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1.
Nutrients ; 15(20)2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37892401

ABSTRACT

Obesity and heavy metals, such as lead (Pb), are detrimental to the adult brain because they impair cognitive function and structural plasticity. However, the effects of co-administration of Pb and a high-fat diet (HFD) on the developing cerebellum is not clearly elucidated. We investigated the effects of Pb exposure (0.3% lead acetate) on developing cerebellum in the pups of an HFD-fed obese rat model. One week before mating, we fed a chow diet (CD) or HFD to the rats for one week and additionally administered Pb to HFD-fed female SD rats. Thereafter, treatment with Pb and a HFD was continued during the gestational and lactational periods. On postnatal day 21, the pups were euthanized to sample the brain tissue and blood for further analysis. Blood Pb levels were significantly higher in HFD-fed rats than in CD-fed rats. Histologically, the prominent degeneration of Purkinje cells was induced by the co-administration of Pb and HFD. The calbindin-28Kd-, GAD67-, NMDAR1-, and PSD95-immunopositive Purkinje cells and inhibitory synapse-forming pinceau structures were significantly decreased following Pb and HFD co-administration. MBP-immunoreactive myelinated axonal fibers were also impaired by HFD but were significantly damaged by the co-administration of HFD and Pb. Oxidative stress-related Nrf2-HO1 signaling was activated by HFD feeding, and Pb exposure further aggravated oxidative stress, as demonstrated by the consumption of endogenous anti-oxidant in HFD-Pb rats. The pro-inflammatory response was also increased by the co-administration of HFD and Pb in the cerebellum of the rat offspring. The present results suggest that HFD and Pb treatment during the gestational and lactational periods are harmful to cerebellar development.


Subject(s)
Diet, High-Fat , Prenatal Exposure Delayed Effects , Rats , Animals , Female , Humans , Diet, High-Fat/adverse effects , Lead/toxicity , Rats, Sprague-Dawley , Cerebellum , Obesity/pathology , Prenatal Exposure Delayed Effects/chemically induced
2.
Front Vet Sci ; 9: 839467, 2022.
Article in English | MEDLINE | ID: mdl-36032288

ABSTRACT

This study aimed to evaluate the clinical safety and validate the radiomitigative effect of KMRC011, against radiation-induced oral mucositis in beagle dogs. Clinical safety was evaluated by assessing tolerability, complete blood tests, and plasma biochemistry after drug administration. The radiomitigative effect of KMRC011 was evaluated macropathologically and histopathologically after inducing oral mucositis iatrogenically using 20 Gy irradiation. The plasma concentration of interleukin-6 was measured via enzyme-linked immunosorbent assay, as a biomarker of KMRC011 bioreactivity. Decreased tolerability, increased neutrophil count, hepatic enzyme concentration, C-reactive protein concentration, and interleukin-6 concentration after the administration was observed and ceased within 24 h without additional treatment. Although all animals included in the present study developed severe mucositis in the late course of the study, animals administered KMRC011 showed less erythema, ulcer, inflammatory infiltration. These results suggest that KMRC011 may be used as an adjuvant for radiotherapy without severe adverse effects, especially during short-term radiotherapy, such as hypofractionated radiotherapy or stereotactic radiotherapy.

3.
Viruses ; 13(8)2021 08 20.
Article in English | MEDLINE | ID: mdl-34452517

ABSTRACT

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.


Subject(s)
COVID-19/virology , Chemoreceptor Cells/virology , Olfactory Mucosa/virology , SARS-CoV-2 , Vomeronasal Organ/virology , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/pathology , Chemoreceptor Cells/pathology , Male , Mesocricetus , Nasal Cavity/pathology , Nasal Cavity/virology , Olfactory Mucosa/metabolism , Olfactory Mucosa/pathology , Olfactory Receptor Neurons/metabolism , Olfactory Receptor Neurons/pathology , Olfactory Receptor Neurons/virology , Receptors, Coronavirus/metabolism , Regeneration , SARS-CoV-2/isolation & purification , Vomeronasal Organ/metabolism , Vomeronasal Organ/pathology
4.
Biomolecules ; 10(3)2020 03 02.
Article in English | MEDLINE | ID: mdl-32131481

ABSTRACT

Gintonin, a novel ginseng-derived lysophosphatidic acid receptor ligand, improves brain functions and protects neurons from oxidative stress. However, little is known about the effects of gintonin against Pb-induced brain maldevelopment. We investigated the protective effects of gintonin on the developing cerebellum after prenatal and postnatal Pb exposure. Pregnant female rats were randomly divided into three groups: control, Pb (0.3% Pb acetate in drinking water), and Pb plus gintonin (100 mg/kg, p.o.). Blood Pb was increased in dams and pups; gintonin treatment significantly decreased blood Pb. On postnatal day 21, the number of degenerating Purkinje cells was remarkably increased while the number of calbindin-, GAD67-, NMDAR1-, LPAR1-immunoreactive intact Purkinje cells, and GABA transporter 1-immunoreactive pinceau structures were significantly reduced in Pb-exposed offspring. Following Pb exposure, gintonin ameliorated cerebellar degenerative effects, restored increased pro-apoptotic Bax, and decreased anti-apoptotic Bcl2. Gintonin treatment attenuated Pb-induced accumulation of oxidative stress (Nrf2 and Mn-SOD) and inflammation (IL-1ß and TNFα,), restoring the decreased cerebellar BDNF and Sirt1. Gintonin ameliorated Pb-induced impairment of myelin basic protein-immunoreactive myelinated fibers of Purkinje cells. Gintonin attenuated Pb-induced locomotor dysfunctions. The present study revealed the ameliorating effects of gintonin against Pb, suggesting the potential use of gintonin as a preventive agent in Pb poisoning during pregnancy and lactation.


Subject(s)
Lactation/metabolism , Lead Poisoning , Maternal Exposure/adverse effects , Panax/chemistry , Plant Extracts/pharmacology , Purkinje Cells/metabolism , Animals , Female , Lead Poisoning/drug therapy , Lead Poisoning/embryology , Lead Poisoning/pathology , Plant Extracts/chemistry , Pregnancy , Purkinje Cells/pathology , Rats
5.
BMC Ophthalmol ; 20(1): 31, 2020 Jan 20.
Article in English | MEDLINE | ID: mdl-31959143

ABSTRACT

BACKGROUND: To evaluate the prevalence and risk factors associated with myopia and high myopia in children in South Korea. METHODS: A total of 983 children 5-18 years of age who participated in the Korean National Health and Nutrition Examination Survey 2016-2017 (KNHANES VII), a nationwide population-based cross-sectional study, were evaluated. Myopia and high myopia were defined as a spherical equivalent (SE) ≤ - 0.5 diopters (D) and SE ≤ --6.0 D. The association between refractive errors and potential risk factors for myopia was analyzed. RESULTS: The prevalence of myopia and high myopia was 65.4 and 6.9%, respectively. Older age and parental myopia were significantly associated with both myopia and high myopia, while higher body mass index (BMI) was associated with high myopia only. Although the proportion of subjects who spent more time on near work activities (≥4 h/day) was sequentially increased with increased refractive error, this tendency was not statistically significant by multivariable logistic regression. CONCLUSIONS: Korean children had a high prevalence of myopia and high myopia. In this age group, the risk of myopia increased with aging and parental myopia. Higher BMI may be associated with high myopia.


Subject(s)
Myopia/epidemiology , Nutrition Surveys/statistics & numerical data , Adolescent , Age Distribution , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Myopia/diagnosis , Myopia, Degenerative/diagnosis , Myopia, Degenerative/epidemiology , Prevalence , Republic of Korea/epidemiology , Risk Factors
6.
J Toxicol Sci ; 44(11): 799-809, 2019.
Article in English | MEDLINE | ID: mdl-31708536

ABSTRACT

In the present study, we investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Female rats were randomly divided into the following groups: control, Pb, and Pb plus ascorbic acid (PA) groups. From one week prior to mating, female rats were administered Pb (0.3% Pb acetate in drinking water) and ascorbic acid (100 mg/kg, oral intubation). The chemical administration was stopped on postnatal day 21 when the morphology of the offspring's cerebellum is similar to that of the adult brain. The blood Pb level was significantly increased following long-term Pb exposure. Ascorbic acid reduced Pb levels in the dams and offspring. Nissl staining demonstrated that the number of Purkinje cells was significantly reduced following Pb exposure, while ascorbic acid ameliorated this effect in the cerebellum of the offspring. Calcium-binding proteins, such as calbindin, calretinin, and parvalbumin were commonly expressed in Purkinje cells, and Pb exposure and ascorbic acid treatment resulted in similar patterns of change, namely Pb-induced impairment and ascorbic acid-mediated amelioration. The gamma-aminobutyric acid transporter 1 (GABAT1) is expressed in the pinceau structure where the somata of Purkinje cells are entwined in inhibitory synapses. The number of GABAT1-immunoreactive synapses was reduced following Pb exposure, and ascorbic acid co-treatment prevented this effect in the cerebellar cortex. Therefore, it can be concluded that ascorbic acid supplementation to mothers during gestation and lactation may have potential preventive effects against Pb-induced impairments in the developing cerebellum via protection of inhibitory neurons and synapses.


Subject(s)
Ascorbic Acid/pharmacology , Calcium-Binding Proteins/metabolism , Cerebellum/drug effects , GABA Plasma Membrane Transport Proteins/metabolism , Lead/toxicity , Maternal-Fetal Exchange , Neuroprotective Agents/pharmacology , Animals , Cerebellum/metabolism , Cerebellum/pathology , Female , Lactation/metabolism , Pregnancy , Prenatal Exposure Delayed Effects , Rats, Sprague-Dawley
7.
Article in English | MEDLINE | ID: mdl-30893812

ABSTRACT

Osteopontin (OPN) is a multi-functional protein that binds to integrin and calcium-binding phosphoprotein. OPN is required for normal neuronal development and its axonal myelination. We studied the combined effect of lead (Pb) and ascorbic acid treatment on OPN expression in the developing cerebellum. We randomly divided pregnant female rats into three groups: control, Pb (lead acetate, 0.3%, drinking water), and Pb plus ascorbic acid (PA; ascorbic acid, 100 mg/kg, oral intubation) groups. The blood level of Pb was significantly increased, while ascorbic acid reduced Pb levels in the dams and pups. At postnatal day (PND) 21, results from Nissl staining and OPN immunohistochemistry demonstrated that OPN was detected in the Purkinje cell layer in the cerebellum. Ascorbic acid treatment mitigated Pb exposure-induced reduction in the number of intact Purkinje cells and OPN immunoreactive Purkinje cells in the cerebellum of pups. In addition, Pb-induced reduction in the number of oligodendrocytes and myelin-associated glycoprotein is associated with the malformation of the myelin sheath. Ascorbic acid provided protection from Pb-induced impairments. Pb-induced structural deficits in the cerebellum resulted in functional deterioration observed during locomotive tests (bar holding test and wire mesh ascending test), while ascorbic acid ameliorated these harmful effects. Present results suggest that the change of OPN is associated with myelination in the developing cerebellum. The results also demonstrated that exposure to Pb is harmful, while ascorbic acid treatment is beneficial.


Subject(s)
Ascorbic Acid/pharmacology , Cerebellum/drug effects , Cerebellum/growth & development , Lead/toxicity , Osteopontin/metabolism , Animals , Axons/drug effects , Female , Gene Expression Regulation, Developmental/drug effects , Hippocampus/drug effects , Male , Nerve Fibers, Myelinated/drug effects , Neurons/drug effects , Osteopontin/genetics , Pregnancy , Random Allocation , Rats
8.
Nutrients ; 11(1)2019 Jan 15.
Article in English | MEDLINE | ID: mdl-30650605

ABSTRACT

Ascorbic acid is essential for normal brain development and homeostasis. However, the effect of ascorbic acid on adult brain aging has not been determined. Long-term treatment with high levels of D-galactose (D-gal) induces brain aging by accumulated oxidative stress. In the present study, mice were subcutaneously administered with D-gal (150 mg/kg/day) for 10 weeks; from the seventh week, ascorbic acid (150 mg/kg/day) was orally co-administered for four weeks. Although D-gal administration alone reduced hippocampal neurogenesis and cognitive functions, co-treatment of ascorbic acid with D-gal effectively prevented D-gal-induced reduced hippocampal neurogenesis through improved cellular proliferation, neuronal differentiation, and neuronal maturation. Long-term D-gal treatment also reduced expression levels of synaptic plasticity-related markers, i.e., synaptophysin and phosphorylated Ca2+/calmodulin-dependent protein kinase II, while ascorbic acid prevented the reduction in the hippocampus. Furthermore, ascorbic acid ameliorated D-gal-induced downregulation of superoxide dismutase 1 and 2, sirtuin1, caveolin-1, and brain-derived neurotrophic factor and upregulation of interleukin 1 beta and tumor necrosis factor alpha in the hippocampus. Ascorbic acid-mediated hippocampal restoration from D-gal-induced impairment was associated with an enhanced hippocampus-dependent memory function. Therefore, ascorbic acid ameliorates D-gal-induced impairments through anti-oxidative and anti-inflammatory effects, and it could be an effective dietary supplement against adult brain aging.


Subject(s)
Aging , Ascorbic Acid/pharmacology , Brain/drug effects , Galactose/adverse effects , Memory/drug effects , Neurogenesis/drug effects , Neuronal Plasticity , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/metabolism , Antioxidants/pharmacology , Brain/cytology , Brain/metabolism , Brain/pathology , Brain-Derived Neurotrophic Factor/metabolism , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Caveolin 1/metabolism , Hippocampus/pathology , Interleukin-1beta/metabolism , Male , Memory Disorders/chemically induced , Memory Disorders/metabolism , Memory Disorders/pathology , Memory Disorders/prevention & control , Mice, Inbred C57BL , Oxidative Stress/drug effects , Sirtuin 1/metabolism , Synaptophysin/metabolism , Tumor Necrosis Factor-alpha/metabolism
9.
Biol Trace Elem Res ; 187(1): 142-150, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29696534

ABSTRACT

We evaluated the effect of lead (Pb) and ascorbic acid treatment of pregnant female rats on cerebellar development in pups. Pb was administered in drinking water (0.2% Pb acetate), and ascorbic acid (100 mg/kg) was administered through oral intubation. Fifteen female rats were randomly classified into control, Pb, and Pb plus ascorbic acid (PA) groups. The treatment of Pb and ascorbic acid treatments were terminated after birth to evaluate the effects on the gestational development of the cerebellum. At postnatal day 21 (PND21), pups were sacrificed, and blood Pb level was analyzed. Blood Pb levels of pups and dams were highest in the Pb group and reduced in the PA group. Immunohistochemistry and immunoblot assays were conducted to study the cerebellar expression levels of synaptic proteins. Along with a significant reduction in Purkinje cells, the reduction in presynaptic (synaptophysin) and postsynaptic (postsynaptic density protein 95, N-methyl-D-aspartate receptor subtype 1) marker proteins was observed in Pb-exposed pups. Ascorbic acid treatment significantly prevented Pb-induced impairment in the cerebellar synaptic proteins. Hypothesizing that brain-derived neurotrophic factor (BDNF) might be affected by Pb exposure given its importance in the regulation of synaptogenesis, we observed a Pb-induced decrease and ascorbic acid-mediated increase of BDNF in the cerebellum. Luxol fast blue staining and myelin basic protein analysis suggest that ascorbic acid treatment ameliorated the Pb exposure-induced reduction in the axonal fibers in the developing cerebellum. Overall, we conclude that ascorbic acid treatment during pregnancy can prevent Pb-induced impairments in the cerebellar development in rats.


Subject(s)
Ascorbic Acid/pharmacology , Cerebellum/drug effects , Cerebellum/growth & development , Lead/toxicity , Synapses/drug effects , Administration, Oral , Animals , Animals, Newborn , Ascorbic Acid/administration & dosage , Cerebellum/metabolism , Female , Lead/administration & dosage , Male , Pregnancy , Rats , Rats, Sprague-Dawley , Synapses/metabolism
10.
Biol Trace Elem Res ; 190(2): 446-456, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30488169

ABSTRACT

We investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Prior to mating, rats were randomly divided into control, Pb, and Pb plus ascorbic acid (PA) groups. Pregnant rats were administered Pb in drinking water (0.3% Pb acetate), and ascorbic acid (100 mg/kg) via oral intubation until the end of the experiment. Offspring were sacrificed at postnatal day 21, the age at which the morphology of the cerebellar cortex in developing pups is similar to that of the adult brain. In the cerebellum, Pb exposure significantly reduced Purkinje cells and ascorbic acid prevented their reduction. Along with the change of the Purkinje cells, long-term Pb exposure significantly reduced the expression of the synaptic marker (synaptophysin), γ-aminobutyric acid (GABA)-synthesizing enzyme (glutamic acid decarboxylase 67), and axonal myelin basic protein while ascorbic acid co-treatment attenuated Pb-mediated reduction of these proteins in the cerebellum of pups. However, glutamatergic N-methyl-D-aspartate receptor subtype 1 (NMDAR1), anchoring postsynaptic density protein 95 (PSD95), and antioxidant superoxide dismutases (SODs) were adversely changed; Pb exposure increased the expression of NMDAR1, PSD95, and SODs while ascorbic acid co-administration attenuated Pb-mediated induction. Although further studies are required about the neurotoxicity of the Pb exposure, the results presented here suggest that developmental Pb exposure disrupted normal development of Purkinje cells by increasing glutamatergic and oxidative stress in the cerebellum. Additionally, ascorbic acid co-treatment is beneficial in attenuating prenatal and postnatal Pb exposure-induced maldevelopment of Purkinje cells in the developing cerebellum.


Subject(s)
Ascorbic Acid/pharmacology , Cerebellum/drug effects , Purkinje Cells/drug effects , Administration, Oral , Animals , Ascorbic Acid/administration & dosage , Cerebellum/growth & development , Cerebellum/metabolism , Disks Large Homolog 4 Protein/metabolism , Female , Glutamate Decarboxylase/antagonists & inhibitors , Glutamate Decarboxylase/metabolism , Lead/administration & dosage , Lead/toxicity , Male , Purkinje Cells/metabolism , Purkinje Cells/pathology , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/metabolism , Superoxide Dismutase/metabolism , Synaptophysin/antagonists & inhibitors , Synaptophysin/metabolism , gamma-Aminobutyric Acid/metabolism
11.
Medicine (Baltimore) ; 97(33): e11792, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30113466

ABSTRACT

BACKGROUND: An assist-as-needed robot-assisted gait training protocol was recently developed. It allows active movement during training, but its exact criteria remain unknown. Asymmetric step length is a common abnormal gait pattern in hemiplegic stroke patients. We compared the effects of assist-as-needed robot-assisted gait training on the unaffected and affected limbs of hemiplegic stroke patients. METHOD: Twenty-four chronic stroke patients with asymmetric step lengths were randomly assigned to 1 of 2 groups. Twelve completed the study protocol. Group 1 underwent 20 sessions of assist-as-needed robot-assisted gait training for the unaffected limb and fully-assisted robot-assisted training for the affected limb. Group 2 underwent 20 sessions of robot-assisted gait training using the opposite protocol. Clinical measurements were obtained and 3-dimensional gait analyses were performed at baseline and after 10 and 20 training sessions. RESULTS: Clinical measurements improved in both groups after 20 training sessions. The unaffected limb's step length asymmetry ratio and hip maximal extension moment significantly improved in group 1. The affected limb's maximal dorsiflexion angle for the ankle in the swing phase significantly improved in group 2. CONCLUSION: Application of the assist-as-needed training mode for the unaffected limb helped improve step length asymmetry in chronic stroke patients.


Subject(s)
Exercise Therapy/instrumentation , Gait Disorders, Neurologic/rehabilitation , Gait/physiology , Hemiplegia/rehabilitation , Robotics/statistics & numerical data , Stroke Rehabilitation/instrumentation , Stroke/therapy , Aged , Ankle Joint/physiology , Biomechanical Phenomena/physiology , Chronic Disease , Exercise Therapy/methods , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Humans , Middle Aged , Prospective Studies , Stroke/complications , Stroke/physiopathology , Stroke Rehabilitation/methods , Treatment Outcome , Veterans , Walking Speed/physiology
12.
Biol Trace Elem Res ; 182(2): 278-286, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28685241

ABSTRACT

In the present study, we investigated the effects of ascorbic acid on lead-exposed developing cerebellum. Female rats were divided into the following three groups: control (distilled water), lead (0.2% lead acetate), and lead plus ascorbic acid (100 mg/kg/day, 10% solution). To evaluate the effect of lead exposure and ascorbic acid treatment accurately on the cerebellar development for the gestational period, we halted further treatment with lead and ascorbic acid in the dams after delivery of the pups. Although the ascorbic acid slightly decreased the lead level in pups, lead level was still high in the group treated with lead plus ascorbic acid group compared with the control group. The blood lead levels indicated that the ascorbic acid could facilitate both the excretion and transfer of lead from a dam to its pups via milk. At postnatal day 21, lead exposure significantly reduced the number of Purkinje cells in the cerebellar cortex of pups. Additionally, lead treatment induced degenerative changes such as reduction of glutamic acid decarboxylase (GAD67) and c-kit expressions are observed in the developing cerebellar cortex. In the cerebellum of the pups from the lead plus ascorbic acid group, reduction of the number of Purkinje cells, GAD67 expression, and c-kit immunopositivity were remarkably restored compared with the lead group. Our present results suggested that ascorbic acid treatment to lead-exposed dam exerted protective effects on the developing cerebellum against lead-induced neurotoxicity.


Subject(s)
Ascorbic Acid/pharmacology , Cerebellar Cortex/drug effects , Glutamate Decarboxylase/biosynthesis , Prenatal Exposure Delayed Effects/prevention & control , Proto-Oncogene Proteins c-kit/biosynthesis , Animals , Animals, Newborn , Antioxidants/pharmacology , Cerebellar Cortex/cytology , Cerebellar Cortex/metabolism , Female , Immunohistochemistry , Lead/toxicity , Lead Poisoning, Nervous System/etiology , Lead Poisoning, Nervous System/metabolism , Lead Poisoning, Nervous System/prevention & control , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Purkinje Cells/drug effects , Rats
13.
Arch Dermatol Res ; 309(8): 665-671, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28752204

ABSTRACT

Maintaining a youthful appearance is a common desire among the aging population. Loss of elasticity and dermal density constitutes major causes of wrinkle formation during skin aging. In particular, periorbital wrinkles comprise the critical assessment point of skin aging. To address these issues, cosmetic industries have been making increasing efforts to develop efficient agents against wrinkle formation. Arg-Gly-Asp (RGD) is a tripeptide sequence used for surface coating because of its integrin-binding property. However, its pharmacological properties on skin have not yet been studied. Here, we synthesize the novel palmitoyl-Arg-Gly-Asp (Palm-RGD) and investigate its effects on periorbital wrinkle formation by clinical and in vitro studies. We observed that Palm-RGD cream application for 12 weeks decreased global photodamage and skin roughness (R1, R2, R3, and Ra) scores without causing skin irritation. In addition, topical application of Palm-RGD cream time-dependently increased skin elasticity and dermal density. An in vitro study using human dermal fibroblasts (HDFs) demonstrated increased type I procollagen production by Palm-RGD treatment. Furthermore, Palm-RGD suppressed MMP-1 expression in HDFs. Our results demonstrate that Palm-RGD has protective effects against wrinkle formation, likely through the activation of collagen expression and the protection against collagen degradation. Therefore, Palm-RGD could be used as a potential agent for the prevention of wrinkle formation consequent to aging.


Subject(s)
Asian People , Face , Oligopeptides/pharmacology , Skin Aging/drug effects , Administration, Topical , Adult , Cells, Cultured , Double-Blind Method , Female , Fibroblasts/drug effects , Gene Expression Regulation/drug effects , Humans , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Middle Aged , Oligopeptides/administration & dosage , Procollagen/genetics , Procollagen/metabolism
14.
Ann Rehabil Med ; 40(2): 190-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27152267

ABSTRACT

OBJECTIVE: To compare tongue thickness, the shortest hyoid-thyroid approximation (distance between the hyoid bone and thyroid cartilage), and the time interval between the initiation of tongue movement and the time of the shortest hyoid-thyroid approximation, by using ultrasonography in healthy controls and patients with Parkinson disease (PD). METHODS: Healthy controls and PD patients with dysphagia were compared. Ultrasonography was performed 3 times for the evaluation of tongue thickness, the shortest hyoid-thyroid approximation, and the time between the initiation of tongue movement and the shortest hyoid-thyroid approximation. RESULTS: A total of 24 healthy controls and 24 PD patients with dysphagia were enrolled. No significant differences were demonstrated between the two groups for the shortest hyoid-thyroid approximation (controls, 1.19±0.34 cm; PD patients, 1.37±0.5 cm; p=0.15) and tongue thickness (controls, 4.42±0.46 cm; PD patients, 4.27±0.51 cm; p=0.3). In contrast, the time to the shortest hyoid-thyroid approximation was significantly different between the two groups (controls, 1.53±0.87 ms; PD patients, 2.4±1.4 ms, p=0.048). CONCLUSION: Ultrasonography can be useful in evaluating dysphagia in patients with PD by direct visualization and measurement of the hyoid bone. Moreover, ultrasonography might contribute to a greater understanding of the pathophysiology of dysphagia in PD.

15.
Appl Microbiol Biotechnol ; 98(8): 3509-15, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24384750

ABSTRACT

The human cell line rF2N78 produces an antibody with a high galactosylation ratio which resembles human IgG. However, it has been observed that the aglycosylated antibody starts to appear when glucose is depleted. To determine whether glucose depletion is a main cause for aglycosylation of the antibody, fed-batch cultures of rF2N78 cells were performed using different feeding cocktails (glucose only, nutrient feeding cocktail without glucose, and nutrient feeding cocktail with glucose). In the fed-batch culture with nutrient feeding cocktail without glucose, aglycosylated antibody was produced in a later phase of culture, when glucose was depleted. Approximately 44 % of antibodies produced were aglycosylated at the end of culture. In contrast, aglycosylated antibody was not produced in cultures with glucose feeding. The expression levels of oligosaccharyl transferases determined by Western blot analysis were similar among the cultures, suggesting that aglycosylation of the antibody was not due to altered expression of oligosaccharyl transferases under glucose-deficient conditions. Thus, it is likely that glucose deficiency led to insufficiency of the precursor for glycosylation and induced aglycosylation of the antibody. Taken together, glucose feeding in fed-batch cultures successfully prevented occurrence of aglycosylated antibody during the cultures, confirming that glucose depletion is a main cause for aglycosylation of antibody.


Subject(s)
Antibodies/metabolism , Culture Media/chemistry , Glucose/metabolism , Antibodies/genetics , Batch Cell Culture Techniques , Cell Line , Glycosylation , Humans , Recombinant Proteins/genetics , Recombinant Proteins/metabolism
16.
J Nanosci Nanotechnol ; 13(12): 8064-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24266192

ABSTRACT

The effect of the dual-etch surface roughening method consisting of dry etching and wet etching on the enhancement of light extraction of vertical light emitting diodes (VLEDs) is investigated. The surface of a VLED was roughened by dry etching using SiO2 spheres as the mask while a KOH solution was used for wet etching. After the surface of the VLED was roughened by the dual-etch method, the luminous efficiency of the VLED increased due to the formation of uniform, nano-scale cone shapes and the decreased flat area ratio of the total GaN surface. The VLED roughened by dual etching showed about 9.3% higher emitted luminous efficiency than the VLED roughened using wet etching.

17.
J Nanosci Nanotechnol ; 13(12): 8090-4, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24266197

ABSTRACT

We investigated the effects of plasma treatment on the sheet resistance of thin films spray-coated with graphene flakes on polyethylene terephthalate (PET) substrates. Thin films coated with graphene flakes show high sheet resistance due to defects within graphene edges, domains, and residual oxygen content. Cl2 plasma treatment led to decreased sheet resistance when treatment time was increased, but when thin films were treated for too long the sheet resistance increased again. Optimum treatment time was related to film thickness. The reduction of sheet resistance may be explained by the donation of holes due to forming pi-type covalent bonds of Cl with carbon atoms on graphene surfaces, or by C--Cl bonding at the sites of graphene defects. However, due to radiation damage caused by plasma treatment, sheet resistance increased with increased treatment time. We found that the sheet resistance of PET film coated with graphene flakes could be decreased by 50% under optimum conditions.

18.
J Nanosci Nanotechnol ; 13(12): 8106-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24266200

ABSTRACT

The properties of Pd/Ir/Au ohmic metallization on p-type GaN have been investigated. Contacts annealed at 400 degrees C in O2 atmosphere demonstrated excellent ohmic characteristics with a specific contact resistivity of 1.5 x 10(-5) Omega-cm2. This is attributed to the formation of Ga vacancies at the contact metal-semiconductor interfacial region due to the out-diffusion of Ga atoms. The out-diffusion of Ga atoms was confirmed by X-ray photoelectron spectroscopy depth profiles, high-resolution transmission electron microscopy, and electron energy loss spectroscopy using a scanning transmission electron microscope.

19.
Appl Microbiol Biotechnol ; 97(12): 5283-91, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23553031

ABSTRACT

The human host cell line, F2N78, is a new somatic hybrid cell line designed for therapeutic antibody production. To verify its potential as a human host cell line, recombinant F2N78 cells that produce antibody against rabies virus (rF2N78) were cultivated at different culture pH (6.8, 7.0, 7.2, 7.4, and 7.6) and temperatures (33.0 °C and 37.0 °C). Regardless of the culture temperature, the highest specific growth rate was obtained at a pH of 7.0-7.4. Lowering the culture temperature from 37.0 °C to 33.0 °C suppressed cell growth while allowing maintenance of high cell viability for a longer period. However, it did not enhance antibody production because specific antibody productivity did not increase at 33.0 °C. The highest maximum antibody concentration was obtained at 37.0 °C and pH 6.8. The N-linked glycosylation of the antibody was affected by the culture pH rather than the temperature. Nevertheless, G1F was dominant and G2F occupied a larger portion than G0F in all culture conditions. Compared to the same antibody produced from recombinant CHO cells, the antibody produced from rF2N78 cells has more galactose capping and was more similar to human plasma IgG. Taken together, the results obtained here demonstrate the potential of F2N78 as an alternative human host cell line for therapeutic antibody production.


Subject(s)
Antibodies, Viral/metabolism , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Culture Media/chemistry , Metabolism/drug effects , Metabolism/radiation effects , Antibodies, Viral/genetics , Cell Culture Techniques , Cell Line , Glycosylation/drug effects , Glycosylation/radiation effects , Humans , Hydrogen-Ion Concentration , Rabies virus/immunology , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Suspensions , Technology, Pharmaceutical/methods , Temperature
20.
Nano Lett ; 12(2): 802-7, 2012 Feb 08.
Article in English | MEDLINE | ID: mdl-22206272

ABSTRACT

Because of its unprecedented theoretical capacity near 4000 mAh/g, which is approximately 10-fold larger compared to those of the current commercial graphite anodes, silicon has been the most promising anode for lithium ion batteries, particularly targeting large-scale energy storage applications including electrical vehicles and utility grids. Nevertheless, Si suffers from its short cycle life as well as the limitation for scalable electrode fabrication. Herein, we develop an electrospinning process to produce core-shell fiber electrodes using a dual nozzle in a scalable manner. In the core-shell fibers, commercially available nanoparticles in the core are wrapped by the carbon shell. The unique core-shell structure resolves various issues of Si anode operations, such as pulverization, vulnerable contacts between Si and carbon conductors, and an unstable sold-electrolyte interphase, thereby exhibiting outstanding cell performance: a gravimetric capacity as high as 1384 mAh/g, a 5 min discharging rate capability while retaining 721 mAh/g, and cycle life of 300 cycles with almost no capacity loss. The electrospun core-shell one-dimensional fibers suggest a new design principle for robust and scalable lithium battery electrodes suffering from volume expansion.


Subject(s)
Electric Power Supplies , Lithium/chemistry , Nanoparticles/chemistry , Nanotechnology , Silicon/chemistry , Electrochemistry , Electrodes , Ions/chemistry , Particle Size , Surface Properties
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