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1.
Oncologist ; 29(1): e15-e24, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37279780

RESUMEN

BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP). PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR). RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107). CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Terapia Neoadyuvante/efectos adversos , Receptor ErbB-2/uso terapéutico , Mastectomía , Resultado del Tratamiento , Paclitaxel , Ciclofosfamida/uso terapéutico , Trastuzumab/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
2.
Sensors (Basel) ; 24(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732987

RESUMEN

Full waveform inversion (FWI) is recognized as a leading data-fitting methodology, leveraging the detailed information contained in physical waveform data to construct accurate, high-resolution velocity models essential for crosshole surveys. Despite its effectiveness, FWI is often challenged by its sensitivity to data quality and inherent nonlinearity, which can lead to instability and the inadvertent incorporation of noise and extraneous data into inversion models. To address these challenges, we introduce the scale-aware edge-preserving FWI (SAEP-FWI) technique, which integrates a cutting-edge nonlinear anisotropic hybrid diffusion (NAHD) filter within the gradient computation process. This innovative filter effectively reduces noise while simultaneously enhancing critical small-scale structures and edges, significantly improving the fidelity and convergence of the FWI inversion results. The application of SAEP-FWI across a variety of experimental and authentic crosshole datasets clearly demonstrates its effectiveness in suppressing noise and preserving key scale-aware and edge-delineating features, ultimately leading to clear inversion outcomes. Comparative analyses with other FWI methods highlight the performance of our technique, showcasing its ability to produce images of notably higher quality. This improvement offers a robust solution that enhances the accuracy of subsurface imaging.

3.
BMC Pediatr ; 22(1): 20, 2022 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-34983444

RESUMEN

BACKGROUND: Preterm infants have higher nutrition needs than term infants. The effectiveness of various feeding supplementation was assessed by the improvement of health outcomes in single specific systematic reviews (SRs). The aim of this review was to comprehensively describe the effectiveness of feeding supplementation in promoting health outcomes of preterm infants. METHODS: A literature search was conducted in the PUBMED, EMBASE, Science Direct, Cochrane library, Web of Science, and Wiley online library. SRs selection followed clear inclusion and exclusion criteria. Pairs of reviewers independently applied the criteria to both titles/abstracts and full texts. Screening and data extraction were performed by using the advanced tables. The methodological quality of SRs and the quality of the evidence were carried out according to the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool and the Grades of Recommendation, Assessment, Development, and Evaluation guidelines (GRADE) respectively. A qualitative synthesis of evidence is presented. RESULTS: Seventeen SRs were included in the review. Fifteen kinds of feeding supplementation were reported in the SRs. In preterm infants, the effectiveness of feeding supplementation in addition to regular breast-feeding was mainly shown in six aspects: physical health, neurodevelopment, biochemical outcomes, other health outcomes, morbidity and all-cause mortality. And the effectiveness of the interventions on health outcomes in preterm infants was found by most systematic reviews. The methodological quality of all the included SRs was high, and most of the evidences was of low or very low quality. CONCLUSIONS: Our results will allow a better understanding of the feeding supplementation in preterm infants. Although the feeling supplements may improve the health outcomes of in preterm infants, the existing evidence is uncertain. Therefore, the clinical use of these supplements should be considered cautiously and more well-designed RCTs are still needed to further address the unsolved problems of the included SRs.


Asunto(s)
Suplementos Dietéticos , Recien Nacido Prematuro , Humanos , Lactante , Recién Nacido , Morbilidad , Revisiones Sistemáticas como Asunto
4.
Langmuir ; 37(35): 10424-10432, 2021 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-34427433

RESUMEN

Core-shell microcapsules with combined features of hydrophilicity and hydrophobicity have become much popular. However, the assembly of biocompatible and edible materials in hydrophilic-hydrophobic core-shell microcapsules is not easy. In this work, based on electrostatic interactions, we prepared controllable calcium alginate (ALG)-zein core-shell particles of different shapes and sizes using hydrophilic ALG and hydrophobic zein by a two-step extrusion method. Negatively charged hydrogel beads of spherical, ellipsoidal, or fibrous shape were added into a positively charged zein solution (dissolved in 70% (v/v) aqueous ethanol solution) to achieve different-shaped core-shell particles. Interestingly, the size, shape, and shell thickness of the particles can be regulated by the needle diameter, stirring speed, and zein concentration. Moreover, for simplification, the core-shell particles were also synthesized by a one-step extrusion method, in which an ALG solution was added dropwise into a 70% (v/v) aqueous ethanol solution containing zein and CaCl2. The particles synthesized in this work showed controlled digestion of encapsulated medium-chain triglyceride (MCT) and sustained release of encapsulated thiamine and ethyl maltol. Our preparation method is simplistic and can be extended to fabricate a variety of hydrophilic and hydrophobic core-shell structures to encapsulate a broad spectrum of materials.


Asunto(s)
Zeína , Alginatos , Cápsulas , Interacciones Hidrofóbicas e Hidrofílicas , Electricidad Estática
5.
Proc Natl Acad Sci U S A ; 115(31): 7869-7878, 2018 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-29987050

RESUMEN

Endocrine therapy resistance invariably develops in advanced estrogen receptor-positive (ER+) breast cancer, but the underlying mechanisms are largely unknown. We have identified C-terminal SRC kinase (CSK) as a critical node in a previously unappreciated negative feedback loop that limits the efficacy of current ER-targeted therapies. Estrogen directly drives CSK expression in ER+ breast cancer. At low CSK levels, as is the case in patients with ER+ breast cancer resistant to endocrine therapy and with the poorest outcomes, the p21 protein-activated kinase 2 (PAK2) becomes activated and drives estrogen-independent growth. PAK2 overexpression is also associated with endocrine therapy resistance and worse clinical outcome, and the combination of a PAK2 inhibitor with an ER antagonist synergistically suppressed breast tumor growth. Clinical approaches to endocrine therapy-resistant breast cancer must overcome the loss of this estrogen-induced negative feedback loop that normally constrains the growth of ER+ tumors.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Estrógenos/farmacología , Proteínas de Neoplasias/biosíntesis , Receptores de Estrógenos/biosíntesis , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proteína Tirosina Quinasa CSK , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Proteínas de Neoplasias/genética , Receptores de Estrógenos/genética , Quinasas p21 Activadas/biosíntesis , Quinasas p21 Activadas/genética , Familia-src Quinasas/biosíntesis , Familia-src Quinasas/genética
6.
J Surg Res ; 251: 180-186, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32155473

RESUMEN

OBJECTIVE: To explore the distribution of biliary ductules in biliary remnants of patients with biliary atresia and to investigate the relationship between the ductules and the prognosis after Kasai portoenterostomy. PATIENTS AND METHODS: From October 01, 2015 to September 30, 2017, 46 patients who were diagnosed as type 3 biliary atresia were enrolled in this study. Continuous sections of biliary remnants were stained with cytokerantin 19 antibody. The number, area, and distribution of micro-biliary ductules of each section were recorded. According to the number of ductules in the most proximal section (n ≥ 20 or n < 20), patients were divided into two groups (A or B) and followed up for 1-3 y, including cholangitis, jaundice clearance, and survival with native liver. RESULTS: Four patients had no micro-biliary ductules. In 17 patients with ductules, the numbers at bilateral parts were similar (P > 0.05), while the ductules in the middle part were significantly less than bilateral parts (P < 0.05). Starting from 2 mm from the proximal end of remnants, the number of ductules significantly and gradually decreased (P < 0.05). The total area of ductules in Group A was significantly increased compared to that in Group B (P < 0.05). Patients in Group A had significantly higher jaundice clearance rate and better survival rate with native liver than patients in Group B (both, P < 0.05). Patients had significantly higher incidence of cholangitis in Group A compared to Group B (P < 0.05). CONCLUSIONS: The number/area of ductules yielded by technical precision is closely related to effective bile drainage, jaundice clearance, and first onset of cholangitis in patients after Kasai procedure.


Asunto(s)
Conductos Biliares/cirugía , Atresia Biliar/cirugía , Portoenterostomía Hepática , Conductos Biliares/patología , Atresia Biliar/patología , Femenino , Humanos , Lactante , Masculino
7.
Growth Factors ; 36(5-6): 246-262, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30600734

RESUMEN

Pulmonary inflammation and progressive lung destruction are the major causes of chronic obstructive pulmonary disease (COPD), resulting in emphysema and irreversible pulmonary dysfunction. Heparin-binding EGF-like growth factor (HB-EGF), is known to play a protective role in the process of various inflammatory diseases. However, its effect on COPD is poorly understood. This study was designed to determine the effect of HB-EGF on lung inflammation and injury in a murine model of pulmonary emphysema. HB-EGF promoted percent survival and body weight, attenuated lung injury, inflammatory cells, and cytokines infiltration, and prevented lung function decline. Additionally, treatment of rHB-EGF suppressed the nuclear translocation of nuclear factor κB (NF-κB)/p65, decreased TUNEL-positive cells and the expression of caspase 3, and increased the expression of PCNA, HB-EGF, and EGF receptor (EGFR). We conclude that HB-EGF attenuates lung inflammation and injury, probably through the activation of EGFR, followed by suppression of NF-ΚB signalling, promotion of cell proliferation, and inhibition of apoptosis.


Asunto(s)
Antiinflamatorios/uso terapéutico , Factor de Crecimiento Similar a EGF de Unión a Heparina/uso terapéutico , Enfisema Pulmonar/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Apoptosis , Receptores ErbB/metabolismo , Factor de Crecimiento Similar a EGF de Unión a Heparina/farmacología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Factor de Transcripción ReIA/metabolismo
8.
Pediatr Surg Int ; 34(4): 387-393, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29368078

RESUMEN

BACKGROUND: The aim of this study was to retrospectively investigate whether Kasai Procedure (KP) improves nutritional status and whether KP decreases liver transplantation (LT)-associated complications in children with biliary atresia (BA). METHODS: From March 1st 2014 to February 28th 2015, 103 patients underwent LT and the other 17 without prior KP died during the waiting period. In 103 patients undergoing LT, 58 patients received KP previously (Group A), and 45 only underwent primary LT (Group B). The nutritional status, liver function and LT-related short-term complications were analyzed. RESULTS: Compared to Group B, patients in Group A had significantly increased time interval when undergoing LT (p < 0.05). Persistently, the bodyweight, albumin and hemoglobin in Group A were significantly increased compared to Group B (all, p < 0.0001). The bilirubin, ALT/AST and PELD score in Group A were all decreased compared to Group B (p < 0.05) prior to LT. The incidences of post-LT severe infection and hypoalbuminemia in Group A were significantly lower than those of Group B (p < 0.05). CONCLUSIONS: KP improves the nutritional status, preserves liver function for patients who finally undergo LT, and decreases the incidence post-LT severe infection and hypoalbuminemia. Mental health can be improved in parents whose children underwent previous KP.


Asunto(s)
Atresia Biliar/cirugía , Trasplante de Hígado/métodos , Estado Nutricional , Portoenterostomía Hepática/métodos , Complicaciones Posoperatorias/prevención & control , Preescolar , China/epidemiología , Femenino , Humanos , Incidencia , Lactante , Masculino , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
9.
Pediatr Surg Int ; 34(4): 399-404, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29468407

RESUMEN

OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG) as add-on treatment for intractable cholangitis (IC) after Kasai portoenterostomy (KPE) in biliary atresia (BA) patients. METHODS: 113 BA patients who had one or more episodes of cholangitis after KPE were recruited in this study. According to whether response to routine conservative treatment, all patients were divided into IC group and simple cholangitis (SC) group. Meanwhile, patients with IC subdivided into IVIG group and control group according to whether application of IVIG. RESULTS: The IC group had higher serum procalcitonin (PCT) (P = 0.014), C-reactive protein (CRP) (P = 0.023), and γ-Gltamyltranspeptidase (γ-GGT) (P = 0.031) level than the SC group. The IVIG group had shorter duration of fever after treatment (P = 0.011) and length of hospital stay (P = 0.018) than the control group. The time until recurrent episode of cholangitis was significant longer in IVIG group than in control group (P = 0.019). CONCLUSIONS: IVIG as add-on treatment may be an effective treatment for the cholangitis acute episode, and we conclude by calling for more prospective studies to attest to the role of IVIG in the treatment of cholangitis.


Asunto(s)
Atresia Biliar/cirugía , Colangitis/tratamiento farmacológico , Inmunoglobulinas Intravenosas/administración & dosificación , Portoenterostomía Hepática/efectos adversos , Complicaciones Posoperatorias/tratamiento farmacológico , Colangitis/etiología , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Lactante , Recién Nacido , Masculino , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
10.
Pediatr Res ; 82(3): 490-500, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28422949

RESUMEN

BackgroundNeonatal necrotizing enterocolitis (NEC) is associated with alterations of the enteric nervous system (ENS), with loss of neuronal nitric oxide synthase (nNOS)-expressing neurons in the intestine. The aim of this study was to investigate the roles of heparin-binding EGF-like growth factor (HB-EGF) in neural stem cell (NSC) differentiation, nNOS expression, and effects on ENS integrity during experimental NEC.MethodsThe effects of HB-EGF on NSC differentiation and nNOS production were determined using cultured enteric NSCs. Myenteric neuronal subpopulations were examined in HB-EGF knockout mice. Rat pups were exposed to experimental NEC, and the effects of HB-EGF treatment on nNOS production and intestinal neuronal apoptosis were determined.ResultsHB-EGF promotes NSC differentiation, with increased nNOS production in differentiated neurons and glial cells. Moreover, loss of nNOS-expressing neurons in the myenteric plexus and impaired neurite outgrowth were associated with absence of the HB-EGF gene. In addition, administration of HB-EGF preserves nNOS expression in the myenteric plexus and reduces enteric neuronal apoptosis during experimental NEC.ConclusionHB-EGF promotes the differentiation of enteric NSCs into neurons in a nitric oxide (NO)-dependent manner, and protects the ENS from NEC-induced injury, providing new insights into potential therapeutic strategies for the treatment of NEC in the future.


Asunto(s)
Sistema Nervioso Entérico/metabolismo , Enterocolitis Necrotizante/metabolismo , Factor de Crecimiento Similar a EGF de Unión a Heparina/fisiología , Óxido Nítrico Sintasa de Tipo I/metabolismo , Animales , Diferenciación Celular , Femenino , Factor de Crecimiento Similar a EGF de Unión a Heparina/genética , Mucosa Intestinal/metabolismo , Ratones , Neuronas/metabolismo , Óxido Nítrico/biosíntesis , Embarazo , Ratas , Ratas Sprague-Dawley
11.
Pediatr Surg Int ; 33(8): 901-906, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28647807

RESUMEN

OBJECTIVE: To explore the preoperative nutrition status in patients with biliary atresia (BA) and its effect on the cholangitis of Kasai portoenterostomy (KPE). METHODS: 106 patients who had been diagnosed with BA type III and were undergoing KPE were divided into two groups according to the score obtained using STRONGkids. Preoperative and postoperative data were collected to compare general characteristics and postoperative outcomes between the different groups. RESULTS: Forty-nine (46.2%) patients were at moderate nutritional risk (MNR) and fifty-seven (53.8%) patients were at high nutritional risk (HNR) preoperatively. The MNR group had shorter postoperative hospitalization times than the HNR group (P = 0.023). The initial postoperative cholangitis occurred later (P = 0.002) and the incidence of early cholangitis was lower (P = 0.029) in patients at MNR than in those at HNR. The ratio of jaundice clearance (P = 0.02) and 2-year native liver survival (P = 0.0109) were significantly higher in MNR group than in HNR group. CONCLUSIONS: Patients with BA presented the greatest nutritional deficiencies and patients at HNR are more vulnerable to the early cholangitis and the rate of jaundice clearance is lower than those at MNR. The occurrence of initial postoperative cholangitis in MNR group was later than in HNR group.


Asunto(s)
Atresia Biliar/cirugía , Colangitis/epidemiología , Desnutrición/epidemiología , Estado Nutricional/fisiología , Complicaciones Posoperatorias/epidemiología , Periodo Preoperatorio , Atresia Biliar/epidemiología , China/epidemiología , Colangitis/fisiopatología , Comorbilidad , Femenino , Humanos , Lactante , Masculino , Portoenterostomía Hepática , Complicaciones Posoperatorias/fisiopatología , Estudios Retrospectivos , Factores de Riesgo
12.
PLoS Pathog ; 10(3): e1004011, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24651485

RESUMEN

Recent studies show that NK cells play important roles in murine biliary atresia (BA), and a temporary immunological gap exists in this disease. In this study, we found high-mobility group box-1 (HMGB1) and TLRs were overexpressed in human and rotavirus-induced murine BA. The overexpressed HMGB1 released from the nuclei of rotavirus-infected cholangiocytes, as well as macrophages, activated hepatic NK cells via HMGB1-TLRs-MAPK signaling pathways. Immature NK cells had low cytotoxicity on rotavirus-injured cholangiocytes due to low expression of TLRs, which caused persistent rotavirus infection in bile ducts. HMGB1 up-regulated the levels of TLRs of NK cells and promoted NK cell activation in an age-dependent fashion. As NK cells gained increasing activation as mice aged, they gained increasing cytotoxicity on rotavirus-infected cholangiocytes, which finally caused BA. Adult NK cells eliminated rotavirus-infected cholangiocytes shortly after infection, which prevented persistent rotavirus infection in bile ducts. Moreover, adoptive transfer of mature NK cells prior to rotavirus infection decreased the incidence of BA in newborn mice. Thus, the dysfunction of newborn NK cells may, in part, participate in the immunological gap in the development of rotavirus induced murine BA.


Asunto(s)
Atresia Biliar/inmunología , Proteína HMGB1/inmunología , Células Asesinas Naturales/inmunología , Activación de Linfocitos/inmunología , Infecciones por Rotavirus/inmunología , Animales , Atresia Biliar/metabolismo , Atresia Biliar/virología , Western Blotting , Diferenciación Celular/inmunología , Separación Celular , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Proteína HMGB1/metabolismo , Humanos , Inmunohistoquímica , Células Asesinas Naturales/citología , Ratones , Ratones Noqueados , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rotavirus/inmunología , Infecciones por Rotavirus/complicaciones , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunología
13.
Am J Physiol Gastrointest Liver Physiol ; 307(2): G233-40, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-24875101

RESUMEN

Interferon (IFN)-γ-driven and CD8+ T cell-dependent inflammatory injury to extrahepatic biliary epithelium (EHBE) is likely to be involved in the development of biliary atresia (BA). We previously showed that viral protein NSP4 is the pathogenic immunogen that causes biliary injury in BA. In this study, NSP4 or four synthetic NSP4 (NSP4(157-170), NSP4(144-152), NSP4(93-110), NSP4(24-32)) identified by computer analysis as candidate CD8+ T cell epitopes were injected into neonatal mice. The pathogenic NSP4 epitopes were confirmed by studying extrahepatic bile duct injury, IFN-γ release and CD8+ T cell response against EHBE. The results revealed, at 7 days postinjection, inoculation of glutathione S-transferase (GST)-NSP4 caused EHBE injury and BA in neonatal mice. At 7 or 14 days postinject, inoculation of GST-NSP4, NSP4(144-152), or NSP4(157-170) increased IFN-γ release by CD8+ T cells, elevated the population of hepatic memory CD8+ T cells, and augmented cytotoxicity of CD8+ T cells to rhesus rotavirus (RRV)-infected or naive EHBE cells. Furthermore, depletion of CD8+ T cells in mice abrogated the elevation of GST-NSP4-induced serum IFN-γ. Lastly, parenteral immunization of mouse dams with GST-NSP4, NSP4(144-152), or NSP4(157-170) decreased the incidence of RRV-induced BA in their offspring. Overall, this study reports the CD8+ T cell response against EHBE is activated by epitopes within rotavirus NSP4 in experimental BA. Neonatal passive immunization by maternal vaccination against NSP4(144-152) or NSP4(157-170) is effective in protecting neonates from developing RRV-related BA.


Asunto(s)
Conductos Biliares Extrahepáticos/inmunología , Atresia Biliar/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T , Glicoproteínas/inmunología , Fragmentos de Péptidos/inmunología , Infecciones por Rotavirus/inmunología , Vacunas contra Rotavirus/inmunología , Toxinas Biológicas/inmunología , Proteínas no Estructurales Virales/inmunología , Animales , Conductos Biliares Extrahepáticos/patología , Conductos Biliares Extrahepáticos/virología , Atresia Biliar/patología , Atresia Biliar/prevención & control , Atresia Biliar/virología , Linfocitos T CD8-positivos/virología , Modelos Animales de Enfermedad , Femenino , Glicoproteínas/administración & dosificación , Inmunización Pasiva , Memoria Inmunológica , Inyecciones Intraperitoneales , Interferón gamma/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Fragmentos de Péptidos/administración & dosificación , Embarazo , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/inmunología , Infecciones por Rotavirus/patología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/virología , Vacunas contra Rotavirus/administración & dosificación , Linfocitos T Citotóxicos/inmunología , Toxinas Biológicas/administración & dosificación , Proteínas no Estructurales Virales/administración & dosificación
14.
Toxicol Appl Pharmacol ; 277(3): 270-8, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24726520

RESUMEN

Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxicity, endocrine disruption and reproductive abnormalities. In order to verify the hypothesis that the PI3K/Akt and MAPK pathways play important roles in hepatotoxicity induced by PCBs, Sprague-Dawley (SD) rats were dosed with PCB153 intraperitoneally at 0, 4, 16 and 32mg/kg for five consecutive days; BRL cells (rat liver cell line) were treated with PCB153 (0, 1, 5, and 10µM) for 24h. Results indicated that the PI3K/Akt and ERK pathways were activated in vivo and in vitro after exposure to PCB153, and protein levels of phospho-Akt and phospho-ERK were significantly increased. Nuclear factor-κB (NF-κB) activation and caspase-3, -8 and -9 inhibition caused by PCB153 were also observed. Inhibiting the ERK pathway significantly attenuated PCB153-induced NF-κB activation, whereas inhibiting the PI3K/Akt pathway hardly influenced phospho-NF-κB level. However, inhibiting the PI3K/Akt pathway significantly elevated caspase-3, -8 and -9 activities, while the ERK pathway only synergistically regulated caspase-9. Proliferating cell nuclear antigen (PCNA), a reliable indicator of cell proliferation, was also induced. Moreover, PCB153 led to hepatocellular hypertrophy and elevated liver weight. Taken together, PCB153 leads to aberrant proliferation and apoptosis of hepatocytes through NF-κB activation and caspase inhibition, and coactivated PI3K/Akt and ERK pathways play critical roles in PCB153-induced hepatotoxicity.


Asunto(s)
Caspasas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Bifenilos Policlorados/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Inhibidores de Caspasas , Caspasas/genética , Quinasas MAP Reguladas por Señal Extracelular/genética , Regulación de la Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Malondialdehído/metabolismo , FN-kappa B/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo
15.
Tumour Biol ; 35(4): 3229-35, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24293393

RESUMEN

Neuroblastoma (NB), an embryonal tumor derived from the neural crest, originates from sympathetic nerve system, manifests as thoracic, paraspinous or abdominal tumors, and metastases to bone in high-risk cases. Although NB stands as the most common solid tumor in early childhood and accounts for about 15% of total pediatric cancer death, there has been limited success in searching for novel therapeutic regimen for this lethal disease during the past two decades. Numerous epidemiological and clinical studies have pinpointed anaplastic lymphoma kinase (ALK) and MYCN as potent governors for NB malignant behavior. ALK and MYCN amplification and constitutive active mutations are common in high-risk NB patients. However, there is still lack of evidence showing that a small molecule compound could simultaneously inhibits ALK and MYCN and plays strong negative regulatory roles in NB. Here, we showed that 17-DMAG, a well-known HSP-90 inhibitor, significantly inhibits NB cell growth, arrests cell cycle, and strongly induces NB cell apoptosis. Interestingly, our data suggests that NB cells with both ALK and MYCN amplification/mutation are more sensitive to 17-DMAG treatment, while NB cells with only ALK or MYCN amplification are less sensitive and NB cells without ALK or MYCN amplification/mutation are least sensitive. Moreover, we also found that knocking down ALK and MYCN additively inhibits NB cell growth and that transduction of MYCN largely abolished the ALK-dependent NB cell growth, indicating that there is a cross-talk between MYCN and ALK signaling machinery. Our results provide proof-of-principle that 17-DMAG strongly inhibits NB cell growth by targeting both ALK and MYCN. Our findings might shed a light for further investigation of novel small molecule compound which is safe and exerts similar strong effects in vivo as novel approaches for management of high-risk NB.


Asunto(s)
Benzoquinonas/farmacología , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Lactamas Macrocíclicas/farmacología , Neuroblastoma/tratamiento farmacológico , Proteínas Nucleares/análisis , Proteínas Oncogénicas/análisis , Proteínas Tirosina Quinasas Receptoras/análisis , Quinasa de Linfoma Anaplásico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Proteína Proto-Oncogénica N-Myc , Neuroblastoma/química , Neuroblastoma/patología , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Oncogénicas/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores
16.
Pathophysiology ; 21(1): 95-104, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24345808

RESUMEN

Throughout the past 20 years, we have been investigating the potential therapeutic roles of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor family, in various models of intestinal injury including necrotizing enterocolitis (NEC), intestinal ischemia/reperfusion (I/R) injury, and hemorrhagic shock and resuscitation (HS/R). Our studies have demonstrated that HB-EGF acts as an effective mitogen, a restitution-inducing reagent, a cellular trophic factor, an anti-apoptotic protein and a vasodilator, via its effects on various cell types in the intestine. In the current paper, we have reviewed the application and therapeutic effects of HB-EGF in three classic animal models of intestinal injury, with particular emphasis on its protection of the intestines from NEC. Additionally, we have summarized the protective functions of HB-EGF on various target cells in the intestine. Lastly, we have provided a brief discussion focusing on the future development of HB-EGF clinical applications for the treatment of various forms of intestinal injury including NEC.

17.
Nanomaterials (Basel) ; 14(2)2024 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-38251103

RESUMEN

In the field of CO2 capture utilization and storage (CCUS), recent advancements in active-source monitoring have significantly enhanced the capabilities of time-lapse acoustical imaging, facilitating continuous capture of detailed physical parameter images from acoustic signals. Central to these advancements is time-lapse full waveform inversion (TLFWI), which is increasingly recognized for its ability to extract high-resolution images from active-source datasets. However, conventional TLFWI methodologies, which are reliant on gradient optimization, face a significant challenge due to the need for complex, explicit formulation of the physical model gradient relative to the misfit function between observed and predicted data over time. Addressing this limitation, our study introduces automatic differentiation (AD) into the TLFWI process, utilizing deep learning frameworks such as PyTorch to automate gradient calculation using the chain rule. This novel approach, AD-TLFWI, not only streamlines the inversion of time-lapse images for CO2 monitoring but also tackles the issue of local minima commonly encountered in deep learning optimizers. The effectiveness of AD-TLFWI was validated using a realistic model from the Frio-II CO2 injection site, where it successfully produced high-resolution images that demonstrate significant changes in velocity due to CO2 injection. This advancement in TLFWI methodology, underpinned by the integration of AD, represents a pivotal development in active-source monitoring systems, enhancing information extraction capabilities and providing potential solutions to complex multiphysics monitoring challenges.

18.
Environ Pollut ; 344: 123391, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38242307

RESUMEN

In recent years, the global prevalence of childhood overweight and obesity has surged. Bisphenol A (BPA), prevalent in the manufacture of polycarbonate plastics and epoxy resins, is associated with this escalating obesity pattern. Both early life stages and pregnancy emerge as pivotal windows of vulnerability. This review systematically evaluates human studies to clarify the nexus between prenatal BPA exposure and offspring obesity. Our extensive literature search covered databases like PubMed, Web of Science, Cochrane Library, Embase, and Scopus, encompassing articles from their inception until July 2023. We utilized the Newcastle-Ottawa Scale (NOS) to evaluate the methodological rigor of the included studies, the Oxford Center for Evidence-Based Medicine Levels of Evidence Working Group (OCEBM) table to determine the level of the evidence, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) guidelines to evaluate the certainty of the evidence with statistical significance. We centered on primary studies investigating the link between urinary BPA levels during pregnancy and offspring obesity. Our analysis included thirteen studies, with participant counts ranging from 173 to 1124 mother-child dyads. Among them, eight studies conclusively linked prenatal BPA exposure to increased obesity in offspring. Evaluation metrics for the effect of prenatal BPA on offspring obesity comprised BMI z-score, waist circumference, overweight/obesity classification, aggregate skinfold thickness, body fat percentage, and more. Present findings indicate that prenatal BPA exposure amplifies offspring obesity risk, with potential effect variations by age and gender. Therefore, further research is needed to explore the causal link between prenatal BPA exposure and obesity at different developmental stages and genders, and to elucidate the underlying mechanisms.


Asunto(s)
Fenoles , Efectos Tardíos de la Exposición Prenatal , Masculino , Embarazo , Humanos , Femenino , Efectos Tardíos de la Exposición Prenatal/epidemiología , Obesidad/epidemiología , Compuestos de Bencidrilo/toxicidad , Sobrepeso
19.
Int J Biol Macromol ; 272(Pt 1): 132796, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38823740

RESUMEN

Core-shell structures exhibit a number of distinct absorptive properties that make them attractive tools for use in a range of industrial contexts including pharmaceuticals, biotechnology, cosmetics, and food/agriculture. Several recent studies have focused on the development and fabrication of zein-based core-shell structures for a range of functional material deliveries. However, no recent review article has evaluated the fabrication of such core-shell structures for food-based applications. In this paper, we therefore survey current approaches to fabricating different zein-based platforms including particles, fibers, films, and hydrogels that have appeared in a variety of functionally relevant applications. In addition, we highlight certain challenges and future research directions in this field, thereby providing a novel perspective on zein-based core-shell structures.


Asunto(s)
Hidrogeles , Zeína , Zeína/química , Hidrogeles/química
20.
Heliyon ; 10(11): e32370, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38961968

RESUMEN

Exploring the spatial distribution characteristics of tourist attractions and the influencing factors is of significant importance for destination development, yet little relevant research has been conducted. This study explores the spatial patterns and determinants of tourist attractions using Hubei Province of China as a case based on the POI (Points of Interest) data, combined with standard deviation ellipse, GeoDetector method and so on. The results show that: (1) The distribution of tourist attractions in Hubei Province is concentrated in Wuhan and Huanggang. (2) The overall spatial patterns of tourist attractions in Hubei Province show a trend of "overall dispersion, partial concentration", with the direction of northwest-southeast. (3) The permanent population, passenger traffic volume, per capita GDP, and the added value of the tertiary industry are the primary factors influencing the spatial distribution of tourist attractions in Hubei Province. Additionally, topography and river systems factors also impact their distribution. This study provides critical information for theory and practice in terms of tourism resources optimization.

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