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OBJECTIVE: This study aims to establish a machine learning (ML) model for predicting the risk of liver and/or lung metastasis in colorectal cancer (CRC). METHODS: Using the National Institutes of Health (NIH)'s Surveillance, Epidemiology, and End Results (SEER) database, a total of 51265 patients with pathological diagnosis of colorectal cancer from 2010 to 2015 were extracted for model development. On this basis, We have established 7 machine learning algorithm models. Evaluate the model based on accuracy, and AUC of receiver operating characteristics (ROC) and explain the relationship between clinical pathological features and target variables based on the best model. We validated the model among 196 colorectal cancer patients in Beijing Electric Power Hospital of Capital Medical University of China to evaluate its performance and universality. Finally, we have developed a network-based calculator using the best model to predict the risk of liver and/or lung metastasis in colorectal cancer patients. RESULTS: 51265 patients were enrolled in the study, of which 7864 (15.3 %) had distant liver and/or lung metastasis. RF had the best predictive ability, In the internal test set, with an accuracy of 0.895, AUC of 0.956, and AUPR of 0.896. In addition, the RF model was evaluated in the external validation set with an accuracy of 0.913, AUC of 0.912, and AUPR of 0.611. CONCLUSION: In this study, we constructed an RF algorithm mode to predict the risk of colorectal liver and/or lung metastasis, to assist doctors in making clinical decisions.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Pulmonares , Aprendizaje Automático , Programa de VERF , Humanos , Neoplasias Colorrectales/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Masculino , Neoplasias Hepáticas/secundario , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Curva ROC , Medición de Riesgo , China/epidemiología , Algoritmos , Adulto , Área Bajo la CurvaRESUMEN
Transmembrane protein 268 (TMEM268) is a novel, tumor growth-related protein first reported by our laboratory. It interacts with the integrin subunit ß4 (ITGB4) and plays a positive role in the regulation of the ITGB4/PLEC signaling pathway. Here, we investigated the effects and mechanism of TMEM268 in anti-infectious immune response in mice. Tmem268 knockout in mice aggravated cecal ligation and puncture-induced sepsis, as evidenced by higher bacterial burden in various tissues and organs, congestion, and apoptosis. Moreover, Tmem268 deficiency in mice inhibited phagocyte adhesion and migration, thus decreasing phagocyte infiltration at the site of infection and complement-dependent phagocytosis. Further findings indicated that TMEM268 interacts with CD11b and inhibits its degradation via the endosome-lysosome pathway. Our results reveal a positive regulatory role of TMEM268 in ß2 integrin-associated anti-infectious immune responses and signify the potential value of targeting the TMEM268-CD11b signaling axis for the maintenance of immune homeostasis and immunotherapy for sepsis and related immune disorders.
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Antígeno CD11b , Proteínas de la Membrana , Ratones Noqueados , Sepsis , Transducción de Señal , Animales , Humanos , Ratones , Antígeno CD11b/metabolismo , Antígeno CD11b/genética , Adhesión Celular/genética , Movimiento Celular/genética , Regulación hacia Abajo , Endosomas/metabolismo , Eliminación de Gen , Lisosomas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Fagocitos/metabolismo , Fagocitos/inmunología , Fagocitosis , Sepsis/genética , Sepsis/inmunología , Sepsis/metabolismoRESUMEN
Purpose: Sevoflurane is the preferred anesthetic agent for induction and maintenance of ambulatory surgery due to its property of fast onset and recovery. However, it has been recognized as one of the major contributors of emergence delirium. The aim of this study was to evaluate the preventive effect of intranasal dexmedetomidine on the occurrence of emergence delirium in pediatric patients under general anesthesia with sevoflurane. Patients and Methods: Ninety pediatric patients undergoing dental rehabilitation under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=30 each in the 2 µg/kg dexmedetomidine, 1 µg/kg dexmedetomidine, and control with saline groups). The same volume (0.02mL/kg) of the mixed solution was dropped into the nasal cavity of the children 30 minutes before surgery. We used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level and incidence of delirium in the post-anesthesia care unit. Results: Compared with the control group, prophylactic use of different dosages of intranasal dexmedetomidine significantly reduces the incidence of ED and severe ED in PACU (P<0.001). Intranasal administration of 2 µg/kg dexmedetomidine was associated with a better acceptance of mask induction and a better tolerance of separation with parents. Conclusion: Both 2 µg/kg and 1 µg/kg intranasal dexmedetomidine can achieve ED preventive effects in PACU in dental rehabilitation under general anesthesia. A dosage of 2 µg/kg is more effective in preventing severe ED and providing better mask acceptance.
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Dexmedetomidina , Delirio del Despertar , Humanos , Niño , Delirio del Despertar/prevención & control , Delirio del Despertar/tratamiento farmacológico , Hipnóticos y Sedantes/uso terapéutico , Sevoflurano , Administración Intranasal , Anestesia General/efectos adversos , Método Doble Ciego , Periodo de Recuperación de la AnestesiaRESUMEN
The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has been linked with the growth of some cancers and immune regulation, which is negatively correlated with prognosis. Here, it is demonstrated that the RNF115 deletion can protect mice from acute liver injury (ALI) induced by the treatment of lipopolysaccharide (LPS)/D-galactosamine (D-GalN), as evidenced by decreased levels of alanine aminotransaminase, aspartate transaminase, inflammatory cytokines (e.g., tumor necrosis factor α and interleukin-6), chemokines (e.g., MCP1/CCL2) and inflammatory cell (e.g., monocytes and neutrophils) infiltration. Moreover, it was found that the autophagy activity in Rnf115-/- livers was increased, which resulted in the removal of damaged mitochondria and hepatocyte apoptosis. However, the administration of adeno-associated virus Rnf115 or autophagy inhibitor 3-MA impaired autophagy and aggravated liver injury in Rnf115-/- mice with ALI. Further experiments proved that RNF115 interacts with LC3B, downregulates LC3B protein levels and cell autophagy. Additionally, Rnf115 deletion inhibited M1 type macrophage activation via NF-κB and Jnk signaling pathways. Elimination of macrophages narrowed the difference in liver damage between Rnf115+/+ and Rnf115-/- mice, indicating that macrophages were linked in the ALI induced by LPS/D-GalN. Collectively, for the first time, we have proved that Rnf115 inactivation ameliorated LPS/D-GalN-induced ALI in mice by promoting autophagy and attenuating inflammatory responses. This study provides new evidence for the involvement of autophagy mechanisms in the protection against acute liver injury.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Fallo Hepático Agudo , Animales , Ratones , Autofagia , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Galactosamina/metabolismo , Lipopolisacáridos/farmacología , Hígado/metabolismo , Fallo Hepático Agudo/metabolismo , FN-kappa B/metabolismoRESUMEN
OBJECTIVES: This study aimed to determine the prevalence and independent risk factors of SDB, and explore its association with malocclusion among 6-11-year-old children in Shanghai, China. METHODS: A cluster sampling procedure was adopted in this cross-sectional study. Pediatric Sleep Questionnaire (PSQ) was applied to evaluate the presence of SDB. Questionnaires including PSQ, medical history, family history, and daily habits/environment were completed by parents under instruction, and oral examinations were implemented by well-trained orthodontists. Multivariable logistic regression was applied to identify independent risk factors for SDB. Chi-square tests and Spearman's Rank Correlation were used to estimate the relationship between SDB and malocclusion. RESULTS: A total of 3433 subjects (1788 males and 1645 females) were included in the study. The SDB prevalence was about 17.7%. Allergic rhinitis (OR 1.39, 95% CI 1.09-1.79), adenotonsillar hypertrophy (OR 2.39, 95% CI 1.82-3.19), paternal snoring (OR 1.97, 95% CI 1.53-2.53), and maternal snoring (OR 1.35, 95% CI 1.05-1.73) were independent risk factors for SDB. The SDB prevalence was higher in children with retrusive mandibles than in proper or excessive ones. No significant difference was observed in the correlation between SDB and lateral facial profile, mandible plane angle, constricted dental arch form, the severity of anterior overjet and overbite, degree of crowding and spacing, and the presence of crossbite and open bite. CONCLUSIONS: The prevalence of SDB in primary students in the Chinese urban population was high and highly associated with mandible retrusion. The independent risk factors included Allergic rhinitis, adenotonsillar hypertrophy, paternal snoring, and maternal snoring. More efforts should be made to enhance public education about SDB and related dental-maxillofacial abnormalities.
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Maloclusión , Síndromes de la Apnea del Sueño , Masculino , Femenino , Humanos , Niño , Ronquido/complicaciones , Ronquido/epidemiología , Estudios Transversales , China/epidemiología , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/epidemiología , Maloclusión/complicaciones , Maloclusión/epidemiología , Factores de Riesgo , Hipertrofia/complicaciones , Encuestas y CuestionariosRESUMEN
Introduction: Parallel distributed processing theory (PDP theory) holds that all brain regions involved in conceptual representation perform a series of activities at the same time. However, the role of emotional experience information in concrete conceptual representation is still unknown. This study further explores whether the emotional experience will also affect the semantic processing of concrete concept representations. Methods: This study used the emotion priming paradigm and semantic judgment task to explore whether emotion priming impacts the processing of animal concepts with different emotional experiences through two experiments. In Experiments 1a and 1b, pleasant or disgusted faces were used as emotional priming stimuli to explore whether the explicit processing of emotions would affect the semantic processing of animal concepts. Experiments 2a and 2b used positive or negative scenery pictures as emotional priming stimuli to explore whether the implicit processing of emotions would affect the semantic processing of animal concepts. Results: The Experiment 1 results showed that the perception of faces promotes the processing of animal words, showing the "word-emotion congruence effect". Experiment 2a did not show the expected results, while Experiment 2b showed that the general negative perception of scenery pictures could significantly promote the processing of disgusted animal words. The results further proved the "word-emotion congruence effect" shown in the results of Experiment 1 from the perspective of implicit emotion processing. Combining the results of two experiments, it can be proven that emotional experience affects the semantic processing process of concrete concepts. Discussion: Both Experiment 1 and Experiment 2b of this study show the "word-emotion congruence effect". PDP theory believes that conceptual representation is represented by the activity patterns of billions of neurons distributed in many areas of the brain, and related semantic processing and sensory processing will occur simultaneously. The results of this experiment well support PDP theory.
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ULK1 is crucial for initiating autophagosome formation and its activity is tightly regulated by post-translational modifications and protein-protein interactions. In the present study, we demonstrate that TMEM189 (Transmembrane protein 189), also known as plasmanylethanolamine desaturase 1 (PEDS1), negatively regulates the proteostasis of ULK1 and autophagy activity. In TMEM189-overexpressed cells, the formation of autophagesome is impaired, while TMEM189 knockdown increases cell autophagy. Further investigation reveals that TMEM189 interacts with and increases the instability of ULK1, as well as decreases its kinase activities. The TMEM189 N-terminal domain is required for the interaction with ULK1. Additionally, TMEM189 overexpression can disrupt the interaction between ULK1 and TRAF6, profoundly impairs K63-linked polyubiquitination of ULK1 and self-association, leading to the decrease of ULK1 stability. Moreover, in vitro and in vivo experiments suggest that TMEM189 deficiency results in the inhibition of tumorigenicity of gastric cancer. Our findings provide a new insight into the molecular regulation of autophagy and laboratory evidence for investigating the physiological and pathological roles of TMEM189.
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Homólogo de la Proteína 1 Relacionada con la Autofagia , Autofagia , Enzimas Ubiquitina-Conjugadoras , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Fosforilación , Enzimas Ubiquitina-Conjugadoras/metabolismo , UbiquitinaciónRESUMEN
INTRODUCTION: Orthodontic treatment and adenotonsillectomy (AT) are both conventional treatments for paediatric obstructive sleep apnoea (OSA). Each approach has distinct treatment advantages; however, there is currently a lack of solid evidence to support their efficacy comparison. We hypothesise that the objective effect of orthodontic treatment is not inferior to AT in children with moderate OSA and mandibular retrognathia, but orthodontic treatment has the advantage of promoting dentofacial growth. METHODS AND ANALYSIS: This is a randomised, open-label, parallel-group, active controlled trial that will study the efficacy of orthodontic treatment versus AT in children with moderate OSA accompanied by tonsillar adenoid hypertrophy and mandibular retrognathia. A total of 98 patients will be enrolled and randomised in a 2:1 ratio to either orthodontic treatment or AT group. Participants will be recruited at Shanghai Stomatological Hospital, Shanghai Children's Hospital of Shanghai Jiaotong University and Children's Hospital of Fudan University, which are all located in Shanghai, China. The primary endpoint is the per cent change in the obstructive apnoea-hypopnoea index from baseline (month 0) to the primary endpoint (month 7), and the mean reduction in A point, nasion and B point angle on cephalometric measurements by lateral X-ray films. Important secondary efficacy endpoints include sleep duration with oxygen saturation below 90% according to polysomnography and subjective symptoms (assessed by the OSA-20 questionnaire), etc. Safety endpoints will also be evaluated. ETHICS AND DISSEMINATION: The study was approved by the ethics committees of Shanghai Stomatological Hospital (approval no. (2021)002), Shanghai Children's Hospital of Shanghai Jiaotong University (approval no. 2021R046-F01) and Children's Hospital of Fudan University (approval no. (2021)136). Before enrolment, a qualified clinical research assistant will obtain written informed consent from both the participants and their guardians after full explanation of this study. The results will be presented at national or international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000037288.
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Retrognatismo , Apnea Obstructiva del Sueño , Tonsilectomía , Adenoidectomía , Niño , China , Humanos , Hipertrofia , Ensayos Clínicos Controlados Aleatorios como Asunto , Retrognatismo/complicaciones , Apnea Obstructiva del Sueño/cirugíaRESUMEN
Host defense systems can invade viral infection through immune responses and cellular metabolism. Recently, many studies have shown that cellular metabolism can be reprogrammed through N6 -methyladenosine (m6 A) modifications during viral infection. Among of them, methyltransferase like-14 enzyme (METTL14) plays an important role in m6 A RNA modification, yet its antiviral function still remains unclear. In this work, it is uncovered that metal-protein nanoparticles designated GSTP1-MT3(Fe2+ ) (MPNP) can polarize macrophages toward the M1 phenotype and activate immune responses to induce Interferon-beta (IFN-ß) production in vesicular stomatitis virus (VSV)-infected macrophages. Further investigation elucidates that a high dose of IFN-ß can promote the expression of METTL14, which has a well anti-VSV capacity. Moreover, it is found that other negative-sense single-stranded RNA viruses, such as influenza viruses (H1N1(WSN)), can also be inhibited through either immune responses or METTL14. Collectively, these findings provide insights into the antiviral function of METTL14 and suggest that the manipulation of METTL14 may be a potential strategy to intervene with other negative-sense single-stranded RNA viruses infections.
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Antivirales/farmacología , Inmunidad Innata/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A , Nanopartículas del Metal/química , Nanocompuestos/química , Animales , Línea Celular , Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Interferón beta/genética , Hierro/química , Metiltransferasas/metabolismo , Ratones , Nanopartículas , Fenotipo , Células RAW 264.7 , Células THP-1 , Virus de la Estomatitis Vesicular Indiana/metabolismo , Vesiculovirus , Replicación Viral/efectos de los fármacosRESUMEN
Previous studies have explored the impact of the cost ratio of individual solutions versus collective solutions on people's cooperation tendency in the presence of individual solutions. This study further explored the impact of team credibility on people's propensity to cooperate in the presence of individual solutions. Study 1 investigated the influence of different level of altruistic tendencies or the self-interest tendencies of teammates on participants' decision-making. Study 2 explored the influence of the distribution of altruistic tendencies or self-interest tendencies on participants' decision-making. The results of Study 1 showed that the proportion of participants who chose the collective solution increased with an increase in the altruistic tendencies of the team. When the altruistic tendencies of the teammates reached a certain value, the proportion of participants taking the collective solution showed a trend to stabilize. Furthermore, the proportion of participants who chose the individual solution increased with the increase in the self-interest tendencies of the team. When the self-interest tendencies of the teammates reached a certain value, the individual solution was stably adopted. The results of Study 2 showed that with the total altruistic tendency remaining unchanged, the more altruistic group members that altruistic tendencies were allocated to, the higher a participant's level of trust in the team would be, which showed the decentralized effect of altruistic tendencies. In the case that the total self-interest tendency was unchanged, the fewer self-interest group members the self-interest tendencies were allocated to, the higher a participant's level of trust in the team would be, which showed the convergent effect of self-interest tendencies.
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Autophagy is a highly conserved lysosome-dependent degradation system in eukaryotic cells. This process removes long-lived intracellular proteins, damaged organelles, and recycles biological material to maintain cellular homeostasis. Dysfunction of autophagy triggers a wide spectrum of human diseases, including cancer and neurodegenerative diseases. In the present study, we show that RNF115, an E3 ubiquitin ligase, regulates autophagosome-lysosome fusion and autophagic degradation under both nutrient-enriched and stress conditions. Depletion of the RNF115 gene caused the accumulation of autophagosomes by impairing fusion with lysosomes, which results in an accumulation of autophagic substrates. Further investigation suggests that RNF115 interacts with STX17 and enhances its stability, which is essential for autophagosome maturation. Importantly, we provide in vitro and in vivo evidence that RNF115 inactivation inhibits the tumorigenesis and metastasis of BGC823 gastric cancer cells. We additionally show that high expression levels of RNF115 mRNA correlate with poor prognosis in gastric cancer patients. These findings indicate that RNF115 may play an evolutionarily conserved role in the autophagy pathway, and may act to maintain protein homeostasis under physiological conditions. These data demonstrate the need to further evaluate the potential therapeutic implications of RNF115 in gastric cancer.
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Autofagosomas/metabolismo , Autofagia/genética , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Desnudos , Neoplasias Gástricas/patología , TransfecciónRESUMEN
BACKGROUND: Pediatric obstructive sleep apnea/hypopnea syndrome (OSAHS) is a multifactorial syndrome caused by many risk factors, such as craniofacial anomalies, adenotonsillar hypertrophy, obesity, and airway inflammation. Although new treatment patterns have recently been proposed, treatment methods for children remain particularly challenging and controversial. This randomized controlled trial was designed to investigate the efficacy of adenotonsillectomy and/or orthodontic treatment for children who have mild OSAHS with mandibular retrognathia. METHODS: A sample of 352 children with mild OSAHS and mandibular retrognathia, who are aged between 7 and 10 years, will be enrolled in the study. They will be randomized into four groups: the drug treatment group, the surgical treatment group, the orthodontic treatment group, or the surgery and postoperative orthodontic group. After randomization the children will receive treatments within 4 weeks. Outcome assessment will take place at the following points: (1) baseline, (2) 7 months after the treatment starting point, (3) 12 months after the treatment starting point, and (4) 24 months after the treatment starting point. The primary endpoint of the trial is the mean change in obstructive apnea/hypopnea index. Other endpoints will consist of the lowest oxygen saturation, apnea index, and hypopnea index assessed by polysomnography, subjective symptoms (assessed by the OSA-20 questionnaire), cephalometric measurements, and morphologic analysis of the upper airway. DISCUSSION: The results of this study will provide valuable evidence for the merits and long-term efficacy of different treatment approaches and contribute to facilitating the multidisciplinary treatment of pediatric OSAHS. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03451318. Registered on 2 March 2018 (last update posted 19 April 2018).
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Adenoidectomía/métodos , Retrognatismo/cirugía , Apnea Obstructiva del Sueño/cirugía , Tonsilectomía/métodos , Adenoidectomía/efectos adversos , Niño , Humanos , Avance Mandibular/métodos , Estudios Multicéntricos como Asunto , Polisomnografía , Ensayos Clínicos Controlados Aleatorios como Asunto , Retrognatismo/complicaciones , Factores de Riesgo , Apnea Obstructiva del Sueño/etiología , Tonsilectomía/efectos adversosRESUMEN
The correlation of ALDH1 and Bmi1 expression in potentially malignant oral erythroplakia (OE) with oral carcinoma development was reported in our earlier study. Interestingly, a model of field cancerization orchestrated by the cancer stem cells (CSC) was proposed and suggested the identification of CSC-specific markers is useful for prognosis and providing novel targets for prevention and treatment of field cancerization. We revisited the correlation of ALDH1 and Bmi1 expression in OE with the second and multiple carcinomas development. Strikingly, we observed that the expression of ALDH1 and Bmi1 within a single potentially malignant OE lesion significantly correlate with subsequently developing multiple and multifocal carcinomas, which parallels the process of oral field cancerization. Significantly, ALDH1 and Bmi1 are well-defined markers of CSC for head and neck cancer. Consequently, we provided a preliminary evidence for CSC driving the process of field cancerization.
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Familia de Aldehído Deshidrogenasa 1/metabolismo , Neoplasias de Cabeza y Cuello , Células Madre Neoplásicas , Complejo Represivo Polycomb 1/efectos adversos , HumanosRESUMEN
Endoplasmic reticulum membrane protein complex subunit 6 (EMC6), also known as transmembrane protein 93 (transmembrane protein 93, TMEM93), is an autophagy-related protein. EMC6 overexpression inhibits cancer cell growth and induces apoptosis, but the interaction partners of EMC6 and its cellular responsibilities remain incompletely understood. In this study, we report that adenovirus-mediated ectopic overexpression of EMC6 (Ad5-EMC6) in BGC823 and SGC7901 gastric cancer cells decreases the activity of ERK1/2, down-regulates the levels of BCL-2 protein and phosphorylated BCL-2, increases the expression of tBID and BAX, and decreases mitochondrial membrane potential and subsequently leading to cell apoptosis. In a xenograft tumor model, we found that Ad5-EMC6 impairs the tumorigenesis of SGC7901 gastric cancer cells in nude mice. Additionally, Ad5-EMC6 enhances the sensitivity of gastric cancer cells to the chemotherapeutic drug etoposide. Collectively, these results demonstrate that EMC6-induced apoptosis of gastric cancer cells occurs at least partially through the mitochondrial-mediated apoptosis pathway. Our study suggests a rational basis for the potential clinical application of Ad5-EMC6 in gastric cancer.
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Carcinogénesis/metabolismo , Proteínas de la Membrana/metabolismo , Mitocondrias/patología , Neoplasias Gástricas/metabolismo , Animales , Apoptosis , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Femenino , Humanos , Sistema de Señalización de MAP Quinasas , Potencial de la Membrana Mitocondrial , Proteínas de la Membrana/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/genética , Mitocondrias/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Regulación hacia ArribaRESUMEN
Background: Polypharmacology is emerging as the next paradigm in drug discovery. However, considerable challenges still exist for polypharmacology modeling. In this study, we developed a rational design to identify highly potential targets (HPTs) for polypharmacological drugs, such as berberine. Methods and Results: All the proven co-crystal structures locate berberine in the active cavities of a redundancy of aromatic, aliphatic, and acidic residues. The side chains from residues provide hydrophobic and electronic interactions to aid in neutralization for the positive charge of berberine. Accordingly, we generated multi-target binding motifs (MBM) for berberine, and established a new mathematical model to identify HPTs based on MBM. Remarkably, the berberine MBM was embodied in 13 HPTs, including beta-secretase 1 (BACE1) and amyloid-ß1-42 (Aß1-42). Further study indicated that berberine acted as a high-affinity BACE1 inhibitor and prevented Aß1-42 aggregation to delay the pathological process of Alzheimer's disease. Conclusion: Here, we proposed a MBM-based drug-target space model to analyze the underlying mechanism of multi-target drugs against polypharmacological profiles, and demonstrated the role of berberine in Alzheimer's disease. This approach can be useful in derivation of rules, which will illuminate our understanding of drug action in diseases.
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The objective is to investigate the influence of PM2.5 exposure on peripheral blood lymphocyte subsets in pregnant mice and the antagonism of quercetin on adverse effects induced by PM2.5 exposure. Pregnant mice were randomly divided into control group, PM2.5 model group and 3 quercetin intervention groups. Dams in all groups except the control group were exposed to PM2.5 suspension by intratracheal instillation on gestational day (GD) 3, 6, 9, 12 and 15. Meanwhile, each dam was given 0.15% carboxymethylcellulose sodium (CMCS) (control group & PM2.5 model group) and different doses of quercetin (quercetin intervention groups) by gavage once a day from GD0 to GD17. The percentage of lymphocyte subsets, Biomarkers of systemic inflammation injuries (IL-2, IL-6, IL-8 & TNF-α) and oxidative stress indicators (CAT, GSH & HO-1) in peripheral blood of the dams were analyzed. The number of T cells increased, accompanied by increased level of IL-2, IL-6, IL-8 and HO-1 due to PM2.5 exposure. Less CD4+ and CD8+ T cells were counted in 100 mg/kg quercetin intervention group, compared with PM2.5 model group. Quercetin may inhibit cytokine production, especially in IL-6 and IL-8 and may upgrade the level of HO-1. Our findings indicate that PM2.5 could significantly influence the distribution of T-lymphocyte subsets, activate inflammatory reaction and elevate oxidative stress level in peripheral blood of pregnant mice. Certain dose of quercetin administration during pregnancy may protect the dams against the adverse effects through various ways.
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Inflamación/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Material Particulado/efectos adversos , Quercetina/farmacología , Animales , Biomarcadores/metabolismo , Citocinas/genética , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/metabolismo , Subgrupos Linfocitarios/efectos de los fármacos , Ratones , Embarazo , Sustancias Protectoras/farmacología , Distribución AleatoriaRESUMEN
Fructus ligustri Lucidi (FLL) is the fruit of Ligustrum lucidum Ait and a traditional Chinese medicine, primarily known for its role in osteoporosis prevention and treatment. The present study aimed to elucidate the effect and underlying mechanism of action of ethanol extract of FLL on osteoclast differentiation and bone resorption, and to identify the active compounds within it. RAW264.7 murine monocyte/macrophage cells were stimulated with the receptor activator of nuclear factor κB ligand (RANKL) to induce osteoclast differentiation in vitro. The present study demosntrated that FLL extract and its two primary components, oleanolic acid (OA) and ursolic acid (UA), significantly suppressed RANKLinduced tartrate resistant acid phosphatase (TRAP) activity and multinucleate osteoclast formation without inducing cytotoxicity; however, no effect was observed on the apoptosis of mature osteoclasts. Additionally, RANKLinduced mRNA expression levels of the key transcription factors, tumor necrosis factor receptor associated factor6, nuclear factor of activated T cellc1 and cFos, and the osteoclast markers, TRAP, cathepsin K and matrix metalloproteinase9 were suppressed by FLL, OA and UA. However, no effect was observed on RANKLinduced mRNA expression levels of Src. These results demonstrated that FLL may inhibit osteoclastogenesis in RAW264.7 cells via RANKL signaling pathways. OA and UA are active compounds in inducing this effect; however, their specific roles remain to be elucidated.
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Resorción Ósea/metabolismo , Frutas/química , Ligustrum/química , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Extractos Vegetales/farmacología , Animales , Apoptosis/efectos de los fármacos , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/genética , Línea Celular , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ligando RANK/metabolismo , Transducción de Señal/efectos de los fármacos , Fosfatasa Ácida Tartratorresistente/metabolismoRESUMEN
BACKGROUND: An epidemiological study on the oral mucosal lesions (OMLs) in general population from China was scarce. The objective of this study was to investigate the prevalence and distribution of OMLs in Shanghai, China and to evaluate their association with demographic factors and smoking/drinking habits based on a large scaled population on a wide spectrum. METHODS: In this population-based cross-sectional study, 11054 community-dwelling individuals (M/F: 5140/5914; age range, 1-96 years) were randomly selected and examined according to WHO criteria. RESULTS: The prevalence of OMLs was 10.8% in this study. A total of 1192 (M/F: 543/649; mean age, 56.9 years) individuals were presented with different types of OMLs. The most common type of OMLs was fissured tongue (prevalence of 3.15%), followed by recurrent aphthae (1.48%), traumatic ulcer (1.13%), and angular cheilitis (0.86%). The two most common potentially malignant disorders were oral lichen planus (0.81%) and leukoplakia (0.22%). Regression analysis revealed that the elderly age, smoking, and alcohol intake were statistically significant risk factors of OMLs with emphasis on leukokeratosis, leukoplakia, and lichen planus. CONCLUSION: The prevalence and distribution of OMLs were elucidated in an eastern area of China, and the importance of tobacco and alcohol in the pathogenesis of OMLs was evidenced. Our data have provided baseline information about epidemiologic aspects of OMLs that can be valuable in organized program targeting on oral health and hygiene.
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Leucoplasia Bucal/epidemiología , Enfermedades de la Boca/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/epidemiología , Niño , Preescolar , China/epidemiología , Estudios Transversales , Femenino , Humanos , Lactante , Leucoplasia/epidemiología , Leucoplasia/etiología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/epidemiología , Salud Bucal , Prevalencia , Factores de Riesgo , Factores Sexuales , Fumar/epidemiología , Estomatitis Aftosa/epidemiología , Estomatitis Aftosa/etiología , Lengua Fisurada/epidemiología , Lengua Fisurada/etiología , Adulto JovenRESUMEN
Interleukin- (IL-) 22 is the signature cytokine of T-helper (Th) 22 cells, and IL-23 is required for IL-22 production. The objective of this study was to examine the immunoexpression of IL-22 and IL-23 in archival paraffin-embedded biopsy specimens from oral LP (n = 42) and cutaneous LP (n = 38) against normal control tissues. The results showed that the percentage of cells expressing IL-22 and IL-23 in LP were significantly higher in LP compared to controls, respectively (both P < 0.001). The correlation between IL-22 and IL-23 expression was significant (P < 0.05). Moreover, the percentage of cells expressing IL-22 and IL-23 in oral LP were significantly higher than cutaneous LP (P < 0.05). Collectively, our findings demonstrated that the increased expression of IL-22 and IL-23 in LP lesions could play roles in the pathogenesis of LP. Moreover, oral LP expressing IL-22 and IL-23 was higher than cutaneous LP, probably due to Th22 cells as an important component of oral mucosal host defense against oral microbiota and tissue antigens. This may be associated with the difference in clinical behaviour of the two variants of the disease.