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1.
iScience ; 27(10): 110862, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39319271

RESUMEN

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood and adolescence. The availability of appropriate and well-characterized preclinical models for RMS is limited, posing a challenge for investigating the molecular mechanisms and evaluating new targeted compounds in preclinical settings. Here, we collected 51 RMS specimens (referred to as ZJUCH-RMS cohort) and established 9 patient-derived cells (PDCs) and validated the identity of these cells by the expression of RMS-specific markers. Whole-transcriptome analysis identified high-confidence mutations in ZJUCH-RMS cohort including RAS, TP53, ARID1A, MYOD1, and MYCN. Further studies showed that RMS PDCs retained the genetic alterations and the expression of RMS hallmark and dependency genes in matched primary tumors and acted as valuable tools to assess drug responses and pharmacogenomic interactions. Our study provides unique PDCs that are available for preclinical studies of RMS and further advances the feasibility of RMS PDCs as valuable tools for developing personalized treatments for patients.

2.
BMC Pharmacol Toxicol ; 25(1): 35, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39103956

RESUMEN

BACKGROUND AND PURPOSES: It is unclear whether the parent Saxagliptin (SAX) in vivo is the same as that in vitro, which is twice that of 5-hydroxy Saxagliptin (5-OH SAX). This study is to construct a Pharmacokinetic-Pharmacodynamic (PK-PD) link model to evaluate the genuine relationship between the concentration of parent SAX in vivo and the effect. METHODS: First, we established a reliable Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) method and DPP-4 inhibition ratio determination method. Then, the T2DM rats were randomly divided into four groups, intravenous injection of 5-OH SAX (0.5 mg/kg) and saline group, intragastric administration of SAX (10 mg/kg) and Sodium carboxymethyl cellulose (CMC-Na) group. Plasma samples were collected at different time points for subsequent testing. Finally, we used the measured concentrations and inhibition ratios to construct a PK-PD link model for 5-OH SAX and parent SAX. RESULTS: A two-compartment with additive model showed the pharmacokinetic process of SAX and 5-OH SAX, the concentration-effect relationship was represented by a sigmoidal Emax model and sigmoidal Emax with E0 model for SAX and 5-OH SAX, respectively. Fitting parameters showed SAX was rapidly absorbed after administration (Tmax=0.11 h, t1/2, ka=0.07 h), widely distributed in the body (V ≈ 20 L/kg), plasma exposure reached 3282.06 ng*h/mL, and the elimination half-life was 6.13 h. The maximum plasma dipeptidyl peptidase IV (DPP-4) inhibition ratio of parent SAX was 71.47%. According to the final fitting parameter EC50, EC50, 5-OH SAX=0.46EC50, SAX(parent), it was believed that the inhibitory effect of 5-OH SAX was about half of the parent SAX, which is consistent with the literature. CONCLUSIONS: The PK-PD link model of the parent SAX established in this study can predict its pharmacokinetic process in T2DM rats and the strength of the inhibitory effect of DPP-4 based on non-clinical data.


Asunto(s)
Adamantano , Diabetes Mellitus Tipo 2 , Dipéptidos , Inhibidores de la Dipeptidil-Peptidasa IV , Ratas Sprague-Dawley , Animales , Adamantano/análogos & derivados , Adamantano/farmacocinética , Adamantano/farmacología , Adamantano/sangre , Dipéptidos/farmacocinética , Dipéptidos/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Ratas , Modelos Biológicos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/sangre , Espectrometría de Masas en Tándem , Dipeptidil Peptidasa 4
3.
Front Endocrinol (Lausanne) ; 15: 1397329, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39076508

RESUMEN

Background: Previous studies have not thoroughly explored the impact of serum osmolality levels on early mortality in heart failure and reduced ejection fraction (HFrEF) patients. The purpose of this study was to investigate the relationship between serum osmolality levels and early all-cause mortality in patients with HFrEF. Methods: The open access MIMIC-IV database was the source of data for our study. We collected demographic data, vital signs, laboratory parameters, and comorbidities of the included patients and divided them into 3 groups based on their initial serum osmolality on admission, with the primary outcome being all-cause mortality within 28 days of admission. Smoothing Spline Fitting Curve, the Kaplan-Meier survival curve, and Threshold effect analysis were used to assess the relationship between serum osmolality and early mortality in HFrEF patients. Results: A total of 6228 patients (55.31% male) were included. All-cause mortality within 28 days on admission was 18.88% in all patients. After adjusting for confounders, higher serum osmolality levels were independently associated with an increased risk of 28-days all-cause mortality compared with the reference group (Reference group Q2: 290-309 mmol/L, Q4: HR, 1.82 [95% CI 1.19-2.78] P<0.05, Q5: HR, 1.99 [95% CI 1.02-3.91] P<0.05). Smooth spline fitting revealed a U-shaped association between serum osmolality and 28-days all-cause mortality. Further threshold effect analysis results suggested that each unit increase in serum osmolality level was associated with a 2% increase in 28-days all-cause mortality when serum osmolality levels were ≥ 298.8 mmol/L (HR, 1.019 [95% CI 1.012-1.025] P<0.05). Conclusion: A U-shaped correlation between initial serum osmolality and 28-days all-cause mortality in HFrEF patients was identified, revealing higher osmolality levels significantly increase mortality risk. These results underscore serum osmolality's critical role in early mortality among HFrEF patients, highlighting the need for further, larger-scale studies for validation.


Asunto(s)
Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Masculino , Femenino , Concentración Osmolar , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Bases de Datos Factuales , Pronóstico , Causas de Muerte , Anciano de 80 o más Años
4.
Heliyon ; 10(11): e32238, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38912455

RESUMEN

Background: Intestinal-type gastric adenocarcinoma, representing 95 % of gastric malignancies, originates from the malignant transformation of gastric gland cells. Despite its prevalence, existing methods for prognosis evaluation of this cancer subtype are inadequate. This study aims to enhance patient-specific prognosis evaluation by analyzing the clinicopathological characteristics and prognostic risk factors of intestinal-type gastric adenocarcinoma patients using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Methods: We extracted clinical data for patients diagnosed with intestinal-type gastric adenocarcinoma between 2010 and 2015 from the SEER database, selecting 257 cases based on predefined inclusion and exclusion criteria. Independent risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified using a Cox regression model. A nomogram model for predicting OS or CSS was developed from the Cox risk regression analysis and validated through the consistency index (C-index), ROC curve, and calibration curve. Results: Age, primary tumor resection, chemotherapy, lymph node metastasis, and tumor size were identified as independent prognostic factors for OS and CSS (P < 0.05). The nomogram model, constructed from these indicators, demonstrated superior predictive consistency for OS and CSS compared to the AJCC-TNM staging system. ROC curve analysis confirmed the model's higher accuracy, and calibration curve analysis indicated good agreement between the nomogram's predictions and actual observed outcomes. Conclusion: The nomogram model derived from SEER database analyses accurately predicts OS and CSS for patients with intestinal-type gastric adenocarcinoma. This model promises to facilitate more tailored treatments in clinical practice.

5.
Int J Mol Med ; 54(1)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38785162

RESUMEN

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post­translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism­related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non­alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.


Asunto(s)
Ácido Láctico , Hepatopatías , Humanos , Ácido Láctico/metabolismo , Hepatopatías/metabolismo , Animales , Hígado/metabolismo , Hígado/patología
6.
J Chromatogr A ; 1720: 464776, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38432109

RESUMEN

Thiol amino acids, with great physiological significance, are unstable, and have small molecular weights, as well as very low endogenous concentrations. Therefore, to quantitatively and directly analyze them using liquid chromatography-tandem mass spectrometry is difficult. To overcome these problems, we aimed to prepare a thiol-free amino acid plasm matrix as blank sample to reduce the background for the first time. Using compounds with maleimide group that react with classical thiols to generate water-insoluble products. Reducing agents Tris(2-carboxyethyl)phosphine (TCEP) was applied to cooperate with bismaleimide (DM) for elimination of thiol amino acids from plasma 10 min at room temperature and pH 7. Further, the residual TCEP from plasma were removed using an anion exchange resin within 10 min. Methodological validation analysis revealed good performance in linearity, precision, extraction recovery (≥ 82 %), and stability (except oxidized glutathione). This quantitative analysis was successfully applied to blood samples of 9 people in good health. This study provides a foundation for the development of accurate and rigorous quantitative analysis methods targeting thiol amino acids in different body fluids or tissues. Moreover, it paves the way toward realizing several clinical applications.


Asunto(s)
Aminoácidos , Fosfinas , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Aminoácidos/química , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida con Espectrometría de Masas , Compuestos de Sulfhidrilo
7.
Food Funct ; 15(7): 3583-3599, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38469921

RESUMEN

Lactobacillus probiotics exert their effects in a strain-specific and metabolite-specific manner. This study aims to identify lactobacilli that can effectively enhance the intestinal barrier function both in vitro and in vivo and to investigate the underlying metabolite and molecular mechanisms involved. Nine Lactobacillus isolates were evaluated for their ability to enhance the IPEC-J2 cellular barrier function and for their anti-inflammatory and anti-apoptotic effects in IPEC-J2 cells after an enterotoxigenic Escherichia coli challenge. Of the nine isolates, L. plantarum T10 demonstrated significant advantages in enhancing the cellular barrier function and displayed anti-inflammatory and anti-apoptotic activities in vitro. The bioactivities of L. plantarum T10 were primarily attributed to the production of exopolysaccharides, which exerted their effects through the TLR-mediated p38 MAPK pathway in ETEC-challenged IPEC-J2 cells. Furthermore, the production of EPS by L. plantarum T10 led to the alleviation of dextran sulfate sodium-induced colitis by reducing intestinal damage and enhancing the intestinal barrier function in mice. The EPS is classified as a heteropolysaccharide with an average molecular weight of 23.0 kDa. It is primarily composed of mannose, glucose, and ribose. These findings have practical implications for the targeted screening of lactobacilli used in the production of probiotics and postbiotics with strain-specific features of exopolysaccharides.


Asunto(s)
Infecciones por Escherichia coli , Lactobacillus plantarum , Probióticos , Animales , Ratones , Mucosa Intestinal/metabolismo , Funcion de la Barrera Intestinal , Infecciones por Escherichia coli/metabolismo , Lactobacillus , Antiinflamatorios/metabolismo
8.
Pediatr Pulmonol ; 59(5): 1438-1448, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38376264

RESUMEN

OBJECTIVES: To evaluate the assortment of tracheobronchial abnormalities on computed tomography angiography (CTA) in children with congenital heart disease (CHD). METHODS: In this study approved by the Institute ethics committee, CTA studies of 182 children (age range: 2 days-8 years) with CHD, performed from July 2021 to March 2023 were analyzed. Two pediatric radiologists independently assessed the tracheobronchial airways (from the trachea to lobar bronchi) for developmental and branching anomalies and airway compromise (narrowing). In cases which demonstrated airway compromise, the extent and the cause of airway narrowing were evaluated, and the etiology were divided into extrinsic and intrinsic causes. Interobserver agreement between the two radiologists was calculated using kappa statistics. RESULTS: One hundred children demonstrated normal airway anatomy and no luminal narrowing. Airway narrowing was observed in 63 (34.6%) children (κ: 0.954), and developmental airway anomalies were seen in 32 (17.5%) children (κ: 0.935). Of the 63 children with airway narrowing, 47 (25.8%) children had extrinsic cause for narrowing, 11 (6%) children had intrinsic causes for narrowing, and 5 (2.7%) children had both intrinsic and extrinsic causes attributing to airway compromise. Significant airway narrowing (>50% reduction) was seen in 35 (19.2%) children (κ: 0.945). CONCLUSION: Tracheobronchial airway abnormalities are frequently associated in children with CHD and need to be appraised preoperatively. Cross-sectional imaging with CTA provides excellent information on tracheobronchial airway anatomy and caliber as well as delineates the possible etiology of airway narrowing, thus accurately diagnosing airway anomalies.


Asunto(s)
Bronquios , Angiografía por Tomografía Computarizada , Cardiopatías Congénitas , Tráquea , Humanos , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/complicaciones , Preescolar , Lactante , Niño , Femenino , Masculino , Tráquea/diagnóstico por imagen , Tráquea/anomalías , Bronquios/diagnóstico por imagen , Bronquios/anomalías , Recién Nacido , Estudios Retrospectivos
9.
Tissue Cell ; 87: 102314, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38309204

RESUMEN

Lymphatic metastasis is a common metastasis of lung adenocarcinoma (LUAD). The current study illustrated the action of lncRNA NKX2-1-AS1 in lymphangiogenesis in LUAD and the underlying mechanisms. Clinical tissue samples were collected for determining NKX2-1-AS1 expression. Then, H441 and H661 cells were selected to perform gain- and loss-of-function assays for dissecting the roles of NKX2-1-AS1 in LUAD cell proliferation and migration. Besides, H441 and H661 cell supernatant was harvested to stimulate HLECs for assessing tube formation ability. Interaction among NKX2-1-AS1, ERG, and fatty acid binding protein 4 (FABP4) was validated through luciferase and RIP assays. NKX2-1-AS1 was highly-expressed in LUAD tissues. Silencing NKX2-1-AS1 suppressed H441 and H661 cell proliferation and migration, reduced expression levels of lymphangiogenesis-related factors (LYVE-1, VEGF-C, VEGFR3, VEGF-A, VEGFR2, and CCR7), and inhibited HLEC tube formation. Interaction validation demonstrated that NKX2-1-AS1 regulated FABP4 transcription by binding to ERG. Overexpression of FABP4 could effectively block the inhibition role of NKX2-1-AS1 silencing in lymphangiogenesis in H441 and H661 cells. This study provided evidence that NKX2-1-AS1 regulated FABP4 transcription by binding to ERG to facilitate the proliferation and migration of LUAD cells and tube formation of HLECs, thus participating in lymphangiogenesis.


Asunto(s)
Adenocarcinoma , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , Adenocarcinoma/genética , Línea Celular Tumoral , Proliferación Celular/genética , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Regulación Neoplásica de la Expresión Génica , Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Linfangiogénesis/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Regulador Transcripcional ERG/genética , Regulador Transcripcional ERG/metabolismo
10.
BMC Gastroenterol ; 24(1): 89, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408896

RESUMEN

BACKGROUND: Metastatic rectal cancer is an incurable malignancy, which is prone to early mortality. We aimed to establish nomograms for predicting the risk of early mortality in patients with metastatic rectal cancer. METHODS: In this study, clinical data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database.We utilized X-tile software to determine the optimal cut-off points of age and tumor size in diagnosis. Significant independent risk factors for all-cause and cancer-specific early mortality were determined by the univariate and multivariate logistic regression analyses, then we construct two practical nomograms. In order to assess the predictive performance of nomograms, we performed calibration plots, time-dependent receiver-operating characteristic curve (ROC), decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: A total of 2570 metastatic rectal cancer patients were included in the study. Multivariate logistic regression analyses revealed that age at diagnosis, CEA level, tumor size, surgical intervention, chemotherapy, radiotherapy, and metastases to bone, brain, liver, and lung were independently associated with early mortality of metastatic rectal cancer patients in the training cohort. The area under the curve (AUC) values of nomograms for all-cause and cancer-specific early mortality were all higher than 0.700. Calibration curves indicated that the nomograms accurately predicted early mortality and exhibited excellent discrimination. DCA and CIC showed moderately positive net benefits. CONCLUSIONS: This study successfully generated applicable nomograms that predicted the high-risk early mortality of metastatic rectal cancer patients, which can assist clinicians in tailoring more effective treatment regimens.


Asunto(s)
Nomogramas , Neoplasias del Recto , Humanos , Área Bajo la Curva , Encéfalo , Bases de Datos Factuales , Pronóstico
12.
World J Pediatr ; 20(3): 250-258, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38070095

RESUMEN

BACKGROUND: Surgery plays an important role in the treatment of neuroblastoma. Perioperative complications may impact the course of neuroblastoma treatment. To date, comprehensive analyses of complications and risk factors have been lacking. METHODS: Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021. The data collected included clinical characteristics, operative details, operative complications and postoperative outcomes. Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed. RESULTS: A total of 571 patients were enrolled in this study. Perioperative complications were observed in 255 (44.7%) patients. Lymphatic leakage (28.4%), diarrhea (13.5%), and injury (vascular, nerve and organ; 7.5%) were the most frequent complications. There were three operation-related deaths (0.53%): massive hemorrhage (n = 1), biliary tract perforation (n = 1) and intestinal necrosis (n = 1). The presence of image-defined risk factors (IDRFs) [odds ratio (OR) = 2.09, P < 0.01], high stage of the International Neuroblastoma Risk Group staging system (INRGSS) (OR = 0.454, P = 0.04), retroperitoneal lymph node metastasis (OR = 2.433, P = 0.026), superior mesenteric artery encasement (OR = 3.346, P = 0.003), and inferior mesenteric artery encasement (OR = 2.218, P = 0.019) were identified as independent risk factors for perioperative complications. CONCLUSIONS: Despite the high incidence of perioperative complications, the associated mortality rate was quite low. Perioperative complications of retroperitoneal neuroblastoma were associated with IDRFs, INRGSS, retroperitoneal lymph node metastasis and vascular encasement. Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma. Video Abstract (MP4 94289 KB).


Asunto(s)
Neuroblastoma , Niño , Humanos , Estudios Retrospectivos , Incidencia , Metástasis Linfática , Neuroblastoma/epidemiología , Neuroblastoma/cirugía , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Estadificación de Neoplasias
14.
J Vis Exp ; (199)2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37811967

RESUMEN

Parents' psychological stress during the perinatal and neonatal periods continues to increase in an environment of declining birthrates, aging populations, and shrinking family sizes. The increase in child abuse and neglect cases, most likely by inexperienced and insufficiently knowledgeable parents, necessitates education on childcare and intervention techniques in nursing and midwifery training. In particular, attachment formation early in life between mother and infant is crucial. To accurately teach sensitive and comprehensive information on intervention techniques for mother-child attachment formation, realistic videos, and educational materials are necessary. Although pseudoeducational materials are available, they might be limited in explaining complex realism, particularly to support breastfeeding that involves both parents and child and that encourages interaction between the two. In a previous study in a common marmoset (Callithrix jacchus) model, we experimentally controlled infant feeding and nurturing through 24 h of constant sensing and collected 1 month of quantitative data on psychological indices that possibly translated to psychological development. Age-dependent dynamic visualization of these data by multivariate analyses inferred causal relationships between early parental feeding and psychobiological rhythm formation. In the same primate model, we identified a spontaneous case of breastfeeding failure in which the father inhibited his neonatal infant's feeding and the mother appeared to abandon nurturing, leading to clinically significant weight loss in the infant. Thus, we explored intervention techniques to promote mother-infant interaction. The mother was trained to allow the infant to spontaneously explore her breast. Initially, the mother refused to display the feeding pose potentially due to pain associated with breast engorgement. Massage was used to soften the breast and feeding was reintroduced. We hypothesize that activation of instinctive attachment formation mechanisms by encouraging spontaneity in each parent and child is the key to successful feeding intervention.


Asunto(s)
Lactancia Materna , Madres , Animales , Femenino , Humanos , Recién Nacido , Masculino , Callithrix , Padre , Madres/psicología , Análisis Multivariante
16.
Front Oncol ; 13: 1230021, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37664039

RESUMEN

Malignant rhabdoid tumors (MRTs) are rare tumors with high mortality rates and poor prognoses. MRTs occur mainly in the central nervous system, kidneys, and soft tissues, but rarely in the omentum. MRTs occur more commonly in infants and children and less frequently in adults. Here, we report the first observed case of MRT in an adult omentum. A 35-year-old man with abdominal distension and pain was admitted to the emergency department. Previously, several hospitals considered patients with cirrhosis who had not received active treatment. Computed tomography and magnetic resonance imaging revealed diffuse omental thickening and massive ascites. The surgery was performed at our hospital, and the pathological diagnosis was MRT with a SMARCB1(INI-1) deletion. Postoperatively, his symptoms improved, and he underwent five cycles of chemotherapy. However, 6 months after surgery, the tumor developed liver metastases, and the patient subsequently died. Primary MRT of the greater omentum is rare, and its pathological diagnosis usually requires extensive clinicopathological evaluation of various differential diagnoses and an appropriate work-up to exclude other malignancies associated with SMARCB1 deletion. At the same time, the lack of specific signs of omental MRT and its rapid progression should alert clinicians.

17.
Front Microbiol ; 14: 1233934, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37645231

RESUMEN

Inflammation, a sophisticated and delicately balanced physiological mechanism, is paramount to the host's immunological defense against pathogens. However, unfettered and excessive inflammation can be instrumental in engendering a plethora of chronic ailments and detrimental health repercussions, notably within the gastrointestinal tract. Lipopolysaccharides (LPS) from bacteria are potent endotoxins capable of instigating intestinal inflammation through the disruption of the intestinal epithelial barrier and the stimulation of a pro-inflammatory immune response. In this study, we sought to investigate the influence of Litsea cubeba essential oil (LCEO) on LPS-induced intestinal inflammation and associated changes in the gut microbiota. We investigated the therapeutic potential of LCEO for gut health, with particular emphasis on its gut protective properties, anti-inflammatory properties and modulation of the gut microbiome. LCEO exhibited protective effects on colonic tissue by protecting crypts and maintaining epithelial integrity, and anti-inflammatory properties by reducing TNF-α, IL-6, and IL-1ß levels in the liver and intestine. Citral, a major component of LCEO, showed robust binding to IL-1ß, IL-6, and TNF-α, exerting anti-inflammatory effects through hydrogen bonding interactions. Using community barplot and LEfSe analyses, we detected significant variation in microbial composition, identified discrete biomarkers, and highlighted the influence of essential oils on gut microbial communities. Our research suggests that LCEO may be a promising natural compound for ameliorating diarrhea and intestinal inflammation, with potential implications for modulating the gut microbiome. These observations provide invaluable insight into the potential therapeutic role of LCEO as a natural anti-inflammatory agent for treating intestinal inflammatory disorders, particularly in the setting of a dysregulated immune response and altered gut microbiota. Furthermore, our findings highlight the need to understand the complex interplay between the host, the gut microbiome and natural products in the context of inflammatory diseases.

18.
Biosci Biotechnol Biochem ; 87(11): 1354-1363, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37604788

RESUMEN

Erythritol is a widely used sugar substitute in food and beverages with beneficial and detrimental roles in obesity and cardiovascular diseases, respectively; however, its influence on inflammatory bowel disease (IBD) and related behavioral disorders is not well understood. Here, we found that erythritol exacerbated gut inflammation by promoting macrophage infiltration and inducing M1 macrophage polarization, thus increasing gut leakage during colitis triggered by acute dextran sulfate sodium (DSS) treatment. Increased gut permeability can cause neuroinflammation and anxiety-like behavioral disorders. In conclusion, our results revealed a negative role for erythritol in gut inflammation and anxiety-like behavioral disorders induced by erythritol administration in a mouse model of acute colitis, suggesting that erythritol intake control may be necessary for IBD treatment.


Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Sulfato de Dextran/toxicidad , Inflamación , Colitis/inducido químicamente , Enfermedades Inflamatorias del Intestino/inducido químicamente , Ansiedad/inducido químicamente , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL
19.
J Clin Invest ; 133(10)2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-37183825

RESUMEN

Childhood neuroblastomas exhibit plasticity between an undifferentiated neural crest-like mesenchymal cell state and a more differentiated sympathetic adrenergic cell state. These cell states are governed by autoregulatory transcriptional loops called core regulatory circuitries (CRCs), which drive the early development of sympathetic neuronal progenitors from migratory neural crest cells during embryogenesis. The adrenergic cell identity of neuroblastoma requires LMO1 as a transcriptional cofactor. Both LMO1 expression levels and the risk of developing neuroblastoma in children are associated with a single nucleotide polymorphism, G/T, that affects a GATA motif in the first intron of LMO1. Here, we showed that WT zebrafish with the GATA genotype developed adrenergic neuroblastoma, while knock-in of the protective TATA allele at this locus reduced the penetrance of MYCN-driven tumors, which were restricted to the mesenchymal cell state. Whole genome sequencing of childhood neuroblastomas demonstrated that TATA/TATA tumors also exhibited a mesenchymal cell state and were low risk at diagnosis. Thus, conversion of the regulatory GATA to a TATA allele in the first intron of LMO1 reduced the neuroblastoma-initiation rate by preventing formation of the adrenergic cell state. This mechanism was conserved over 400 million years of evolution, separating zebrafish and humans.


Asunto(s)
Predisposición Genética a la Enfermedad , Neuroblastoma , Animales , Niño , Humanos , Pez Cebra/genética , Pez Cebra/metabolismo , Adrenérgicos , Genotipo , Neuroblastoma/patología , Proteína Proto-Oncogénica N-Myc/genética
20.
Biol Res Nurs ; 25(4): 606-614, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37138370

RESUMEN

BACKGROUND: Epilepsy is a prevalent comorbidity in patients with brain metastases (BM) and could result in sudden and accidental damage, as well as increased disease burden due to its rapid onset. Foreseeing the potential for the development of epilepsy may permit timely and efficient measures. This study aimed to analyze the influencing factors of epilepsy in advanced lung cancer (ALC) patients with BM and construct a nomogram model to predict the likelihood of developing epilepsy. METHODS: Socio-demographic and clinical data of ALC patients with BM were retrospectively collected from the First Affiliated Hospital of Zhejiang University School of Medicine between September 2019 and June 2021. Univariate and multivariate logistic regression analyses were applied to determine the influencing factors for epilepsy in ALC patients with BM. Based on the results of the logistic regression analysis, a nomogram was built to represent the contribution of each influencing factor in predicting the probability of epilepsy development in ALC patients with BM. The Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were utilized to evaluate the goodness of fit and prediction performance of the model. RESULTS: The incidence of epilepsy among 138 ALC patients with BM was 29.7%. On the multivariate analysis, having a higher number of supratentorial lesions (odds ratio [OR] = 1.727; p = 0.022), hemorrhagic foci (OR = 4.922; p = .021), and a high-grade of peritumoral edema (OR = 2.524; p < .001) were independent risk factors for developing epilepsy, while undergoing gamma knife radiosurgery (OR = .327; p = .019) was an independent protective factor. The p-value of the Hosmer-Lemeshow test was .535 and the area under the ROC curve (AUC) was .852 (95% CI: .807-.897), suggesting the model had a good fit and exhibited strong predictive accuracy. CONCLUSION: The nomogram was constructed that can predict the probability of epilepsy development for ALC patients with BM, which is helpful for healthcare professionals to identify high-risk groups early and allows for individualized interventions.


Asunto(s)
Neoplasias Encefálicas , Epilepsia , Neoplasias Pulmonares , Humanos , Nomogramas , Estudios Retrospectivos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Neoplasias Encefálicas/secundario , Epilepsia/complicaciones
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