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1.
J Pathol ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39022843

RESUMEN

Metastasis is the primary culprit behind cancer-related fatalities in multiple cancer types, including prostate cancer. Despite great advances, the precise mechanisms underlying prostate cancer metastasis are far from complete. By using a transgenic mouse prostate cancer model (TRAMP) with and without Phf8 knockout, we have identified a crucial role of PHF8 in prostate cancer metastasis. By complexing with E2F1, PHF8 transcriptionally upregulates SNAI1 in a demethylation-dependent manner. The upregulated SNAI1 subsequently enhances epithelial-to-mesenchymal transition (EMT) and metastasis. Given the role of the abnormally activated PHF8/E2F1-SNAI1 axis in prostate cancer metastasis and poor prognosis, the levels of PHF8 or the activity of this axis could serve as biomarkers for prostate cancer metastasis. Moreover, targeting this axis could become a potential therapeutic strategy for prostate cancer treatment. © 2024 The Pathological Society of Great Britain and Ireland.

2.
Int J Biol Macromol ; 269(Pt 1): 132099, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38710256

RESUMEN

Iron deficiency anemia (IDA) is the most common nutritional disease worldwide. In this study, a low methoxyl pectin (LMP)­iron(III) complex was prepared. The physicochemical and structural properties were characterized by HPSEC, HPIC, CV, FTIR, 1H NMR, XRD, SEM and CD. The results showed that iron increased the molecular weight of the LMP­iron(III) from 11.50 ± 0.32 to 12.70 ± 0.45 kDa and improved its crystallinity. Moreover, the findings demonstrated that -OH and -COOH groups in LMP coordinate with Fe3+ to form ß-FeOOH. The water-holding capacity, emulsion stability, and antioxidant activities of the LMP­iron(III) were lower than those of LMP. Furthermore, the therapeutic effects of LMP­iron(III) on IDA were investigated in rats. Following LMP­iron(III) supplementation, compared with the model group, the administration of LMP­iron(III) significantly increased the body weight, hemoglobin concentration, and serum iron concentration as well as decreased free erythrocyte protoporphyrin concentration. Therefore, the LMP­iron(III) can potentially treat IDA in rats experiments, providing a theoretical basis for the development of a promising iron supplement.


Asunto(s)
Anemia Ferropénica , Hierro , Pectinas , Animales , Pectinas/química , Pectinas/farmacología , Ratas , Anemia Ferropénica/tratamiento farmacológico , Hierro/química , Masculino , Antioxidantes/farmacología , Antioxidantes/química , Fenómenos Químicos , Hemoglobinas/química , Hemoglobinas/metabolismo , Peso Molecular , Peso Corporal/efectos de los fármacos , Ratas Sprague-Dawley
3.
Cancer Immunol Immunother ; 73(2): 24, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38280010

RESUMEN

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Pene , Masculino , Humanos , Receptores de Antígenos de Linfocitos T , Neoplasias del Pene/genética , Neoplasias del Pene/metabolismo , Regiones Determinantes de Complementariedad/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Linfocitos T CD8-positivos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Microambiente Tumoral
4.
Life Sci ; 336: 122347, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38103728

RESUMEN

AIMS: The increasing resistance to anti-seizure medications (ASMs) and the ambiguous mechanisms of epilepsy highlight the pressing demand for the discovery of pioneering lead compounds. Berberine (BBR) has received significant attention in recent years within the field of chronic metabolic disorders. However, the reports on the treatment of epilepsy with BBR are not systematic and the mechanism remains unclear. MAIN METHODS: In this study, the seizure behaviors of mice were recorded following subcutaneous injection of pentetrazol (PTZ). Non-targeted metabolomics was used to analyze the serum metabolites based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Meanwhile, multivariate statistical methods were used for metabolite identification and pathway analysis. Furthermore, network pharmacology, molecular docking, and quantitative real-time PCR assay were used for the target identification. KEY FINDINGS: BBR had anti-seizure effects on PTZ-induced seizure mice after long-term treatment. Tryptophan metabolism and phenylalanine metabolism were involved in regulating the therapeutic effects of BBR. SIGNIFICANCE: This study reveals the potential mechanism of BBR for epilepsy treatment based on non-targeted metabolomics and network pharmacology, which provides evidence for uncovering the pathogenesis of epilepsy, suggesting that BBR is a potential lead compound for anti-epileptic treatment.


Asunto(s)
Berberina , Epilepsia , Ratones , Animales , Berberina/farmacología , Berberina/uso terapéutico , Berberina/metabolismo , Farmacología en Red , Simulación del Acoplamiento Molecular , Metabolómica/métodos , Pentilenotetrazol/toxicidad , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico
5.
ACS Omega ; 8(49): 46934-46945, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38107954

RESUMEN

Eco-friendly self-doped carbon quantum dots (ZCQDs) with excellent corrosion inhibition ability were prepared via solid-phase pyrolysis only using Zanthoxylum bungeanum leaves as the raw material. Compared with the relevant research, a simpler and higher yield (25%) preparation process for carbon quantum dots was proposed. ZCQDs were characterized by transmission electron microscopy and X-ray photoelectron spectroscopy, and the average size of ZCQDs with multitudes of O- and N-containing functional groups was about 2.53 nm. The prepared ZCQDs were used to inhibit the corrosion of Q235 steel in HCl solution, and the inhibition behavior was investigated through weight loss, electrochemical test, surface analysis, and adsorption thermodynamic analyses. The results showed that the ZCQDs, acted as a mixed corrosion inhibitor, have an effective corrosion inhibition for Q235, the corrosion inhibition efficiency reached 95.98% at 200 mg/L, and at this concentration, effective protection of at least 132h (IE > 90%) is provided. Moreover, the adsorption mechanism of ZCQDs was consistent with that of Redlich-Peterson adsorption, including chemisorption and physisorption. A new corrosion inhibition mechanism of ZCQDs has been thoroughly studied and proposed; ZCQDs have functional groups containing O and N, which can form a protective barrier through physical adsorption and chemisorption, but the coverage of the protective film is low at low concentrations. With the increase of concentration, the protective film formed by ZCQDs on the metal surface will first increase the coverage and then adsorb more ZCQDs on the protective film to form a thicker and denser protective film to protect the metal. The carbon quantum dots prepared in this paper have advantages including a green, renewable precursor, a fast method, high yield, and excellent corrosion inhibition. Therefore, this work can inspire and facilitate, to a certain extent, the future application of doped carbon quantum dots as efficient corrosion inhibitors in HCl solutions.

6.
ACS Appl Mater Interfaces ; 15(37): 44097-44108, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37669219

RESUMEN

The great problem of food spoilage is causing food waste worldwide. However, prolonging the shelf life of food and responding to spoilage are good strategies for dealing with this problem. Herein, we present the design of multifunctional chitosan-based hydrogel-incorporated tryptophan carbon quantum dots (Trp-CDs) with antibacterial properties and pH-mediated fluorescence response (pH = 1-13). This chitosan (CS)/tannic acid (TA)/Trp-CDs hydrogel (CTTC hydrogel) was rapidly formed by a high density of hydrogen bonds and has the advantages of good mechanical properties (1628.55 kPa, 280%), washability (5-10 min), antioxidant activity (95.83%), and antibacterial properties. In practical application with fruits, the hydrogel significantly prolonged the shelf life of strawberries by at least 5 days and oranges by 20 days under ambient conditions. In particular, the hydrogel has good pH-mediated fluorescence responsiveness and reversibility due to doping with Trp-CDs, laying a foundation for its application in response to food spoilage.


Asunto(s)
Quitosano , Puntos Cuánticos , Eliminación de Residuos , Materiales Inteligentes , Hidrogeles/farmacología , Quitosano/farmacología , Fluorescencia , Triptófano , Antibacterianos/farmacología , Carbono , Conservación de Alimentos , Frutas , Concentración de Iones de Hidrógeno
7.
Heliyon ; 9(6): e16994, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37389051

RESUMEN

Background: Procyanidins have antioxidative properties that may protect against age-related brain oxidative stress. Previous studies indicated that procyanidin-rich foods could improve cognitive function and prevent neurodegenerative diseases. This study hypothesized that grape seed procyanidins extract (GSPE) would have a favorable effect on cognitive function in elderly people with mild cognitive impairment (MCI). Methods: A community-based, randomized, double-blind, placebo-controlled trial was conducted. Participants aged 60 years or older with MCI were randomly assigned into the GSPE group (n = 35, 320 mg/d) or placebo group (n = 36), and received capsules for 6 months. Cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA). The change in MoCA scores between groups were tested by the time ✕ treatment interaction in mixed-design ANOVA. Results: After 6 months of intervention, the MoCA score was higher than the baseline both in the intervention group and placebo control group, while the there was no significant difference for mean change in MoCA score from baseline between the intervention group and the placebo group (2.35 ± 3.20 vs. 1.28 ± 2.93, P = 0.192). Conclusions: Present study showed that 6-month supplementation with GSPE did not significantly improve cognitive function in subjects with MCI. Further investigations regarding the longer-term intervention effect of procyanidins extract on mild or moderate cognitive disorders are needed.

8.
Psychol Med ; 53(15): 7300-7308, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37092864

RESUMEN

BACKGROUND: Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD. METHODS: We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity. RESULTS: Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11-1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12-2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24-1.60). CONCLUSIONS: In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.


Asunto(s)
Artritis Reumatoide , Trastorno del Espectro Autista , Trastorno Autístico , Efectos Tardíos de la Exposición Prenatal , Masculino , Niño , Femenino , Humanos , Trastorno del Espectro Autista/etiología , Trastorno del Espectro Autista/complicaciones , Estudios de Cohortes , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios Prospectivos , Artritis Reumatoide/epidemiología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Inflamación/complicaciones , Artralgia/complicaciones , Factores de Riesgo
9.
Membranes (Basel) ; 13(3)2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36984751

RESUMEN

At present, the types of pollutants in wastewater are more and more complicated, however, the multifunctional membrane materials are in short supply. To prepare a membrane with both high efficient oil-in-water emulsion separation performance and photocatalytic degradation performance of organic dyes, the bifunctional separation membrane was successfully prepared by electrostatic spinning technology of PVDF/PEMA and in situ deposition of anatase TiO2 nanoparticles containing Ti3+ and oxygen vacancies (Ov). The prepared composite membrane has excellent hydrophilic properties (WCA = 15.65), underwater oleophobic properties (UOCA = 156.69), and photocatalytic performance. These composite membranes have high separation efficiency and outstanding anti-fouling performance, the oil removal efficiency reaches 98.95%, and the flux recovery rate (FRR) reaches 99.19% for soybean oil-in-water emulsion. In addition, the composite membrane has outstanding photocatalytic degradation performance, with 97% and 90.2% degradation of RhB and AG-25 under UV conditions, respectively. Several oil-in-water separation and dye degradation experiments show that the PVDF composite membrane has excellent reuse performance. Based on these results, this study opens new avenues for the preparation of multifunctional reusable membranes for the water treatment field.

10.
RSC Adv ; 12(55): 35543-35555, 2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36540403

RESUMEN

The anti-fouling performance of membranes is an important performance in the separation of oil/water. However, the membrane with anti-fouling performance will also have surface scaling phenomenon when it runs for a long time. Therefore, there is still a great demand for stain-resistant membranes with good self-cleaning ability and high flux recovery rate. Based on this, this paper firstly prepared a hydrophilic membrane with carboxyl group and carboxyl ion by blending poly(ethylene-alt-maleic anhydride) (PEMA) and polyvinylidene fluoride (PVDF), and then prepared a self-cleaning composite membrane by in situ mineralization of ß-FeOOH particles on the surface of the membrane for efficient oil-in-water emulsion separation. A large number of -COOH/COO- and ß-FeOOH particles on the membrane surface make the composite membrane have strong hydrophilic properties (WCA = 20.34°) and underwater superoleophobicity (UOCA = 155.10°). These composite membranes have high separation efficiency (98.8%) and high flux (694.56 L m-2 h-1 bar-1) for soybean oil-in-water emulsion. Importantly, the as-prepared membrane shows excellent flux recovery rate (over 99.93%) attributed to the robust photo-Fenton catalytic activity of ß-FeOOH, and the ß-FeOOH is chemically bonded to the as-prepared membrane, which makes the as-prepared membrane have good reusability. This work provides hope for the application of self-cleaning membranes in the construction of anti-fouling membranes for wastewater remediation.

11.
ACS Omega ; 7(29): 25066-25077, 2022 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-35910172

RESUMEN

With the rapid industrial development, the coexistence of multiple pollutants in wastewater has become a common phenomenon. Thus, developing highly efficient decontamination methods is imperative. In this work, a string of UiO-66-NH2/BiOBr heterojunctions with varying ratios of BiOBr were prepared and applied to remove hexavalent chromium Cr(VI) and rhodamine B (RhB). The possible growth process of BiOBr nanosheets on UiO-66-NH2, removal activity of contaminants, and photocatalysis mechanism were investigated. When the mass ratio of UiO-66-NH2 to BiOBr reaches 1:0.75, the heterojunction (NB-75) shows optimal photocatalytic activity. After 30 min of adsorption, the total removal rates of Cr(VI) (50 mg/L) and RhB (10 mg/L) over NB-75 (0.25 g/L) reaches 96.7% within 120 min of illumination and 98.9% within 80 min of illumination, respectively. For the removal process, there are two factors. The first is the high adsorption capacity for RhB and Cr(VI) owing to the high porosity of UiO-66-NH2 and interlayer surface positive charge of BiOBr. The second is the improved visible-light photocatalytic performance of the UiO-66-NH2/BiOBr heterojunction via rapid separation of photoinduced carriers. In addition, the active species capture study reveals that the electrons (e-) and the superoxide radicals (•O2 -) play key roles in Cr(VI) reduction, while the holes (h+) are major reactive groups participating in the degradation of RhB. This work demonstrated a kind of promising MOF-based photocatalysis material for eliminating Cr(VI) and RhB simultaneously.

12.
Transl Androl Urol ; 11(1): 9-19, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35242637

RESUMEN

BACKGROUND: The prediction of new baseline renal function after partial nephrectomy (PN) has important clinical implications. This study aimed to establish a precise personalized nomogram integrating pre-, intra- and post-operative variables to predict new baseline function after PN. METHODS: This nomogram was constructed based on 213 consecutive PN cases at a large-volume institution from 2014 to 2017 and externally validated by a prospective cohort from January to December 2018 at the same institution. Multivariate cox regression and logistic least absolute shrinkage and selection operator (LASSO) regression were used to select predictors. The performance of the nomogram was assessed by the concordance index (C-index), calibration plot, decision curve analysis and Kaplan-Meier plot. RESULTS: The average drop percent of the estimated glomerular filtration rate (eGFR) was -8.6% (-12.3%, -7.2%). Multivariate Cox regression analysis and LASSO regression revealed that age, baseline eGFR, RENAL nephrometry score, ischemia time, and AKI were independent predictive factors. These five factors were subsequently incorporated to establish an integrated nomogram, with a C-index of 0.910, excellent calibration plot and net clinical benefit. An external validation of 67 patients showed a C-index of 0.801, excellent calibration and clinical net benefit. CONCLUSIONS: Our proposed nomogram based on pre-, intra- and post-operative outcomes accurately predicts personalized new baseline eGFR after PN. The successful personalized prediction of at-risk individuals at an early stage can provide multi-professional consideration and timely management.

13.
Polymers (Basel) ; 13(13)2021 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-34209853

RESUMEN

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.

14.
Bioelectrochemistry ; 140: 107809, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33862547

RESUMEN

SRB is one of the main bacteria causing marine microbial corrosion. In order to reduce the loss of microbial corrosion, a Gemini surfactant (12-B-12) containing semi-rigid spacer was used to investigate the anti-bacterial and anti-corrosion performances of carbon steel in simulated seawater by weight-loss test, electrochemical method and surface morphology analysis. The results showed that the inhibition efficiency of 0.01 mM 12-B-12 was as high as 98.3% after 30 days of incubation in simulated seawater with SRB, and the planktonic and sessile SRB on the carbon steel surface can be reduced to undetectable level. Quantum chemical calculation and molecular dynamics simulation were used to study the structure-activity relationship.


Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Calcitriol/análogos & derivados , Carbono/química , Agua de Mar/química , Agua de Mar/microbiología , Acero/química , Antibacterianos/química , Calcitriol/química , Corrosión , Electroquímica , Fenómenos Mecánicos , Conformación Molecular , Simulación de Dinámica Molecular , Relación Estructura-Actividad , Tensoactivos/química , Tensoactivos/farmacología
15.
ACS Omega ; 6(2): 1391-1399, 2021 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-33490798

RESUMEN

In the present study, apple pectin (AP) extracted from apple pomace was used to chelate with Fe(III) to synthesize an AP-Fe(III) complex. The obtained AP-Fe(III) complex was characterized by UV-vis spectroscopy, FTIR, XPS, and TG analysis. The Fe content in the AP-Fe(III) complex was determined to be 24.5%. Moreover, the reduction properties of the complex were also investigated. The AP-Fe(III) complex was found to be soluble in water and maintained stability in the pH range of 3-8. The complex was reduced to Fe(II) after 6 h. In addition, the AP-Fe(III) complex did not release iron ions in the simulated gastric fluid, and Fe release of the complex reached 96.5% after 4 h of digestion in simulated intestinal fluid. In particular, the antioxidant activity of the AP-Fe(III) complex against free DPPH and ABTS radicals was evaluated. The results obtained in this study demonstrate the potential of the AP-Fe(III) complex as a novel iron supplement.

16.
J Vis Exp ; (163)2020 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-32986029

RESUMEN

Based on twice transverse aortic constrictions (TACs) in mice, it is proved that myocardial hypertrophic preconditioning (MHP) could attenuate cardiomyocyte hypertrophy and slow down progression to heart failure. For novices, however, the MHP model is usually quite difficult to establish because of the technical obstacles in ventilator operation, opening the chest repeatedly, and bleeding caused by debanding. To facilitate this model, to increase the surgical success rate and to reduce the incidence of bleeding, we switched to absorbable sutures for the first TAC combing with a ventilator-free technique. Using a 2-week absorbable suture, we demonstrated that this procedure could cause significant myocardial hypertrophy in 2 weeks; and 4 weeks after surgery, myocardial hypertrophy was almost completely regressed to the baseline. Using this protocol, the operators could master the MHP model easily with a lower operation mortality.


Asunto(s)
Aorta/patología , Aorta/cirugía , Cardiomegalia/etiología , Miocardio/patología , Suturas , Anestesia , Animales , Aorta/diagnóstico por imagen , Cardiomegalia/diagnóstico por imagen , Cardiomegalia/fisiopatología , Constricción , Modelos Animales de Enfermedad , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Ligadura , Masculino , Ratones Endogámicos C57BL , Presión , Sístole
17.
FEBS Open Bio ; 10(10): 2157-2165, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32750222

RESUMEN

Vortioxetine is a potent antagonist of the 5-hydroxytryptamine receptor and serotonin transporter and has been reported to function as an antidepressant in the treatment of major depressive disorder. However, its antitumor effects remain unclear. Here, we examined whether vortioxetine affects the characteristics of GC cells. Cell viability was measured by a colony formation assay and, in addition, cell invasion, migration and apoptosis assays were performed with a transwell assay and a flow cytometry assay. Protein levels were measured by western blotting. We found that vortioxetine inhibited the proliferation, invasion and migration abilities of AGS cells. Additionally, vortioxetine could induce apoptosis and autophagy by increasing the levels of Bax, active caspase-3/-9, Beclin-1 and light chain 3, as well as by downregulating Bcl-2 and P62. Further investigations indicated that vortioxetine regulated apoptosis and autophagy via activation of the phosphoinositide 3-kinase/AKT pathway. Taken together, our data suggest that vortioxetine has cytotoxic effects against GC AGS cells as a result of inhibiting proliferation, invasion and migration, as well as by inducing apoptosis and autophagy through the phosphoinositide 3-kinase/AKT pathway.


Asunto(s)
Neoplasias Gástricas/metabolismo , Vortioxetina/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , China , Humanos , Invasividad Neoplásica/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Vortioxetina/metabolismo
18.
Cardiovasc Res ; 116(1): 101-113, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30689763

RESUMEN

AIMS: Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. METHODS AND RESULTS: Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3ß, and active ß-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active ß-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. CONCLUSION: Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3ß/ß-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.


Asunto(s)
Insuficiencia Cardíaca/prevención & control , Hipertrofia Ventricular Izquierda/prevención & control , Lansoprazol/farmacología , Miocitos Cardíacos/efectos de los fármacos , Inhibidores de la Bomba de Protones/farmacología , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , beta Catenina/antagonistas & inhibidores , Animales , Aorta/fisiopatología , Aorta/cirugía , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Constricción , Modelos Animales de Enfermedad , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de Señal , beta Catenina/metabolismo
19.
Biochim Biophys Acta Mol Basis Dis ; 1866(3): 165623, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31778748

RESUMEN

The role of the cardiac isoform of the electrogenic sodium-bicarbonate ion cotransporter (NBCe1) in cardiac remodeling is not fully understood. The aim of this study was to assess the effects of NBCe1 overexpression on cardiac remodeling induced by myocardial infarction (MI) in mice. We generated NBCe1 transgenic (Tg) mice and NBCe1 overexpressing adult mouse ventricular myocytes (AMVMs) to investigate the role of NBCe1 on post-MI remodeling and calcium kinetics. Tg mice showed a markedly higher mortality rate and larger infarct size after MI. At 6 weeks after MI, the maximum rising rates of left ventricular pressure (dp/dt), contractility index, and the exponential time constant of relaxation (τ) were markedly lower, and there was higher cardiomyocyte apoptosis, in Tg mice compared with WT mice. In cultured AMVMs, overexpression of NBCe1 decreased sarcomere shortening and calcium amplitude. In WT AMVMs, the rates of the rise and decay phase of calcium transients, indicated by the rising time (Tpeak, time to peak) and decay time constant (τd), and the number of apoptotic cells, were increased following hypoxia, while overexpression of NBCe1 further increased Tpeak and cellular apoptosis, but not τd. Intracellular resting calcium and sodium concentrations were significantly increased following both hypoxia and NBCe1 overexpression. Co-treatment with S0859, an NBCe1 antagonist, blocked the hypoxia-induced increase in Tpeak, τd, intracellular resting calcium and sodium concentrations, and apoptosis in cardiomyocytes. These findings indicate that NBCe1 overexpression promotes cardiac remodeling by increasing intracellular calcium overload. Therefore, NBCe1 should be a potential target for treatment of cardiac remodeling.


Asunto(s)
Bicarbonatos/metabolismo , Calcio/metabolismo , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Simportadores de Sodio-Bicarbonato/metabolismo , Sodio/metabolismo , Remodelación Ventricular/fisiología , Animales , Apoptosis/fisiología , Masculino , Ratones , Ratones Transgénicos , Contracción Miocárdica/fisiología
20.
ACS Omega ; 4(25): 21148-21160, 2019 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-31867508

RESUMEN

Three sunflower head pectin (SFHP) with different molecular weights (M w = 4.50, 97.23, and 254.64 kDa) were obtained by enzyme-assisted extraction and characterized by FTIR and 1H NMR spectroscopy. The corrosion inhibition of mild steel in 1 M HCl solution was evaluated by the weight loss measurement. The inhibition efficiency (IE%) increased as its concentration increases and decreased as the temperature increases. The SFHP with the lowest M w of 4.50 kDa exhibited an IEmax of 92.05% at the medium concentration (2.0 g L-1). The inhibition properties of SFHP (M w = 4.50 kDa) were investigated electrochemically and theoretically. The electrochemical impedance spectroscopy (EIS) revealed that the charge-transfer resistance increased as its concentration increases, the double-layer capacitance decreased as concentration increases, and the IE% also increased as concentration increases. The potentiodynamic polarization (PP) revealed that the SFHP acted as mixed-type inhibitor. The IE% reached 90.3% at the medium concentration (2.0 g L-1) of SHFP. The three-dimensional super depth digital microscopy and scanning electron microscopy tests confirmed the formation of inhibitor films on the surface of mild steel. The adsorption of SFHP on the mild steel surface was proved to obey the Langmuir adsorption isotherm. The theoretical studies via density functional theory and molecular dynamics simulation further revealed the mechanism of corrosion inhibition.

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