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1.
Phys Chem Chem Phys ; 25(4): 3182-3189, 2023 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-36622128

RESUMEN

The structure and electronic and spintronic properties of two-dimensional (2D) ternary compounds ABC (A = Sb, Bi; B = Se, Te; C = Br; I) monolayers are investigated using the first-principles method. The ABC monolayers possess typical Janus structures with a considerable potential gradient normal to the surface, inducing intrinsic Rashba spin splitting (RSS) at the conduction band minimum near the Γ point. Among them, the splitting strength of the BiSeI monolayer is the largest and its Rashba coefficient can reach 1.84 eV Å. The projected energy band of the BiSeI monolayer suggests that the RSS state is mainly rooted in the Bi-pz orbital. The RSS strength can be modulated by applying the in-plane strain. The tensile strain can improve the RSS strength, which is ascribed to the increase of the potential gradient normal to the surface. These results indicate that these 2D ternary compounds have great potential for application in tunable spintronic devices.

2.
J Geriatr Psychiatry Neurol ; 35(2): 223-228, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35245996

RESUMEN

OBJECTIVE: To examine prevalence and correlates of insomnia symptoms in older Chinese adults (OCAs) during the COVID-19 outbreak. BACKGROUND: During the COVID-19 pandemic, insomnia is a major health concern of elderly individuals, but its subtypes have not been investigated. METHODS: Altogether, 590 OCAs (50+ years) were recruited via snowball sampling during the COVID-19 outbreak. Standardized self-report questions were used to assess the presence of difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA). Classification tree analysis (CTA) was used to identify correlates of insomnia. RESULTS: The one-month prevalence (95% confidence interval) of any subtype of insomnia symptoms was 23.4% (20.0-26.8%), with DIS, DMS, and EMA being 15.4% (12.5-18.3%), 17.1% (14.1-20.2%), and 11.2% (8.64-13.7%), respectively. Worry about being infected with COVID-19 emerged as the most salient correlate of insomnia (P < .001); compared to participants who were not worried about being infected, those who were worried and very worried were 3.2-fold (24.3% vs 7.5%) and 5.5-fold (24.3% vs 7.5%) more likely to have insomnia, respectively. Among participants in the "very worried" branch, those residing in Wuhan were 1.8-fold more likely to have insomnia than those residing in other places (50.0% vs 27.5%, P = .011). Among participants in the "worried" branch, unemployed persons were 2.0-fold more likely to have insomnia than employed persons (37.0% vs 18.1%, P < .001). CONCLUSIONS: Insomnia symptoms were prevalent among OCAs during the COVID-19 outbreak. Selective intervention programs targeting elderly individuals who are worried about being infected, living in the epicenter of COVID-19, and unemployed might be effective.


Asunto(s)
COVID-19 , Trastornos del Inicio y del Mantenimiento del Sueño , Anciano , COVID-19/epidemiología , China/epidemiología , Brotes de Enfermedades , Humanos , Persona de Mediana Edad , Pandemias , Prevalencia , SARS-CoV-2 , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología
3.
BMC Med Inform Decis Mak ; 22(1): 205, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35915457

RESUMEN

BACKGROUND: Kidney disease progression rates vary among patients. Rapid and accurate prediction of kidney disease outcomes is crucial for disease management. In recent years, various prediction models using Machine Learning (ML) algorithms have been established in nephrology. However, their accuracy have been inconsistent. Therefore, we conducted a systematic review and meta-analysis to investigate the diagnostic accuracy of ML algorithms for kidney disease progression. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Chinese Biomedicine Literature Database, Chinese National Knowledge Infrastructure, Wanfang Database, and the VIP Database for diagnostic studies on ML algorithms' accuracy in predicting kidney disease prognosis, from the establishment of these databases until October 2020. Two investigators independently evaluate study quality by QUADAS-2 tool and extracted data from single ML algorithm for data synthesis using the bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model. RESULTS: Fifteen studies were left after screening, only 6 studies were eligible for data synthesis. The sample size of these 6 studies was 12,534, and the kidney disease types could be divided into chronic kidney disease (CKD) and Immunoglobulin A Nephropathy, with 5 articles using end-stage renal diseases occurrence as the primary outcome. The main results indicated that the area under curve (AUC) of the HSROC was 0.87 (0.84-0.90) and ML algorithm exhibited a strong specificity, 95% confidence interval and heterogeneity (I2) of (0.87, 0.84-0.90, [I2 99.0%]) and a weak sensitivity of (0.68, 0.58-0.77, [I2 99.7%]) in predicting kidney disease deterioration. And the the results of subgroup analysis indicated that ML algorithm's AUC for predicting CKD prognosis was 0.82 (0.79-0.85), with the pool sensitivity of (0.64, 0.49-0.77, [I2 99.20%]) and pool specificity of (0.84, 0.74-0.91, [I2 99.84%]). The ML algorithm's AUC for predicting IgA nephropathy prognosis was 0.78 (0.74-0.81), with the pool sensitivity of (0.74, 0.71-0.77, [I2 7.10%]) and pool specificity of (0.93, 0.91-0.95, [I2 83.92%]). CONCLUSION: Taking advantage of big data, ML algorithm-based prediction models have high accuracy in predicting kidney disease progression, we recommend ML algorithms as an auxiliary tool for clinicians to determine proper treatment and disease management strategies.


Asunto(s)
Aprendizaje Automático , Insuficiencia Renal Crónica , Algoritmos , Progresión de la Enfermedad , Humanos , Riñón , Insuficiencia Renal Crónica/diagnóstico
4.
Angew Chem Int Ed Engl ; 61(15): e202111443, 2022 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-34997699

RESUMEN

In photon-conversion processes, rapid cooling of photo-induced hot carriers is a dominant energy loss channel. We herein report a 3-fold reduced hot carrier cooling rate in CsPbBr3 nanocrystals capped with a cross-linked polysiloxane shell in comparison to single alkyl-chain oleylamine ligands. Relaxation of hot charge carriers depends on the carrier-phonon coupling (CPC) process as an important channel to dissipate energies in nanostructured perovskite materials. The CPC strengths in the two samples were measured through cryogenic photoluminescence spectroscopic measurements. The effect of organic ligands on the CPC in CsPbBr3 nanocrystals is elucidated based on a damped oscillation model. This supplements the conventional polaron-based CPC model, by involving a damping effect on the CPC from the resistance of the ligands against nanocrystal lattice vibrations. The model also accounts for the observed linear temperature-dependence of the CPC strength. Our work enables predictions about the effect of the ligands on the performance of perovskite nanocrystals in future applications.

5.
Phys Chem Chem Phys ; 23(34): 18338-18348, 2021 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-34612375

RESUMEN

Protic ionic liquids (PILs) have currently been indicated as promising alternative electrolytes in electrical storage devices, such as lithium-ion batteries and supercapacitors. However, compared with the well-studied aprotic ionic liquids (AILs), the knowledge of the interface between PILs and electrode material surfaces is very rare to date. In this work, the adsorption behaviors of three groups of PILs, i.e. pyrrolidinium-based, imidazolium-based, and ammonium-based, on graphite was systematically investigated using first-principles calculations. The corresponding AILs were also taken into account for comparison. The adsorption mechanism of these ILs on the surface is controlled by the interplay of strong electrostatic interactions between adsorbed ions, weak vdW forces between ILs and substrate, and many aromatic interactions including π-π stacking and C-H/N-Hπ contacts. PILs do show quite different preferential interfacial interactions and structures on the graphite surface with respect to AILs, arising mainly from the anion-substrate interactions. Particularly, proton transfer takes place in the PILs consisting of the imidazolium/ammonium cation and the nitrate anion in the gas phase, but it tends to be attenuated or even disappears on graphite caused by interfacial interactions.

6.
BMC Microbiol ; 20(1): 274, 2020 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-32878596

RESUMEN

BACKGROUND: Clostridioides (formerly Clostridium) difficile infection is the leading cause of antibiotic-associated colitis. Studies have demonstrated that C. difficile toxin A (TcdA) can cause apoptosis of many human cell types. The purpose of this study was to investigate the relationships among exposure to TcdA, the role of the receptor for the globular heads of C1q (gC1qR) gene and the underlying intracellular apoptotic mechanism in human colonic epithelial cells (NCM 460). In this study, gC1qR expression was examined using real-time polymerase chain reaction (PCR), western blotting and immunohistochemical staining. Cell viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, and cell apoptosis was assessed by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Mitochondrial function was assessed based on reactive oxygen species (ROS) generation, changes in the mitochondrial membrane potential (ΔΨm) and the content of ATP. RESULTS: Our study demonstrated that increasing the concentration of TcdA from 10 ng/ml to 20 ng/ml inhibited cell viability and induced cell apoptosis (p < 0.01). Moreover, the TcdA-induced gC1qR expression and enhanced expression of gC1qR caused mitochondrial dysfunction (including production of ROS and decreases in the ΔΨm and the content of ATP) and cell apoptosis. However, silencing of the gC1qR gene reversed TcdA-induced cell apoptosis and mitochondrial dysfunction. CONCLUSION: These data support a mechanism by which gC1qR plays a crucial role in TcdA-induced apoptosis of human colonic epithelial cells in a mitochondria-dependent manner.


Asunto(s)
Apoptosis/efectos de los fármacos , Toxinas Bacterianas/toxicidad , Colon/citología , Enterotoxinas/toxicidad , Glicoproteínas de Membrana/metabolismo , Mitocondrias/efectos de los fármacos , Receptores de Complemento/metabolismo , Adenosina Trifosfato/metabolismo , Apoptosis/fisiología , Línea Celular , Colon/patología , Células Epiteliales , Regulación de la Expresión Génica/efectos de los fármacos , Silenciador del Gen , Humanos , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Complemento/química , Receptores de Complemento/genética
7.
Toxicol Appl Pharmacol ; 388: 114869, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-31863799

RESUMEN

Ammonia (NH3), a toxic gas, is an important cause of atmospheric haze and one of the main pollutants in air environment of poultry houses, threatening the health of human beings and poultry. However, little is known about the effect of NH3 on liver apoptotic damage. This study aimed to investigate the mechanism of oxidative stress-mediated apoptosis caused by NH3 in chicken livers and whether miR-187-5p/apaf-1 axis was involved in this mechanism. Here we duplicated NH3 poisoning model of chickens for fattening to study the ultrastructure of chicken livers, apoptosis rate, oxidative stress indexes, miR-187-5p, and apoptosis-related genes. Obvious apoptotic characteristics of liver tissues exposed to excess NH3 were observed, and the apoptosis rate increased. Excess NH3 decreased the activities of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px), and increased the content of malondialdehyde (MDA), suggesting that oxidative stress occurred. miR-187-5p decreased, and apoptotic protease activating factor-1 (apaf-1) increased, indicating that excess NH3 dysregulated miR-187-5p/apaf-1 axis. The expression of tumor protein p53 (p53), Bcl-2 associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), Cytochrome-c (Cyt-c), Caspase-9, Caspase-8, and Caspase-3 was promoted, and the expression of B-cell lymphoma-2 (Bcl-2) was inhibited, resulting in apoptosis. Moreover, oxidative stress indexes, miR-187-5p, and apoptosis-related genes changed in dose- and time-dependent manner. Altogether, miR-187-5p/apaf-1 axis participated in oxidative stress-mediated apoptosis caused by NH3 via mitochondrial pathway in the livers of chickens for fattening. This study may provide new ideas to study the mechanism of liver apoptotic damage induced by NH3 exposure.


Asunto(s)
Amoníaco/envenenamiento , Factor Apoptótico 1 Activador de Proteasas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , MicroARNs/metabolismo , Mitocondrias/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Pollos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Hígado/citología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Mitocondrias/patología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Regulación hacia Arriba/efectos de los fármacos
8.
Ecotoxicol Environ Saf ; 203: 110974, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32888622

RESUMEN

Ammonia (NH3), an environmental pollutant, poses a serious threat to human and avian health. Although previous studies have showed that NH3 caused kidney injury, the molecular mechanisms of nephrotoxicity induced by NH3 remain unclear. To explore the mechanisms of NH3 nephrotoxicity, a total of 36 broiler chicks at one day of age were exposed to NH3. After 42 days of exposure, blood samples were collected to determine creatinine and uric acid; and kidney samples were weighted and then collected to detect ultrastructural changes, oxidative stress parameters, ATPases, necroptosis- and mitochondrial dynamics-related genes. The results showed that chickens exposed to NH3 showed lower relative kidney weight and an increase concentration in serum creatinine and uric acid. NH3 exposure caused nephrocyte necrosis and increased the expression of necroptosis-related genes (TNF-α, RIPK1, RIPK3, MLKL, and JNK). Besides, the activities of antioxidant systems (SOD, CAT, GSH-Px, and T-AOC) were reduced, whereas the concentrations of H2O2 and MDA were elevated. Lower activities of ATPases were obtained in NH3 treatment groups. Furthermore, the mitochondrial fission-related genes drp1 and mff were activated, and mitochondrial fusion-related genes opa1, mfn1 and mfn2 were suppressed after NH3 exposure. Based on the above results, we conclude that NH3 caused-oxidative stress and mitochondrial dysfunction mediated nephrocyte necroptosis in chickens. This study may provide new insight into NH3 nephrotoxicity.


Asunto(s)
Amoníaco/toxicidad , Contaminantes Ambientales/toxicidad , Riñón/efectos de los fármacos , Dinámicas Mitocondriales/efectos de los fármacos , Necroptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Pollos , Expresión Génica/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/metabolismo , Riñón/ultraestructura , Pruebas de Función Renal , Dinámicas Mitocondriales/genética , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética
9.
Ecotoxicol Environ Saf ; 190: 110078, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31841897

RESUMEN

Ammonia (NH3) is considered as environmental pollutant and toxic agent for animals and humans including poultry. Previous reports demonstrated that NH3 suppressed broilers immunity. However, the harmful effects of NH3 on broilers bursa of fabricius (BF) is still unknown. Functionally, apoptosis is very important for many physiological processes including homeostasis of lymphocyte population. Therefore, the present study was aimed to investigate the underlying mechanisms of NH3 toxicity in the broilers BF. Histological observation showed lymphocyte accumulation, cavities and increased interstitial cells in BF. Ultrastructural observation indicated mitochondrial vacuoles, deformation and disappearance of mitochondrial membranes. Oxidative stress markers (CAT, MDA, H2O2, GGT, GSH-Px and GSH) showed that NH3-induced oxidative stress in BF. Meanwhile, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed increased apoptotic cells. In addition, the mRNA and protein expression of dynamin-related protein 1 (Drp1), mitochondrial fission factor (Mff), mitofusin 1 and 2 (Mfn1 and Mfn2), optic atrophy 1 (Opa1) indicated imbalance between mitochondrial inner and outer membrane and results in mitochondrial dysfunction in broilers BF. The mRNA and protein expression of apoptosis-related genes including Caspase-3, Caspase-9, Caspase-8, Cytochrome-C (Cyt-C), p53, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) were significantly altered in broilers BF. Conclusively, these results displayed that excessive NH3 causes BF damage and mitochondrial dysfunction through oxidative stress and apoptosis in BF and could affect immune function of BF. These findings provide possible therapeutic targets to prevent NH3 induced toxicity in the BF of broilers.


Asunto(s)
Amoníaco/toxicidad , Bolsa de Fabricio/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Bolsa de Fabricio/inmunología , Bolsa de Fabricio/metabolismo , Pollos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Mitocondrias/ultraestructura , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Estrés Oxidativo/efectos de los fármacos
10.
Fish Shellfish Immunol ; 86: 239-245, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30176333

RESUMEN

As one of the mucosal lymphatic tissues, the gill is an important immune organ in fish. Water environmental pollutants enter fish body through the gill. Therefore, the gill is the initial site where pollutants produce toxic effects in water. Chlorpyrifos (CPF), a broad-spectrum organophosphate insecticide, is widely used for agricultural pests and causes river pollution. In the present study, we investigated histopathological effect, oxidative stress indexes (SOD, GSH, T-AOC, and MDA), and apoptosis-related genes (P53, PUMA, Bax, Bcl-2, Apaf-1, Caspase-9, and Caspase-3) in the gills of common carp exposed to CPF. The results indicated that CPF exposure decreased SOD, T-AOC, and GSH; increased MDA; decreased Bcl-2 mRNA expression; and increased P53, PUMA, Bax, Apaf-1, Caspase-9, and Caspase-3 mRNA expressions in common carp gills. Our results proved that CPF exposure caused oxidative stress and apoptosis in common carp gills; CPF exposure destroyed the structural integrity and affected the immune function through oxidative stress and apoptosis in common carp gills. These will provide evidence for the toxic effects of water environmental pollutants on immune function and structural integrity in fish gills.


Asunto(s)
Carpas/inmunología , Cloropirifos/toxicidad , Branquias/inmunología , Branquias/patología , Contaminantes Químicos del Agua/toxicidad , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Expresión Génica/efectos de los fármacos , Insecticidas/toxicidad , Estrés Oxidativo/efectos de los fármacos
11.
J Geriatr Psychiatry Neurol ; 32(6): 312-318, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31480989

RESUMEN

OBJECTIVE: To estimate the prevalence of depressive symptoms (depression thereafter) and to identify the sociodemographic and clinical correlates of depression in a sample of elderly patients treated in the primary care setting in Wuhan, China. BACKGROUND: Primary care is an opportune setting for the management of late-life depression in China, but there have been no representative studies on the clinical epidemiology of depression in elderly Chinese primary care patients. METHODS: In total, 752 elderly patients (≥ 65 years) were consecutively recruited from 13 primary care centers in Wuhan, China, and interviewed with a standardized questionnaire. Depression was assessed with the 15-item Geriatric Depression Scale (GDS-15). RESULTS: Of the elderly Chinese primary care patients, 30.6% had depression (GDS-15 ≥ 5). Correlates of depression were an education level of primary school or less (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.36-2.77, P < .001), poor financial status (OR: 2.19, 95% CI: 1.16-4.15, P = .016), lack of an exercise habit (OR: 1.40, 95% CI: 1.06-1.74, P = .023), 2 or more chronic medical conditions (OR: 1.90, 95% CI: 1.34-2.69, P < .001), and loneliness (OR: 3.53, 95% CI: 2.46-5.08, P < .001). CONCLUSIONS: Depression is prevalent among elderly Chinese primary care patients, indicating that elderly patients treated in primary care have a high level of need for mental health services in China. There is an urgent need to integrate mental health services into primary health care.


Asunto(s)
Depresión/diagnóstico , Atención Primaria de Salud/normas , Anciano , China/epidemiología , Depresión/epidemiología , Femenino , Humanos , Masculino , Prevalencia
12.
Avian Pathol ; 48(3): 230-237, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30663336

RESUMEN

Lead (Pb) is an environmental pollutant and can damage organisms. Selenium (Se) can alleviate Pb poisoning. The present study aimed to investigate the alleviative effect of Se on Pb-induced immune toxicity in chicken hearts. One-hundred-and-eighty Hy-line male chickens were randomly divided into four groups at 7 days of age. The control group was offered a standard commercial diet (SD) and drinking water (DW); the Se group was offered SD supplemented with sodium selenite (SeSD) and DW; the Pb + Se group was offered SeSD and DW supplemented with lead acetate (PbDW); and the Pb group was offered SD and PbDW. Relative mRNA expression of inducible nitric oxide synthase (iNOS), interleukins (IL-2, IL-4, IL-6, IL-12ß, IL-17 and IFN-γ), and heat shock proteins (HSP27, HSP40, HSP60, HSP70, and HSP90) were determined by means of quantitative real-time PCR. Relative protein expression of iNOS, HSP60, HSP70, and HSP90 was assessed, as well as nitric oxide (NO) content and iNOS activity in heart tissue. The results indicated a down-regulation of interleukin (IL)-2 and IFN-γ and an up-regulation of NO, iNOS, interleukins (IL-4, IL-6, IL-12ß, IL-17), and heat shock proteins (HSP27, HSP40, HSP60, HSP70, and HSP90) in Pb-damaged hearts. Se alleviated all of the above Pb-induced changes. There were time-dependent effects on NO content, iNOS activity, and mRNA levels of iNOS, IL-2, IL-4, IL-6, IL-17, HSP27, HSP40, HSP60, HSP70, and HSP90 after Pb treatment in the chicken hearts. Se alleviated Pb-induced immune toxicity in the chicken hearts.


Asunto(s)
Pollos/inmunología , Suplementos Dietéticos , Plomo/efectos adversos , Selenio/farmacología , Animales , Dieta/veterinaria , Agua Potable/efectos adversos , Corazón/efectos de los fármacos , Proteínas de Choque Térmico/análisis , Inmunidad/efectos de los fármacos , Interleucinas/análisis , Masculino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxidos de Nitrógeno/análisis , Distribución Aleatoria
13.
Br J Haematol ; 181(3): 360-371, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29637550

RESUMEN

T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia (ALL). However, the difference between CD28 and 4-1BB costimulatory signalling in CAR-T treatment has not been well elucidated in clinical trials. In this study, we treated 10 relapsed or refractory ALL patients with the second generation CD19 CAR-T. The first 5 patients were treated with CD28-CAR and the other 5 patients were treated with 4-1BB CAR-T. All the 10 patients were response-evaluable. Three patients achieved complete remission and 1 patient with extramedullary disease achieved partial response after CD28-CAR-T treatment. In the 4-1BB CAR-T treatment group, 3 patients achieved complete remission. Furthermore, FLT-3 ligand (FLT3LG) was highly correlated with response time and may serve as a prognosis factor. No severe adverse events were observed in these 10 treated patients. Our study showed that both CD28 CAR-T and 4-1BB CAR-T both worked for response but they differed in response pattern (peak reaction time, reaction lasting time and reaction degree), adverse events, cytokine secretion and immune-suppressive factor level.


Asunto(s)
Antígenos CD19/inmunología , Antígenos CD28/inmunología , Inmunoterapia Adoptiva , Proteínas de Neoplasias/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos/inmunología , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
14.
Hepatology ; 64(1): 117-29, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26910875

RESUMEN

UNLABELLED: Hepatocellular carcinoma (HCC) is a highly aggressive liver tumor containing cancer stem cells (CSCs) that participate in tumor propagation, resistance to conventional therapy, and promotion of tumor recurrence, causing poor patient outcomes. The protein SRY (sex determining region Y)-box 9 (Sox9) is a transcription factor expressed in some solid tumors, including HCC. However, the molecular mechanisms underlying Sox9 function in liver CSCs remain unclear. Here, we show that Sox9 is highly expressed in liver CSCs and that high levels of Sox9 predict a decreased probability of survival in HCC patients. We demonstrate that Sox9 is required for maintaining proliferation, self-renewal, and tumorigenicity in liver CSCs. Overexpression of exogenous Sox9 in liver non-CSCs restored self-renewal capacity. Additionally, a reduction in the asymmetrical cell division of spheroid-cultured liver CSCs was observed when compared with differentiated cancer cells or liver CSCs with inhibited Notch signaling. Furthermore, we demonstrate that Sox9 is responsible for the asymmetrical-to-symmetrical cell division switch in liver CSCs. Sox9 also negatively regulates Numb expression, contributing to a feedback circuit that maintains Notch activity and directs symmetrical cell division. Clinical analyses revealed that the Sox9(High) Numb(Low) profile is associated with poor prognosis in human HCC patients. CONCLUSION: We demonstrate that Sox9 plays a critical role in self-renewal and tumor propagation of liver CSCs and identify the molecular mechanisms regulated by Sox9 that link tumor initiation and cell division. (Hepatology 2016;64:117-129).


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Autorrenovación de las Células , Neoplasias Hepáticas/metabolismo , Células Madre Neoplásicas/fisiología , Factor de Transcripción SOX9/metabolismo , Animales , Femenino , Células HEK293 , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Proteínas del Tejido Nervioso/metabolismo
15.
Hepatology ; 64(3): 814-27, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27312708

RESUMEN

UNLABELLED: Hepatocellular carcinoma (HCC) is a highly aggressive liver tumor containing cancer stem cells (CSCs), which participate in tumor invasion, therapeutic resistance, and tumor relapse leading to poor outcome and limited therapeutic options. Histone deacetylatase sirtuin 1 (SIRT1) has been shown to be up-regulated in human cancers; however, its role in liver CSCs is unknown. In this study, we explored the biological functions of SIRT1 in liver CSCs. Our data show that SIRT1 is highly expressed in liver CSCs and decreases during differentiation. In addition, high levels of SIRT1 predict a decreased probability of survival in patients with HCC. SIRT1 is responsible for the maintenance of self-renewal and tumorigenicity of liver CSCs, and overexpression of exogenous SIRT1 can restore self-renewal of non-CSCs. We demonstrated that SOX2 is a main downstream regulator of SIRT1-mediated self-renewal and tumorigenicity potential of liver CSCs. Mechanistically, SIRT1 regulates transcription of the SOX2 gene by way of chromatin-based epigenetic changes, which are dependent on DNA methylation. This effect is achieved by alternation of histone modification and interaction with DNA methyltransferase 3A, resulting in hypermethylation of SOX2 promoter. Furthermore, we demonstrated that insulin growth factor signaling plays an important role in maintaining SIRT1 expression through increased SIRT1 protein stability. CONCLUSIONS: These findings highlight the importance of SIRT1 in the biology of liver CSCs and suggest that SIRT1 may serve as a molecular target for HCC therapy. (Hepatology 2016;64:814-827).


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Autorrenovación de las Células , Neoplasias Hepáticas/metabolismo , Células Madre Neoplásicas/metabolismo , Factores de Transcripción SOXB1/metabolismo , Sirtuina 1/metabolismo , Animales , ADN Metiltransferasa 3A , Epigénesis Genética , Femenino , Células HEK293 , Humanos , Masculino , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Sirtuina 1/antagonistas & inhibidores , Sirtuina 1/genética , Somatomedinas/metabolismo
16.
Stem Cells ; 34(4): 820-31, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26840943

RESUMEN

Discovery of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are two milestones in people exploring the nature of malignant tumor in recent decades. Although some studies have presented the potential connections between them, the link details, underneath their superficial correlation, are largely unknown. In this study, we identified a small subpopulation of NANOG-positive colorectal cancer (CRC) cells, and demonstrated that they exhibited characteristics of CSCs and EMT traits simultaneously. Furthermore, we found that NANOG was a core factor in regulating both of EMT and stemness in CRC cells, NANOG modulate EMT and metastasis by binding to Slug promoter and transcriptionally regulate Slug expression. For the first time, we demonstrated that NANOG was regulated by extracellular IGF signaling pathway via STAT3 phosphorylation in CRC. This coincides with that IGF receptor IGF-1R is often increasing expressed in malignant metastasis colon cancer. Taken together, our data define the crucial functions of IGF/STAT3/NANOG/Slug signaling axis in the progression of CRC by operating EMT and CSCs properties, which make them served as potential therapeutic targets for treatment of CRC.


Asunto(s)
Neoplasias Colorrectales/genética , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Proteína Homeótica Nanog/biosíntesis , Receptores de Somatomedina/biosíntesis , Factor de Transcripción STAT3/biosíntesis , Factores de Transcripción de la Familia Snail/biosíntesis , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Proteína Homeótica Nanog/genética , Metástasis de la Neoplasia , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Receptor IGF Tipo 1 , Receptores de Somatomedina/genética , Factor de Transcripción STAT3/genética , Factores de Transcripción de la Familia Snail/genética
17.
Am J Emerg Med ; 34(3): 398-402, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26643157

RESUMEN

OBJECTIVES: To investigate the clinical characteristics of patients with the fragmented QRS complexes (fQRS) and the predictive value of fQRS in patients undergoing primary percutaneous coronary intervention (p-PCI). METHODS: The study enrolled 227 consecutive patients with ST-elevation myocardial infarction who underwent p-PCI. Baseline clinical characteristics, the percentage of ST-segment resolution, and parameters of electrocardiography and coronary angiography were investigated. The relationship between fQRS on pre-PCI and post-PCI electrocardiogram and the percentage of ST-segment resolution after PCI were studied. RESULTS: Patients with fQRS have higher troponin I, creatine kinase-MB levels, prolonged QRS duration, higher Gensini score, lower percentage of total ST-segment resolution, and left ventricular ejection fraction compared with patients without fQRS. Gensini score (odds ratio [OR], 1.013; 95% confidence interval [CI], 1.002-1.024; P < .006) and percentage of total ST-segment resolution (OR, 0.384; 95% CI, 0.186-0.795; P = .01) were independently associated with the presence of fQRS. A multivariate logistic regression analysis selected presence of fQRS pre-PCI (OR, 2.908; 95% CI, 1.095-7.723; P = .032) and the number of leads with fQRS before PCI (OR, 1.582; 95% CI, 1.250-2.002; P < .001) as independent predictors of imperfect ST-segment resolution. CONCLUSIONS: The presence of fQRS is a predictor in ST-elevation myocardial infarction patients undergoing p-PCI. The occurrence of fQRS is beneficial to identify the patients with severe coronary lesion, left ventricular contraction dysfunction, and larger areas of ischemic injury.


Asunto(s)
Síndrome de Brugada/fisiopatología , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea , Biomarcadores/sangre , Trastorno del Sistema de Conducción Cardíaco , Comorbilidad , Angiografía Coronaria , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo
18.
Cardiology ; 131(1): 58-67, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25871909

RESUMEN

Atrial fibrillation (AF) is a highly prevalent condition associated with pronounced cardiovascular-related morbidity, mortality and socioeconomic burden. It accounts for more hospitalization days than does any other arrhythmia. This article reviews the basic electrophysiology of AF, electrical and structural remodeling in AF and recent advances in understanding the molecular mechanisms of AF in relation to specific microRNAs. This paper also reviews the potential role of microRNAs as novel therapeutic targets as well as biomarkers in the management of AF. AF shows characteristics typical of altered electrophysiology that promote ectopic activity and facilitate reentry, thereby contributing to the progression from short paroxysmal AF to a persistent, permanent form via atrial remodeling, even in the absence of progressive underlying heart disease. MicroRNAs have been suggested to influence the development of AF by regulating gene expression at the post-transcriptional level. Increasing evidence has identified various microRNA modifications and their impacts on AF initiation and maintenance through electrical and structural remodeling. The discovery of specific microRNAs as novel therapeutic targets and some experimental evidence implicating microRNAs as potential molecular diagnostic markers have had a significant impact on the diagnosis and management of AF and demand further research.


Asunto(s)
Fibrilación Atrial/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , MicroARNs/metabolismo , Animales , Fibrilación Atrial/metabolismo , Remodelación Atrial , Calcio/metabolismo , Fenómenos Electrofisiológicos , Humanos
20.
Chemosphere ; 354: 141497, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452981

RESUMEN

During the anammox process, mitigation of biomass washout to increase sludge retention is an important parameter of process efficiency. Signal molecular stimulants (SMS) initiate the sludge granulations controlled by programmed cell death (PCD) of microorganisms. In this study, the aerobic granular sludge (AGS), cell fragments, extracellular polymeric substances (EPS), and AGS process effluent were tested as SMS to identify their effect on anammox granulation. The results showed that the addition of SMS increased the nitrogen removal efficiency to varying degrees, whereas the addition of AGS process supernatant, as SMS, increased the ammonia removal efficiency up to 96%. The addition of SMS was also found to increase EPS production and contributed to sludge granulation. In this process, the proportion of PCD increased and both Gaiella and Denitratisoma abundance increased from 3.54% to 5.59%, and from 1.8% to 3.42%, respectively. In conclusion, PCD was found important to increase anaerobic ammonia oxidation performance through the granulation mechanism.


Asunto(s)
Oxidación Anaeróbica del Amoníaco , Aguas del Alcantarillado , Reactores Biológicos , Amoníaco , Nitrógeno/metabolismo , Apoptosis , Oxidación-Reducción
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