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1.
Am J Gastroenterol ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382852

RESUMEN

INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

2.
Cytokine ; 179: 156598, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38583255

RESUMEN

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.


Asunto(s)
Aloinjertos , Rechazo de Injerto , Trasplante de Corazón , Interleucina-1 , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas Recombinantes , Animales , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Ratones , Proteínas Recombinantes/farmacología , Interleucina-1/metabolismo , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Células TH1/inmunología , Células TH1/efectos de los fármacos , Células Th17/inmunología , Células Th17/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Masculino , Serina-Treonina Quinasas TOR/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
3.
Clin Gastroenterol Hepatol ; 20(12): 2826-2837.e9, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-34902570

RESUMEN

BACKGROUND & AIMS: Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking. METHODS: Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions. RESULTS: One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 log10 IU/mL, respectively. TAF was well-tolerated, and the most common adverse event was nausea (29.1%) during a mean of 2 years of treatment. Notably, 1 (1.0%) TAF-treated pregnant woman underwent induced abortion due to noncausal fetal cleft lip and palate. No infants in either group had birth defects. In the TAF group, the hepatitis B e antigen seroconversion rate was 20.7% at postpartum month 6, infants had normal growth parameters, and no infants were positive for HBsAg at 7 months. The TDF group had comparable safety and effectiveness profiles. CONCLUSIONS: TAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.


Asunto(s)
Labio Leporino , Fisura del Paladar , Hepatitis B Crónica , Hepatitis B , Femenino , Humanos , Embarazo , Recién Nacido , Adulto , Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Mujeres Embarazadas , Estudios Prospectivos , Labio Leporino/inducido químicamente , Labio Leporino/tratamiento farmacológico , Fisura del Paladar/inducido químicamente , Fisura del Paladar/tratamiento farmacológico , Tenofovir/efectos adversos , Adenina/efectos adversos , China , Antivirales/efectos adversos , Hepatitis B/diagnóstico
4.
Acta Pharmacol Sin ; 43(4): 941-953, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34341511

RESUMEN

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that is increasingly prevalent worldwide. Liver inflammation is an important contributor to disease progression from nonalcoholic fatty liver (NAFL) to NASH, but there is a lack of efficient therapies. In the current study we evaluated the therapeutic potential of givinostat, a histone deacetylase (HDAC) inhibitor, in the treatment of NASH in vivo and in vitro. Liver inflammation was induced in mice by feeding a methionine- and choline-deficient diet (MCD) or a fructose, palmitate, cholesterol diet (FPC). The mice were treated with givoinostat (10 mg·kg-1·d-1, ip) for 8 or 10 weeks. At the end of the experiment, the livers were harvested for analysis. We showed that givoinostat administration significantly alleviated inflammation and attenuated hepatic fibrosis in MCD-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed that givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In human hepatocellular carcinoma cell line HepG2 and human derived fetal hepatocyte cell line L02, givinostat significantly decreased palmitic acid-induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in FPC-induced NASH mice. Givinostat administration significantly attenuated hepatic steatosis, inflammation as well as liver injury in this mouse model. In conclusion, givinostat is efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for the treatment of human NASH.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Carbamatos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Hígado/metabolismo , Cirrosis Hepática/patología , Metionina , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo
5.
Hepatobiliary Pancreat Dis Int ; 21(2): 106-112, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34583911

RESUMEN

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Humanos , Inmunosupresores/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos , Calidad de Vida , Sirolimus/efectos adversos , Resultado del Tratamiento
6.
Clin Infect Dis ; 73(9): e3324-e3332, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33395488

RESUMEN

BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSIONS: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Complicaciones Infecciosas del Embarazo , Alanina , Antivirales/efectos adversos , Femenino , Hepatitis B/tratamiento farmacológico , Hepatitis B/prevención & control , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/prevención & control , Estudios Prospectivos , Tenofovir/análogos & derivados , Carga Viral
7.
Clin Sci (Lond) ; 135(7): 925-941, 2021 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-33786590

RESUMEN

Liver diseases present a significant public health burden worldwide. Although the mechanisms of liver diseases are complex, it is generally accepted that inflammation is commonly involved in the pathogenesis. Ongoing inflammatory responses exacerbate liver injury, or even result in fibrosis and cirrhosis. Here we report that roscovitine, a cyclin-dependent kinase (CDK) inhibitor, exerts beneficial effects on acute and chronic liver inflammation as well as fibrosis. Animal models of lipopolysaccharide (LPS)/d-galactosamine- and acute or chronic CCl4-induced liver injury showed that roscovitine administration markedly attenuated liver injury, inflammation and histological damage in LPS/d-galactosamine- and CCl4-induced acute liver injury models, which is consistent with the results in vitro. RNA sequencing (RNA-seq) analysis showed that roscovitine treatment repressed the transcription of a broad set of pro-inflammatory genes involved in many aspects of inflammation, including cytokine production and immune cell proliferation and migration, and inhibited the TGF-ß signaling pathway and the biological process of tissue remodeling. For further validation, the beneficial effect of roscovitine against inflammation was evaluated in chronic CCl4-challenged mice. The anti-inflammation effect of roscovitine was observed in this model, accompanied with reduced liver fibrosis. The anti-fibrotic mechanism involved inhibition of profibrotic genes and blocking of hepatic stellate cell (HSC) activation. Our data show that roscovitine administration protects against liver diseases through inhibition of macrophage inflammatory actions and HSC activation at the onset of liver injury.


Asunto(s)
Inflamación/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Roscovitina/farmacología , Animales , Tetracloruro de Carbono/toxicidad , Línea Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Galactosamina/toxicidad , Humanos , Inflamación/genética , Lipopolisacáridos/toxicidad , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7 , Análisis de Secuencia de ARN
8.
BMC Infect Dis ; 21(1): 818, 2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34399709

RESUMEN

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.


Asunto(s)
COVID-19/complicaciones , Hígado/virología , Adulto , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , COVID-19/sangre , COVID-19/epidemiología , Femenino , Humanos , Hígado/patología , Pruebas de Función Hepática/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad
9.
J Infect Dis ; 222(1): 38-43, 2020 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-32348485

RESUMEN

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.


Asunto(s)
Anticuerpos Antivirales/uso terapéutico , Betacoronavirus/genética , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/terapia , Neumonía Viral/mortalidad , Neumonía Viral/terapia , Esparcimiento de Virus/inmunología , Adulto , Anciano , Donantes de Sangre , COVID-19 , China , Infecciones por Coronavirus/virología , Enfermedad Crítica , Femenino , Humanos , Inmunización Pasiva/efectos adversos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , SARS-CoV-2 , Tasa de Supervivencia , Resultado del Tratamiento , Sueroterapia para COVID-19
10.
Anal Chem ; 90(11): 6675-6682, 2018 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-29762010

RESUMEN

A series of isomorphic lanthanide metal-organic frameworks (Ln-MOFs), namely [Ln(dcbba)(DMF)2] n·H2O·0.5DMF [Ln = La (1), Eu (2) and Tb (3); H3dcbba = 4-(3, 5-dicarboxylatobenzyloxy)benzoic acid; DMF = N, N'-dimethylformamide] have been designed and synthesized by the solvothermal reactions of H3dcbba and La(NO3)3·6H2O. Single-crystal X-ray diffraction analysis reveals that the complexes 1-3 exhibit a (3,6)-connected open framework structure with binuclear [Ln2(COO)6] n secondary building units as 6-connected nodes and H3dcbba ligands as 3-connected nodes. The isostructural mixed La/Eu/Tb-dcbba (4) was obtained via the in-suit doping of different Ln3+ ions into the host framework, which is able to emit pure orange, white, and blue light when excited at 300, 305, and 350 nm, respectively. Subsequently, a novel and multifunctional sensing process was designed based on the excitation wavelength sensitive color tunable luminescent sample 4, which can detect HS- ions, THF (tetrahydrofuran), and Ag+ ions via different luminescence color change mechanisms. The remarkable color change, excellent selectivity, and high sensitivity further indicate the promise of this type of multifunctional luminescent materials for the sensing of anion, cation, and organic small molecule.

11.
Luminescence ; 33(6): 1040-1047, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29984521

RESUMEN

Reactions of N,N'-bis (salicylidene)-1,2-cyclohexanediamine (H2 L) with mixed lanthanide counterions of LnCl3 ·6H2 O and Ln (NO3 )3 ·6H2 O afford six H2 L lanthanide coordination polymers, e.g. {[Pr(H2 L)2 (NO3 )2 Cl]·2CH2 Cl2 }n (1); {[Ln(H2 L)1.5 (NO3 )3 ]2 ·5CHCl3 ·mCH3 OH}n [Ln = Sm (2), Eu (3), Gd (4), Tb (5) and Yb (6); m = 1 (2-5); m = 0 (6)]. X-ray crystallographic analysis reveals that complex 1 exhibits three-dimensional diamondoid topologic structure and complexes 2-6 are of two-dimensional structure. Luminescent spectra show that complexes 1 and 6 have characteristic near-infrared (NIR) emission of praseodymium (III) and ytterbium (III) ions and complexes 2-5 emit luminescence in the visible region. Complexes 3 and 6 reveal sensitive luminescence responses to formaldehyde.


Asunto(s)
Complejos de Coordinación/química , Etilenodiaminas/química , Colorantes Fluorescentes/química , Elementos de la Serie de los Lantanoides/química , Mediciones Luminiscentes , Polímeros/química , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular
12.
Water Sci Technol ; 74(1): 212-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27386999

RESUMEN

The treatment and disposal of sewage sludge is a growing problem for sewage treatment plants. One method of disposal is to use sewage sludge as partial replacement for raw material in cement manufacture. Although this process has been well researched, little attention has been given to the thermal properties of cement that has had sewage sludge incorporated in the manufacturing process. This study investigated the fire endurance of eco-cement to which lime-dried sludge (LDS) had been added. LDS was added in proportions of 0%, 3%, 6%, 9%, and 12% (by weight) to the raw material. The eco-cement was exposed to 200, 400, or 600 °C for 3 h. The residual strength and the microstructural properties of eco-cement were then studied. Results showed that the eco-cement samples suffered less damage than conventional cement at 600 °C. The microstructural studies showed that LDS incorporation could reduce Ca(OH)(2) content. It was concluded that LDS has the potential to improve the heat resistance of eco-cement products.


Asunto(s)
Materiales de Construcción/análisis , Aguas del Alcantarillado/química , Compuestos de Calcio/química , Materiales de Construcción/economía , Calor , Óxidos/química
13.
Tumour Biol ; 36(6): 4747-55, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25647261

RESUMEN

MicroRNAs (miRNAs) regulate gene expression by inhibiting translation of target messenger RNAs (mRNAs) through pairing with miRNA recognition elements (MREs), usually in 3'-UTRs. miRNAs are involved in the pathogenesis of several types of cancers. Specifically, microRNA-32 (miR-32) is overexpressed in colorectal carcinoma, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-32 in hepatocellular carcinoma (HCC) has not been totally elucidated. In the present study, we found the expression of miR-32 was up-regulated in HCC tissue and cell lines, inversely the expression of phosphatase and tensin homolog (PTEN) decreased. Besides, miRNA-32 down-regulates PTEN through binding to 3'-UTR of PTEN mRNA from luciferase reporter assay, and the expression level of miR-32 could affect the proliferation, migration, and invasion of liver cancer cell lines via PTEN/Akt signaling pathway. Down-expression of PTEN could significantly attenuate the inhibitory effects of knockdown miR-32 on the proliferation, migration, and invasion of liver cancer cells, suggesting that miR-32 could be a potential target for HCC treatment.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Fosfohidrolasa PTEN/genética , Regiones no Traducidas 3' , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , MicroARNs/biosíntesis , Invasividad Neoplásica/genética , Fosfohidrolasa PTEN/biosíntesis , Transducción de Señal
14.
Inorg Chem ; 54(1): 221-8, 2015 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-25495352

RESUMEN

A series of rigid hexadentate salen-type (H2L) ytterbium complexes, namely, [Yb2L3(CH3OH)]·3CH3CN (1), [Yb2LL'L″(CH3OH)(H2O)2](ClO4)2·CH3OH·H2O (2), [Yb2L(OAc)4(CH3OH)2]·2CH3OH (3), and {[Yb2L(OAc)4]·3H2O}n (4) (H2L = N,N'-bis(2-oxy-3-methoxybenzylidene)-1,2-phenylenediamine, HL' = 2-(2'-hydroxy-3'-methyloxy-phenyl)benzimidazole and HL" = 3-methoxysalicylaldehyde) have been synthesized by reactions of H2L with multifarious Yb(3+) salts. X-ray crystallographic analyses demonstrate that complex 1 is of a triple-decker sandwich-type Yb2L3 structure with a ratio of H2L/Yb = 3:2, 2 and 3 possess the unique Yb2 core with a ratio of H2L/Yb = 2:2 and 1:2, respectively, 4 exhibits one dimensional coordination polymers in which the polymeric structures are formed by acetate (OAc(-)) groups. All complexes 1-4 exhibit near-IR luminescence, which can be rationalized on the basis of the disparate structural effects. The magnetic analysis unveils that all complexes 1-4 are of field-induced single-molecule magnet behavior with the energy barriers (Ueff/kB) of 14.5, 2.0, 9.5, and 2.4 K at 3 kOe direct current fields, respectively.

15.
Front Med (Lausanne) ; 11: 1389695, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873211

RESUMEN

Acute kidney injury (AKI) is a major complication following liver transplantation (LT), which utilizes grafts from donors after cardiac death (DCD). We developed a machine-learning-based model to predict AKI, using data from 894 LT recipients (January 2015-March 2021), split into training and testing sets. Five machine learning algorithms were employed to construct the prediction models using 17 clinical variables. The performance of the models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. The best-performing model was further validated in an independent cohort of 195 LT recipients who received DCD grafts between April 2021 and December 2021. The Shapley additive explanations method was utilized to elucidate the predictions and identify the most crucial features. The gradient boosting machine (GBM) model demonstrated the highest AUC (0.76, 95% CI: 0.70-0.82), F1-score (0.73, 95% CI: 0.66-0.79) and sensitivity (0.74, 95% CI: 0.66-0.80) in the testing set and a comparable AUC (0.75, 95% CI: 0.67-0.81) in the validation set. The GBM model identified high preoperative indirect bilirubin, low intraoperative urine output, prolonged anesthesia duration, low preoperative platelet count and graft steatosis graded NASH Clinical Research Network 1 and above as the top five important features for predicting AKI following LT using DCD grafts. The GBM model is a reliable and interpretable tool for predicting AKI in recipients of LT using DCD grafts. This model can assist clinicians in identifying patients at high risk and providing timely interventions to prevent or mitigate AKI.

16.
J Sep Sci ; 36(2): 288-300, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23203907

RESUMEN

The complexity of natural triacylglycerols (TAGs) in various edible oils is prodigious due to the hundreds of set is of TAG compositions, which makes the identification of TAGs quite difficult. In this investigation, the off-line 2D system coupling of nonaqueous RP and silver-ion HPLC with atmospheric pressure chemical ionization MS detection has been applied to the identification and quantification of TAGs in peanut oil. The method was successful in the separation of a high number of TAG solutes, and the TAG structures were evaluated by analyzing their atmospheric pressure chemical ionization mass spectra information. HPLC and MS conditions have been optimized and the fragmentation mechanisms of isomers have been validated. In addition, an internal standard approach has been developed for TAG quantification. Then this system was applied in peanut oil samples and there was a total of 48 TAGs including regioisomers that have been determined and quantified.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Aceites de Plantas/química , Triglicéridos/análisis , Cromatografía Líquida de Alta Presión/instrumentación , Aceite de Cacahuete
18.
Heliyon ; 9(8): e19067, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37636395

RESUMEN

Objective: To develop a logistic regression model that combines clinical and radiological parameters for prediction of complicated appendicitis. Methods: 248 patients with histologically proven uncomplicated (n = 214) and complicated (n = 34) acute appendicitis were analyzed retrospectively. All patients had undergone a presurgical abdominal and/or pelvic computed tomography (CT) scan, assessed by two radiologists. A model using univariate and multivariate logistic regression analyses was developed, and the strength of association between independent predictors and complicated acute appendicitis was evaluated by adjusted odds radio. Clinical parameters were gender, age, anorexia, vomiting, duration of symptoms, right lower abdominal quadrant (RLQ) tenderness, rebound tenderness, body temperature, white blood cell (WBC) count, and neutrophil ratio. Radiological parameters were appendix diameter, appendicolith, caecal wall thickening, mesenteric lymphadenopathy, extraluminal air, abscess, fat stranding, and periappendicular fluid. Results: Four features (body temperature>37.2 °C, vomiting, appendicolith, and periappendiceal fluid) were included in the logistic regression model, and yielded an area under the curve (AUC) of 0.87 (95% confidence interval (CI), 0.80-0.93), sensitive of 88%, and specificity of 74%. Conclusion: The logistic regression model makes an accurate and simple prediction of complicated appendicitis possible.

19.
J Investig Med ; 71(1): 17-22, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35948388

RESUMEN

The study aimed to investigate the diagnostic role of multislice spiral CT (MSCT) combined with clinical manifestations and laboratory tests in acute appendicitis subtypes. Patients diagnosed with acute appendicitis were included for retrospective analysis and their clinical manifestations and MSCT signs were analyzed. The clinical manifestations of different subtypes of acute appendicitis, including simple appendicitis, suppurative appendicitis and gangrenous appendicitis, were compared. The clinical manifestations were anorexia in 51.1% of patients, nausea and vomiting in 62.0%, shifting right lower abdominal pain in 51.1%, elevated body temperature in 31.2%, right lower quadrant abdominal tenderness in 91.4%, rebound tenderness in 91.4%, increased white cell count in 89.1%, high neutrophil count in 88.2%, increased appendiceal diameter enlargement in 100%, surrounding exudate in 95.0%, fecal stones in 51.6%, appendiceal wall thickening in 94.6%, lymph node in 82.8% and intestinal stasis in 18.6%. There were statistically significant differences in body temperature and neutrophil percentage among the subtypes of appendicitis and they were lowest in simple appendicitis and highest in gangrenous appendicitis. There were statistically significant differences in appendix diameter and the surrounding exudate among the subtypes of appendicitis and they were lowest in simple appendicitis and highest in gangrenous appendicitis. Clinical manifestations and MSCT signs, especially body temperature, percentage of neutrophils and the surrounding exudate, might have significant diagnostic value in acute appendicitis.


Asunto(s)
Apendicitis , Apéndice , Humanos , Apendicitis/diagnóstico por imagen , Estudios Retrospectivos , Apéndice/diagnóstico por imagen , Apéndice/patología , Tomografía Computarizada Espiral , Dolor Abdominal/diagnóstico , Enfermedad Aguda
20.
Artículo en Inglés | MEDLINE | ID: mdl-22259359

RESUMEN

In the title complex, [Co(C(22)H(18)N(2)O(4))(CN)(H(2)O)]·0.5CH(3)CN, the Co(III) cation is N,N',O,O'-chelated by a 6,6'-dimeth-oxy-2,2'-[1,2-phenyl-enebis(nitrilo-methanylyl-idene)]diphenolate dianion, and is further coordinated by a cyanide anion and a water mol-ecule in the axial sites, completing a distorted octa-hedral coordination geometry. In the crystal, pairs of bifurcated O-H⋯(O,O) hydrogen bonds link adjacent mol-ecules, forming centrosymmetric dimers. The acetonitrile solvent mol-ecule shows 0.5 occupancy.

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