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Localization of messenger RNA (mRNA) in dendrites is crucial for regulating gene expression during long-term memory formation. mRNA binds to RNA-binding proteins (RBPs) to form messenger ribonucleoprotein (mRNP) complexes that are transported by motor proteins along microtubules to their target synapses. However, the dynamics by which mRNPs find their target locations in the dendrite have not been well understood. Here, we investigated the motion of endogenous ß-actin and Arc mRNPs in dissociated mouse hippocampal neurons using the MS2 and PP7 stem-loop systems, respectively. By evaluating the statistical properties of mRNP movement, we found that the aging Lévy walk model effectively describes both ß-actin and Arc mRNP transport in proximal dendrites. A critical difference between ß-actin and Arc mRNPs was the aging time, the time lag between transport initiation and measurement initiation. The longer mean aging time of ß-actin mRNP (~100 s) compared with that of Arc mRNP (~30 s) reflects the longer half-life of constitutively expressed ß-actin mRNP. Furthermore, our model also permitted us to estimate the ratio of newly generated and pre-existing ß-actin mRNPs in the dendrites. This study offers a robust theoretical framework for mRNP transport, which provides insight into how mRNPs locate their targets in neurons.
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Actinas , Ribonucleoproteínas , Camundongos , Animais , Actinas/metabolismo , Ribonucleoproteínas/metabolismo , Dendritos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Autism spectrum disorder (ASD) is a major neurodevelopmental disorder in which patients present with core symptoms of social communication impairment, restricted interest, and repetitive behaviors. Although various studies have been performed to identify ASD-related mechanisms, ASD pathology is still poorly understood. CNTNAP2 genetic variants have been found that represent ASD genetic risk factors, and disruption of Cntnap2 expression has been associated with ASD phenotypes in mice. In this study, we performed an integrative multi-omics analysis by combining quantitative proteometabolomic data obtained with Cntnap2 knockout (KO) mice with multi-omics data obtained from ASD patients and forebrain organoids to elucidate Cntnap2-dependent molecular networks in ASD. To this end, a mass spectrometry-based proteometabolomic analysis of the medial prefrontal cortex in Cntnap2 KO mice led to the identification of Cntnap2-associated molecular features, and these features were assessed in combination with multi-omics data obtained on the prefrontal cortex in ASD patients to identify bona fide ASD cellular processes. Furthermore, a reanalysis of single-cell RNA sequencing data obtained from forebrain organoids derived from patients with CNTNAP2-associated ASD revealed that the aforementioned identified ASD processes were mainly linked to excitatory neurons. On the basis of these data, we constructed Cntnap2-associated ASD network models showing mitochondrial dysfunction, axonal impairment, and synaptic activity. Our results may shed light on the Cntnap2-dependent molecular networks in ASD.
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Transtorno do Espectro Autista , Camundongos , Animais , Multiômica , Camundongos Knockout , Neurônios/metabolismo , Axônios/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismoRESUMO
Recent emphasis on the design of drug delivery systems typically involves the effective transport of a pharmaceutical substance to the disease site with the desired therapeutic efficacy and minimal cytotoxicity. Organelle-targeted peptides have become an integral part of designing an important class of prodrug/prodrug assemblies for new supramolecular therapeutics owing to their favorable biocompatibility, synthetic ease, tunability of their aggregation behavior, and desired functionalization for site-specificity. However, it is still limited due to the low selectivity. We designed a folic acid-functionalized ß-cyclodextrin (FA-CD) as a delivery platform for specific and selective delivery of organelle-targeted (such as microtubule, lysosome, and mitochondria) peptide chemotherapeutics to the folate receptor (FR) overexpressing cancer cell lines. Low toxicity was found for the FA-CD and organelle-targeted peptide inclusion complex in FR-negative normal cells, but superior inhibition of tumor growth with no in vivo toxicity was found for the inclusion complex in the xenograft tumor model.
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Senolytics, which eliminate senescent cells from tissues, represent an emerging therapeutic strategy for various age-related diseases. Most senolytics target antiapoptotic proteins, which are overexpressed in senescent cells, limiting specificity and inducing severe side effects. To overcome these limitations, we constructed self-assembling senolytics targeting senescent cells with an intracellular oligomerization system. Intracellular aryl-dithiol-containing peptide oligomerization occurred only inside the mitochondria of senescent cells due to selective localization of the peptides by RGD-mediated cellular uptake into integrin αvß3-overexpressed senescent cells and elevated levels of reactive oxygen species, which can be used as a chemical fuel for disulfide formation. This oligomerization results in an artificial protein-like nanoassembly with a stable α-helix secondary structure, which can disrupt the mitochondrial membrane via multivalent interactions because the mitochondrial membrane of senescent cells has weaker integrity than that of normal cells. These three specificities (integrin αvß3, high ROS, and weak mitochondrial membrane integrity) of senescent cells work in combination; therefore, this intramitochondrial oligomerization system can selectively induce apoptosis of senescent cells without side effects on normal cells. Significant reductions in key senescence markers and amelioration of retinal degeneration were observed after elimination of the senescent retinal pigment epithelium by this peptide senolytic in an age-related macular degeneration mouse model and in aged mice, and this effect was accompanied by improved visual function. This system provides a strategy for the treatment of age-related diseases using supramolecular senolytics.
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Senescência Celular , Senoterapia , Camundongos , Animais , Espécies Reativas de Oxigênio , Peptídeos/farmacologia , IntegrinasRESUMO
Environmental problems such as global warming are one of the most prominent global challenges. Researchers are investigating various methods for decreasing CO2 emissions. The CO2 reduction reaction via electrochemical, photochemical, and photoelectrochemical processes has been a popular research topic because the energy it requires can be sourced from renewable sources. The CO2 reduction reaction converts stable CO2 molecules into useful products such as CO, CH4 , C2 H4 , and C2 H5 OH. To obtain economic benefits from these products, it is important to convert them into hydrocarbons above C2 . Numerous investigations have demonstrated the uniqueness of the CC coupling reaction of Cu-based catalysts for the conversion of CO2 into useful hydrocarbons above C2 for electrocatalysis. Herein, the principle of semiconductors for photocatalysis is briefly introduced, followed by a description of the obstacles for C2+ production. This review presents an overview of the mechanism of hydrocarbon formation above C2 , along with advances in the improvement, direction, and comprehension of the CO2 reduction reaction via electrochemical, photochemical, and photoelectrochemical processes.
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Skin hydration is one of the primary aims of beauty and anti-aging treatments. Barley (Hordeum vulgare) and soybean (Glycine max) are major food crops, but can also be used as ingredients for the maintenance of skin health. We developed a natural product-based skin treatment using a barley and soybean formula (BS) incorporating yeast fermentation, and evaluated its skin hydration effects as a dietary supplement in a clinical study. Participants ingested a placebo- (n = 33) or BS- (3 g/day) containing drink (n = 32) for 8 weeks. A significant increase in hydration in the BS group as compared to the placebo group was observed on the faces of subjects after 4 and 8 weeks, and on the forearm after 4 weeks. Decreases in stratum corneum (SC) thickness were also observed on the face and forearm. BS enhanced hyaluronan (HA) and skin barrier function in vitro and reduced Hyal2 expression in human dermal fibroblasts (HDF). BS also recovered ultraviolet (UV) B-induced downregulation of HA in HaCaT cells. These results suggest that BS has promising potential for development as a health functional food to enhance skin health.
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Various health effects have been attributed to the ginsenoside metabolite 20-O-ß-D-glucopyranosyl-20(S)-protopanaxadiol (GPD); however, its effect on ultraviolet (UV)-induced matrix metalloproteinase (MMP)-1 expression and the mechanism underlying this effect are unknown. We examined the inhibitory effect of GPD on UV-induced MMP-1 expression and its mechanisms in human dermal fibroblasts (HDFs). GPD attenuated UV-induced MMP-1 expression in HDFs and suppressed the UV-induced phosphorylation of mammalian target of rapamycin (mTOR) and p70(S6K) without inhibiting the activity of phosphatidylinositol 3-kinase and Akt, which are well-known upstream kinases of mTOR. GPD augmented the phosphorylation of liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK), which are inhibitors of mTOR, to a greater extent than UV treatment alone. Similar to GPD, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranosyl 5'-monophosphate (AICAR), an activator of AMPK, augmented UV-induced AMPK phosphorylation to a greater extent than UV treatment alone, resulting in the inhibition of MMP-1 expression. AICAR also decreased the phosphorylation of mTOR and p70(S6K). However, compound C, an antagonist of AMPK, increased MMP-1 expression. In HDF cells with AMPK knock-down using shRNA, MMP-1 expression was increased. These results indicate that AMPK activation plays a key role in MMP-1 suppression. Additionally, the cAMP-dependent protein kinase (PKA) inhibitor, H-89, antagonized GPD-mediated MMP-1 suppression via the inhibition of LKB1. Our results suggest that the suppressive activity of GPD on UV-induced MMP-1 expression is due to the activation of AMPK as a downstream of the PKA-LKB1 pathway.
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Proteínas Quinases Ativadas por AMP/biossíntese , Ginsenosídeos/farmacologia , Metaloproteinase 1 da Matriz/biossíntese , Serina-Treonina Quinases TOR/antagonistas & inibidores , Quinases Proteína-Quinases Ativadas por AMP , Proteínas Quinases Ativadas por AMP/genética , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Linhagem Celular , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fibroblastos , Humanos , Isoquinolinas/farmacologia , Oxazinas/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Ribonucleotídeos/farmacologia , Proteínas Quinases S6 Ribossômicas 70-kDa/antagonistas & inibidores , Sulfonamidas/farmacologia , Raios UltravioletaRESUMO
AIMS: To determine the effectiveness of non-pharmacological interventions on sleep outcomes among patients with coronary artery disease and recognize pertinent characteristics that potentially affect the effectiveness of such interventions. METHODS AND RESULTS: Relevant studies conducted before 27 April 2022 were identified through four core electronic databases using terms related to coronary artery disease, sleep outcomes, and randomized controlled trials. Two authors independently conducted study selection, data extraction, and risk-of-bias assessment. Meta-analysis, sub-group analysis, publication bias analysis, and sensitivity analysis were conducted using R version 4.2.2. Of the 4755 retrieved articles, 42 studies were selected for systematic review and 30 studies were included in the meta-analysis. The findings of this study revealed that non-pharmacological interventions significantly improved self-reported sleep quality (standardized mean difference = -0.85, 95% confidence interval -1.08, -0.63), but had no effects on objectively measured sleep efficiency and duration. Regarding the types of interventions involved, environmental control was the most effective in improving self-reported sleep quality, followed by relaxation, self-care behaviour management, and relaxation and cognitive/psychological complex interventions. Through subgroup analysis, we did not find any covariates that were significantly related to self-reported sleep quality. CONCLUSION: Non-pharmacological interventions have been shown to play beneficial roles in improving self-reported sleep quality among patients with coronary artery disease. Additional studies are required to elucidate the effect of non-pharmacological interventions on objectively measured sleep outcomes and to characterize their optimal frequencies and durations. REGISTRATION: PROSPERO CRD42022366851.
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Doença da Artéria Coronariana , Transtornos do Sono-Vigília , Humanos , Doença da Artéria Coronariana/terapia , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia , Depressão , SonoRESUMO
PURPOSE: Evidence on non-pharmacological interventions for adolescents with type 1 diabetes is unclear. This review aimed to evaluate the effectiveness of non-pharmacological intervention in adolescents with type 1 diabetes. METHODS: We conducted a search on databases from November 11 to 19, 2022, for randomized controlled trials for the effects of non-pharmacological intervention in adolescents with type 1 diabetes. To identify recent research trends, we included studies published from 2017 to November 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool 2.0. To estimate the effect size, a meta-analysis was performed using RevMan 5.4 program and R Studio. RESULTS: A total of 45 studies were included in the systematic review. Among those, 30 studies were included in the meta-analysis. Non-pharmacological interventions were significantly effective in improving Glycated hemoglobin (HbA1c) (standardized mean difference [SMD] = -0.26, 95% confidence interval [CI]: -0.42, -0.09), quality of life (SMD = 0.44, 95% CI: 0.13 to 0.76), and anxiety (SMD = -0.91, 95% CI: -1.26, -0.56). Subgroup analysis showed that duration of intervention was not a covariate related to HbA1c levels. CONCLUSIONS: Non-pharmacological interventions have shown effectiveness in improving the HbA1c, quality of life, and anxiety in adolescents with type 1 diabetes. Future studies with more rigorous methodology are needed to confirm and strengthen the validity of these findings. Additionally, attention to changes in the lipid profile and self-care motivation among adolescents with type 1 diabetes is warranted. TRIAL REGISTRATION NUMBER: Prospective Register of Systematic Reviews (CRD42022382190).
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Diabetes Mellitus Tipo 1 , Humanos , Adolescente , Diabetes Mellitus Tipo 1/terapia , Qualidade de Vida , Hemoglobinas Glicadas , Ansiedade , AutocuidadoRESUMO
PURPOSE: Providing continuous self-care support to the growing diabetes population is challenging. Strategies are needed to enhance engagement in self-care, utilizing innovative technologies for personalized feedback. This study aimed to assess the feasibility of the Automated Personalized Self-Care program among type 2 diabetes patients and evaluate its preliminary effectiveness. METHODS: A parallel randomized pilot trial with qualitative interviews occurred from May 3, 2022, to September 27, 2022. Participants aged 40-69 years with type 2 diabetes and HbA1c ≥ 7.0% were recruited. The three-month program involved automated personalized goal setting, education, monitoring, and feedback. Feasibility was measured by participants' engagement and intervention usability. Preliminary effectiveness was examined through self-care self-efficacy, self-care behaviors, and health outcomes. Qualitative interviews were conducted with the intervention group. RESULTS: A total of 404 patients were screened. Out of the 61 eligible patients, 32 were enrolled, resulting in a recruitment rate of 52.5%. Retention rates at three months were 84.2% and 84.6% in the intervention and control groups, respectively. Among the intervention group, 81.3% satisfied adherence criteria. Mobile application's usability scored 66.25, and participants' satisfaction was 8.06. Intention-to-treat analysis showed improvements in self-measured blood glucose testing, grain intake, and HbA1c in the intervention group. Qualitative content analysis identified nine themes. CONCLUSION: Feasibility of the program was verified. A larger randomized controlled trial is needed to determine its effectiveness in self-care self-efficacy, self-care behaviors, and health outcomes among type 2 diabetes patients. This study offers insights for optimizing future trials assessing clinical effectiveness. TRIAL REGISTRATION: Clinical Research Information Service, KCT0008202 (registration date: 17 February 2023).
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Diabetes Mellitus Tipo 2 , Autocuidado , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicologia , Pessoa de Meia-Idade , Projetos Piloto , Feminino , Masculino , Autocuidado/métodos , Idoso , Adulto , Estudos de Viabilidade , Autoeficácia , Aplicativos MóveisRESUMO
PURPOSE: Preventing diabetic complications involves regular outpatient follow-up and maintaining low variability in hemoglobin A1c (HbA1c) levels. This study investigated the factors associated with diabetic complications, with a specific focus on the impact of regular outpatient follow-up and HbA1c variability, among patients with type 2 diabetes. METHODS: The study design was secondary data analysis of electronic medical records from a university hospital in Korea. It included patients aged 40-79 with type 2 diabetes who were prescribed diabetes medication within three months of their first HbA1c test by an endocrinologist and were followed up for at least five years. Follow-up regularity, adjusted standard deviation of HbA1c levels, and diabetic complication indices were collected. Data were analyzed using the Chi-square test, independent t-test, repeated measures analysis of variance, and multiple regression analysis. RESULTS: The study included 1566 patients. Lower follow-up regularity was observed in patients of older age, with comorbidities, diabetic complications, insulin treatment, a history of hospitalization, lower baseline estimated glomerular filtration rate (eGFR) and total cholesterol (TC), and higher HbA1c variability. Higher HbA1c variability was observed in younger patients without comorbidity but with insulin treatment, a history of hospitalization, higher baseline blood glucose (BG), HbA1c, TC, and triglyceride levels. HbA1c variability had the strongest influence on BG and HbA1c levels at the five-year follow-up. Baseline eGFR and TC were the most influential factors for their respective levels at the five-year follow-up. Follow-up regularity significantly affected BG, HbA1c, eGFR, and TC at five-year follow-up. CONCLUSIONS: It has been shown that several variables besides regular follow-up and HbA1c variability have an influence. However, these are the two that can be corrected through nursing intervention and are important, so intervention on these is important.
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Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Insulinas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Seguimentos , Pacientes Ambulatoriais , Complicações do Diabetes/complicações , Estudos Retrospectivos , Glicemia/análiseRESUMO
Diffusion-weighted imaging (DWI) utilizing maximum-intensity projection (MIP) was suggested as a cost-effective alternative tool without the risk of gadolinium-based contrast agents. The purpose of this study was to investigate whether DWI MIPs played a supportive role in young (≤60) patients with marked background parenchymal enhancement (BPE) on contrast-enhanced MRI (CE-MRI). The research included 1303 patients with varying degrees of BPE, and correlations between BPE on CE-MRI, the background diffusion signal (BDS) on DWI, and clinical parameters were analyzed. Lesion detection scores were compared between CE-MRI and DWI, with DWI showing higher scores. Among the 186 lesions in 181 patients with marked BPE on CE-MRI, the main lesion on MIPs of CE-MRI was partially or completely seen in 88.7% of cases, while it was not seen in 11.3% of cases. On the other hand, the main lesion on MIPs of DWI was seen in 91.4% of cases, with only 8.6% of cases showing no visibility. DWI achieved higher scores for lesion detection compared to CE-MRI. The presence of a marked BDS was significantly associated with a lower likelihood of a higher DWI score (p < 0.001), and non-mass lesions were associated with a decreased likelihood of a higher DWI score compared with mass lesions (p = 0.196). In conclusion, the inclusion of MIPs of DWI in the preoperative evaluation of breast cancer patients, particularly young women with marked BPE, proved highly beneficial in improving the overall diagnostic process.
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/ß-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.
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Transtorno do Espectro Autista , Ubiquitina-Proteína Ligases , Via de Sinalização Wnt , Animais , Feminino , Camundongos , Gravidez , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/genética , Modelos Animais de Doenças , Proteômica , Ubiquitina-Proteína Ligases/metabolismo , Regulação para Cima , Ácido Valproico/efeitos adversosRESUMO
PURPOSE: The study aimed to design and develop an automated personalized self-care (APSC) program for patients with type 2 diabetes mellitus. The secondary aim was to present a clinical protocol as a mixed-method research to test the program effects. METHODS: The APSC program was developed in the order of analysis, design, implementation, and evaluation according to the software development life cycle, and was guided by the self-regulatory theory. The content validity, heuristics, and usability of the program were verified by experts and patients with type 2 diabetes mellitus. RESULTS: The APSC program was developed based on goal setting, education, monitoring, and feedback components corresponding to the phases of forethought, performance/volitional control, and self-reflection of self-regulatory theory. Using the mobile application, the participants are able to learn from educational materials, monitor their health behaviors, receive weekly-automated personalized goals and feedback messages, and use an automated conversation system to solve the problems related to self-care. The ongoing two-year study utilizes a mixed method design, with 180 patients having type 2 diabetes mellitus randomized to receive either the intervention or usual care. The participants will be reviewed for self-care self-efficacy, health behaviors, and health outcomes at 6, 12, 18, and 24 months. Participants in the intervention group will be interviewed about their experiences. CONCLUSION: The APSC program can serve as an effective tool for facilitating diabetes health behaviors by improving patients' self-care self-efficacy and self-regulation for self-care. However, the clinical effectiveness of this program requires further investigation.
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Diabetes Mellitus Tipo 2 , Aplicativos Móveis , Humanos , Autocuidado/métodos , AutoeficáciaRESUMO
To achieve spatiotemporal control, an enzyme-instructed self-assembly system is widely used, but this approach typically has a small effect on cellular fate. In this study, we show that the intralysosomal assembly by a carbonic anhydrase IX (CAIX)-targeting peptide amphiphile (Pep-AT) can control cellular fate with a low therapeutic dose by tuning the surface charge based on pH change. Pep-AT self-assembles into a fibrous aggregate with a negative surface charge in an extracellular environment near CAIX. During endocytosis, it changes into a nanofiber with a positive surface charge at the lysosome. Then, it can disrupt the lysosomal membrane and induce cellular apoptosis. This study demonstrates that a spatiotemporal assembly induced by a cancer enzyme and specific organelle can control the cellular fate of cancer.
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BACKGROUND: As society becomes more complex, the incidence of mandibular fractures is increasing. This study aimed to analyze the incidence and type and identify etiological factors of mandibular fractures to use them in future treatments. MATERIAL AND METHODS: Data were collected from 224 patients who visited the department of oral and maxillofacial surgery at the Kyung Hee Medical Center dental hospital during a 6-year period (2016 to 2021). A logistic regression model was used for data analysis. RESULTS: In a total of 224 patients, 362 fractures were appeared. The average age of the patients was 34.1 years, with the highest incidence in the 20s. And the ratio between male and female was 4.09:1. Symphysis fractures were the most prevalent of all patients (52.7%), followed by unilateral condyle (37.1%), angle (36.2%), bilateral condyle (9.4%), body (8%), and coronoid (2.2%). The most common cause of fracture was daily-life activity (57.6%), followed by violence (30.4%), traffic accidents (8.5%), and syncope (3.6%). Patients with symphysis fracture were at low risk (OR < 1) of angle, body, and unilateral condyle fractures. Similarly, patients with unilateral fracture were at low risk (OR < 1) of symphysis, angle, body, and others site fractures. In contrast, patient with bilateral condyle fracture were at high risk (OR > 1) of coronoid fractures. And younger patients were high risk of mandibular angle fractures. CONCLUSION: Through this study, it was confirmed that etiological factors of mandibular fractures were like those of previous studies.
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Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that sequesters ATP by self-assembling with ATP inside mitochondria. MNP interacts strongly with ATP through electrostatic and hydrogen bonding interactions. MNP exhibits higher binding affinity for ATP (-637.5 kJ mol-1) than for adenosine diphosphate (ADP) (-578.2 kJ mol-1). To improve anticancer efficacy, the small-sized MNP/ADP complex formed large assemblies with ATP inside cancer cell mitochondria. ATP sequestration and formation of large assemblies of the MNP/ADP-ATP complex inside mitochondria caused physical stress by large structures and metabolic disorders in cancer cells, leading to apoptosis. This work illustrates a facile approach to developing cancer therapeutics that relies on molecular assemblies.
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To diagnose autism spectrum disorder (ASD), researchers have sought biomarkers whose alterations correlate with the susceptibility to ASD. However, biomarkers closely related to the pathophysiology of ASD are lacking. Even though excitation/inhibition (E/I) imbalance has been suggested as an underlying mechanism of ASD, few studies have investigated the actual ratio of glutamate (Glu) to γ-aminobutyric acid (GABA) concentration in vivo. Moreover, there are controversies in the directions of E/I ratio alterations even in extensively studied ASD animal models. Here, using proton magnetic resonance spectroscopy (1H-MRS) at 9.4T, we found significant differences in the levels of different metabolites or their ratios in the prefrontal cortex and hippocampus of Cntnap2-/- mice compared to their wild-type littermates. The Glu/GABA ratio, N-acetylaspartate (NAA)/total creatine (tCr) ratio, and tCr level in the prefrontal cortex were significantly different in Cntnap2-/- mice compared to those in wild-type mice, and they significantly correlated with the sociability of mice. Moreover, receiver operating characteristic (ROC) analyses indicated high specificity and selectivity of these metabolites in discriminating genotypes. These results suggest that the lowered Glu/GABA ratio in the prefrontal cortex along with the changes in the other metabolites might contribute to the social behavior deficit in Cntnap2-/- mice. Our results also demonstrate the utility of 1H-MRS in investigating the underlying mechanisms or the diagnosis of ASD.
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Transtorno do Espectro Autista , Ácido Glutâmico , Ácido gama-Aminobutírico , Animais , Transtorno do Espectro Autista/metabolismo , Ácido Glutâmico/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Córtex Pré-Frontal/metabolismo , Comportamento Social , Ácido gama-Aminobutírico/metabolismoRESUMO
Although medial prefrontal cortex (mPFC) is known to play important roles in social behaviors, how early social experiences affect the mPFC and its subcortical circuit remains unclear. We report that mice singly housed (SH) for 8 weeks after weaning show a social recognition deficit, even after 4 weeks of resocialization. In SH mice, prefrontal infralimbic (IL) neurons projecting to the shell region of nucleus accumbens (NAcSh) show decreased excitability compared with group-housed (GH) mice. NAcSh-projecting IL neurons are activated when GH mice encounter a familiar conspecific, which is not observed in SH mice. Chemogenetic inhibition of NAcSh-projecting IL neurons in normal mice impairs social recognition without affecting social preference, whereas activation of these neurons reverses social recognition deficit in SH mice. Our findings demonstrate that early social experience critically affects mPFC IL-NAcSh projection, the activation of which is required for social recognition by encoding information for social familiarity.
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Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/fisiologia , Reconhecimento Psicológico/fisiologia , Comportamento Social , Isolamento Social/psicologia , Animais , Masculino , Camundongos , Modelos AnimaisRESUMO
OBJECTIVE: To assess heart failure (HF) knowledge, adherence to lifestyle recommendations, and quality of life (QOL) among Koreans with HF and identify factors influencing QOL. METHODS: A cross-sectional and correlational design was used and a total of 142 Koreans with HF were recruited between April 2012 and September 2013. Data were analyzed using multiple logistic regression with SPSS version 21.0. RESULTS: The mean age of participants was 64.1 ± 7.4 years. A higher proportion of participants were male, married, unemployed, had a high education level, and class I New York Heart Association (NYHA) functional status. A higher proportion of participants had ≥2 comorbidities and the most prevalent comorbidity was diabetes. The mean score of HF knowledge was 6.9 (possible range 0-15) and the most frequent incorrect items were "proper actions to reduce thirst" and "causes of leg swelling" in both better and worse QOL groups. Among the recommended lifestyle, pneumococcal vaccination had the least adherence in both groups. Multiple logistic regression showed that patients in NYHA class I, with a higher left ventricular ejection fraction, who had knowledge of "amount of fluid intake a day" and consumed more than moderate alcohol tended to have better QOL. Conclusion: More active interventions targeting HF knowledge in proper actions to reduce thirst, causes of leg swelling, and the amount of fluid intake per day are required. Patients with HF in more serious condition need special attention regarding the risk of worse QOL. The role of alcohol consumption in QOL among HF patients in Korea needs further exploration.