfactory sensation) stressed with the help of a communication box. Vehicle (distilled water) or fermented L. japonica extract (50 mg/kg) were orally administered to the mice once a day for 21 days. On the 19th day of the treatment, physical and psychological stress was induced by foot shock using a communication box and thereafter for three days. Plasma corticosterone levels were significantly increased after exposure to physical stress and decreased Ki67 positive proliferating cells and doublecortin immunoreactive neuroblasts. In addition, western blot analysis demonstrated that physical stress as well as psychological stress decreased the expression levels of brain-derived neurotrophic factor (BDNF) and the number of phosphorylated cAMP response element binding protein (pCREB) positive nuclei in the dentate gyrus. Fermentation of L. japonica extract significantly increased the contents of reduced sugar and phenolic compounds. Supplementation with fermented L. japonica extract significantly ameliorated the increases of plasma corticosterone revels and decline in the proliferating cells, neuroblasts, and expression of BDNF and pCREB in the physically stressed mice. These results indicate that fermented L. japonica extract has positive effects in ameliorating the physical stress induced reduction in neurogenesis by modulating BDNF and pCREB expression in the dentate gyrus.


Assuntos
Proliferação de Células/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Fermentação , Laminaria/microbiologia , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Corticosterona/sangue , Giro Denteado/metabolismo , Giro Denteado/patologia , Antígeno Ki-67/metabolismo , Laminaria/metabolismo , Masculino , Camundongos Endogâmicos ICR , Proteínas Associadas aos Microtúbulos/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Neuropeptídeos/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Fosforilação , Transdução de Sinais , Estresse Fisiológico , Estresse Psicológico
9.
Cells ; 9(12)2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33352833

RESUMO

Entacapone, a reversible inhibitor of catechol-O-methyl transferase, is used for patients in Parkinson's disease because it increases the bioavailability and effectiveness of levodopa. In the present study, we observed that entacapone increases novel object recognition and neuroblasts in the hippocampus. In the present study, two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were performed to compare the abundance profiles of proteins expressed in the hippocampus after entacapone treatment in mice. Results of 2-DE, MALDI-TOF mass spectrometry, and subsequent proteomic analysis revealed an altered protein expression profile in the hippocampus after entacapone treatment. Based on proteomic analysis, 556 spots were paired during the image analysis of 2-DE gels and 76 proteins were significantly changed more than two-fold among identified proteins. Proteomic analysis indicated that treatment with entacapone induced expressional changes in proteins involved in synaptic transmission, cellular processes, cellular signaling, the regulation of cytoskeletal structure, energy metabolism, and various subcellular enzymatic reactions. In particular, entacapone significantly increased proteins related to synaptic trafficking and plasticity, such as dynamin 1, synapsin I, and Munc18-1. Immunohistochemical staining showed the localization of the proteins, and western blot confirmed the significant increases in dynamin I (203.5% of control) in the hippocampus as well as synapsin I (254.0% of control) and Munc18-1 (167.1% of control) in the synaptic vesicle fraction of hippocampus after entacapone treatment. These results suggest that entacapone can enhance hippocampal synaptic trafficking and plasticity against various neurological diseases related to hippocampal dysfunction.


Assuntos
Catecóis/uso terapêutico , Hipocampo/efeitos dos fármacos , Nitrilas/uso terapêutico , Vesículas Sinápticas/efeitos dos fármacos , Animais , Transporte Biológico , Ciclo Celular , Diferenciação Celular , Eletroforese em Gel Bidimensional , Endocitose , Hipocampo/metabolismo , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Mitose , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sinapses/metabolismo
10.
Int J Mol Sci ; 21(24)2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33327462

RESUMO

p27Kip1 (p27), a well-known cell regulator, is involved in the regulation of cell death and survival. In the present study, we observed the effects of p27 against oxidative stress induced by H2O2 in HT22 cells and transient ischemia in gerbils. Tat (trans-acting activator of transcription) peptide and p27 fusion proteins were prepared to facilitate delivery into cells and across the blood-brain barrier. The tat-p27 fusion protein, rather than its control protein Control-p27, was delivered intracellularly in a concentration and incubation time-dependent manner and showed its activity in HT22 cells. The localization of the delivered Tat-p27 protein was also confirmted in the HT22 cells and hippocampus in gerbils. In addition, the optimal concentration (5 µM) of Tat-p27 was determined to protect neurons from cell death induced by 1 mM H2O2. Treatment with 5 µM Tat-p27 significantly ameliorated H2O2-induced DNA fragmentation and the formation of reactive oxygen species (ROS) in HT22 cells. Tat-p27 significantly mitigated the increase in locomotor activity a day after ischemia and neuronal damage in the hippocampal CA1 region. It also reduced the ischemia-induced membrane phospholipids and ROS formation. In addition, Tat-p27 significantly increased microtubule-associated protein 1A/1B light chain 3A/3B expression and ameliorated the H2O2 or ischemia-induced increases of p62 and decreases of beclin-1 in the HT22 cells and hippocampus. These results suggest that Tat-p27 protects neurons from oxidative or ischemic damage by reducing ROS-induced damage and by facilitating the formation of autophagosomes in hippocampal cells.


Assuntos
Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Animais , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p27/genética , Gerbillinae , Humanos , Peróxido de Hidrogênio/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/farmacologia
11.
Int J Mol Sci ; 21(19)2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33050051

RESUMO

Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that increases glycolytic flux in the brain. In the present study, we examined the effects of PGAM1 in conditions of oxidative stress and ischemic damage in motor neuron-like (NSC34) cells and the rabbit spinal cord. A Tat-PGAM1 fusion protein was prepared to allow easy crossing of the blood-brain barrier, and Control-PGAM1 was synthesized without the Tat peptide protein transduction domain. Intracellular delivery of Tat-PGAM1, not Control-PGAM1, was achieved in a time- and concentration-dependent manner. Immunofluorescent staining confirmed the intracellular expression of Tat-PGAM1 in NSC34 cells. Tat-PGAM1, but not Control-PGAM1, significantly alleviated H2O2-induced oxidative stress, neuronal death, mitogen-activated protein kinase, and apoptosis-inducing factor expression in NSC34 cells. After ischemia induction in the spinal cord, Tat-PGAM1 treatment significantly improved ischemia-induced neurological impairments and ameliorated neuronal cell death in the ventral horn of the spinal cord 72 h after ischemia. Tat-PGAM1 treatment significantly mitigated the ischemia-induced increase in malondialdehyde and 8-iso-prostaglandin F2α production in the spinal cord. In addition, Tat-PGAM1, but not Control-PGAM1, significantly decreased microglial activation and secretion of pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α induced by ischemia in the ventral horn of the spinal cord. These results suggest that Tat-PGAM1 can be used as a therapeutic agent to reduce spinal cord ischemia-induced neuronal damage by lowering the oxidative stress, microglial activation, and secretion of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α.


Assuntos
Morte Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Neurônios Motores/metabolismo , Mielite/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Fosfoglicerato Mutase/administração & dosagem , Isquemia do Cordão Espinal/tratamento farmacológico , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Células Híbridas , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos , Neurônios Motores/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Transdução de Sinais/efeitos dos fármacos , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química
12.
Int J Mol Sci ; 21(15)2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32759679

RESUMO

We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil (n = 5 per group). Serum pyridoxal 5'-phosphate levels were significantly decreased in Pyridoxine-deficient diet (PDD)-fed gerbils, while homocysteine levels were significantly increased in sham- and ischemia-operated gerbils. PDD-fed gerbil showed a reduction in neuronal nuclei (NeuN)-immunoreactive neurons in the medial part of the hippocampal CA1 region three days after. Reactive astrocytosis and microgliosis were found in PDD-fed gerbils, and transient ischemia caused the aggregation of activated microglia in the stratum pyramidale three days after ischemia. Lipid peroxidation was prominently increased in the hippocampus and was significantly higher in PDD-fed gerbils than in Control diet (CD)-fed gerbils after ischemia. In contrast, pyridoxine deficiency decreased the proliferating cells and neuroblasts in the dentate gyrus in sham- and ischemia-operated gerbils. Nuclear factor erythroid-2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) levels also significantly decreased in PDD-fed gerbils sham 24 h after ischemia. These results suggest that pyridoxine deficiency accelerates neuronal death by increasing serum homocysteine levels and lipid peroxidation, and by decreasing Nrf2 levels in the hippocampus. Additionally, it reduces the regenerated potentials in hippocampus by decreasing BDNF levels. Collectively, pyridoxine is an essential element in modulating cell death and hippocampal neurogenesis after ischemia.


Assuntos
Isquemia Encefálica/metabolismo , Gerbillinae/metabolismo , Neurônios/metabolismo , Estresse Oxidativo/genética , Piridoxina/metabolismo , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Fator Neurotrófico Derivado do Encéfalo/genética , Proliferação de Células/efeitos dos fármacos , Dieta , Gerbillinae/genética , Hipocampo/metabolismo , Fator 2 Relacionado a NF-E2/genética , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Piridoxina/deficiência , Piridoxina/farmacologia
13.
Cells ; 9(8)2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32756411

RESUMO

Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the C-terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function of CRIP1a in neuroprotection following oxidative stress in HT22 hippocampal cells and transient forebrain ischemia in gerbils. Purified exogenous Tat-CRIP1a was penetrated into HT22 cells in a time and concentration-dependent manner and prevented H2O2-induced reactive oxygen species formation, DNA fragmentation, and cell damage. Tat-CRIP1a fusion protein also ameliorated the reduction of 14-3-3η expression by H2O2 treatment in HT22 cells. Ischemia-reperfusion damage caused motor hyperactivity in the open field test of gerbils; however, the treatment of Tat-CRIP1a significantly reduced hyperactivity 1 day after ischemia. Four days after ischemia, the administration of Tat-CRIP1a restored the loss of pyramidal neurons and decreased reactive astrocytosis and microgliosis induced by ischemic damage in the hippocampal cornu Ammonis (CA)1 region. Ischemic damage decreased 14-3-3η expression in all hippocampal sub-regions 4 days after ischemia; however, the treatment of Tat-CRIP1 ameliorated the reduction of 14-3-3η expression. These results suggest that Tat-CRIP1a attenuates neuronal damage and hyperactivity induced by ischemic damage, and it restores normal expression levels of 14-3-3η protein in the hippocampus.


Assuntos
Proteínas 14-3-3/genética , Produtos do Gene tat/genética , Isquemia/patologia , Proteínas de Membrana/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas 14-3-3/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Dano ao DNA , Gerbillinae , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Proteínas de Membrana/administração & dosagem , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Atividade Motora/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia
14.
Lab Anim Res ; 36: 20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32647628

RESUMO

Fat-mass and obesity-associated protein (Fto) is highly expressed in the brain including, the hippocampus, and its expression is significantly decreased in the brain of Alzheimer's disease patients. In the present study, we measured Fto immunoreactivity and protein levels in the hippocampus of obese and aged mice, which were induced by high-fat diet for 12 weeks and D-galactose treatment for 10 weeks, respectively. The obesity and aging phenotypes were assessed by physiological parameters and Morris water maze test, respectively. High fat diet fed mice showed significant increases in body weight and blood glucose levels compared to that in the control or D-galactose-induced aged mice. In addition, treatment with D-galactose significantly decreased the spatial memory. Fto immunoreactivity in the control group was mainly detected in the pyramidal cells of the CA1 and CA3 regions and in the granule cells of the dentate gyrus. In the hippocampus of high-fat diet-fed mice, Fto immunoreactive structures were similarly found in the hippocampus compared to that in the control group, but Fto immunoreactivity in high-fat diet-fed mice was also found in the stratum oriens and radiatum of the CA1 and CA3 regions and the polymorphic layer of the dentate gyrus. In the hippocampus of D-galactose-induced aged mice, fewer Fto immunoreactive structures were detected in the granule cell layer of the dentate gyrus compared to the control group. Fto mRNA and protein levels based on quantitative real-time polymerase chain reaction and western blot assays were slightly increased in the hippocampus of high-fat diet-fed mice compared to that in control mice. In addition, Fto mRNA and protein levels were significantly decreased in the aged hippocampus compared to that in the control group. Fto protein levels are susceptible to the aging process, but not in the hippocampus of high-fat diet-induced obesity. The reduction of Fto in aged mice may be associated with reduced memory impairment in mice.

15.
Cells ; 9(6)2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531881

RESUMO

In the present study, we investigated the effects of cuprizone on cell death, glial activation, and neuronal plasticity induced by hypothermia after ischemia in gerbils. Food was supplemented with cuprizone at 0.2% ad libitum for eight weeks. At six weeks after diet feeing, gerbils received transient forebrain ischemia with or without hypothermic preconditioning. Cuprizone treatment for 8 weeks increased the number of astrocytes, microglia, and pro-inflammatory cytokine levels in the hippocampus. In addition, cuprizone treatment significantly decreased the number of proliferating cells and neuroblasts in the dentate gyrus. Brain ischemia caused cell death, disruption of myelin basic proteins, and reactive gliosis in CA1. In addition, ischemia significantly increased pro-inflammatory cytokines and the number of proliferating cells and differentiating neuroblasts in the dentate gyrus. In contrast, hypothermic conditioning attenuated these changes in CA1 and the dentate gyrus. However, cuprizone treatment decreased cell survival induced by hypothermic preconditioning after ischemia and increased the number of reactive microglia and astrocytes in CA1 as well as that of macrophages in the subcallosal zone. These changes occurred because the protective effect of hypothermia in ischemic damage was disrupted by cuprizone administration. Furthermore, cuprizone decreased ischemia-induced proliferating cells and neuroblasts in the dentate gyrus.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Cuprizona/uso terapêutico , Hipotermia/complicações , Inibidores da Monoaminoxidase/uso terapêutico , Neuroproteção/efeitos dos fármacos , Animais , Isquemia Encefálica/fisiopatologia , Morte Celular , Diferenciação Celular , Cuprizona/farmacologia , Gerbillinae , Humanos , Masculino , Inibidores da Monoaminoxidase/farmacologia
16.
J Bone Metab ; 27(2): 79-83, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32572368

RESUMO

Osteoporosis and osteoporosis related fractures contribute a large part of the medical cost in developed countries. Considering the preventive effect of osteoporotic medications, high rate of mortality and complications, poor quality of life after osteoporosis related fractures, the growing trend of older populations in the future, osteoporosis and osteoporosis related fractures are important targets of preventive treatment and also targets of socioeconomic cost reduction. Treating osteoporosis and preventing osteoporosis related fractures have become an essential element in Korean medical system. Despite the various differences in the health care system, hospitals in many other countries are operating fracture liaison service and they have confirmed its cost-effectiveness. In Korea's health care system, further research on cost-effectiveness as well as its clinical effects is needed.

17.
Sensors (Basel) ; 20(10)2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32443808

RESUMO

This paper proposes a method to simultaneously detect and classify objects by using a deep learning model, specifically you only look once (YOLO), with pre-processed automotive radar signals. In conventional methods, the detection and classification in automotive radar systems are conducted in two successive stages; however, in the proposed method, the two stages are combined into one. To verify the effectiveness of the proposed method, we applied it to the actual radar data measured using our automotive radar sensor. According to the results, our proposed method can simultaneously detect targets and classify them with over 90% accuracy. In addition, it shows better performance in terms of detection and classification, compared with conventional methods such as density-based spatial clustering of applications with noise or the support vector machine. Moreover, the proposed method especially exhibits better performance when detecting and classifying a vehicle with a long body.

18.
Cells ; 9(5)2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32344819

RESUMO

Pyridoxine, one of the vitamin B6 vitamers, plays a crucial role in amino acid metabolism and synthesis of monoamines as a cofactor. In the present study, we observed the effects of pyridoxine deficiency on novel object recognition memory. In addition, we examined the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenethylamine (DA), 3,4-dihydroxyphenylacetic acid, and homovanillic acid and the number of proliferating cells and neuroblasts in the hippocampus. We also examined the effects of pyridoxine deficiency on protein profiles applying a proteomic study. Five-week-old mice fed pyridoxine-deficient diets for 8 weeks and showed a significant decrease in the serum and brain (cerebral cortex, hippocampus, and thalamus) levels of pyridoxal 5'-phosphate, a catalytically active form of vitamin-B6, and decline in 5-HT and DA levels in the hippocampus compared to controls fed a normal chow. In addition, pyridoxine deficiency significantly decreased Ki67-positive proliferating cells and differentiated neuroblasts in the dentate gyrus compared to controls. A proteomic study demonstrated that a total of 41 spots were increased or decreased more than two-fold. Among the detected proteins, V-type proton ATPase subunit B2 (ATP6V1B2) and heat shock cognate protein 70 (HSC70) showed coverage and matching peptide scores. Validation by Western blot analysis showed that ATP6V1B2 and HSC70 levels were significantly decreased and increased, respectively, in pyridoxine-deficient mice compared to controls. These results suggest that pyridoxine is an important element of novel object recognition memory, monoamine levels, and hippocampal neurogenesis. Pyridoxine deficiency causes cognitive impairments and reduction in 5-HT and DA levels, which may be associated with a reduction of ATP6V1B2 and elevation of HSC70 levels in the hippocampus.


Assuntos
Hipocampo/fisiologia , Piridoxina/deficiência , ATPases Vacuolares Próton-Translocadoras/metabolismo , Animais , Dopamina/análise , Proteínas de Choque Térmico HSC70/metabolismo , Resposta ao Choque Térmico/efeitos dos fármacos , Masculino , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Teste de Campo Aberto/fisiologia , Proteômica , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/análise , Fosfato de Piridoxal/metabolismo , Piridoxina/metabolismo , Serotonina/análise , ATPases Vacuolares Próton-Translocadoras/fisiologia , Deficiência de Vitamina B 6/metabolismo
19.
Theranostics ; 10(6): 2612-2620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194823

RESUMO

225Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models of disseminated prostate cancer (PCa) to evaluate effectiveness of 225Ac-PSMA-617 at various disease stages. Methods: C4-2, C4-2B, or 22Rv1 cells were injected into the left ventricle of male NSG mice. Disease progression was monitored using bioluminescence imaging (BLI). For treatment, mice were injected with 40 kBq 225Ac-PSMA-617 at one (early treatment cohort) or three weeks (late treatment cohort) post-inoculation. Treatment efficacy was monitored by BLI of whole-body tumor burden. Mice were sacrificed based on body conditioning score. Results: C4-2 cells yielded metastases in liver, lungs, spleen, stomach, bones, and brain - achieving a clinically relevant model of widespread metastatic disease. The disease burden in the early treatment cohort was stable over 27 weeks in 5/9 mice and progressive in 4/9 mice. These mice were sacrificed due to brain metastases. Median survival of the late treatment cohort was superior to controls (13 vs. 7 weeks; p<0.0001) but inferior to that in the early treatment cohort (13 vs. 27 weeks; p<0.001). Late cohort mice succumbed to extensive liver involvement. The 22Rv1 and C4-2B systemic models were not used for treatment due to high kidney metastatic burden or low take rate, respectively. Conclusion: C4-2 cells reproduced metastatic cancer spread most relevantly. Early treatment with 225Ac-PSMA-617 prevented liver metastases and led to significant survival benefit. Late treatment improved survival without reducing tumor burden in the liver, the main site of metastasis. The current findings suggest that early 225Ac-PSMA-617 intervention is more efficacious in the setting of widespread metastatic PCa.


Assuntos
Actínio/uso terapêutico , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Compostos Radiofarmacêuticos/uso terapêutico , Partículas alfa/uso terapêutico , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Estudos de Viabilidade , Humanos , Masculino , Camundongos
20.
BMC Neurosci ; 21(1): 11, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32204694

RESUMO

BACKGROUND: Pyridoxine (PDX; vitamin B6), is an essential vitamin. PDX deficiency induces various symptoms, and when PDX is misused it acts as a neurotoxicant, inducing severe sensory neuropathy. RESULTS: To assess the possibility of creating a reversible sensory neuropathy model using dogs, 150 mg/kg of PDX was injected subcutaneously into dogs for 7 days and body weight measurements, postural reaction assessments, and electrophysiological recordings were obtained. In addition, the morphology of dorsal root ganglia (DRG) and changes in glial fibrillary acidic protein (GFAP) immunoreactive satellite glial cells and ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia/macrophages were assessed at 1 day, 1 week, and 4 weeks after the last PDX treatment. During the administration period, body weight and proprioceptive losses occurred. One day after the last PDX treatment, electrophysiological recordings showed the absence of the H-reflex in the treated dogs. These phenomena persisted over the four post-treatment weeks, with the exception of body weight which recovered to the pre-treatment level. Staining (CV and HE) results revealed significant losses of large-sized neurons in the DRG at 1 day and 1 week after PDX treatment cessation, but the losses were recovered at 4 weeks post-treatment. The Iba-1 and GFAP immunohistochemistry results showed pronounced increases in reactive microglia/macrophage and satellite glial cell at 1 day and 1 week, respectively, after the last PDX treatment, and thereafter, immunoreactivity decreased with increasing time after PDX treatment. CONCLUSIONS: The results suggest that PDX-induced neuropathy is reversible in dogs; thus, dogs can be considered a good experimental model for research on neuropathy.


Assuntos
Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/patologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia , Piridoxina/toxicidade , Complexo Vitamínico B/toxicidade , Animais , Modelos Animais de Doenças , Cães , Reflexo H/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia
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