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Immune-mediated acute hepatic injury is characterized by the destruction of a large number of hepatocytes and severe liver function damage. Interleukin-28A (IL-28A), a member of the IL-10 family, is notable for its antiviral properties. However, despite advances in our understanding of IL-28A, its role in immune-mediated acute injury remains unclear. The present study investigated the role of IL-28A in concanavalin A (Con A)-induced acute immune liver injury. After Con A injection in mice, IL-28A level significantly increased. IL-28A deficiency was found to protect mice from acute liver injury, prolong survival time, and reduce serum aspartate aminotransferase and alanine aminotransferase levels. In contrast, recombinant IL-28A aggravated liver injury in mice. The proportion of activated M1 macrophages was significantly lower in the IL-28A-deficiency group than in the wild-type mouse group. In adoptive transfer experiments, M1 macrophages from WT could exacerbate mice acute liver injury symptoms in the IL-28A deficiency group. Furthermore, the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-12, IL-6, and IL-1ß, by M1 macrophages decreased significantly in the IL-28A-deficiency group. Western blotting demonstrated that IL-28A deficiency could limit M1 macrophage polarization by modulating the nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), and interferon regulatory factor (IRF) signaling pathways. In summary, IL-28A deletion plays an important protective role in the Con A-induced acute liver injury model and IL-28A deficiency inhibits the activation of M1 macrophages by inhibiting the NF-κB, MAPK, and IRF signaling pathways. These results provide a potential new target for the treatment of immune-related hepatic injury.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Citocinas , Interferón lambda , Interleucinas , Animales , Ratones , Concanavalina A , Factores Reguladores del Interferón , Hígado , Macrófagos , Proteínas Quinasas Activadas por Mitógenos , Interferón lambda/genética , Interleucinas/genéticaRESUMEN
Vitamin A is an essential nutrient in animals, playing important roles in animal health. In the pig industry, proper supplementation of vitamin A in the feed can improve pork production performance, while deficiency or excessive intake can lead to growth retardation or disease. However, the specific molecular mechanisms through which vitamin A operates on pig skeletal muscle growth as well as muscle stem cell function remain unexplored. Therefore, in this study, we isolated the pig primary skeletal muscle stem cells (pMuSCs) and treated with retinoic acid (RA), the natural metabolite of vitamin A, and then examined the myogenic capacity of pMuSCs via immunostaining, real-time PCR, CCK8 and western-blot analysis. Unexpectedly, the RA caused a significant decrease in the proliferation and differentiation of pMuSCs. Mechanistically, the RA addition induced the activation of retinoic acid receptor gamma (RARγ), which inhibited the myogenesis through the blockage of protein translation of the master myogenic regulator myogenic differentiation 1 gene (MYOD). Specifically, RARγ inactivate AKT kinase (AKT) signalling and lead to dephosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1), which in turn repress the eukaryotic translation initiation factor 4E (eIF4E) complex and block mRNA translation of MYOD. Inhibition of AKT could rescue the myogenic defects of RA-treated pMuSCs. Our findings revealed that retinoid acid signalling inhibits the skeletal muscle stem cell proliferation and differentiation in pigs. Therefore, the vitamin A supplement in the feedstuff should be cautiously optimized to avoid the potential adverse consequences on muscle development associated with the excessive levels of retinoic acid.
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Diferenciación Celular , Desarrollo de Músculos , Proteína MioD , Transducción de Señal , Tretinoina , Animales , Tretinoina/farmacología , Porcinos , Desarrollo de Músculos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteína MioD/genética , Proteína MioD/metabolismo , Diferenciación Celular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Receptores de Ácido Retinoico/metabolismo , Receptores de Ácido Retinoico/genética , Proliferación Celular/efectos de los fármacos , Biosíntesis de Proteínas/efectos de los fármacos , Células CultivadasRESUMEN
BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is a more common non-Hodgkin lymphoma (NHL). This study aims to explore the prognostic value of PIM kinase family in DLBCL and its relationship with the immune microenvironment, to provide a certain reference for the prognosis and treatment of DLBCL. METHODS: The prognostic value of PIM kinase family in DLBCL from the data set GSE10846 was verified through survival analysis and cox regression analysis. Mutations in PIM kinase family and its relationship with immune cell infiltration were explored with online cBioPortal, TIMER database, and single-gene GSEA analysis. Finally, the expression of PIM kinase family in tissues from DLBCL clinical samples was validated through immunohistochemical staining. RESULTS: The proteins of PIM kinase family were highly expressed in DLBCL patients, which are good prognostic factors for DLBCL patients. Then, PIM1-3 proteins were positively correlated with the immune infiltration of B cells, whose types of mutations also showed different degrees of correlation with B cells. PIM kinase family proteins also showed a high correlation with PDL1. In addition, PIM kinase family was also associated with the commonly mutated genes in DLBCL, such as MYD88, MYC, and BTK. CONCLUSION: PIM kinase family may be a potential therapeutic target for DLBCL patients.
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Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Bases de Datos Factuales , Mutación , Coloración y Etiquetado , Microambiente TumoralRESUMEN
Group B coxsackieviruses (CVBs) are the main cause of virus-induced myocarditis. CVBs use coxsackievirus and adenovirus receptor (CAR) for infection and targeting CAR has been shown to ameliorate CVBs-induced myocarditis. Ligand-of-Numb protein X1 (LNX1) is an E3 ubiquitin ligase that was shown to interact with CAR. However, the precise effect of LNX1 on CAR and the roles of LNX1 on CVBs-induced myocarditis remain unknown. In the present study, we generated mice deficient in LNX1 in the heart and evaluated the symptoms of myocarditis after CVB3 infection. We also monitored the expression and ubiquitination of CAR in LNX1-deficient cardiomyocytes after CVBs infection. We found that CVBs infection decreased CAR expression while promoted the expression of LNX1. Mice with deficiency of LNX1 in the heart had normal myocardial development while had deteriorated myocarditis symptoms after CVB3 infection. In LNX1-deficient cardiomyocytes, decreased ubiquitination of CAR and upregulation of CAR were observed after CVB3 infection. In summary, LNX1 controls CVB3-induced myocarditis by regulating the expression of CAR.
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Infecciones por Coxsackievirus , Enterovirus , Miocarditis , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Infecciones por Coxsackievirus/genética , Enterovirus Humano B/fisiología , Ligandos , Proteínas de la Membrana , Ratones , Miocarditis/genética , Miocarditis/metabolismo , Proteínas del Tejido Nervioso , Receptores ViralesRESUMEN
Emission benefits of transit buses depend on ridership. Declines in ridership caused by COVID-19 leads uncertainty about the emission reduction capacity of buses. This paper provides a method framework for analyzing spatio-temporal emission patterns of buses in combination with real-time ridership and potential emission changes in the post-COVID-19 future. Based on GPS trajectory and Smart Card data of 2056 buses from 278 routes covering 1.5 million ridership in Qingdao, China, spatio-temporal emissions characteristics of buses are studied. 7589 taxis with 0.2 million passengers' trips are used for acquiring private cars' emissions to evaluate the emissions difference between buses and cars. Empirical results show that the average difference between buses and cars with 2 persons can reach up to 117 g/km-person during 7:00-8:59 and 115 g/km-person during 17:00-18:59. However, buses have various emission benefits around the city at different periods. A double increase in emissions during non-rush hours can be observed compared with rush hours. 224 online survey data are used to study the potential ridership reduction trend in post-COVID-19. Results show that 56.3% of respondents would decrease the usage of buses in the post-COVID-19 future. Based on this figure, our analysis shows that per kilometer-person emissions of buses are higher than cars during non-rush hours, however, still lower than cars during rush hours. We conclude that when ridership reduces by more than 40%, buses cannot be "greener" travel modal than cars as before. Finally, several feasible policies are suggested for this potential challenge. Our study provides convincing evidence for understanding the emission patterns of buses, to support better buses investment decisions and promotion on eco-friendly public transport service in the post-COVID-19 future.
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Porcine circovirus-associated disease (PCVAD) is one of the most serious infectious diseases in pigs worldwide. The primary causative agent of PCVAD is porcine circovirus type 2 (PCV2), which can cause lymphoid depletion and immunosuppression in pigs. Our previous study demonstrated that Laiwu (LW) pigs, a Chinese indigenous pig breed, have stronger resistance to PCV2 infection than Yorkshire × Landrace (YL) pigs. In this study, we found that the YL pigs showed more severe lymphocyte apoptosis and higher viral load in the spleen tissue than LW pigs. To illustrate the differential gene expression between healthy and infected spleens, transcriptome profiling of spleen tissues from PCV2-infected and control YL pigs was compared by RNA sequencing. A total of 90 differentially expressed genes (DEGs) was identified, including CD207, RSAD2, OAS1, OAS2, MX2, ADRB3, CXCL13, CCR1, and ADRA2C, which were significantly enriched in gene ontology (GO) terms related to the defense response to virus and cell-cell signaling, and another nine DEGs, KLF11, HGF, PTGES3, MAP3K11, XDH, CYCS, ACTC1, HSPH1, and RYR2, which were enriched in GO terms related to regulation of cell proliferation or apoptosis. Among these DEGs, the CXCL13 gene, which can suppress lymphocyte apoptosis during PCV2 infection, was significantly down-regulated in response to PCV2 infection in YL but not in LW pigs. By analysis of the regulatory elements in the promoter and 3'-untranslated region (3'-UTR) of porcine CXCL13, we found that the single nucleotide polymorphism (SNP) -1014 G (LW) > A (YL) and the Sus scrofa microRNA-296-5p (ssc-miR-296-5p) participated in regulating CXCL13 expression during the response to PCV2 infection.
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Apoptosis , Quimiocina CXCL13/metabolismo , Infecciones por Circoviridae/veterinaria , Circovirus , Linfocitos/virología , Bazo/virología , Enfermedades de los Porcinos/virología , Animales , Western Blotting/veterinaria , Infecciones por Circoviridae/inmunología , Infecciones por Circoviridae/metabolismo , Infecciones por Circoviridae/virología , Circovirus/metabolismo , ADN Viral/genética , Citometría de Flujo/veterinaria , Perfilación de la Expresión Génica/veterinaria , Regulación Viral de la Expresión Génica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Análisis de Secuencia de ARN/veterinaria , Bazo/metabolismo , Bazo/patología , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/metabolismo , Carga Viral/veterinariaRESUMEN
GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-ß superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K(+) currents and Kv2.1 α subunit expression through TßRII (TGF-ß receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca(2+) concentration ([Ca(2+)]i) in response to membrane depolarization, as determined by Ca(2+) imaging. Whole-cell current recordings indicated that GDF-15 increased the inward Ca(2+) current (ICa) without altering steady-state activation of Ca(2+) channels. Treatment with nifedipine, an inhibitor of L-type Ca(2+) channels, abrogated GDF-15-induced increases in [Ca(2+)]i and ICa The GDF-15-induced increase in ICa was mediated via up-regulation of the Cav1.3 α subunit, which was attenuated by inhibiting Akt/mTOR and ERK (extracellular-signal-regulated kinase) pathways and by pharmacological inhibition of Src-mediated TßRII phosphorylation. Given that Cav1.3 is not only a channel for Ca(2+) influx, but also a transcriptional regulator, our data confirm that GDF-15 induces protein expression via TßRII and activation of a non-Smad pathway, and provide novel insight into the mechanism of GDF-15 function in neurons.
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Canales de Calcio/metabolismo , Calcio/metabolismo , Cerebelo/citología , Factor 15 de Diferenciación de Crecimiento/farmacología , Neuronas/metabolismo , Animales , Bloqueadores de los Canales de Calcio/farmacología , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Neuronas/efectos de los fármacos , Nifedipino/farmacología , Proteína Oncogénica v-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Dementia has been increasingly paid attention by policymakers in China. However, the majority of the public has an indistinct concept of dementia and its diagnostic criteria. Therefore, many abnormal characteristics and actions of older people are labeled as having dementia while diagnosed without dementia. We examined a multi-stage cluster sample of 11,223 participants aged 60 years and above who have been clinically confirmed by general practitioners as not having dementia in 2013, and 7,861 participants were willing to participate the following study and were followed-up in 2014. To assess the differences of status of older people who were mistakenly labeled as having dementia or not, we asked main caregivers 'Do you think this older person suffers from dementia?', and found out that 244 participants had been mistakenly labeled as having dementia since 2013. Related effects were measured using international generic scales as well, and the results showed that participants with better physical status deteriorated more rapidly if they were mistakenly labeled as having dementia. Additionally, the mental health of these 244 participants also deteriorated more quickly. Older adults that were not labeled as having dementia were more willing to participate in social activities relative to their labeled counterparts. In conclusion, being mistakenly labeled as having dementia without a medical diagnosis impaired older adults' physical functioning and mental health. Moreover, the reduction of social activities of labeled older people leads to separation and social exclusion.
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Demencia/epidemiología , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Humanos , Incidencia , Vida Independiente , MasculinoRESUMEN
GDF15 (growth/differentiation factor 15), a novel member of the TGFß (transforming growth factor ß) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFßR2 (TGFß receptor 2), not TGFßR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFßRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFßRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling.
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Cerebelo/fisiología , Factor 15 de Diferenciación de Crecimiento/fisiología , Proteína Oncogénica v-akt/fisiología , Proteínas Serina-Treonina Quinasas/fisiología , Receptores de Factores de Crecimiento Transformadores beta/fisiología , Canales de Potasio Shab/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/fisiología , Animales , Animales Recién Nacidos , Células Cultivadas , Cerebelo/citología , Humanos , Ratas , Ratas Sprague-Dawley , Receptor Tipo II de Factor de Crecimiento Transformador beta , Transducción de Señal/genéticaRESUMEN
The accuracy of traditional CT image segmentation algorithms is hindered by issues such as low contrast and high noise in the images. While numerous scholars have introduced deep learning-based CT image segmentation algorithms, they still face challenges, particularly in achieving high edge accuracy and addressing pixel classification errors. To tackle these issues, this study proposes the MIS-Net (Medical Images Segment Net) model, a deep learning-based approach. The MIS-Net model incorporates multi-scale atrous convolution into the encoding and decoding structure with symmetry, enabling the comprehensive extraction of multi-scale features from CT images. This enhancement aims to improve the accuracy of lung and liver edge segmentation. In the evaluation using the COVID-19 CT Lung and Infection Segmentation dataset, the left and right lung segmentation results demonstrate that MIS-Net achieves a Dice Similarity Coefficient (DSC) of 97.61. Similarly, in the Liver Tumor Segmentation Challenge 2017 public dataset, the DSC of MIS-Net reaches 98.78.
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COVID-19 , Aprendizaje Profundo , Neoplasias Hepáticas , Humanos , Algoritmos , COVID-19/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Procesamiento de Imagen Asistido por ComputadorRESUMEN
The aggregation of monomeric amyloid ß protein (Aß) into oligomers and amyloid plaque in the brain is associated with Alzheimer's disease. The hydrophobic central core Aß16-22 has been widely studied due to its essential role in the fibrillization of full-length Aß peptides. Compared to the homogeneous antiparallel structure of Aß16-22 at the late stage, the early-stage prefibrillar aggregates contain varying proportions of different ß structures. In this work, we studied the appearance probabilities of various self-assembly structures of Aß16-22 and the effects of Zn2+ on these probabilities by replica exchange molecular dynamics simulations. It was found that at room temperature, Aß16-22 can readily form assembled ß-sheet structures in pure water, where a typical antiparallel arrangement dominates (24.8% of all sampled trimer structures). The addition of Zn2+ to the Aß16-22 solution will dramatically decrease the appearance probability of antiparallel trimer structures to 12.5% by disrupting the formation of the Lys16-Glu22 salt bridge. Meanwhile, the probabilities of hybrid antiparallel/parallel structures increase. Our simulation results not only reveal the competition between antiparallel and parallel structures in the Aß16-22 oligomers but also show that Zn2+ can affect the oligomer structures. The results also provide insights into the role of metal ions in the self-assembly of short peptides.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Humanos , Péptidos beta-Amiloides/química , Enfermedad de Alzheimer/metabolismo , Simulación de Dinámica Molecular , Conformación Proteica en Lámina beta , Zinc , Fragmentos de Péptidos/químicaRESUMEN
Introduction: This study explored the correlative factors of falls among the older adult with cognitive impairment, to provide distinct evidence for preventing falls in the older adult with cognitive impairment compared with the general older adult population. Methods: This study was based on a cross-sectional survey, with an older adult population of 124,124 was included. The data was sourced from the Elderly Care Unified Needs Assessment for Long-Term Care Insurance in Shanghai. Binary and multivariable logistic regression analyses were conducted sequentially on the correlative factors of falls. Multivariable logistic regression was performed on variables that were significant, stratified by cognitive function levels. Results: The incidence of fall in the past 90 days was 17.67% in this study. Specific variables such as gender (male), advanced age (≥80), residence with a elevator (or lift), mild or moderate disability, quality of sleep (acceptable/poor) were negatively correlated with falls, while higher education level, living alone, residence with indoor steps, unclean and untidy living environment, MCI or dementia, chronic diseases, restricted joints, impaired vision, and the use of diaper were positively correlative factors of falls. Comparing with older adult with normal cognitive functions, older adult with dementia faced a higher risk of falling due to accessibility barrier in the residence. For general older adults, less frequency of going outside and poor social interactions were positively correlated with falls, while for older adult with cognitive impairments, going outside moderately (sometimes) was found positively correlated with falls. Older adults with cognitive impairments have increased fall risks associated with chronic diseases, restricted joints, and the use of diaper. The risk of falling escalated with the greater number of chronic diseases. Discussion: For older adult with cognitive impairments, it is advisable to live with others. Additionally, creating an accessible living environment and maintaining the cleanness and tidiness can effectively reduce the risk of falls, particularly for those with MCI or dementia. Optimal outdoor activity plans should be developed separately based on the cognitive function of older adults. Older adult with dementia who have comorbidities should be paid special attention in fall prevention compared to the general older adult population.
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Accidentes por Caídas , Disfunción Cognitiva , Humanos , Accidentes por Caídas/estadística & datos numéricos , Masculino , Femenino , Estudios Transversales , Anciano , Disfunción Cognitiva/epidemiología , Anciano de 80 o más Años , China/epidemiología , Factores de Riesgo , IncidenciaRESUMEN
This study was designed based on a cross-sectional investigation conducted Shanghai, China. Demographic characteristics, diaper utilization, Activities of Daily Living (ADL) and emotion were collected by Unified Needs Assessment Form for Elderly Care Questionnaire. Cognition function was assessed by Mini-mental State Examination (MMSE) scale. Multivariate logistic regression was used for statistical analysis. The diaper utilization rate was 31.2%. Female, higher level of education, poorer ADL and cognition, more severe incontinence and financial dependence on others were facilitating factors for diaper usage (P < 0.05). The possibility of using diaper differed according to the intimacy of caregivers. Among incontinent individuals with relatively good ADL and cognition level, diaper utilization can significantly decrease the risk of going out only once a month (OR: 2.63 vs 4.05), and going out less than once a month (OR: 5.32 vs 6.53). Incontinence people who going out at least once a week had a lower risk of some negative emotion. Significantly, diaper utilization further decreased this risk. In conclusion, for incontinence elderly people with relatively independent ability, proper use of diaper may improve the frequency of outdoor activity and emotion. Nevertheless, diaper utilization should be decided based on elderly people's own will.
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Actividades Cotidianas , Incontinencia Urinaria , Humanos , Femenino , Anciano , Estudios Transversales , China/epidemiología , Emociones , Incontinencia Urinaria/epidemiologíaRESUMEN
Neuregulin-1 (NRG-1) is a member of a family of neurotrophic factors that is required for the differentiation, migration, and development of neurons. NRG-1 signaling is thought to contribute to both neuronal development and the neuropathology of schizophrenia, which is believed to be a neurodevelopmental disorder. However, few studies have investigated the role of NRG-1 on voltage-gated ion channels. In this study, we report that NRG-1 specifically increases the density of transient outward K(+) currents (IA) in rat cerebellar granule neurons (CGNs) in a time-dependent manner without modifying the activation or inactivation properties of IA channels. The increase in IA density is mediated by increased protein expression of Kv4.2, the main α-subunit of the IA channel, most likely by upregulation of translation. The effect of NRG-1 on IA density and Kv4.2 expression was only significant in immature neurons. Mechanistically, both Akt and mammalian target of rapamycin (mTOR) signaling pathways are required for the increased NRG-1-induced IA density and expression of Kv4.2. Moreover, pharmacological blockade of the ErbB4 receptor reduced the effect of NRG-1 on IA density and Kv4.2 induction. Our data reveal, for the first time, that stimulation of ErbB4 signaling by NRG-1 upregulates the expression of K(+) channel proteins via activation of the Akt/mTOR signaling pathway and plays an important role in neuronal development and maturation. NRG1 does not acutely change IA and delayed-rectifier outward (IK) of rat CGNs, suggesting that it may not alter excitability of immature neurons by altering potassium channel property.
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Receptores ErbB/metabolismo , Neurregulina-1/metabolismo , Potasio/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Canales de Potasio Shal/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Movimiento Celular , Receptores ErbB/genética , Regulación de la Expresión Génica/fisiología , Potenciales de la Membrana , Neurregulina-1/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor ErbB-4 , Canales de Potasio Shal/genética , Transducción de Señal , Serina-Treonina Quinasas TOR/genéticaRESUMEN
PURPOSE: Cuproptosis-related long non-coding RNA (lncRNA) diseases are associated with the occurrence and development of tumors. This study aimed to investigate whether cuproptosis-related lncRNA can predict the prognosis of patients with lung adenocarcinoma (LUAD). METHODS: Cuproptosis-related lncRNA prognosis (CLPS) model was successfully constructed through cox regression and lasso regression analyses. Then, the prognostic value of CLPS model was tested through the survival analysis, the ROC curve and the nomogram. Finally, the correlation of CLPS model with tumor immunity and tumor mutation burden was analyzed, and the potential susceptibility of drugs for LUAD were predicted. RESULTS: CLPS model for LUAD (AC090948.1, CRIM1-DT, AC026356.2, AC004832.5, AL161431.1) was successfully constructed, which has an independent prognostic value. Furthermore, the risk score of CLPS model was correlated with tumor immune characteristics and immune escape, which can predict the sensitivity of drugs including Cisplatin, Etoposide, Gemcitabine, and Erlotinib. CONCLUSIONS: In conclusion, it was found that CLPS model was associated with tumor immunity and tumor mutation load, which also predicted four potentially sensitive drugs for LUAD patients at different risks.
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Adenocarcinoma , Apoptosis , ARN Largo no Codificante , Humanos , Adenocarcinoma/genética , Pulmón , Nomogramas , Pronóstico , ARN Largo no Codificante/genética , CobreRESUMEN
Pulmonary angiosarcomas are usually secondary tumors, and a primary angiosarcoma of the lung is extremely rare. The present study reports a case of an elderly patient diagnosed with primary pulmonary angiosarcoma (PPA). A 78-year-old man presented with a 3-month history of cough and blood in phlegm. A computed tomography scan of the chest indicated pulmonary infection with ground-glass opacity in the right upper lobe. The patient underwent lobectomy of the right upper lobe as his clinical symptoms did not significantly improve after anti-infection treatment. The postoperative pathological examination confirmed a diagnosis of PPA. He developed left lung and pelvic metastases 1 month after surgery. After four cycles of liposomal doxorubicin therapy, the patient achieved partial remission. The patient remained in sustained remission after 6 months of follow-up. The present case report is intended to provide diagnostic insight into PPA. In addition, the findings indicate that timely diagnosis and treatment of PPA are very important due to its increased risk of local recurrence and distant metastasis.
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DNAX activating protein of 12 kDa (DAP12)-deficiency mice showed impaired differentiation of oligodendrocytes and reduced myelin in the central nervous system. Whether DAP12 is expressed by Schwann cells and its roles in the peripheral nervous system (PNS) remains unknown. In this study, expression of DAP12 was detected in Schwann cells in vivo and in vitro. The DAP12-knockout (KO) mice showed age-related motor deficits and thinner myelin in the sciatic nerve than WT mice but significantly faster clinical recovery after sciatic nerve crush injury. In sciatic nerves of DAP12 KO and WT mice, proteomic profiles analysis identified 158 differentially expressed proteins (DEPs) at 8-week-old, 29 DEPs at 54-week-old and 33 DEPs at two weeks after crush injury. Typically, of the DEPs at 54-week-old, up-regulated Lgmn and down-regulated RecK and Yap1 were associated with myelin loss in the sciatic nerve of DAP12 KO mice. Upregulation of nicotinamide nucleotide transhydrogenase and haptoglobin were associated with the accumulation of macrophages in the crushed sciatic nerve of DAP12 KO mice. After crush injury, there were significantly more M1 macrophages at one-week and more M2 macrophages at two-week in sciatic nerve of DAP12 KO mice than WT mice, indicating that DAP12 deletion promotes the phenotype conversion of macrophages from M1 to M2. Collectively, our findings suggest that DAP12 may exert dual roles in the PNS including promoting the physiological myelin formation and maintenance of Schwann cells but delaying nerve repair after injury by modulating the recruitment of macrophages and phenotype conversion.
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Lesiones por Aplastamiento , Traumatismos de los Nervios Periféricos , Ratones , Animales , Proteómica , Nervio Ciático/lesiones , Compresión Nerviosa , Traumatismos de los Nervios Periféricos/genética , Células de Schwann , Regeneración Nerviosa/fisiologíaRESUMEN
Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) can lead to severe kidney injury. However, the molecular mechanisms underlying the pathological process of kidney injury are still incompletely understood. In the present study, we demonstrate that microRNA-146b (miR-146b) deficiency aggravates kidney injury during UTIs caused by UPEC. In a mouse kidney infection model utilizing urosepsis isolate CFT073, we found that miR-146b expression significantly increased in the early stages of UPEC infection. Also, miR-146b-deficient mice displayed exacerbated inflammation in the kidney injury with severe M1 macrophage infiltration. Additionally, the results showed that miR-146b targeted interferon regulatory factor 5-regulated M1 macrophage polarization during UTIs. The results suggested that miR-146b contributed significantly to the control of kidney damage during UTIs, highlighting that miR-146b might be used as a novel therapeutic target for treating kidney injury during UTIs. IMPORTANCE Kidney injury during acute urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) is an important public health problem. However, how kidney injury develops during UPEC infection is still unclear. Although antibiotic therapy is currently an effective treatment for UTI, it cannot avoid kidney injury. MicroRNAs have gained extensive attention as essential molecules capable of regulating the autoimmune response. Among these, microRNA-146b (miR-146b) is involved in regulating inflammatory responses. In the present study, we demonstrated that miR-146b played an essential role in the development of kidney injury during UTIs caused by UPEC. The results showed that miR-146b may suppress M1 macrophage polarization and alleviate acute kidney injury. Furthermore, the miR-146b activator, agomir, in order to upregulate miR-146b, was effective in treating kidney damage by inhibiting the activation of M1 macrophages. In conclusion, our findings elucidated the mechanisms by which miR-146b alleviated kidney injury induced by UTIs, shed new light on the relationship between microRNA and bacterial infection, and provided a novel therapeutic target for treating this common bacterial infection.
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OBJECTIVE: To explore the rate and effect factors of hearing aids utilization in Chinese community elderly people, as well as the benefit role of hearing aids in the association of hearing loss and cognition decline. METHODS: This study was designed based on a longitudinal 7-years follow-up conducted in Shanghai (China). Demographic characteristics, hearing level, hearing aids utilization and Activities of Daily Living (ADL) of participants were collected by Unified Needs Assessment Form for Elderly Care Questionnaire. Cognition function was assessed by Mini-mental State Examination (MMSE) scale. Multivariate logistic regression and linear regression were used for statistical analysis. RESULTS: Hearing aids utilization rate in Chinese community elderly people is below 10 %. Participants with older age (≥80 years old), higher education (7-12 years and >12 years), who can manage money more independently were more likely to use hearing aids (P < 0.05). Whether hearing aids are used or not, hearing level is significantly associated with cognition in elderly people, but participants with hearing aids showed a slower cognitive decline speed. CONCLUSION: Hearing aids utilization may slow down the cognition descent via assisting hearing in daily life, so strategies need to be concerned in order to protect hearing function in all elderly and improve the use of hearing aids in HL elderly.
Asunto(s)
Disfunción Cognitiva , Audífonos , Humanos , Anciano , Anciano de 80 o más Años , Actividades Cotidianas , Estudios de Seguimiento , China/epidemiología , Audición , CogniciónRESUMEN
We conducted a study to assess the characteristics, scope of activity, and negative emotions in elderly women with urinary incontinence (UI) based on a longitudinal follow-up conducted in Shanghai, China from 2013 to 2019. A total of 3,531 elderly women were included in the final analysis, and 697 women who experienced UI during follow-up were included in the UI group. Subjects with UI were subdivided into those with partial UI (UI once a day or less) and UI (frequent UI). Two thousand eight hundred and thirty-four women who did not have UI during the same period served as the control group. The prevalence of UI was 19.74% in this study. Logistic regression analysis revealed that being older (> 80 years of age), having a high level of education (> 12 years; elderly people with a high level of education may pay more attention to their health and notice UI more readily), a low personal monthly income (≤ 3,000 RMB), more gravidity/parity, and having a chronic disease (chronic obstructive pulmonary disease (COPD), dementia, or Parkinson's disease) were risk factors for UI (p < 0.05). About 60% of women in the partial UI group engaged in daily activities outdoors, while this number decreased sharply to 3.6% in the UI group. Women in the UI group were more likely to have negative emotions, such as depression, anxiety, irritability, or feeling worthless (p < 0.001). Among elderly women with dementia, those with UI had defects in terms of judgment in everyday life, the ability of convey information, and the ability to understand information (p < 0.05). More attention needs to be paid to the adverse effects of UI on activities of daily living (ADL) and mental health in the future.