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1.
Proteomics ; 24(11): e2300021, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38171844

RESUMEN

The link between metabolism and tumor progression has been extensively researched for a long time. With the increasing number of studies uncovering the multiple functions of metabolic reprogramming in tumor microenvironments, the regulatory network seems to become even more intricate at the same time. Small extracellular vesicles (sEV), as crucial mediators facilitating intercellular communications, exhibit significant involvement in regulating metabolic reprogramming within the complicated network of tumor microenvironments. sEV derived from tumor cells and those released by other cell populations such as tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) can mutually influence each other, giving rise to diverse complex feedback loops. This review includes multiple studies conducted in recent years to summarize the functions of sEV in altering metabolism in various cell types within tumor microenvironments. Additionally, it aims to highlight potential therapeutic targets based on the commonly observed mechanisms identified in different studies.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Microambiente Tumoral , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Animales , Macrófagos Asociados a Tumores/metabolismo , Reprogramación Celular , Comunicación Celular , Reprogramación Metabólica
2.
BMC Surg ; 24(1): 275, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39354481

RESUMEN

BACKGROUD: Intussusception is a common acute abdominal disease in children, often leading to acute ileus in infants and young children. OBJECTIVE: This study aimed to develop and validate a nomogram for predicting recurrent intussusception in children within 48 h after pneumatic reduction of primary intussusception. METHODS: Clinical data of children with acute intussusception admitted to multiple hospitals from March 2019 to March 2021 were retrospectively analyzed. The children were divided into a successful reductioncontrol group (control group) and a recurrent intussusception group (RI group) according to the results of pneumatic reduction. RESULTS: A total of 2406 cases were included in this study, including 2198 control group and 208 RI group. In the total sample, 1684 cases were trained and 722 cases were verified. A logistic regression analysis was conducted to establish a predictive model based on age, abdominal pain time, white blood cells count, and hypersensitive C-reactive protein levels as independent predictors of intussusception recurrence. The nomogram successfully predicted recurrent intussusception after pneumatic reduction. CONCLUSION: In this study, a nomogram was developed based on clinical risk factors to predict recurrent intussusception following pneumatic reduction in children. Age, abdominal pain time, white blood cell counts, and hypersensitive C-reactive protein levels were identified as predictors and incorporated into the nomogram. Internal validation demonstrated that this nomogram can offer a clear and convenient tool for identifying risk factors for recurrence of intussusception in children undergoing pneumatic reduction.


Asunto(s)
Intususcepción , Nomogramas , Recurrencia , Humanos , Intususcepción/terapia , Intususcepción/diagnóstico , Masculino , Femenino , Lactante , Estudios Retrospectivos , Preescolar , Factores de Riesgo , Niño
3.
Int J Mol Sci ; 24(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37108526

RESUMEN

The goal of the present study was to characterize acute oxidative damage in ocular structure and retinal function after exposure to spaceflight, and to evaluate the efficacy of an antioxidant in reducing spaceflight-induced changes in the retina. Ten-week-old adult C57BL/6 male mice were flown aboard the ISS on Space-X 24 over 35 days, and returned to Earth alive. The mice received a weekly injection of a superoxide dismutase mimic, MnTnBuOE-2-PyP 5+ (BuOE), before launch and during their stay onboard the ISS. Ground control mice were maintained on Earth under identical environmental conditions. Before the launch, intraocular pressure (IOP) was measured using a handheld tonometer and retinal function was evaluated using electroretinogram (ERG). ERG signals were recorded when the mouse eye was under dark-adapted conditions in response to ultraviolet monochromatic light flashes. Within 20 h after splashdown, IOP and ERG assessments were repeated before euthanasia. There were significant increases in body weight for habitat control groups post-flight compared to pre-flight measurements. However, the body weights were similar among flight groups before launch and after splashdown. The IOP measurements were similar between pre- and post-flight groups with no significant differences between BuOE-treated and saline controls. Immunofluorescence evaluation showed increases in retinal oxidative stress and apoptotic cell death after spaceflight. BuOE treatment significantly decreased the level of the oxidative stress biomarker. ERG data showed that the average amplitudes of the a- and b-wave were significantly decreased (39% and 32% by spaceflight, respectively) compared to that of habitat ground controls. These data indicate that spaceflight conditions induce oxidative stress in the retina, which may lead to photoreceptor cell damage and retinal function impairment.


Asunto(s)
Retina , Vuelo Espacial , Masculino , Ratones , Animales , Ratones Endogámicos C57BL , Retina/fisiología , Presión Intraocular , Células Fotorreceptoras
4.
Int J Mol Sci ; 24(17)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37686374

RESUMEN

The demands of deep space pose a health risk to the central nervous system that has long been a concern when sending humans to space. While little is known about how spaceflight affects transcription spatially in the brain, a greater understanding of this process has the potential to aid strategies that mitigate the effects of spaceflight on the brain. Therefore, we performed GeoMx Digital Spatial Profiling of mouse brains subjected to either spaceflight or grounded controls. Four brain regions were selected: Cortex, Frontal Cortex, Corunu Ammonis I, and Dentate Gyrus. Antioxidants have emerged as a potential means of attenuating the effects of spaceflight, so we treated a subset of the mice with a superoxide dismutase mimic, MnTnBuOE-2-PyP 5+ (BuOE). Our analysis revealed hundreds of differentially expressed genes due to spaceflight in each of the four brain regions. Both common and region-specific transcriptomic responses were observed. Metabolic pathways and pathways sensitive to oxidative stress were enriched in the four brain regions due to spaceflight. These findings enhance our understanding of brain regional variation in susceptibility to spaceflight conditions. BuOE reduced the transcriptomic effects of spaceflight at a large number of genes, suggesting that this compound may attenuate oxidative stress-induced brain damage caused by the spaceflight environment.


Asunto(s)
Vuelo Espacial , Transcriptoma , Humanos , Animales , Ratones , Antioxidantes/farmacología , Perfilación de la Expresión Génica , Encéfalo
5.
J Hepatol ; 76(4): 883-895, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34922977

RESUMEN

BACKGROUND & AIMS: Extracellular vesicles (EVs) play a pivotal role in connecting tumor cells with their local and distant microenvironments. Herein, we aimed to understand the role (on a molecular basis) patient-derived EVs play in modulating cancer stemness and tumorigenesis in the context of hepatocellular carcinoma (HCC). METHODS: EVs from patient sera were isolated, quantified and characterized. The EVs were vigorously tested, both in vitro and in vivo, through various functional assays. Proteomic analysis was performed to identify the functional components of EVs. The presence and level of polymeric immunoglobulin receptor (pIgR) in circulating EVs and tumor and non-tumorous tissues of patients with HCC were determined by ELISA, immunoblotting, immunohistochemistry and quantitative PCR. The functional role and underlying mechanism of EVs with enhanced pIgR expression were elucidated. Blockade of EV-pIgR with neutralizing antibody was performed in nude mice implanted with patient-derived tumor xenografts (PDTXs). RESULTS: Circulating EVs from patients with late-stage HCC (L-HCC) had significantly elevated pIgR expression compared to the EVs released by control individuals. The augmenting effect of L-HCC-EVs on cancer stemness and tumorigenesis was hindered by an anti-pIgR antibody. EVs enriched with pIgR consistently promoted cancer stemness and cancerous phenotypes in recipient cells. Mechanistically, EV-pIgR-induced cancer aggressiveness was abrogated by Akt and ß-catenin inhibitors, confirming that the role of EV-pIgR depends on the activation of the PDK1/Akt/GSK3ß/ß-catenin signaling axis. Furthermore, an anti-pIgR neutralizing antibody attenuated tumor growth in mice implanted with PDTXs. CONCLUSIONS: This study illustrates a previously unknown role of EV-pIgR in regulating cancer stemness and aggressiveness: EV-pIgR activates PDK1/Akt/GSK3ß/ß-catenin signaling cascades. The blockade of the intercellular communication mediated by EV-pIgR in the tumor microenvironment may provide a new therapeutic strategy for patients with cancer. LAY SUMMARY: The World Health Organization estimates that more than 1 million patients will die from liver cancer, mostly hepatocellular carcinoma (HCC), in 2030. Understanding the underlying mechanism by which HCC acquires aggressive attributes is crucial to improving the diagnosis and treatment of patients. Herein, we demonstrated that nanometer-sized extracellular vesicles released by tumors promote cancer stemness and tumorigenesis. Within these oncogenic vesicles, we identified a key component that functions as a potent modulator of cancer aggressiveness. By inhibiting this functional component of EVs using a neutralizing antibody, tumor growth was profoundly attenuated in mice. This hints at a potentially effective therapeutic alternative for patients with cancer.


Asunto(s)
Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Receptores de Inmunoglobulina Polimérica , Animales , Anticuerpos Neutralizantes , Carcinogénesis/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Vesículas Extracelulares/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Neoplasias Hepáticas/genética , Ratones , Ratones Desnudos , Proteómica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Inmunoglobulina Polimérica/metabolismo , Microambiente Tumoral , beta Catenina/genética
6.
Zhongguo Zhong Yao Za Zhi ; 47(11): 3095-3104, 2022 Jun.
Artículo en Zh | MEDLINE | ID: mdl-35718534

RESUMEN

This study aims to summarize the research hotspots of Hedysari Radix and predict the research trend with bibliometric methods, which is expected to serve as a reference for future research. CiteSpace V 5.8.R2 was employed for visualization of the number, authors, author affiliations, journals, funds, and keywords of the Chinese and English articles on Hedysari Radix in China National Knowledge Infrastructure(CNKI) and Web of Science(WOS) from 2001 to 2021. A total of 693 Chinese articles and 167 English articles were finally included. According to the knowledge map, most of the articles were from China and the authors from China had a close cooperation with the related institutions in the United States and Australia. Gansu University of Chinese Medicine(288) and Lanzhou University(151) respectively came out on top of the author affiliations in the number of Chinese and English articles. The journals were mainly about Chinese medicine, mainly including Chinese Journal of Information on Traditional Chinese Medicine and Evidence-based Complementary and Alternative Medicine. Papers(191 in Chinese and 60 in English) funded by National Natural Science Foundation of China were the most. Keyword analysis suggested that the main research directions were pharmacological action and mechanism, component analysis, content determination, and industrialization of medicinal materials of Hedysari Radix and that the research hotspots were the prevention and treatment of diabetes and its complications, tumors, myocardial injury, liver fibrosis and other diseases with active components such as polysaccharides, ultrafiltrate, formononetin, and calycosin. The targets, signaling pathways, and genes related to the anti-tumor, heart protection, prevention and treatment of diabetes and its complications, and regulation of immunity should be further studied.


Asunto(s)
Bibliometría , Medicina Tradicional China , China , Humanos , Raíces de Plantas , Estados Unidos
7.
Eur Radiol ; 31(10): 7925-7935, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33856514

RESUMEN

OBJECTIVES: To develop and validate a machine learning model for the prediction of adverse outcomes in hospitalized patients with COVID-19. METHODS: We included 424 patients with non-severe COVID-19 on admission from January 17, 2020, to February 17, 2020, in the primary cohort of this retrospective multicenter study. The extent of lung involvement was quantified on chest CT images by a deep learning-based framework. The composite endpoint was the occurrence of severe or critical COVID-19 or death during hospitalization. The optimal machine learning classifier and feature subset were selected for model construction. The performance was further tested in an external validation cohort consisting of 98 patients. RESULTS: There was no significant difference in the prevalence of adverse outcomes (8.7% vs. 8.2%, p = 0.858) between the primary and validation cohorts. The machine learning method extreme gradient boosting (XGBoost) and optimal feature subset including lactic dehydrogenase (LDH), presence of comorbidity, CT lesion ratio (lesion%), and hypersensitive cardiac troponin I (hs-cTnI) were selected for model construction. The XGBoost classifier based on the optimal feature subset performed well for the prediction of developing adverse outcomes in the primary and validation cohorts, with AUCs of 0.959 (95% confidence interval [CI]: 0.936-0.976) and 0.953 (95% CI: 0.891-0.986), respectively. Furthermore, the XGBoost classifier also showed clinical usefulness. CONCLUSIONS: We presented a machine learning model that could be effectively used as a predictor of adverse outcomes in hospitalized patients with COVID-19, opening up the possibility for patient stratification and treatment allocation. KEY POINTS: • Developing an individually prognostic model for COVID-19 has the potential to allow efficient allocation of medical resources. • We proposed a deep learning-based framework for accurate lung involvement quantification on chest CT images. • Machine learning based on clinical and CT variables can facilitate the prediction of adverse outcomes of COVID-19.


Asunto(s)
COVID-19 , Humanos , Aprendizaje Automático , Estudios Retrospectivos , SARS-CoV-2 , Tomografía Computarizada por Rayos X
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(3): 262-268, 2020 Mar 28.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-32386017

RESUMEN

OBJECTIVES: To investigate imaging features of the coronavirus disease 2019 (COVID-19), and to provide concrete evidences for diagnosis of COVID-19. METHODS: Imaging data of the first chest CT examination and clinical data (age, sex, clinical history, epidemiological history, and laboratory tests) of 163 patients with COVID-19 from 2 hospitals were collected for retrospective analysis. Imaging features of the first chest CT examination and the correspondence between CT manifestations and the nucleic acid test results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were analyzed. RESULTS: The first chest CT images of 163 COVID-19 patients showed that 92.02% of lesions were ground-glass opacity (GGO), 76.69% were consolidation, and 73.62% were GGO together with consolidation. Multiple lesions were found in 71.17% patients and multiple lobules in 86.50% patients. Lesions in 53.37% patients were found with bronchial inflation signs and those in 36.20% patients presented with "crazy paving" pattern, while only 7.36% were found with hilar node enlargement and pleural effusion. First CT findings of 18 patients were found to be inconsistent with the results of pathogen examination. CONCLUSIONS: COVID-19 patients showed specific features in the first chest CT examination. The combination of the first chest CT imaging features and SARS-CoV-2 nucleic acid test results as well as reexamination if necessary can help to make the diagnosis of SARS-CoV-2 infection accurately.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , COVID-19 , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Tomografía Computarizada por Rayos X
9.
Int Heart J ; 60(3): 512-520, 2019 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-30971629

RESUMEN

Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes mellitus. Reactive oxygen species produced excessively in diabetes mellitus cause necrosis, apoptosis, ferroptosis, inflammation, and fibrosis of the myocardium as well as impair the cardiac structure and function. It is increasingly clear that oxidative stress is a principal cause of diabetic cardiomyopathy. The transcription factor nuclear factor-erythroid 2 p45-related factor 2 (NRF2) activates the transcription of more than 200 genes in the human genome. Most of the proteins translated from these genes possess anti-oxidant, anti-inflammatory, anti-apoptotic, anti-ferroptotic, and anti-fibrotic actions. There is a growing body of evidence indicating that NRF2 and its target genes are crucial in preventing high glucose-induced oxidative damage in diabetic cardiomyopathy. Recently, many natural and synthetic activators of NRF2 are shown to possess promising therapeutic effects on diabetic cardiomyopathy in animal models of diabetic cardiomyopathy. Targeting NRF2 signaling by pharmacological entities is a potential approach to ameliorating diabetic cardiomyopathy. However, the persistent high expression of NRF2 in cancer tissues also protects the growth of cancer cells. This "dark side" of NRF2 increases the challenges of using NRF2 activators to treat diabetic cardiomyopathy. In addition, some NRF2 activators were found to have off-target effects. In this review, we summarize the current status and challenges of NRF2 as a potential therapeutic target for diabetic cardiomyopathy.


Asunto(s)
Cardiomiopatías Diabéticas/tratamiento farmacológico , Terapia Molecular Dirigida/métodos , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Ensayos Clínicos como Asunto , Cardiomiopatías Diabéticas/metabolismo , Humanos , Estrés Oxidativo , Transducción de Señal/efectos de los fármacos
10.
Cell Physiol Biochem ; 45(5): 2107-2121, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29533954

RESUMEN

BACKGROUND/AIMS: Protein kinase C(PKC)-ε activation is a mechanism of preconditioning cardioprotection but its role in repeated non-invasive limb ischemic preconditioning (rNLIP) mediated cardioprotection against myocardial ischemia/reperfusion (I/R) injury in diabetes is unknown. METHODS: Eight-week streptozotocin-induced diabetic and non-diabetic Sprague-Dawley rats were subjected to I/R without or with rNLIP. In vitro, H9C2 cells were cultured with high glucose (HG) and subjected to hypoxia/re-oxygenation (H/R) without or with PKC-ε or STAT3 gene knock-down in the absence or presence of remote time hypoxia preconditioning (HPC). RESULTS: Diabetic rats displayed larger post-ischemic myocardial infarct size and higher troponin-I release with concomitant cardiac PKC-ԑ overexpression and activation manifested as increased membrane translocation, while phosphorylated STAT3 (p-STAT3) and Akt (p-Akt) were lower compared to non-diabetic rats (all P<0.05). rNLIP reduced infarct size in both non-diabetic and diabetic rats. rNLIP reduced post-ischemic cardiac PKC-ԑ activation in diabetic while increased PKC-ԑ activation in non-diabetic rats, resulting in increased cardiac p-STAT3 and p-Akt. In H9C2 cells, HG increased PKC-ԑ expression and exacerbated post-H/R injury, accompanied with reduced p-STAT3 and p-Akt, which were all reverted by HPC. These HPC protective effects were abolished by either PKC-ԑ or STAT3 gene knock-down, except that PKC-ԑ gene knock-down reverted HG and H/R-induced reduction of p-STAT3. CONCLUSION: rNLIP attenuates diabetic heart I/R injury by mitigating HG-induced PKC-ԑ overexpression and, subsequently, activating STAT3.


Asunto(s)
Diabetes Mellitus Experimental/patología , Daño por Reperfusión Miocárdica/prevención & control , Proteína Quinasa C-epsilon/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Hipoxia de la Célula , Línea Celular , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Glucosa/farmacología , Precondicionamiento Isquémico , L-Lactato Deshidrogenasa/metabolismo , Masculino , Potencial de la Membrana Mitocondrial , Daño por Reperfusión Miocárdica/patología , Oxígeno/farmacología , Fosforilación , Proteína Quinasa C-epsilon/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/genética , Transducción de Señal , Estreptozocina/toxicidad , Troponina I/metabolismo , Proteína X Asociada a bcl-2/metabolismo
11.
Crit Care Med ; 44(3): e131-45, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26468894

RESUMEN

OBJECTIVES: Remifentanil preconditioning attenuates myocardial ischemia reperfusion injury, but the underlying mechanism is incompletely understood. The Janus activated kinase-2 (JAK2)/signal transducers and activators of transcription-3 (STAT3) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways are critical in both ischemic and pharmacologic preconditioning cardioprotection, which involve the inactivation of glycogen synthase kinase-3ß. We hypothesized that remifentanil preconditioning confers cardioprotection via the JAK2/STAT3 and/or PI3K/Akt activation-mediated glycogen synthase kinase-3ß inhibition. DESIGN: Pharmacologic intervention. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: In vivo and in vitro treatments. MEASUREMENTS AND MAIN RESULTS: Male Sprague-Dawley rats (n = 6 per group) were sham operated or subjected to myocardial ischemia reperfusion injury. The JAK2 inhibitor AG490 (3 mg/kg), the PI3K inhibitor wortmannin (15 µg/kg), or the glycogen synthase kinase-3ß inhibitor SB216763 (600 µg/kg) were given before inducing in vivo myocardial ischemia reperfusion injury achieved by occluding coronary artery for 30 minutes followed by 120 minutes of reperfusion in the absence or presence of remifentanil preconditioning (6 µg/kg/min). Also, isolated rat hearts were Langendorff perfused and subjected to 30 minutes of global ischemia and 120 minutes of reperfusion without or with remifentanil preconditioning (100 ng/mL) in the presence or absence of AG490 and/or SB216763. Isolated rat cardiomyocytes and H9C2 cells were subjected to hypoxia/reoxygenation alone or in combination with AG490 (100 µM), wortmannin (100 nM), or SB216763 (3 µM) without or with remifentanil preconditioning (2.5 µM). Remifentanil preconditioning reduced postischemic myocardial infarction and hemodynamic dysfunction induced by myocardial ischemia reperfusion injury concomitant with increased phosphorylation of STAT3 at tyr-705 (p-STAT3) and glycogen synthase kinase-3ß but not Akt. AG490 but not wortmannin cancelled remifentanil preconditioning cardioprotection, and SB216763 restored it despite the presence of AG490. In Langendorff-perfused hearts, AG490-mediated cancellation of remifentanil preconditioning cardioprotection in attenuating postischemic myocardial infarction and creatinine kinase-MB release was reverted by concomitant administration of SB216763. Remifentanil preconditioning also attenuated posthypoxic cardiomyocyte injury and increased p-STAT3 and glycogen synthase kinase-3ß in isolated primary cardiomyocytes and H9C2 cells. STAT3 gene knockdown with specific synthetic RNA cancelled remifentanil preconditioning cardioprotection, whereas glycogen synthase kinase-3ß gene knockdown, which per se did not affect STAT3 under hypoxia/reoxygenation condition, preserved remifentanil preconditioning cardioprotection regardless of STAT3 abrogation. CONCLUSIONS: Remifentanil preconditioning confers cardioprotection primarily via activation of JAK2/STAT3 signaling that can function independent of PI3K/Akt activation. Glycogen synthase kinase-3ß is a critical downstream effector of remifentanil preconditioning cardioprotection.


Asunto(s)
Glucógeno Sintasa Quinasa 3/metabolismo , Precondicionamiento Isquémico/métodos , Janus Quinasa 2/metabolismo , Infarto del Miocardio/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Piperidinas/administración & dosificación , Función Ventricular Izquierda/efectos de los fármacos , Animales , Glucógeno Sintasa Quinasa 3 beta , Masculino , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Remifentanilo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/fisiología , Función Ventricular Izquierda/fisiología
12.
Clin Sci (Lond) ; 130(10): 801-12, 2016 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-26846682

RESUMEN

Isoflurane postconditioning (IsoPostC) attenuates myocardial ischaemia/reperfusion injury (IRI). Signal transducer and activator of transcription-3 (STAT3) is critical in ischaemic postconditioning cardioprotection, which can be regulated by the Brahma-related gene (Brg1) and nuclear factor-erythroid 2-related factor 2 (Nrf2), although they are both reduced in diabetic hearts. We hypothesized that reduced Brg1/Nrf2 and STAT3 activation may jeopardize IsoPostC-mediated cardioprotection in diabetic hearts. In the present study, Langendorff-perfused, non-diabetic (control) and 8-week-old streptozotocin-induced Type 1 diabetic rat hearts were subjected to 30 min of global ischaemia and 120 min of reperfusion without or with IsoPostC, which was achieved by administering emulsified isoflurane (2.0%, v/v) in Krebs-Henseleit (KH) solution immediately at the onset of reperfusion for 10 min and switching to KH solution perfusion alone thereafter. Cultured H9C2 cells were exposed to normal glucose (NG, 5.5 mM) or high glucose (HG, 30 mM) and subjected to hypoxia/reoxygenation (HR) in the presence or absence of IsoPostC. Diabetic rats displayed larger post-ischaemic myocardial infarction and more severe haemodynamic dysfunction, associated with increased myocardial oxidative stress and reduced cardiac Brg1, Nrf2 and STAT3 phosphorylation/activation (p-STAT3), compared with controls. These changes were reversed/prevented by IsoPostC in control but not in diabetic rats. In H9C2 cells exposed to NG but not HG, IsoPostC significantly attenuated HR-induced cellular injury and superoxide anion production with increased Brg1, Nrf2 and p-STAT3. These beneficial effects of IsoPostC were abolished by Brg1, Nrf2 or STAT3 gene knockdown. Brg1 or Nrf2 gene knockdown abolished IsoPostC-induced STAT3 activation. N-acetylcysteine restored Brg1, Nrf2 and p-STAT3, and IsoPostC-induced protection in H9C2 cells exposed to HG and HR. In conclusion, IsoPostC confers cardioprotection through Brg1/Nrf2/STAT3 signalling, and impairment of this pathway may be responsible for the loss of IsoPostC cardioprotection in diabetes.


Asunto(s)
ADN Helicasas/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Isoflurano/farmacología , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismo , Animales , Diabetes Mellitus Experimental/complicaciones , Modelos Animales de Enfermedad , Poscondicionamiento Isquémico/métodos , Isoflurano/administración & dosificación , Masculino , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Ratas Sprague-Dawley , Estreptozocina
13.
Crit Care Med ; 42(8): e583-94, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24810525

RESUMEN

OBJECTIVES: Heme oxygenase-1 is inducible in cardiomyocytes in response to stimuli such as oxidative stress and plays critical roles in combating cardiac hypertrophy and injury. Signal transducer and activator of transcription 3 plays a pivotal role in heme oxygenase-1-mediated protection against liver and lung injuries under oxidative stress. We hypothesized that propofol, an anesthetic with antioxidant capacity, may attenuate hyperglycemia-induced oxidative stress in cardiomyocytes via enhancing heme oxygenase-1 activation and ameliorate hyperglycemia-induced cardiac hypertrophy and apoptosis via heme oxygenase-1/signal transducer and activator of transcription 3 signaling and improve cardiac function in diabetes. DESIGN: Treatment study. SETTING: Research laboratory. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: In vivo and in vitro treatments. MEASUREMENTS AND MAIN RESULTS: At 8 weeks of streptozotocin-induced type 1 diabetes in rats, myocardial 15-F2t-isoprostane was significantly increased, accompanied by cardiomyocyte hypertrophy and apoptosis and impaired left ventricular function that was coincident with reduced heme oxygenase-1 activity and signal transducer and activator of transcription 3 activation despite an increase in heme oxygenase-1 protein expression as compared to control. Propofol infusion (900 µg/kg/min) for 45 minutes significantly improved cardiac function with concomitantly enhanced heme oxygenase-1 activity and signal transducer and activator of transcription activation. Similar to the changes seen in diabetic rat hearts, high glucose (25 mmol/L) exposure for 48 hours led to cardiomyocyte hypertrophy and apoptosis, both in primary cultured neonatal rat cardiomyocytes and in H9c2 cells compared to normal glucose (5.5 mmol/L). Hypertrophy was accompanied by increased reactive oxygen species and malondialdehyde production and caspase-3 activity. Propofol, similar to the heme oxygenase-1 inducer cobalt protoporphyrin, significantly increased cardiomyocyte heme oxygenase-1 and p-signal transducer and activator of transcription protein expression and heme oxygenase-1 activity and attenuated high-glucose-mediated cardiomyocyte hypertrophy and apoptosis and reduced reactive oxygen species and malondialdehyde production (p < 0.05). These protective effects of propofol were abolished by heme oxygenase-1 inhibition with zinc protoporphyrin and by heme oxygenase-1 or signal transducer and activator of transcription 3 gene knockdown. CONCLUSIONS: Heme oxygenase-1/signal transducer and activator of transcription 3 signaling plays a critical role in propofol-mediated amelioration of hyperglycemia-induced cardiomyocyte hypertrophy and apoptosis, whereby propofol improves cardiac function in diabetic rats.


Asunto(s)
Factor de Transcripción Activador 3/efectos de los fármacos , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Hemo-Oxigenasa 1/metabolismo , Propofol/farmacología , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Cardiomegalia/etiología , Diabetes Mellitus Tipo 1/inducido químicamente , Activación Enzimática , Hemo-Oxigenasa 1/efectos de los fármacos , Hiperglucemia/complicaciones , Masculino , Miocitos Cardíacos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
14.
Ther Clin Risk Manag ; 20: 313-323, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808299

RESUMEN

Purpose: The objective of this study was to develop and validate a nomogram for predicting the need for surgical intervention in pediatric intussusception after pneumatic reduction. Patients and Methods: This retrospective study analyzed the clinical data of children with acute intussusception admitted to four hospitals in China from January 2019 to January 2022. Based on the results of pneumatic reduction, the patients were divided into two groups: the successful reduction group (control group) and the failed reduction group (operation group). The total sample was randomly divided into a training set and a validation set in a 7:3 ratio. Logistic regression analysis was performed to establish a predictive model for surgical risk. Results: A total of 1041 samples were included in this study, with 852 in the control group and 189 in the operation group. Among the total sample, 728 cases were used for training and 313 cases were used for validation. Logistic regression analysis of the training set identified age, time of abdominal pain, presence or absence of hematostoecia, C-reactive protein value from blood test on admission, and nested position indicated by B-ultrasound as independent predictors of intussusception intervention. Based on the five independent risk factors identified through multivariate logistic regression, a nomogram was successfully constructed to predict the failure of resetting by air enema under X-ray. Conclusion: A nomogram was developed to predict the need for surgical intervention after intussusception pneumatic reduction in children. The nomogram was based on clinical risk factors including age, time of abdominal pain, presence or absence of blood in stool, value of C-reactive protein in blood test on admission, and nested position indicated by B-ultrasound. Our internal validation demonstrated that this nomogram can serve as a useful tool for identifying risk factors associated with failure of air enema in children with intussusception.

15.
Cells ; 12(17)2023 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-37681880

RESUMEN

In the emerging era of cancer immunotherapy, immune checkpoint blockades (ICBs) and adoptive cell transfer therapies (ACTs) have gained significant attention. However, their therapeutic efficacies are limited due to the presence of cold type tumors, immunosuppressive tumor microenvironment, and immune-related side effects. On the other hand, dendritic cell (DC)-based vaccines have been suggested as a new cancer immunotherapy regimen that can address the limitations encountered by ICBs and ACTs. Despite the success of the first generation of DC-based vaccines, represented by the first FDA-approved DC-based therapeutic cancer vaccine Provenge, several challenges remain unsolved. Therefore, new DC vaccine strategies have been actively investigated. This review addresses the limitations of the currently most adopted classical DC vaccine and evaluates new generations of DC vaccines in detail, including biomaterial-based, immunogenic cell death-inducing, mRNA-pulsed, DC small extracellular vesicle (sEV)-based, and tumor sEV-based DC vaccines. These innovative DC vaccines are envisioned to provide a significant breakthrough in cancer immunotherapy landscape and are expected to be supported by further preclinical and clinical studies.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Vesículas Extracelulares , Humanos , Materiales Biocompatibles , Células Dendríticas , Muerte Celular Inmunogénica
16.
Ther Clin Risk Manag ; 19: 801-810, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37850071

RESUMEN

Purpose: To compare and analyze the therapeutic effects of endoscopy-assisted laparoscopic surgery (EALS) and laparoscopic surgery (LS) in the treatment of gastric duplication cysts (GDCs). Patients and Methods: We reviewed the clinical data of children with GDCs who underwent surgical treatment at Hubei Maternal and Child Health Hospital, Yijishan Hospital of Wannan Medical College, and Qingdao Women and Children's Medical Center from September 2014 to November 2022. Results: The study comprised 29 children with GDCs, including 14 in the EALS group and 15 in the LS group. There was no significant difference between the two groups in terms of age, sex, weight, and cyst size characteristics. There was a significant difference between the two groups in terms of average surgical time (P>0.05), which was 1.100 ± 0.833 hours in the EALS group and 1.933 ± 0.159 hours in the LS group. There was a significant difference between the two groups (P<0.05) in average intraoperative blood loss, which was 7.93 ± 3.81 milliliters in the EALS group and 11.80 ± 2.72 milliliters in the LS group. There was a significant difference between the two groups (P<0.05) in average postoperative fasting time, which was 73.79 ± 8.36 hours in the EALS group and 114.1 ± 9.24 hours in the LS group. There was a significant difference between the two groups (P<0.05) in average postoperative hospital stay, which was 10.21 ± 4.25 days in the EALS group and 14.47 ± 4.36 days in the LS group. Conclusion: EALS technology can not only shorten surgical time, accurately locate GDCs, reduce injuries, and decrease the probability of complications but also achieve treatment goals safely and reliably.

17.
Front Pediatr ; 11: 1224113, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37492606

RESUMEN

Objective: The aim of this study was to evaluate the clinical efficacy of single-incision laparoscopy appendectomy (SILA) and traditional three-hole laparoscopy appendectomy (THLA) for the treatment of acute appendicitis in children. Methods: The clinical data of children (<14 years old) who underwent laparoscopic appendectomy at Yijishan Hospital of Wannan Medical College, Hubei Provincial Maternal Health Hospital and Qingdao Women and Children's Medical Center from January 2019 to June 2022 were retrospectively analyzed. According to the operation method, the patients were assigned to the SILA group or the THLA group. The clinical data, including the efficacy, and the surgical details, including the complications, of the two surgical methods were compared. The personal information of the children and the time of disease onset were recorded. Results: In this study, the data of 588 patients, including 385 patients in the THLA group and 203 patients in the SILA group were collected. The baseline characteristics between the two groups of patients before surgery were comparable. There was no significant difference in the average operation time between the THLA group and the SILA group (56.31 ± 1.83 min vs. 57.48 ± 1.15 min, P > 0.05). There was also no significant difference in the average length of hospital stay between the THLA group and the SILA group (6.91 ± 0.24 days vs. 7.16 ± 0.36 days, P > 0.05). However, the FLACC scores of the SILA group (3.71 ± 0.78) were significantly lower than those of the THLA group (3.99 ± 0.56) on the second postoperative day, and the difference was significant (P < 0.05). The score of the questionnaire evaluating cosmetic appearance of the postoperative abdomen was significantly higher in the SILA group (15.81 ± 0.36) than in the THLA group (13.10 ± 0.24) (P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P > 0.05). Conclusion: SILA is more advantageous in terms of postoperative FLACC scores and cosmetic appearance in children than THLA. There was no significant difference in the incidence of complications or other aspects between the two surgical methods.

18.
Chem Commun (Camb) ; 59(19): 2747-2750, 2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36757177

RESUMEN

Dihydroartemisinin non-covalently binds liver fatty acid binding protein (FABP1) with micromolar affinity, acts as a FABP1-dependent peroxisome proliferator-activated receptor alpha agonist and inhibits metastatic hepatocellular carcinoma growth.


Asunto(s)
Artemisininas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas de Unión a Ácidos Grasos/metabolismo , Hígado/metabolismo
19.
Adv Sci (Weinh) ; 10(26): e2302677, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37387563

RESUMEN

Hepatocellular carcinoma (HCC) is a hypervascular malignancy by which its growth and dissemination are largely driven by the modulation of tumor-derived small extracellular vesicles (sEVs). Proteomic profiling of circulating sEVs of control individuals and HCC patients identifies von Willibrand factor (vWF) to be upregulated progressively along HCC stages. Elevated sEV-vWF levels are found in a larger cohort of HCC-sEV samples and metastatic HCC cell lines compared to their respective normal counterparts. Circulating sEVs of late-stage HCC patients markedly augment angiogenesis, tumor-endothelial adhesion, pulmonary vascular leakiness, and metastasis, which are significantly compromised by anti-vWF antibody. The role of vWF is further corroborated by the enhanced promoting effect of sEVs collected from vWF-overexpressing cells. sEV-vWF modulates endothelial cells through an elevated level of vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor 2 (FGF2). Mechanistically, secreted FGF2 elicits a positive feedback response in HCC via the FGFR4/ERK1 signaling pathway. The co-administration of anti-vWF antibody or FGFR inhibitor significantly improves the treatment outcome of sorafenib in a patient-derived xenograft mouse model. This study reveals mutual stimulation between HCC and endothelial cells by tumor-derived sEVs and endothelial angiogenic factors, facilitating angiogenesis and metastasis. It also provides insights into a new therapeutic strategy involving blocking tumor-endothelial intercellular communication.


Asunto(s)
Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Animales , Humanos , Ratones , Carcinoma Hepatocelular/metabolismo , Células Endoteliales/metabolismo , Vesículas Extracelulares/metabolismo , Retroalimentación , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Neoplasias Hepáticas/metabolismo , Proteómica , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de von Willebrand/metabolismo
20.
Life Sci Space Res (Amst) ; 37: 78-87, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37087182

RESUMEN

PURPOSE: Astronauts on missions beyond low Earth orbit will be exposed to galactic cosmic radiation, and there is concern about potential adverse cardiovascular effects. Most of the research to identify cardiovascular risk of space radiation has been performed in rodent models. To aid in the translation of research results to humans, the current study identified long-term effects of high-energy charged particle irradiation on cardiovascular function and structure in a larger non-rodent animal model. MATERIALS AND METHODS: At the age of 12 months, male New Zealand white rabbits were exposed to whole-body protons (250 MeV) or oxygen ions (16O, 600 MeV/n) at a dose of 0 or 0.5 Gy and were followed for 12 months after irradiation. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 10- and 12-months post-irradiation. At 12 months after irradiation, blood cell counts and blood chemistry values were assessed, and cardiac tissue and aorta were collected for histological as well as molecular and biochemical analyses. Plasma was used for metabolomic analysis and to quantify common markers of cardiac injury. RESULTS: A small but significant decrease in the percentage of circulating lymphocytes and an increase in neutrophil percentage was seen 12 months after 0.5 Gy protons, while 16O exposure resulted in an increase in monocyte percentage. Markers of cardiac injury, cardiac troponin I (cTnI) and N-Terminal pro-B-type Natriuretic Peptide were modestly increased in the proton group, and cTnI was also increased after 16O. On the other hand, metabolomics on plasma at 12 months revealed no changes. Both types of irradiation demonstrated alterations in cardiac mitochondrial morphology and an increase in left ventricular protein levels of inflammatory cell marker CD68. However, changes in cardiac function were only mild. CONCLUSION: Low dose charged particle irradiation caused mild long-term changes in inflammatory markers, cardiac function, and structure in the rabbit heart, in line with previous studies in mouse and rat models.


Asunto(s)
Radiación Cósmica , Protones , Humanos , Conejos , Masculino , Ratas , Ratones , Animales , Lactante , Oxígeno , Iones , Corazón/efectos de la radiación , Relación Dosis-Respuesta en la Radiación
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