RESUMEN
The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70-Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.
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Roturas del ADN de Doble Cadena , Reparación del ADN por Unión de Extremidades , Neuroblastoma , ARN Largo no Codificante , Humanos , ADN/genética , Reparación del ADN por Unión de Extremidades/genética , Reparación del ADN/genética , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , ARN Largo no Codificante/genéticaRESUMEN
The aim of this study was to investigate the prognostic role of blood-based nutritional biomarkers, including red blood cell (RBC count), hemoglobin (Hb), total protein (TP), albumin, the serum albumin to globulin ratio (AGR) and the prognostic nutritional index (PNI) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 501 NMIBC patients who received intravesical Bacillus Calmette-Guerin (BCG) treatment following transurethral resection of bladder tumor (TURBT) were included. The optimal cutoff values for these nutrition-based indicators were determined using receiver operating characteristic curve analysis. We observed a significantly higher recurrence-free survival (RFS) rate in patients with elevated levels of RBC count, Hb, TP, and albumin. Cox univariate and multivariate Cox regression analyses demonstrated that serum albumin (P = 0.002, HR = 0.51, 95%CI: 0.33-0.78), RBC count (P = 0.002, HR = 0.50, 95%CI: 0.32-0.77), TP (P = 0.028, HR = 0.62, 95%CI: 0.41-0.95), Hb (P = 0.004, HR = 0.53, 95%CI: 0.33-0.84), AGR (P = 0.003, HR = 0.46, 95%CI: 0.27-0.76) and PNI (P = 0.019, HR = 0.56, 95%CI: 0.35-0.91) were significant independent factors predicting RFS. These cost-effective and convenient blood-based nutritional biomarkers have the potential to serve as valuable prognostic indicators for predicting recurrence in NMIBC patients undergoing BCG-immunotherapy.
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Adyuvantes Inmunológicos , Vacuna BCG , Invasividad Neoplásica , Evaluación Nutricional , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/cirugía , Vacuna BCG/uso terapéutico , Vacuna BCG/administración & dosificación , Masculino , Femenino , Anciano , Pronóstico , Persona de Mediana Edad , Administración Intravesical , Adyuvantes Inmunológicos/uso terapéutico , Adyuvantes Inmunológicos/administración & dosificación , Estudios Retrospectivos , Albúmina Sérica/análisis , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Biomarcadores/sangre , Periodo Preoperatorio , Recuento de Eritrocitos , Estado Nutricional , Neoplasias Vesicales sin Invasión MuscularRESUMEN
Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.
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Antineoplásicos , Ácido Oleanólico , Ácido Oleanólico/farmacología , Antineoplásicos/farmacologíaRESUMEN
BACKGROUND This retrospective study aimed to investigate co-infections with common respiratory pathogens and SARS-CoV-2 and laboratory biochemistry findings in patients with COVID-19 in the Zhuzhou area of China, in order to provide a reference for the disease assessment and clinical treatment of COVID-19. MATERIAL AND METHODS The clinical data of COVID-19 patients admitted to the hospital of Zhuzhou City from January 28 to March 15, 2020, as well as laboratory test results for respiratory pathogens and biochemical indicators, were collected to conduct correlation analyses. All patients were diagnosed based on fluorescence-based PCR assay for SARS-CoV-2. RESULTS Eleven of the 78 patients (14.1%) were co-infected with other respiratory pathogens, among which Mycoplasma pneumoniae (n=5, 45.5%) and respiratory syncytial virus (n=4, 36.4%) were the most frequent. There were 8 patients co-infected with 1 other pathogen and 3 patients co-infected with 2 other pathogens. Compared with mono-infected COVID-19 patients, patients with co-infections had significantly higher levels of procalcitonin (P=0.002). CONCLUSIONS The findings showed that Mycoplasma pneumonia and respiratory syncytial virus were the most common co-infections in patients with COVID-19 pneumonia. Increased levels of PCT in patients with COVID-19 pneumonia were associated with co-infection.
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COVID-19/epidemiología , Coinfección/epidemiología , Pandemias , Infecciones del Sistema Respiratorio/epidemiología , SARS-CoV-2/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Biomarcadores , Proteína C-Reactiva/análisis , COVID-19/sangre , COVID-19/diagnóstico , Prueba de Ácido Nucleico para COVID-19 , Niño , Preescolar , China/epidemiología , Creatina Quinasa/sangre , Estudios Transversales , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Neumonía por Mycoplasma/sangre , Neumonía por Mycoplasma/epidemiología , Polipéptido alfa Relacionado con Calcitonina/sangre , Infecciones por Virus Sincitial Respiratorio/sangre , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto Joven , Tratamiento Farmacológico de COVID-19RESUMEN
INTRODUCTION AND OBJECTIVE: Several studies have focused on the treatment and recurrence of urethral diverticulum (UD). However, few investigations have addressed sexual function in pati-ents with UD. Therefore, we sought to examine sexual function in women affected by UD. MATERIALS AND METHODS: There were 108 accepted cases involving transvaginal diverticulectomy at our institution. Ultimately, 83 women were included for further analysis, only 61 of these wo-men had sexual partners. We collected data for the Female Sexual Function Index (FSFI) from the female patients and the Male Sexual Health Questionnaire (MSHQ) from their male partners before and after surgery. RESULTS: Preoperatively, the UD size affected the female patient's arousal and lubrication (p=0.04), and the UD location affected their satisfaction. However, no significant between-group differences were found in the total FSFI score. For all women, sexual activity improved after surgery (p=0.0087). In addition to improvements in arousal for women with a large UD, improvements in lubrication were affected by the UD size, number and shape, increases in sa-tisfaction scores were impacted by the UD location and shape, and pain relief was linked to the UD number and shape. Analysis of the MSHQ results revealed no between-group differences among the male partners. CONCLUSION: Only the UD size and location affected sexual function in women with a small UD. Surgery could improve female sexual function but did not affect the sexual function of the patient's partners.
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Divertículo/cirugía , Complicaciones Posoperatorias/etiología , Disfunciones Sexuales Fisiológicas/etiología , Enfermedades Uretrales/cirugía , Adulto , Divertículo/fisiopatología , Eyaculación/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias/fisiopatología , Valores de Referencia , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Disfunciones Sexuales Fisiológicas/fisiopatología , Parejas Sexuales , Encuestas y Cuestionarios , Enfermedades Uretrales/fisiopatologíaRESUMEN
Nitric oxide (NO) and ethylene respond to biotic and abiotic stresses through either similar or independent processes. This study examines the mechanism underlying the effects of NO and ethylene on promoting root hair development in Arabidopsis under magnesium (Mg) deficiency. The interaction between NO and ethylene in the regulation of Mg deficiency-induced root hair development was investigated using NO- and ethylene-related mutants and pharmacological methods. Mg deficiency triggered a burst of NO and ethylene, accompanied by a stimulated development of root hairs. Interestingly, ethylene facilitated NO generation by activation of both nitrate reductase and nitric oxide synthase-like (NOS-L) in the roots of Mg-deficient plants. In turn, NO enhanced ethylene synthesis through stimulating the activities of 1-aminocyclopropane-1-carboxylate (ACC) oxidase and ACC synthase (ACS). These two processes constituted an NO-ethylene feedback loop. Blocking either of these two processes inhibited the stimulation of root hair development under Mg deficiency. In conclusion, we suggest that Mg deficiency increases the production of NO and ethylene in roots, each influencing the accumulation and role of the other, and thus these two signals interactively regulate Mg deficiency-induced root hair morphogenesis.
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Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Etilenos/metabolismo , Magnesio/metabolismo , Óxido Nítrico/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Modelos Biológicos , Óxido Nítrico/biosíntesis , Transducción de SeñalRESUMEN
Aim We aimed to identify clinical characteristics and risk factors associated with onset of high-altitude headache (HAH) after acute exposure at 3700 m. Method In two hours, 163 individuals ascended by plane to 3700 m. Demographic information, physiological and psychological measurements, cognitive function, physical work capacity tests and profile of mood states within one week prior to the departure and within 24 hours after arrival were examined. Results HAH patients featured significantly higher vertebral artery diastolic velocity (Vd), heart rate (HR) and pulmonary artery diameter. HAH was also associated with a more negative mood state, including scores for tension anxiety, depression, hostility, fatigue and confusion, as well as lower vigor (all p values <0.05). Furthermore, negative emotions were positively related to HAH severity. HAH slightly decreased cognitive functioning. HR, Vd, lack of vigor, confusion and self-reported anxiety (all p values <0.05) were independent risk factors for HAH. We have identified three independent baseline predictors for HAH including internal diameter of the left ventricle (LVD), Athens Insomnia Scale (AIS) and confusion score. Conclusions Higher HR, Vd, confusion and self-reported anxiety and insufficient vigor were independent risk factors for HAH. Furthermore, higher baseline LVD, AIS and confusion score are independent predictors of HAH.
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Mal de Altura/fisiopatología , Mal de Altura/psicología , Cefalea/etiología , Hemodinámica/fisiología , Adolescente , Pueblo Asiatico , Ventrículos Cardíacos/anatomía & histología , Humanos , Masculino , Factores de RiesgoRESUMEN
BACKGROUND: This study aimed to identify the systemic and cerebral hemodynamic characteristics and their roles in high-altitude headache (HAH) among young Chinese men following acute exposure. METHODS: The subjects (n = 385) were recruited in June and July of 2012. They completed case report form questionnaires, as well as heart rate (HR), blood pressure, echocardiogram and transcranial Doppler examinations at 3700 m following a two-hour plane flight. A subgroup of 129 participants was examined at two altitudes (500 and 3700 m). RESULTS: HAH was characterized by increased HR and cardiac output (CO) and lower saturation pulse oxygen (SpO(2)) (all p < 0.05). The change in tricuspid regurgitation was also different between the HAH positive (HAH+) and HAH negative (HAH-) subjects. Furthermore, the HAH+ subjects exhibited faster mean (V(m)), systolic (V(s)) and diastolic (V(d)) velocities in the basilar artery (BA; all p < 0.05) and a faster V(d) ( 25.96 ± 4.97 cm/s vs. 24.76 ± 4.76 cm/s, p = 0.045) in the left vertebral artery (VA). The bilateral VA asymmetry was also significantly different between the two groups. The pulsatility index (PI) and resistance index (RI) of left VA were lower in the HAH subjects (p < 0.05) and were negatively correlated with HAH (p < 0.05). Baseline CO and Vm in left VA (or right MCA in different regressions) were independent predictors for HAH, whereas CO/HR and ΔV(d) (V(d) difference between bilateral VAs) were independent risk factors for HAH at 3700 m. CONCLUSIONS: HAH was characterized, in part, by increased systemic hemodynamics and posterior cerebral circulation, which was reflected by the BA and left VA velocities, and lower arterial resistance and compliance. Furthermore, baseline CO and V(m) in left VA or right MCA at sea level were independent predictors for HAH, whilst bilateral VA asymmetry may contribute to the development of HAH at high altitude.
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Mal de Altura/fisiopatología , Circulación Cerebrovascular/fisiología , Cefalea/fisiopatología , Hemodinámica/fisiología , Adolescente , Adulto , Altitud , Mal de Altura/complicaciones , Presión Sanguínea/fisiología , Cefalea/etiología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
PURPOSE: We aimed at identifying the cerebral hemodynamic characteristics of acute mountain sickness (AMS). METHODS: Transcranial Doppler (TCD) sonography examinations were performed between 18 and 24 h after arrival at 3,700 m via plane from 500 m (n = 454). A subgroup of 151 subjects received TCD examinations at both altitudes. RESULTS: The velocities of the middle cerebral artery, vertebral artery (VA) and basilar artery (BA) increased while the pulsatility indexes (PIs) and resistance indexes (RIs) decreased significantly (all p < 0.05). Velocities of BA were higher in AMS (AMS+) individuals when compared with non-AMS (AMS-) subjects (systolic velocity: 66 ± 12 vs. 69 ± 15 cm/s, diastolic velocity: 29 ± 7 vs. 31 ± 8 cm/s and mean velocity, 42 ± 9 vs. 44 ± 10 cm/s). AMS was characterized by higher diastolic velocity [V d_VA (26 ± 4 vs. 25 ± 4, p = 0.013)] with lower PI and RI (both p = 0.004) in VA. Furthermore, the asymmetry index (AI) of VAs was significantly lower in the AMS + group [-5.7 % (21.0 %) vs. -2.5 % (17.8 %), p = 0.016]. The AMS score was closely correlated with the hemodynamic parameters of BA and the V d_VA, PI, RI and AI of VA. CONCLUSION: AMS is associated with alterations in cerebral hemodynamics in the posterior circulation rather than the anterior one, and is characterized by higher blood velocity with lower resistance. In addition, the asymmetry of VAs may be involved in AMS.
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Mal de Altura/fisiopatología , Circulación Cerebrovascular , Hemodinámica , Adolescente , Adulto , Factores de Edad , Altitud , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. SIGNIFICANCE: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.
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Proliferación Celular , Factor 1 de Elongación Peptídica , Biosíntesis de Proteínas , ARN Largo no Codificante , ARN de Transferencia , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Humanos , Femenino , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Animales , Ratones , Factor 1 de Elongación Peptídica/metabolismo , Factor 1 de Elongación Peptídica/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Phosphorus (P) is an essential element for plant growth and development but it is often a limiting nutrient in soils. Hence, P acquisition from soil by plant roots is a subject of considerable interest in agriculture, ecology and plant root biology. Root architecture, with its shape and structured development, can be considered as an evolutionary response to scarcity of resources. SCOPE: This review discusses the significance of root architecture development in response to low P availability and its beneficial effects on alleviation of P stress. It also focuses on recent progress in unravelling cellular, physiological and molecular mechanisms in root developmental adaptation to P starvation. The progress in a more detailed understanding of these mechanisms might be used for developing strategies that build upon the observed explorative behaviour of plant roots. CONCLUSIONS: The role of root architecture in alleviation of P stress is well documented. However, this paper describes how plants adjust their root architecture to low-P conditions through inhibition of primary root growth, promotion of lateral root growth, enhancement of root hair development and cluster root formation, which all promote P acquisition by plants. The mechanisms for activating alterations in root architecture in response to P deprivation depend on changes in the localized P concentration, and transport of or sensitivity to growth regulators such as sugars, auxins, ethylene, cytokinins, nitric oxide (NO), reactive oxygen species (ROS) and abscisic acid (ABA). In the process, many genes are activated, which in turn trigger changes in molecular, physiological and cellular processes. As a result, root architecture is modified, allowing plants to adapt effectively to the low-P environment. This review provides a framework for understanding how P deficiency alters root architecture, with a focus on integrated physiological and molecular signalling.
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Regulación de la Expresión Génica de las Plantas , Fósforo/metabolismo , Desarrollo de la Planta , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Plantas/genética , Adaptación Fisiológica , Transporte Biológico , Óxido Nítrico , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/anatomía & histología , Raíces de Plantas/metabolismo , Plantas/anatomía & histología , Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Several observational studies and clinical trials have shown that the gut microbiota is associated with urological cancers. However, the causal relationship between gut microbiota and urological cancers remains to be elucidated due to many confounding factors. METHODS: In this study, we used two thresholds to identify gut microbiota GWAS from the MiBioGen consortium and obtained data for five urological cancers from the UK biobank and Finngen consortium, respectively. We then performed a two-sample Mendelian randomization (MR) analysis with Wald ratio or inverse variance weighted as the main method. We also performed comprehensive sensitivity analyses to verify the robustness of the results. In addition, we performed a reverse MR analysis to examine the direction of causality. RESULTS: Our study found that family Rikenellaceae, genus Allisonella, genus Lachnospiraceae UCG001, genus Oscillibacter, genus Eubacterium coprostanoligenes group, genus Eubacterium ruminantium group, genus Ruminococcaceae UCG013, and genus Senegalimassilia were related to bladder cancer; genus Ruminococcus torques group, genus Oscillibacter, genus Barnesiella, genus Butyricicoccus, and genus Ruminococcaceae UCG005 were related to prostate cancer; class Alphaproteobacteria, class Bacilli, family Family XI, genus Coprococcus2, genus Intestinimonas, genus Lachnoclostridium, genus Lactococcus, genus Ruminococcus torques group, and genus Eubacterium brachy group were related to renal cell cancer; family Clostridiaceae 1, family Christensenellaceae, genus Eubacterium coprostanoligenes group, genus Clostridium sensu stricto 1, and genus Eubacterium eligens group were related to renal pelvis cancer; family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum were related to testicular cancer. Comprehensive sensitivity analyses proved that our results were reliable. CONCLUSIONS: Our study confirms the role of specific gut microbial taxa on urological cancers, explores the mechanism of gut microbiota on urological cancers from a macroscopic level, provides potential targets for the screening and treatment of urological cancers, and is dedicated to providing new ideas for clinical research.
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Microbioma Gastrointestinal , Neoplasias Renales , Lactobacillales , Neoplasias Testiculares , Neoplasias Urológicas , Masculino , Humanos , Microbioma Gastrointestinal/genética , Análisis de la Aleatorización Mendeliana , Neoplasias Urológicas/genética , Clostridiaceae , Bacteroidetes , Estudio de Asociación del Genoma CompletoRESUMEN
Mechanical cues play a crucial role in activating myofibroblasts from quiescent fibroblasts during fibrosis, and the stiffness of the extracellular matrix is of significant importance in this process. While intracellular force mediated by myosin II and calcium influx regulated by Piezo1 are the primary mechanisms by which cells sense and respond to mechanical forces, their intercellular mechanical interaction remains to be elucidated. Here, hydrogels with tunable substrate are used to systematically investigate the crosstalk of myosin II and Piezo1 in fibroblast to myofibroblast transition (FMT). The findings reveal that the two distinct signaling pathways are integrated to convert mechanical stiffness signals into biochemical signals during bladder-specific FMT. Moreover, it is demonstrated that the crosstalk between myosin II and Piezo1 sensing mechanisms synergistically establishes a sustained feed-forward loop that contributes to chromatin remodeling, induces the expression of downstream target genes, and ultimately exacerbates FMT, in which the intracellular force activates Piezo1 by PI3K/PIP3 pathway-mediated membrane tension and the Piezo1-regulated calcium influx enhances intracellular force by the classical FAK/RhoA/ROCK pathway. Finally, the multifunctional Piezo1 in the complex feedback circuit of FMT drives to further identify that targeting Piezo1 as a therapeutic option for ameliorating bladder fibrosis and dysfunction.
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Actomiosina , Calcio , Humanos , Actomiosina/metabolismo , Calcio/metabolismo , Fibroblastos/metabolismo , Fibrosis , Miosina Tipo II/metabolismoRESUMEN
CX3C chemokine ligand 1 (CX3CL1) belongs to the CX3C chemokine family and is involved in various disease processes. However, its role in intervertebral disc degeneration (IDD) remains to be elucidated. In the present study, western blotting, reverse transcription-quantitative PCR and ELISA assays were used to assess target gene expression. In addition, immunofluorescence and TUNEL staining were used to assess macrophage infiltration, monocyte migration and apoptosis. The present study aimed to reveal if and how CX3CL1 regulates IDD progression by exploring its effect on macrophage polarization and apoptosis of human nucleus pulposus cells (HNPCs). The data showed that CX3CL1 bound to CX3C motif chemokine receptor 1 (CX3CR1) promoted the M2 phenotype polarization via JAK2/STAT3 signaling, followed by increasing the secretion of anti-inflammatory cytokines from HNPCs. In addition, HNPC-derived CX3CL1 promoted M2 macrophage-derived C-C motif chemokine ligand 17 release thereby reducing the apoptosis of HNPCs. In clinic, the reduction of mRNA and protein levels CX3CL1 in degenerative nucleus pulposus tissues (NPs) was measured. Increased M1 macrophages and pro-inflammatory cytokines were found in NPs of IDD patients with low CX3CL1 expression. Collectively, these findings suggested that the CX3CL1/CX3CR1 axis alleviates IDD by reducing inflammation and apoptosis of HNPCs via macrophages. Therefore, targeting CX3CL1/CX3CR1 axis is expected to produce a new therapeutic approach for IDD.
RESUMEN
BACKGROUND AND AIMS: Formation of cluster roots is one of the most specific root adaptations to nutrient deficiency. In white lupin (Lupinus albus), cluster roots can be induced by phosphorus (P) or iron (Fe) deficiency. The aim of the present work was to investigate the potential shared signalling pathway in P- and Fe-deficiency-induced cluster root formation. METHODS: Measurements were made of the internal concentration of nutrients, levels of nitric oxide (NO), citrate exudation and expression of some specific genes under four P × Fe combinations, namely (1) 50 µm P and 10 µm Fe (+P + Fe); (2) 0 P and 10 µm Fe (-P + Fe); (3) 50 µm P and 0 Fe (+P-Fe); and (4) 0 P and 0 Fe (-P-Fe), and these were examined in relation to the formation of cluster roots. KEY RESULTS: The deficiency of P, Fe or both increased the cluster root number and cluster zones. It also enhanced NO accumulation in pericycle cells and rootlet primordia at various stages of cluster root development. The formation of cluster roots and rootlet primordia, together with the expression of LaSCR1 and LaSCR2 which is crucial in cluster root formation, were induced by the exogenous NO donor S-nitrosoglutathione (GSNO) under the +P + Fe condition, but were inhibited by the NO-specific endogenous scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl- 3-oxide (cPTIO) under -P + Fe, +P-Fe and -P-Fe conditions. However, cluster roots induced by an exogenous supply of the NO donor did not secrete citrate, unlike those formed under -P or -Fe conditions. CONCLUSIONS: NO plays an important role in the shared signalling pathway of the P- and Fe-deficiency-induced formation of cluster roots in white lupin.
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Deficiencias de Hierro , Lupinus/fisiología , Óxido Nítrico/metabolismo , Fósforo/deficiencia , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Adaptación Fisiológica , Raíces de Plantas/efectos de los fármacos , Transducción de SeñalRESUMEN
BACKGROUND: Iron plays an important role in neurodevelopmental functions in the brain. Serum ferritin levels are different in children with attention deficit hyperactivity disorder and tic disorder than in healthy children. AIM: To explore the current status of iron deficiency in children with neurodevelopmental disorders and its sex and age effects. METHODS: A total of 1565 children with attention deficit hyperactivity disorder (ADHD), 1694 children with tic disorder (TD), 93 children with ASD and 1997 healthy control children were included between January 1, 2020, and December 31, 2021 at Beijing Children's Hospital. We describe the differences in age levels and ferritin levels between different disease groups and their sex differences. The differences between the sexes in each disease were analyzed using the t test. The incidence rate of low serum ferritin was used to describe the differences between different diseases and different age groups. A chi-square test was used to analyze the difference in the incidence of low serum ferritin between the disease group and the control group. Analysis of variance was used for comparisons between subgroups, and regression analysis was used for confounding factor control. RESULTS: A total of 1565 ADHD patients aged 5-12 years were included in this study, and the average serum ferritin levels of male and female children were 36.82 ± 20.64 µg/L and 35.64 ± 18.56 µg/L, respectively. A total of 1694 TD patients aged 5-12 years were included in this study, and the average serum ferritin levels of male and female children were 35.72 ± 20.15 µg/L and 34.54 ± 22.12 µg/L, respectively. As age increased, the incidence of low serum ferritin in ADHD and TD first decreased and then increased, and 10 years old was the turning point of rising levels. The incidence of ADHD with low serum ferritin was 8.37%, the incidence of TD with low serum ferritin was 11.04%, and the incidence of the healthy control group with low serum ferritin was 8.61%, among which male children with TD accounted for 9.25% and female children with TD accounted for 11.62%. There was a significant difference among the three groups (P < 0.05). In addition, there were 93 children with ASD with an average serum ferritin level of 30.99 ± 18.11 µg/L and a serum ferritin incidence of 15.05%. CONCLUSION: In conclusion, low serum ferritin is not a risk factor for ADHD or TD. The incidence of low serum ferritin levels in children with ADHD and TD between 5 and 12 years old decreases first and then increases with age.
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Objective: To study the effects of psychological nursing intervention on anxiety, depression, and life events in puerperal women with fetal abnormalities. Methods: From January 2020 to January 2022, eighty women with abnormal fetal induction and puerperium-treated were selected in our hospital as the subjects. The research group (n = 40) and control group (n = 40) were arbitrarily selected from 80 women with abnormal fetal induction and puerperium. The research group was given psychological nursing intervention based on routine nursing, and the control cases were given routine nursing. The scores of Generalized Anxiety Scale (GAD-7), Patient Health Questionnaire (PHQ-9), Event Impact Scale (IES-R), Life Events Scale (LES), and Newcastle Nursing Satisfaction Scale (NSNS) were studied before nursing and 4 weeks after discharge. Results: Four weeks after discharge, the score of GAD-7 in the research group was lower, and the difference was statistically significant (P < 0.05). The score of PHQ-9 in the research group was lower, and the difference was statistically significant (P < 0.05). The IES-R score of the research group was lower, and the difference was statistically significant (P < 0.05). The LES score of the research group was lower, and the difference was statistically significant (P < 0.05). And the NSNS score of the research group was higher, and the difference was statistically significant (P < 0.05). Conclusion: The value of psychological care interventions in women with abnormally induced labor is more remarkable, contributing to the reduction of anxiety and depression and increasing the satisfaction of care for women with abnormally induced labor.
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Ansiedad , Depresión , Femenino , Feto , Humanos , Trabajo de Parto Inducido , Periodo Posparto , Embarazo , Calidad de Vida/psicologíaRESUMEN
The aim of this study is to present a summary of current evidence concerning the various treatments in the management of penile rehabilitation after radical prostatectomy (RP) and provide recommendations for future research. Randomized controlled trials (RCTs) were identified from electronic databases including PubMed, the Cochrane Library, Embase, and Web of Science from inception through March 2020 with no limitation to language. Comparable data from each study were combined in a meta-analysis where possible, otherwise data were synthesized narratively. The data analysis was completed by Review Manager version 5.3. A total of 39 RCTs were included in this study. At present, phosphodiesterase type 5 inhibitors (PDE5is) remain the first-line treatment for patients with erectile dysfunction (ED) after RP. Compared with the placebo group, patients in regular PDE5is group (mean difference (MD): 0.76; 95% confidence interval (CI): 1.69-4.44; p < 0.0001) and on demand group (MD: 3.92; 95% CI: 2.95-4.88; p < 0.00001) had a significantly higher mean Erectile Function domain of the International Index of Erectile Function (IIEF-EF) scores within 3 months after RP. As for the proportion of IIEF-EF ≥ 22, patients in regular PDE5is group and on demand PDE5is group had significantly higher proportion than those in placebo group 6 months after RP, and the odds ratios were 1.87 (95% CI: 1.32-2.66; p = 0.0005) and 2.17 (95% CI: 1.20-3.93; p = 0.01), respectively. No significant difference was observed between regular PDE5is group and on demand group regardless of mean IIEF-EF score or the proportion of IIEF-EF ≥ 22. Intracorporeal injection therapy seemed to have similar efficacy to PDE5is. The International Index of Erectile Function-5 items (IIEF-5) scores were significantly higher in vacuum constriction devices group than control group at 6-9 months after RP (MD: 6.70, 95% CI: 2.30-11.10, p = 0.003) with great between-study heterogeneity (p = 0.06, I2 = 72%). The other therapeutics including low-intensity extracorporeal shockwave therapy, statin therapy, psychotherapy interventions, and pelvic floor muscle training plus electrical stimulation showed certain improvement on erectile function. We found that the combination therapy showed certain advantages over monotherapy. Currently, PDE5is-based combination therapy remains the mainstream treatment for ED after RP. Intracorporeal injection therapy and vacuum therapy could be served as alternative treatments if PDE5is are ineffective and contraindicated.
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Disfunción Eréctil , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/etiología , Humanos , Masculino , Erección Peniana , Inhibidores de Fosfodiesterasa 5 , Próstata/cirugía , Prostatectomía/efectos adversosRESUMEN
BACKGROUND & AIMS: Capsaicin, a functional component of chili pepper, possesses anti-inflammatory, analgesic, and anti-cancer properties. This study aimed to determine the property of capsaicin against hepatocarcinogenesis in vivo and investigate the role of the SIRT1/SOX2 pathway in the mode of action of capsaicin in hepatic progenitor cells (HPCs), which is related to hepatocarcinogenesis. MATERIALS & METHODS: We prepared a diethylnitrosamine-induced liver cancer model in rats to examine hepatocarcinogenesis, and delivered liposomal capsaicin through the subcutaneous transposition of the spleen to the liver. Liver sections from rats and hepatocarcinoma patients were stained for the markers of HPCs or SIRT1/SOX2 signaling. SIRT1/SOX2 signalling expression was measured using immunoprecipitation and western blot. RESULTS: We found that capsaicin significantly inhibited hepatocarcinogenesis. Notably, capsaicin inhibited HPCs activation in vivo but did not induce apoptosis in the normal hepatic progenitor cell line in rats in vitro. This suggests that capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of HPCs. Moreover, capsaicin can induce this inhibition by reducing the stability of SOX2. SIRT1 is overexpressed in liver cancer and acts as a tumor promoter via SOX2 deacetylation. Using immunoprecipitation, we identified direct binding between SIRT1 and SOX2. The capsaicin treatment resulted in SIRT1 downregulation which reduced deacetylation, and increased nuclear export as well as subsequent ubiquitous degradation of SOX2. CONCLUSIONS: Altogether, we report that capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of HPCs via SIRT1/SOX2 signaling. It may serve as a promising therapeutic candidate for liver cancer.