Growth-associated protein 43 (GAP-43) is known as a neuronal plasticity protein because it is widely expressed at high levels in neuronal growth cones during axonal regeneration. GAP-43 expressed in ...mature adult neurons is functionally important for the neuronal communication of synapses in learning and memory. Brain-derived neurotrophic factor (BDNF) is closely related to neurodegeneration and synaptic plasticity during the aging process. However, the molecular mechanisms regulating neurodegeneration and synaptic plasticity underlying the pathogenesis and progression of Alzheimer's disease (AD) still remain incompletely understood.
Remarkably, the expressions of GAP-43 and BDNF perfectly match in various neurons in the Human Brain Atlas database. Moreover, GAP-43 and BDNF are highly expressed in a healthy adults' hippocampus brain region and are inversely correlated with the amyloid beta (Aβ), which is the pathological peptide of amyloid plaques found in the brains of patients with AD.
These data led us to investigate the impact of the direct molecular interaction between GAP-43 and BDNF in hippocampal neuron fate. In this study, we show that GAP-43 and BDNF are inversely associated with pathological molecules for AD (Tau and Aβ). In addition, we define the three-dimensional protein structure for GAP-43 and BDNF, including the predictive direct binding sites
analysis using ClusPro 2.0, and demonstrate that the deprivation of GAP-43 and BDNF triggers hippocampal neuronal death and memory dysfunction, employing the GAP-43 or BDNF knock-down cellular models and 5XFAD mice.
These results show that GAP-43 and BDNF are direct binding partners in hippocampal neurons and that their molecular signaling might be potential therapeutic targets for AD.
Atopic dermatitis (AD) is a chronic inflammatory disease.
(
) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of
ethanol ...extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.
Background
Brain abscess is a life-threatening condition that occurs due to complications during a neurosurgical procedure, direct cranial trauma, or the presence of local or distal infection. ...Infection in the oral cavity can also be considered a source of brain abscess.
Case presentation
A 45-year-old male patient was transported with brain abscess in the subcortical white matter. Navigation-guided abscess aspiration and drainage was performed in the right mid-frontal lobe, but the symptoms continued to worsen after the procedure. A panoramic radiograph showed alveolar bone resorption around the maxillary molars. The compromised maxillary molars were extracted under local anesthesia, and antibiotics were applied based on findings from bacterial culture. A brain MRI confirmed that the three brain abscesses in the frontal lobe were reduced in size, and the patient’s symptoms began to improve after the extractions.
Conclusion
This is a rare case report about multiple uncontrolled brain abscesses treated by removal of infection through the extraction of maxillary molars with odontogenic infection. Untreated odontogenic infection can also be considered a cause of brain abscess. Therefore, it is necessary to recognize the possibility that untreated odontogenic infection can lead to serious systemic inflammatory diseases such as brain abscess. Through a multidisciplinary approach to diagnosis and treatment, physicians should be encouraged to consider odontogenic infections as a potential cause of brain abscesses.
We demonstrate a simple and easy technique to reliably count the number of layers in graphenes with stacking faults. Using lasers with wavelengths of 514 and 633nm, the optical transmittances of ...multilayer graphene with Bernal, rhombohedral and artificial stacking orders were systematically measured depending on the number of layers. It was found that the optical transmittance of the multilayer graphene is linearly proportional to the number of layers up to 7 regardless of its stacking order. Measurement of optical transmittance can be a useful approach to reliably determine the number of layers in multilayer graphene, thus aiding investigation of its layer-dependent properties and applications.
The global prevalence of obesity has increased steadily in recent years. Waist circumference (WC) reflects body composition better than body mass index. The Korean Society for the Study of Obesity ...released the 2018 Obesity Fact Sheet to address the incidence of obesity-related comorbidities according to WC levels.
Data from the Korean National Health Insurance Service health examination database from 2009 to 2016 were analyzed. Abdominal obesity was defined as a WC ≥90 cm in men and ≥85 cm in women. Incidence rates of comorbidities and all-cause mortality rates were calculated after standardizing by age and sex based on the 2010 census.
From 2009 to 2015, the incidence rates of type 2 diabetes mellitus, hypertension, myocardial infarction, and ischemic stroke increased both in men and women. Individuals with the lowest WC levels had the highest all-cause mortality rates followed by those with the highest WC levels in men, women, and the total population. The incidence rates of total cancer increased as WC levels escalated between 2009 and 2016. In men, the incidence rates of colorectal, prostate, and liver cancers increased as WC levels increased. The incidence rates of thyroid, colorectal, and stomach cancers increased as WC levels rose in women. In addition, medical expenses continuously increased as WC increased in both men and women.
Based on the 2018 Obesity Fact Sheet, strategies for reducing the abdominal obesity and related comorbidities and medical expenses are a public health priority.
Abstract Objectives The purpose of this study is to compare the various magnetic resonance imaging (MRI) sequences when they are used to visualize and evaluate cerebral venous thrombosis. Methods ...Eleven patients with cerebral venous thrombosis were retrospectively analyzed using computed tomography, MRI, magnetic resonance angiography (MRA), and conventional angiography. The MR sequence included T1-weighted spin echo (SE) imaging, obtained before and after administration of contrast medium, T2-weighted turbo spin echo (TSE), fluid-attenuated inversion recovery (FLAIR), T2*-weighted conventional gradient-echo (GRE), as well as three-dimensional (3D) venous time-of-flight MRA and conventional angiography. Results In all of our patients, the venous sinus thromboses were most successfully detected during the T2*-weighted GRE sequence. The thrombosis was well visualized with the T1-weighted SE sequence in three of four patients in whom it was in the subacute stage. The T2*-weighted GRE sequence was superior to the T2-weighted TSE, T1-weighted SE, and FLAIR sequences in all patients. Enhanced 3D MR venography showed the thrombosed segment of the venous sinus and well correlated with the conventional angiographic findings. Conclusions The T2*-weighted conventional GRE sequences may be the best method for detecting of cerebral venous thrombosis. Therefore, it would seem to be beneficial to integrate a T2*-weighted conventional GRE sequence into the MR protocol to diagnose cerebral venous thrombosis.
Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the ...underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from −287 to −158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the positive effect of Pdx-1 on Gck transcriptional regulation, enhanced recruitment of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the interaction of Hdac1/Pdx-1 on the Gck promoter, which were diminished by Atf3 siRNA. In vivo Atf3-silencing reversed ethanol-mediated Gck down-regulation and β-cell dysfunction, followed by the amelioration of impaired glucose tolerance and insulin resistance. Together, we identified that ethanol-induced Atf3 fosters β-cell dysfunction via Gck down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes. The Atf3 gene is associated with the induction of type 2 diabetes and alcohol consumption-induced metabolic impairment and thus may be the major negative regulator for glucose homeostasis.
In 2014, the highly pathogenic avian influenza (HPAI) virus H5N8 triggered outbreaks in wild birds and poultry farms in South Korea. In the present study, we investigated the pathogenicity of the ...H5N8 HPAI virus, belonging to the clade 2.3.4.4, in different species of poultry. For this, we examined clinical signs and viral shedding levels following intranasal inoculation of the virus in 3-week-old commercial layer chickens and quails, 10-week-old Korean native chickens, and 8-week-old Muscovy ducks. Intranasal inoculation with 10 ⁶.⁰ viruses at 50% egg-infective dose resulted in 100% mortality in the layer chickens (8/8) and quails (4/4), but 60% and 0% deaths in the Korean native chickens (3/5) and Muscovy ducks (0/4), respectively. In addition, transmission of the inoculated virus to contact-exposed birds was evident in all the species used in this study. Based on our results, we conclude that the H5N8 HPAI virus has lower pathogenicity and transmissibility in poultry species compared with previously reported H5N1 HPAI viruses.
PurposeWe sought to analyze the visual outcome and systemic prognostic factors for diabetic vitrectomy and predicted outcomes using these factors. MethodsThis was a multicenter electronic medical ...records (EMRs) review study of 1504 eyes with type 2 diabetes that underwent vitrectomy for proliferative diabetic retinopathy at 6 university hospitals. Demographics, laboratory results, intra-operative findings, and visual acuity (VA) values were analyzed and correlated with visual outcomes at 1 year after the vitrectomy. Prediction models for visual outcomes were obtained using machine learning. ResultsAt 1 year, VA was 1.0 logarithm of minimal angle resolution (logMAR) or greater (poor visual outcome group) in 456 eyes (30%). Baseline visual acuity, duration of diabetes treatment, tractional membrane, silicone oil tamponade, smoking, and vitreous hemorrhage correlated with logMAR VA at 1 year (r = 0.450, -0.159, 0.221, 0.280, 0.067, and -0.105; all P ≤ 0.036). An ensemble decision tree model trained using all variables generated accuracy, specificity, F1 score (the harmonic means of which precision and sensitivity), and receiver-operating characteristic curve area under curve values of 0.77, 0.66, 0.85, and 0.84 for the prediction of poor visual outcomes at 1 year after vitrectomy. ConclusionsVisual outcome after diabetic vitrectomy is associated with pre- and intra-operative findings and systemic factors. Poor visual outcome after diabetic vitrectomy was predictable using clinical factors. Intensive care in patients who are predicted to result in poor vision may limit vision loss resulting from type 2 diabetes. Translational RelevanceThis study demonstrates that a real world EMR big data could predict outcome after diabetic vitrectomy using clinical factors.
Botropase is a snake venom-based hemocoagulase with thrombin-like activity 1. Despite its clinical use over several decades, its therapeutic effect has been controversial, and no study about ...botropase effect on platelet function has been reported. In this report, we present two cases with markedly decreased platelet function after receiving intravenous botropase, especially one of whom, with end stage renal disease (ESRD), showed a severe bleeding complication. On April 20, 2020, a 59-year-old man (case 1) visited our hospital for spinal stenosis surgery. His past medical history was pertinent, with diabetes diagnosed at the age of 40 and hemodialysis since February 2017. He did not take any antiplatelet medications for several months before the surgery. Initial laboratory findings showed white blood cell count 8.8 × 103 /µL, hemoglobin 10.0 g/dL, hematocrit 29%, platelet count 162 × 103 /µL, blood urea nitrogen 45 mg/dL, creatinine 6.3 mg/dL, glucose 92 mg/dL, prothrombin time 13.4 seconds, protein C activity 97%, protein S activity 78%, von Willebrand factor 150%, antithrombin III 80%, and fibrinogen 116 mg/dL. KCI Citation Count: 0
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