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BACKGROUND: Augmented reality (AR) technology has been shown to be effective in displaying information and presenting three-dimensional objects. Although AR applications are commonly used by learners via mobile devices, plastic models or two-dimensional images are still commonly used in tooth carving practice. Learners practicing tooth carving face a challenge due to the three-dimensional features of teeth as there is a lack of tools available that provide sequential guidance. In this study, we developed an AR-based tooth carving practice tool (AR-TCPT) and compared it to a plastic model to evaluate its potential as a practice tool as well as its user experience. METHODS: To model tooth carving, we created a three-dimensional object from sequential steps that included the maxillary canines and maxillary first premolars (16 steps), mandibular first premolars (13 steps), and mandibular first molars (14 steps). Image markers, created using Photoshop software, were assigned to each tooth. An AR-based mobile application was developed using the Unity engine. For tooth carving, 52 participants were randomly assigned to a control group (n = 26; using a plastic tooth model) or an experimental group (n = 26; using the AR-TCPT). User experience was evaluated using a 22-item questionnaire. Data were comparatively analyzed using the nonparametric Mann-Whitney U test via the SPSS program. RESULTS: The AR-TCPT detects image markers with the mobile device camera and displays three-dimensional objects for tooth fragmentation. Users can manipulate the device to view each step or examine the shape of a tooth. The results of the user experience survey revealed that the AR-TCPT experimental group scored significantly higher in tooth carving experience compared with the control group that used the plastic model. CONCLUSION: Compared with the conventional plastic model, the AR-TCPT provided a better user experience for tooth carving. The tool is highly accessible as it is designed to be used on mobile devices by users. Further studies are required to determine the educational impact of the AR-TCTP on quantitative scoring of carved teeth as well as individual user's carving abilities.
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Realidade Aumentada , Educação em Odontologia , Aplicativos Móveis , Dente , Computadores de Mão , Estudos Prospectivos , Dente/anatomia & histologia , Modelos Anatômicos , Educação em Odontologia/métodos , Estudantes de Odontologia , HumanosRESUMO
Diplogasteroides sp., a cryptic population of D. haslacheri, and Parasitorhabditis terebranus were reported from the frass of Monochamus alternatus galleries in dead Pinus thunbergii for the first time in Korea. Females and males are morphologically characterized and their linked DNA barcodes (18S-rRNA, 28S-rRNA, ITS-rRNA and COI) supplied. Females and males of the two species from Korea conform to the original species descriptions from Europe and the USA, with variations in a few details in morphometrics. Specifically, Diplogasteroides sp. is morphologically very similar to D. haslacheri. However, it cannot be designated as D. haslacheri due to the existence of cryptic species complex within the haslacheri group (D. haslacheri, D. asiaticus, D. nix, D. andrassyi, and D. carinthiacus), a condition requiring hybridization studies to test species identity within the group. Based on analysis of COI sequences, differences among these cryptic species are evident. Thus, in addition to hybridization tests, the COI might be a powerful DNA barcoding marker for the precise identification of these cryptic species within the genus. Additionally, this is the first molecular characterization of P. terebranus, and the species is herein recorded for the first time outside its type locality.
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Background: Atrial flutter is an infrequent yet potentially fatal arrhythmia. Digoxin is the preferred first-line treatment for fetal atrial flutter due to its efficacy and favorable safety profile. The optimal digoxin serum target level for neonatal atrial flutter management remains uncertain, with the standard target level ranging from 1.0 to 2.0 ng/mL due to potential toxicity concerns above this threshold. Case Presentation: We present a case of atrial flutter in a fetus within a monochorionic diamniotic (MCDA) twin pregnancy that was successfully managed using a higher-than-standard target level of digoxin. A 34-year-old nulliparous woman was referred to our institution at 31 + 3 weeks of gestation due to fetal distress in an MCDA twin pregnancy. Fetal echocardiography revealed a ventricular rate of 214 bpm in twin A, while twin B exhibited no abnormal findings. Conclusions: Our case highlights a distinct correlation between the serum digoxin level and its impact on atrial flutter. A higher target serum level of digoxin may be necessary to achieve sinus conversion due to the unique maternal and fetal circulatory characteristics in MCDA pregnancies.
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Flutter Atrial , Gravidez , Recém-Nascido , Feminino , Humanos , Adulto , Flutter Atrial/tratamento farmacológico , Digoxina/uso terapêutico , Gravidez de Gêmeos , Gêmeos , Ecocardiografia , Estudos RetrospectivosRESUMO
Alveolar bone loss, the major feature of periodontitis, results from the activation of osteoclasts, which can consequently cause teeth to become loose and fall out; the development of drugs capable of suppressing excessive osteoclast differentiation and function is beneficial for periodontal disease patients. Given the difficulties associated with drug discovery, drug repurposing is an efficient approach for identifying alternative uses of commercially available compounds. Here, we examined the effects of PF-3845, a selective fatty acid amide hydrolase (FAAH) inhibitor, on receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis, its function, and the therapeutic potential for the treatment of alveolar bone destruction in experimental periodontitis. PF-3845 significantly suppressed osteoclast differentiation and decreased the induction of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific markers. Actin ring formation and osteoclastic bone resorption were also reduced by PF-3845, and the anti-osteoclastogenic and anti-resorptive activities were mediated by the suppression of phosphorylation of rapidly accelerated fibrosarcoma (RAF), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase, (ERK) and nuclear factor κB (NF-κB) inhibitor (IκBα). Furthermore, the administration of PF-3845 decreased the number of osteoclasts and the amount of alveolar bone destruction caused by ligature placement in experimental periodontitis in vivo. The present study provides evidence that PF-3845 is able to suppress osteoclastogenesis and prevent alveolar bone loss, and may give new insights into its role as a treatment for osteoclast-related diseases.
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Perda do Osso Alveolar/tratamento farmacológico , Amidoidrolases/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Osteogênese/efeitos dos fármacos , Periodontite/tratamento farmacológico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Animais , Reabsorção Óssea/tratamento farmacológico , Células Cultivadas , Modelos Animais de Doenças , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/metabolismo , Ligante RANK/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: A certain degree of pulmonary stenosis after total correction of tetralogy of Fallot has been considered acceptable. But the long-term outcomes are not well understood. We observed the natural course of immediate pulmonary stenosis and investigated related factors for progression. METHODS: Fifty-two patients with acceptable pulmonary stenosis immediately after operation were enrolled. Acceptable pulmonary stenosis was defined as peak pressure gradient between 15 and 45 mmHg by Doppler echocardiography. Latent class linear mixed model was used to differentiate patients with progressed pulmonary stenosis, and the factors related to progression were analysed. RESULTS: Pulmonary stenosis progressed in 14 patients (27%). Between the progression group and no progression group, there were no significant differences in operative age, sex, and the use of the transannular patch technique. However, immediate gradient was higher in the progression group (32.1 mmHg versus 25.7 mmHg, p = 0.009), and the cut-off value was 26.8 mmHg (sensitivity = 65.3%, specificity = 65.8%). Main stenosis at the sub-valve was observed more frequently in the progression group (85.7% versus 52.6%, p = 0.027). Despite no difference in the preoperative pulmonary valve z value, the last follow-up pulmonary valve z value was significantly lower in the progression group (-1.15 versus 0.35, p = 0.002). CONCLUSIONS: Pulmonary stenosis immediately after tetralogy of Fallot total correction might progress in patients with immediate pulmonary stenosis higher than ≥26.8 mmHg and the main site was sub-valve area.
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Progressão da Doença , Estenose da Valva Pulmonar/diagnóstico por imagem , Estenose da Valva Pulmonar/fisiopatologia , Tetralogia de Fallot/cirurgia , Criança , Pré-Escolar , Ecocardiografia Doppler , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Valva Pulmonar/anormalidades , Valva Pulmonar/diagnóstico por imagem , Estenose da Valva Pulmonar/etiologia , República da Coreia , Tetralogia de Fallot/complicações , Tetralogia de Fallot/fisiopatologia , Resultado do TratamentoRESUMO
Objectives: We aimed to investigate the outcome of tricuspid valve repair (TVR) performed concomitantly with pulmonary valve replacement in repaired tetralogy of Fallot (TOF) patients. Design: This retrospective study included all patients who underwent pulmonary vale replacement from 2000 to 2016 after TOF correction. TVR patient data were compared to those of patients who underwent pulmonary vale replacement alone. Results: Thirty-eight patients were enrolled. The degree of tricuspid regurgitation was significantly decreased after operation in the TVR group. Tricuspid valve annulus and annuloectasia before operation did not vary between groups (21.1 ± 6.3 and 41.4% in no TVR vs. 21.3 ± 4.8 and 52.6% in TVR). However pre-operative right ventricular volumes were larger in the TVR group. Normal tricuspid valve coaptation (body to body) was observed less frequently in the TVR group than in the other group (52.6% vs. 93.1%, p < .001). Pre-operative tricuspid regurgitation had a linear correlation with right ventricular volume, but not with tricuspid annulus size. Conclusion: Tricuspid annulus diameter decreased significantly regardless of TVR. Abnormal coaptations were observed more in patients group and the degree of pre-operative tricuspid regurgitation was linearly correlated with right ventricular volume rather than tricuspid annulus size.
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Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Pulmonar/cirurgia , Valva Pulmonar/cirurgia , Tetralogia de Fallot/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Adolescente , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Valva Pulmonar/fisiopatologia , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/fisiopatologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Tetralogia de Fallot/complicações , Tetralogia de Fallot/fisiopatologia , Resultado do Tratamento , Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/fisiopatologia , Adulto JovemRESUMO
AIM: The aim of this study was to investigate the involvement and immunophenotype of macrophages in acute chorioamnionitis (ACA) and chronic chorioamnionitis (CCA), marking amniotic fluid infection and anti-fetal rejection, respectively. METHODS: Chorioamniotic membranes from (1) gestational age-matched cases without chorioamnionitis, (2) cases with ACA, and (3) cases with CCA were studied after immunohistochemical staining using antibodies against CD14, CD68, CD163, and DC-SIGN. RESULTS: Macrophages increased prominently in the chorionic trophoblastic layer of both ACA and CCA cases in contrast to non-inflammatory cases. Macrophages in the decidua and the chorioamniotic membranes of ACA cases expressed CD14. Macrophages in the chorionic trophoblastic layer of CCA cases were characterized by CD68 positivity. DC-SIGN-positive cells were increased in the chorioamniotic mesodermal layer of CCA cases. CONCLUSIONS: Macrophages participate in the inflammatory response in ACA and CCA. The differential immunophenotypes of macrophages in the decidua and chorioamniotic membranes of ACA and CCA cases suggest their disease-specific and region-specific roles at the feto-maternal interface.
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Corioamnionite/imunologia , Macrófagos/imunologia , Adulto , Antígenos CD/análise , Moléculas de Adesão Celular/análise , Córion/imunologia , Estudos Transversais , Decídua/imunologia , Feminino , Humanos , Lectinas Tipo C/análise , Gravidez , Receptores de Superfície Celular/análise , Estudos RetrospectivosRESUMO
BACKGROUND: Sevoflurane is commonly usedin pediatric anesthesia due to its non-irritating airway properties, and rapid induction and emergence. However, it is associated with emergence agitation (EA) in children. EA may cause injury to the child or damage to the surgical site and is a cause of stress to both caregivers and families. The efficacy of remifentanil and additional alfentanil on EA in the pediatric patients underwent ophthalmic surgery with sevofluraneanesthesiawas not well evaluated to date. This study was designed to compare the effects of remifentanil and remifentanil plus alfentanil on EA in children undergoing ophthalmic surgery with sevofluraneanesthesia. METHODS: Children (aged 3-9 years) undergoing ophthalmic surgery undersevoflurane anesthesia were randomly assigned to group S (sevoflurane alone), group R (sevofluraneandremifentanil infusion, 0.1 µg/kg/min), or group RA (sevoflurane withremifentanil infusion and intravenous injection of alfentanil 5 µg/kg 10 min before the end of surgery). Mean arterial pressure (MAP), heart rate (HR), and sevoflurane concentration were checked every 15 min after induction of anesthesia. The incidence of EA, time to extubation from discontinuation of sevoflurane inhalation, and time to discharge from the postanesthesia care unit was assessed. RESULTS: The incidence of EA was significantly lower in groups R (32 %, 11/34; P = 0.01) and RA (31 %, 11/35; P = 0.008) than group S (64 %, 21/33). The time to extubation was prolonged in group RA (11.2 ± 2.3 min; P = 0.004 and P = 0.016) compared with groups S (9.2 ± 2.3 min) andR (9.5 ± 2.4 min). MAP and HR were similar in all three groups, apart from a reduction in HR at 45 min in groups R and RA. However, the sevoflurane concentration was lower in groups R and RA than group S (P < 0.001). CONCLUSIONS: The administration of remifentanil to children undergoing ophthalmic surgery undersevoflurane anesthesia reduced the incidence of EA without clinically significant hemodynamic changes. However, the addition of alfentanil(5 µg/kg)10 min before the end of surgery provided no additional benefit compared withremifentanil alone. CLINICAL TRIAL NUMBER: NCT02486926 , June.29.2015.
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Alfentanil/administração & dosagem , Delírio do Despertar/epidemiologia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Piperidinas/administração & dosagem , Extubação , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Incidência , Masculino , Éteres Metílicos/administração & dosagem , Remifentanil , Sevoflurano , Fatores de TempoRESUMO
The crystal structure of Ton1535, a hypothetical protein from Thermococcus onnurineus NA1, was determined at 2.3 Å resolution. With two antiparallel α-helices in a helix-turn-helix motif as a repeating unit, Ton1535 consists of right-handed coiled N- and C-terminal regions that are stacked together using helix bundles containing a left-handed helical turn. One left-handed helical turn in the right-handed coiled structure produces two unique structural properties. One is the presence of separated concave grooves rather than one continuous concave groove, and the other is the contribution of α-helices on the convex surfaces of the N-terminal region to the extended surface of the concave groove of the C-terminal region and vice versa.
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Proteínas Arqueais/química , Thermococcus , Sequência de Aminoácidos , Cristalografia por Raios X , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Dados de Sequência Molecular , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de ProteínaRESUMO
Identification of Helicotylenchus species is very challenging due to phenotypic plasticity and existence of cryptic species complexes. Recently, the use of rDNA barcodes has proven to be useful for identification of Helicotylenchus. Molecular markers are a quick diagnostic tool and are crucial for discriminating related species and resolving cryptic species complexes within this speciose genus. However, DNA barcoding is not an error-free approach. The public databases appear to be marred by incorrect sequences, arising from sequencing errors, mislabeling, and misidentifications. Herein, we provide a comprehensive analysis of the newly obtained, and published DNA sequences of Helicotylenchus, revealing the potential faults in the available DNA barcodes. A total of 97 sequences (25 nearly full-length 18S-rRNA, 12 partial 28S-rRNA, 16 partial internal transcribed spacer [ITS]-rRNA, and 44 partial cytochrome c oxidase subunit I [COI] gene sequences) were newly obtained in the present study. Phylogenetic relationships between species are given as inferred from the analyses of 103 sequences of 18S-rRNA, 469 sequences of 28S-rRNA, 183 sequences of ITS-rRNA, and 63 sequences of COI. Remarks on suggested corrections of published accessions in GenBank database are given. Additionally, COI gene sequences of H. dihystera, H. asiaticus and the contentious H. microlobus are provided herein for the first time. Similar to rDNA gene analyses, the COI sequences support the genetic distinctness and validity of H. microlobus. DNA barcodes from type material are needed for resolving the taxonomic status of the unresolved taxonomic groups within the genus.
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Penicillin-binding proteins (PBPs), which catalyze the biosynthesis of the peptidoglycan chain of the bacterial cell wall, are the major molecular target of bacterial antibiotics. Here, we present the crystal structures of the bifunctional peptidoglycan glycosyltransferase (GT)/transpeptidase (TP) PBP4 from Listeria monocytogenes in the apo-form and covalently linked to two ß-lactam antibiotics, ampicillin and carbenicillin. The orientation of the TP domain with respect to the GT domain is distinct from that observed in the previously reported structures of bifunctional PBPs, suggesting interdomain flexibility. In this structure, the active site of the GT domain is occluded by the close apposition of the linker domain, which supports the hypothesis that interdomain flexibility is related to the regulation of GT activity. The acylated structures reveal the mode of action of ß-lactam antibiotics toward the class A PBP4 from the human pathogen L. monocytogenes. Ampicillin and carbenicillin can access the active site and be acylated without requiring a structural rearrangement. In addition, the active site of the TP domain in the apo-form is occupied by the tartrate molecule via extensive hydrogen bond interactions with the catalytically important residues; thus, derivatives of the tartrate molecule may be useful in the search for new antibiotics to inhibit PBPs.
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Domínio Catalítico , Listeria monocytogenes/química , Proteínas de Ligação às Penicilinas/química , Ampicilina/química , Carbenicilina/química , Parede Celular/química , Ativação Enzimática , Ligação de Hidrogênio , Listeria monocytogenes/enzimologia , Ligação Proteica , Mapeamento de Interação de Proteínas , Estrutura Terciária de Proteína , Tartaratos/químicaRESUMO
Acetyl-CoA carboxylases (ACCs) are crucial metabolic enzymes and have been targeted for drug development against obesity, diabetes, and other diseases. The carboxyltransferase (CT) domain of this enzyme is the site of action for three different classes of herbicides, as represented by haloxyfop, tepraloxydim, and pinoxaden. Our earlier studies have demonstrated that haloxyfop and tepraloxydim bind in the CT active site at the interface of its dimer. However, the two compounds probe distinct regions of the dimer interface, sharing primarily only two common anchoring points of interaction with the enzyme. We report here the crystal structure of the CT domain of yeast ACC in complex with pinoxaden at 2.8-Å resolution. Despite their chemical diversity, pinoxaden has a similar binding mode as tepraloxydim and requires a small conformational change in the dimer interface for binding. Crystal structures of the CT domain in complex with all three classes of herbicides confirm the importance of the two anchoring points for herbicide binding. The structures also provide a foundation for understanding the molecular basis of the herbicide resistance mutations and cross resistance among the herbicides, as well as for the design and development of new inhibitors against plant and human ACCs.
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Acetil-CoA Carboxilase , Carboxil e Carbamoil Transferases , Inibidores Enzimáticos/química , Compostos Heterocíclicos com 2 Anéis/química , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimologia , Acetil-CoA Carboxilase/antagonistas & inibidores , Acetil-CoA Carboxilase/química , Domínio Catalítico , Cristalografia por Raios X , Herbicidas/química , Ligação Proteica , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/química , Relação Estrutura-AtividadeRESUMO
The pine wood nematode (PWN), Bursaphelenchus xylophilus is a well-known devastating pathogen of economic importance in the Republic of Korea and other countries. In the Republic of Korea, trunk injection of nematicides is the preferred method of control. In this study, the efficacy of 16 locally produced formulations of emamectin benzoate against the PWN are compared through determining their sublethal toxicities and reproduction inhibition potentials. Nematodes were treated with varying concentrations of the tested chemicals in multi-well culture plates, and rates of paralysis and mortality were determined after 24 h. Reproduction inhibition potential was tested by inoculating pre-treated nematodes onto Botrytis cinerea, and in pine twig cuttings. Despite the uniformity in the concentration of the active ingredient, efficacy was contrastingly different among formulations. The formulations evidently conformed to three distinct groups based on similarities in sublethal activity (group 1: LC95 of 0.00768-0.01443 mg/ml; group 2: LC95 of 0.03202-0.07236 mg/ml, and group 3: LC95 of as high as 0.30643-0.40811 mg/ml). Nematode paralysis generally occurred at the application dose of 0.0134-0.1075 µg/ml, and there were significant differences in nematode paralysis rates among the products. Nematode reproduction was only evident at lower doses both on B. cinerea and pine twigs, albeit the variations among formulations. Group 1 formulations significantly reduced nematode reproduction even at a lower dose of 0.001075 µg/ml. The variations in efficacy might be attributed to differences in inert ingredients. Therefore, there is need to analyze the potential antagonistic effects of the large number of additives used in formulations.
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Ample evidence demonstrates that α-synuclein (α-syn) has a critical role in the pathogenesis of Parkinson's disease (PD) with evidence indicating that its propagation from one area of the brain to others may be the primary mechanism for disease progression. Uric acid (UA), a natural antioxidant, has been proposed as a potential disease modifying candidate in PD. In the present study, we investigated whether UA treatment modulates cell-to-cell transmission of extracellular α-syn and protects dopaminergic neurons in the α-syn-enriched model. In a cellular model, UA treatment decreased internalized cytosolic α-syn levels and neuron-to-neuron transmission of α-syn in donor-acceptor cell models by modulating dynamin-mediated and clathrin-mediated endocytosis. Moreover, UA elevation in α-syn-inoculated mice inhibited propagation of extracellular α-syn which decreased expression of phosphorylated α-syn in the dopaminergic neurons of the substantia nigra leading to their increased survival. UA treatment did not lead to change in markers related with autophagolysosomal and microglial activity under the same experimental conditions. These findings suggest UA may control the pathological conditions of PD via additive mechanisms which modulate the propagation of α-syn.
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Chronic kidney disease (CKD) gradually leads to loss of renal function and is associated with inflammation and fibrosis. Chrysanthemum coronarium L., a leafy vegetable, possesses various beneficial properties, including anti-oxidative, anti-inflammatory, and antiproliferative effects. In this study, we investigated the renoprotective effect of Chrysanthemum coronarium L. extract (CC) on adenine (AD)-induced CKD in mice. CKD was induced by feeding mice with an AD diet (0.25% w/w) for 4 weeks. Changes in renal function, histopathology, inflammation, and renal interstitial fibrosis were analyzed. The adenine-fed mice were characterized by increased blood urea nitrogen, serum creatinine, and histological changes, including inflammation and fibrosis; however, these changes were significantly restored by treatment with CC. Additionally, CC inhibited the expression of the inflammatory markers, monocyte chemoattractant protein-1, interleukins-6 and -1ß, intercellular adhesion molecule-1, and cyclooxygenase 2. Moreover, CC suppressed the expression of the fibrotic markers, type IV collagen, and fibronectin. Furthermore, CC attenuated the expression of profibrotic genes (tumor growth factor-ß and α-smooth muscle actin) in AD-induced renal injury mice. Thus, our results suggest that CC has the potential to attenuate AD-induced renal injury and might offer a new option as a renoprotective agent or functional food supplement to manage CKD.
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BACKGROUND: Mesenchymal stem cells (MSCs) may be one of candidates for disease-modifying therapy in Parkinsonian diseases. As knowledge regarding the therapeutic properties of MSCs accumulates, some obstacles still remain to be overcome, especially, successful clinical translation requires the development of culture systems that mimic the natural MSC niche, while allowing clinical-scale cell expansion without compromising quality and function of the cells. In recent years, priming approaches using bioactive peptide or complement components have been investigated to enhance the therapeutic potential of MSCs. METHODS: We investigated an innovative priming strategy by conditioning the MSCs with α-synuclein (α-syn). To induce priming, MSCs were treated with different concentrations of α-syn and various time course. We evaluated whether α-syn enhances stemness properties of MSCs and priming MSCs with α-syn would modulate autophagy-related gene expression profiles. RESULTS: Treatment of naïve MSCs with α-syn upregulated transcriptional factors responsible for regulation of stemness, which was associated with the elevated expression of genes involved in glycolysis and cell re-programming. Primed MSCs with α-syn enhanced the expression of autophagy-regulating miRNA, and exosomes derived from primed MSCs were packed with autophagy-associated miRNA. In α-syn-overexpressing neuronal cells, primed MSCs with α-syn enhanced neuronal viability relative to naïve MSCs, through the induction of autophagy and lysosome activity. Animal study using an α-syn-overexpressing mice showed that the pro-survival effect of MSCs on dopaminergic neurons was more prominent in primed MSC-treated mice compared with that in naïve MSC-treated mice. CONCLUSIONS: The present data suggest that MSC priming with α-syn exerts neuroprotective effects through augmented stemness and possibly the enhancement of autophagy-mediated α-syn modulation in Parkinsonian models.
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Células-Tronco Mesenquimais , MicroRNAs , Fármacos Neuroprotetores , Animais , Autofagia/genética , Neurônios Dopaminérgicos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Fármacos Neuroprotetores/farmacologia , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , alfa-Sinucleína/farmacologiaRESUMO
Background: Adult neurogenesis is the process of generating new neurons to enter neural circuits and differentiate into functional neurons. However, it is significantly reduced in Parkinson's disease (PD). Uric acid (UA), a natural antioxidant, has neuroprotective properties in patients with PD. This study aimed to investigate whether UA would enhance neurogenesis in PD. Methods: We evaluated whether elevating serum UA levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mouse model would restore neurogenesis in the subventricular zone (SVZ). For a cellular model, we primary cultured neural precursor cells (NPCs) from post-natal day 1 rat and evaluated whether UA treatment promoted cell proliferation against 1-methyl-4-phenylpyridinium (MPP+). Results: Uric acid enhanced neurogenesis in both in vivo and in vitro parkinsonian model. UA-elevating therapy significantly increased the number of bromodeoxyuridine (BrdU)-positive cells in the SVZ of PD animals as compared to PD mice with normal UA levels. In a cellular model, UA treatment increased the expression of Ki-67. In the process of modulating neurogenesis, UA elevation up-regulated the expression of mitochondrial fusion markers. Conclusion: In MPTP-induced parkinsonian model, UA probably enhanced neurogenesis via regulating mitochondrial dynamics, promoting fusion machinery, and inhibiting fission process.
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A Gram-negative bacterium, designated KIS13-15(T), was isolated from soil in Korea. Cells were strictly aerobic rods and were motile with 1-3 subpolar flagella. 16S rRNA gene sequence analysis revealed that strain KIS13-15(T) belonged to the order Xanthomonadales of the class Gammaproteobacteria and was closely related to Nevskia soli GR15-1(T) (97.9 % 16S rRNA gene sequence similarity) and Nevskia ramosa Soe1(T) (96.8 %). Strain KIS13-15(T) exhibited 38 and 29 % DNA-DNA relatedness with N. soli KACC 11703(T) and N. ramosa DSM 11499(T), respectively. The major fatty acids (>10 % of the total) were C(18 : 1)ω7c (40.6 %) and C(16 : 0) (12.4 %). The major isoprenoid quinone was ubiquinone 8. DNA G+C content was 67.3 mol%. The phenotypic characterization combined with 16S rRNA gene sequence analysis and DNA-DNA hybridization clearly classified strain KIS13-15(T) in a novel species of the genus Nevskia, for which the name Nevskia terrae sp. nov. is proposed. The type strain is KIS13-15(T) (â=âKACC 12736(T) â=âJCM 15425(T)).
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Microbiologia do Solo , Xanthomonadaceae/classificação , Xanthomonadaceae/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/metabolismo , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Xanthomonadaceae/genética , Xanthomonadaceae/metabolismoRESUMO
Two bacterial strains, 01-96(T) and 15-51(T), isolated from rhizosphere soil of Chinese cabbage (Brassica campestris) were characterized by using a polyphasic approach. 16S rRNA gene sequence analysis showed that strain 01-96(T) was phylogenetically related most closely to Pedobacter suwonensis 15-52(T) and Pedobacter roseus CL-GP80(T) (96.7 and 96.7% similarity, respectively), and strain 15-51(T) to Pedobacter borealis G-1(T) and P. suwonensis 15-52(T) (97.2 and 97.1%, respectively). However, levels of DNA-DNA relatedness between strain 15-51(T) and P. borealis KACC 14287(T) and P. suwonensis KACC 11317(T) were low (<50%). The G+C content of the genomic DNA was 37.8 mol% for strain 01-96(T) and 38.6 mol% for strain 15-51(T). The major fatty acids of the two strains were iso-C(17:0) 3-OH, iso-C(15:0) and summed feature 3 (iso-C(15:0) 2-OH and/or C(16:1)ω7c). The results of DNA-DNA hybridization and phenotypic data showed that strains 01-96(T) and 15-51(T) could be distinguished from their closest phylogenetic relatives, and that these strains represented two novel species of the genus Pedobacter, for which the names Pedobacter rhizosphaerae sp. nov. (type strain 01-96(T) =KACC 14938(T) =NBRC 107690(T)) and Pedobacter soli sp. nov. (type strain 15-51(T) =KACC 14939(T) =NBRC 107691(T)) are proposed.
Assuntos
Brassica/microbiologia , Pedobacter/classificação , Pedobacter/isolamento & purificação , Rizosfera , Composição de Bases , DNA Bacteriano/genética , DNA Ribossômico/genética , Ácidos Graxos/metabolismo , Dados de Sequência Molecular , Pedobacter/genética , Pedobacter/metabolismo , Filogenia , RNA Ribossômico 16S/genética , Microbiologia do SoloRESUMO
A novel bacterial strain, designated M2T2B15(T), was isolated from fermented bovine products and was characterized by using a polyphasic approach. Colonies were reddish pink and circular with entire margins. Cells were strictly aerobic, Gram-reaction-negative, oxidase- and catalase-positive rods that lacked flagella and were motile by gliding. Flexirubin-type pigments were absent. 16S rRNA gene sequence analysis indicated that strain M2T2B15(T) was related most closely to Larkinella insperata LMG 22510(T) (94.4â% similarity) but shared <87â% similarity with other members of the phylum Bacteroidetes. The major cellular fatty acids were C(16â:â1)ω5c, iso-C(15â:â0) and iso-C(17â:â0) 3-OH. The polar lipids were phosphatidylethanolamine, phosphatidylserine, two unidentified aminophospholipids and two unidentified polar lipids. Menaquinone 7 (MK-7) was the major respiratory quinone. The G+C content of the DNA of strain M2T2B15(T) was 52 mol%. The phenotypic, genotypic and phylogenetic data presented clearly indicate that strain M2T2B15(T) represents a novel species of the genus Larkinella, for which the name Larkinella bovis sp. nov. is proposed. The type strain is M2T2B15(T) (=KACC 14040(T) =NBRC 106324(T)). Emended descriptions of the genus Larkinella and of Larkinella insperata Vancanneyt et al. 2006 are also proposed.