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1.
Cytopathology ; 35(3): 398-403, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38441189

RESUMEN

The cytomorphology of MPNST in effusion specimens is rarely described. In this paper, the detailed cytopathological and immunohistochemical characteristics of metastatic MPNST has been described in pleural effusion. Patients' medical history and the judicious utilization of ancillary studies contribute to ensure precise cytological diagnoses. The cytomorphology of malignant peripheral nerve sheath tumour (MPNST) in effusion specimens can be diagnostically challenging. The author presents detailed cytopathological and immunohistochemical characteristics of a case of metastatic MPNST in pleural effusion.


Asunto(s)
Neoplasias Primarias Secundarias , Neurofibrosarcoma , Derrame Pleural Maligno , Derrame Pleural , Humanos , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patología
2.
Phys Rev Lett ; 131(24): 246301, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38181146

RESUMEN

Valleytronics is a research field utilizing a valley degree of freedom of electrons for information processing and storage. A strong valley polarization is critical for realistic valleytronic applications. Here, we predict a tunneling valley Hall effect (TVHE) driven by tilted Dirac fermions in all-in-one tunnel junctions based on a two-dimensional (2D) valley material. Different doping of the electrode and spacer regions in these tunnel junctions results in momentum filtering of the tunneling Dirac fermions, generating a strong transverse valley Hall current dependent on the Dirac-cone tilting. Using the parameters of an existing 2D valley material, we demonstrate that such a strong TVHE can host a giant valley Hall angle even in the absence of the Berry curvature. Finally, we predict that resonant tunneling can occur in a tunnel junction with properly engineered device parameters such as the spacer width and transport direction, providing significant enhancement of the valley Hall angle. Our work opens a new approach to generate valley polarization in realistic valleytronic systems.

3.
Phys Rev Lett ; 130(21): 216702, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37295086

RESUMEN

Ferromagnets are known to support spin-polarized currents that control various spin-dependent transport phenomena useful for spintronics. On the contrary, fully compensated antiferromagnets are expected to support only globally spin-neutral currents. Here, we demonstrate that these globally spin-neutral currents can represent the Néel spin currents, i.e., staggered spin currents flowing through different magnetic sublattices. The Néel spin currents emerge in antiferromagnets with strong intrasublattice coupling (hopping) and drive the spin-dependent transport phenomena such as tunneling magnetoresistance (TMR) and spin-transfer torque (STT) in antiferromagnetic tunnel junctions (AFMTJs). Using RuO_{2} and Fe_{4}GeTe_{2} as representative antiferromagnets, we predict that the Néel spin currents with a strong staggered spin polarization produce a sizable fieldlike STT capable of the deterministic switching of the Néel vector in the associated AFMTJs. Our work uncovers the previously unexplored potential of fully compensated antiferromagnets and paves a new route to realize the efficient writing and reading of information for antiferromagnetic spintronics.

4.
J Biochem Mol Toxicol ; 37(12): e23508, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37623816

RESUMEN

Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid compound in herbal plants, can suppress growth in hepatocellular carcinoma (HCC). However, the microRNA (miRNA) expression profiles that are influenced by wogonin have not been thoroughly described. To explore the novel miRNAs and the biological mechanism underlying the effect of wogonin on HCC cells. The effect of wogonin on Huh7 cell growth was assessed both in vitro and in vivo. The expression profiles of miRNAs were obtained by small RNA sequencing. Luciferase reporter experiment and bioinformatics analysis were conducted to determine whether tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) can bind to miR-27b-5p. Effects of the ectopic expression of YWHAZ and miR-27b-5p on Huh7 cells proliferation and apoptosis were evaluated. Furthermore, the cell cycle, apoptosis and multiple signaling pathway-related molecules were detected by Western blot analysis. Wogonin substantially inhibited the growth of Huh7 cells both in vitro and in vivo. Seventy miRNAs exhibited greater than twofold changes in wogonin-treated cells. Upregulation of miR-27b-5p inhibited Huh7 cell proliferation, and the anticancer effect of wogonin was reversed after miR-27b-5p knockdown. miR-27b-5p directly targeted YWHAZ in HCC cells. The proliferation-inhibiting effect of miR-27b-5p was revoked by YWHAZ overexpression. Meanwhile, inhibition of HCC growth was achieved by downregulating YWHAZ. Wogonin exerted antitumor activity through multiple signaling molecules, such as focal adhesion kinase, protein kinase B, mammalian target of rapamycin and molecules related to apoptosis and cell cycle by upregulating miR-27b-5p and downregulating YWHAZ. Our findings suggest that miR-27b-5p/YWHAZ axis contributes to the inhibitory effect of wogonin in HCC by targeting related genes and multiple signaling pathways.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo
5.
Ecotoxicol Environ Saf ; 241: 113791, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35753272

RESUMEN

Sodium propionate is widely used as a preservative in food. The widespread use of preservatives is known to cause both environmental and public health problems. This study aimed to investigate the effects of sodium propionate on the developmental behavior and glucose metabolism of zebrafish. Our results showed that sodium propionate had no significant effect on the embryonic morphological development of zebrafish embryos but changed the head eye area. Then we found sodium propionate disturbed the thigmotaxis behavior, impaired neural development. Moreover, changes in clock gene expression disrupted the circadian rhythm of zebrafish. Circadian genes regulated insulin sensitivity and secretion in various tissues. Then our results showed that the disorder of circadian rhythm in zebrafish affected glucose metabolism and insulin resistance, which damaged the development of retina. Therefore, the safety of propionate should be further evaluated.


Asunto(s)
Resistencia a la Insulina , Pez Cebra , Animales , Ritmo Circadiano , Glucosa/metabolismo , Propionatos/toxicidad , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismo
6.
BMC Plant Biol ; 21(1): 209, 2021 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-33964877

RESUMEN

BACKGROUND: Bagging is one of the most important techniques for producting high-quality fruits. In the actual of cultivating, we found a new kind of browning in peel of apple fruit that occurs before harvest and worsen during storage period. There are many studies on metabonomic analysis of browning about storage fruits, but few studies on the mechanism of browning before harvest. RESULTS: In this study, five-year-old trees of 'Rui Xue' (CNA20151469.1) were used as materials. Bagging fruits without browning (BFW) and bagging fruits with browning (BFB) were set as the experimental groups, non-bagging fruits (NBF) were set as control. After partial least squares discriminant analysis (PLS-DA), 50 kinds of metabolites were important with predictive VIP > 1 and p-value < 0.05. The most important differential metabolites include flavonoids and lipids molecules, 11 flavonoids and 6 lipids molecules were significantly decreased in the BFW compared with NBF. After browning, 11 flavonoids and 7 lipids were further decreased in BFB compared with BFW. Meanwhile, the significantly enriched metabolic pathways include galactose metabolism, ABC membrane transporter protein, flavonoid biosynthesis and linoleic acid metabolism pathways et al. Physiological indicators show that, compared with NBF, the content of malondialdehyde (MDA), hydrogen peroxide (H2O2), superoxide anion (O2-) in peel of BFW and BFB were significantly increased, and the difference of BFB was more significant. Meanwhile, the antioxidant enzyme activities of BFW and BFB were inhibited, which accelerated the destruction of cell structure. In addition, the metabolome and physiological data showed that the significantly decrease of flavonoid was positively correlated with peel browning. So, we analyzed the expression of flavonoid related genes and found that, compared with NBF, the flavonoid synthesis genes MdLAR and MdANR were significantly up-regulated in BFW and BFB, but, the downstream flavonoids-related polymeric genes MdLAC7 and MdLAC14 were also significantly expressed. CONCLUSIONS: Our findings demonstrated that the microenvironment of fruit was changed by bagging, the destruction of cell structure, the decrease of flavonoids and the increase of triterpenoids were the main reasons for the browning of peel.


Asunto(s)
Frutas/crecimiento & desarrollo , Frutas/genética , Frutas/metabolismo , Malus/crecimiento & desarrollo , Malus/genética , Malus/metabolismo , China , Productos Agrícolas/genética , Productos Agrícolas/metabolismo , Variación Genética , Genotipo , Reacción de Maillard , Metaboloma
7.
Ann Diagn Pathol ; 55: 151828, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34571341

RESUMEN

Ductal plate malformations (DPM) arise from abnormal remodeling of the embryologic ductal plate of the liver. Malignant transformation of DPMs to intrahepatic cholangiocarcinoma (iCCA) has been reported in very rare instances but is viewed with some skepticism. We report the clinicopathological findings in five cases of iCCA, occurring in liver with DPM-like features. All tumors were less than 5 cm, often presented as stage T1a tumors. Histologically, a typical tumor showed a vague multinodular architecture with larger, irregular, tortuous glandular structures with microcystic dilation, intraluminal fibroepithelial projection, and bridge/island formation. The tumor cells were relatively small, bland, and without obvious pleomorphism. Interestingly, DPM presented as a histopathological transition sequence of definitively benign to biliary intraepithelial neoplasia (bilIN), then finally to iCCA. A complete pushing border, with entrapped portal tracts at the edge of the main tumor, suggested a replacing growth pattern. There was gradually increased expression of Ki-67 and p53 in these transition phases from benign to bilIN then to iCCA with DPM-like features. The neoplastic epithelium exhibited immunoreactivity in EpCAM, MUC1, NCAM, and CK19. KRAS mutation was found in 2 of the 5 iCCA cases with DPM-like features. Multifocal DPMs or VMCs with bilIN were dispersed in the non-tumor liver parenchyma in 3 of the 5 cases. The neoplasm was interpreted as iCCA arising in DPM, which may have originated from small bile duct or hepatic precursor cells. More studies are needed to verify this scarce entity and its premalignant properties.


Asunto(s)
Conductos Biliares Intrahepáticos , Colangiocarcinoma , Adulto , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/patología , Carcinogénesis , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Molécula de Adhesión Celular Epitelial/metabolismo , Femenino , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Inmunohistoquímica , Hígado/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
8.
Phys Rev Lett ; 124(6): 067203, 2020 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-32109084

RESUMEN

Antiferromagnetic (AFM) spintronics exploits the Néel vector as a state variable for novel spintronic devices. Recent studies have shown that the fieldlike and antidamping spin-orbit torques (SOTs) can be used to switch the Néel vector in antiferromagnets with proper symmetries. However, the precise detection of the Néel vector remains a challenging problem. In this Letter, we predict that the nonlinear anomalous Hall effect (AHE) can be used to detect the Néel vector in most compensated antiferromagnets supporting the antidamping SOT. We show that the magnetic crystal group symmetry of these antiferromagnets combined with spin-orbit coupling produce a sizable Berry curvature dipole and hence the nonlinear AHE. As a specific example, we consider the half-Heusler alloy CuMnSb, in which the Néel vector can be switched by the antidamping SOT. Based on density-functional theory calculations, we show that the nonlinear AHE in CuMnSb results in a measurable Hall voltage under conventional experimental conditions. The strong dependence of the Berry curvature dipole on the Néel vector orientation provides a new detection scheme of the Néel vector based on the nonlinear AHE. Our predictions enrich the material platform for studying nontrivial phenomena associated with the Berry curvature and broaden the range of materials useful for AFM spintronics.

9.
Bioorg Med Chem ; 28(5): 115325, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31982241

RESUMEN

G-Quadruplex DNAs, formed by G-rich DNA sequences in human genes, are promising targets for design of cancer drugs. In this study, two naphthalimide substituted styryl dyes with different sizes of aromatic groups were synthesized. The spectral analysis showed that the dye X-2 with a large aromatic group formed aggregates in buffer solution displaying very weak fluorescence intensity, and disaggregated in the presence of G-Quadruplex DNAs with large intensity enhancements (up to ~1800 fold). Moreover, X-2 displayed good selectivity to G-Quadruplex DNAs. In contrast, dye X-3 with the smaller aromatic group had much lower fluorescence enhancements and poor selectivity to G-Quadruplex DNAs, suggesting that the suitably sized aromatic ring was essential for the interaction with G-Quadruplex. Further binding studies suggested that X-2 mainly bound on G-quartet surface through end-stacking mode. Cytotoxicity assay showed that both of the two dyes showed good anti-proliferative activities against the cancer cell lines and less cytotoxicity in non-malignant cell lines, which were better than a standard drug 5-fluorouracil. In addition, living cell imaging was also studied and demonstrated the potential applications of the new dye X-2 in bioassays and cell imaging.


Asunto(s)
Antineoplásicos/farmacología , ADN/química , Colorantes Fluorescentes/farmacología , Naftalimidas/farmacología , Estirenos/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Sitios de Unión/efectos de los fármacos , Bovinos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/química , G-Cuádruplex/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Naftalimidas/síntesis química , Naftalimidas/química , Relación Estructura-Actividad , Estirenos/síntesis química , Estirenos/química
10.
Phys Rev Lett ; 122(7): 077203, 2019 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-30848649

RESUMEN

Topological antiferromagnetic (AFM) spintronics is an emerging field of research, which exploits the Néel vector to control the topological electronic states and the associated spin-dependent transport properties. A recently discovered Néel spin-orbit torque has been proposed to electrically manipulate Dirac band crossings in antiferromagnets; however, a reliable AFM material to realize these properties in practice is missing. In this Letter, we predict that room-temperature AFM metal MnPd_{2} allows the electrical control of the Dirac nodal line by the Néel spin-orbit torque. Based on first-principles density functional theory calculations, we show that reorientation of the Néel vector leads to switching between the symmetry-protected degenerate state and the gapped state associated with the dispersive Dirac nodal line at the Fermi energy. The calculated spin Hall conductivity strongly depends on the Néel vector orientation and can be used to experimentally detect the predicted effect using a proposed spin-orbit torque device. Our results indicate that AFM Dirac nodal line metal MnPd_{2} represents a promising material for topological AFM spintronics.

11.
J Pineal Res ; 66(1): e12530, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30269372

RESUMEN

Environmental endocrine chemicals have various adverse effects on the development of vertebrates. Fluorene-9-bisphenol (BHPF), a substitute of bisphenol A (BPA), is widely used in commercial production. The effects of BHPF on development and behavior are unclear. Melatonin plays a protective role under many unfavorable conditions. In this study, we investigated the effects of BHPF on the development and behaviors of zebrafish and whether melatonin reverses effects induced by BHPF. Zebrafish embryos were exposed to 0.1, 10, or 1000 nmol/L BHPF with or without 1 µmol/L melatonin from 2 hours postfertilization to 6 days postfertilization. The results showed that 0.1 and 10 nmol/L BHPF had little effect on development. High-dose BHPF (1000 nmol/L) delayed the development, increased mortality and surface tension of embryonic chorions, caused aberrant expression of the key genes (ntl, shh, krox20, pax2, cmlc2) in early development detected by in situ hybridization, and damaged the CaP motor neurons, which were associated with locomotion ability detected by immunofluorescence. Melatonin addition reversed or weakened these adverse effects of BHPF on development, and melatonin alone increased surface tension as the effects of high-dose BHPF. However, all groups of BHPF exposure triggered insomnia-like behaviors, with increased waking activity and decreased rest behaviors. BHPF acted on the hypocretin (hcrt) system and upregulated the expression of sleep/wake regulators such as hcrt, hcrt receptor (hcrtr), arylalkylamine N-acetyltransferase-2 (aanat2). Melatonin recovered the alternation of sleep/wake behaviors induced by BHPF and restored abnormal gene expression to normal levels. This study showed that high-dose BHPF had adverse effects on early development and induced behavioral alternations. However, melatonin prevented BHPF-induced aberrant development and sleep/wake behaviors.


Asunto(s)
Desarrollo Embrionario/efectos de los fármacos , Fluorenos/toxicidad , Melatonina/farmacología , Fenoles/toxicidad , Sueño/efectos de los fármacos , Vigilia/efectos de los fármacos , Animales , Femenino , Fluorenos/química , Masculino , Fenoles/química , Pez Cebra
12.
Int J Mol Sci ; 19(8)2018 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-30061546

RESUMEN

Aquaporins play important regulatory roles in the transport of water and small molecules in plants. In this study, a ThellungiellasalsugineaTsPIP1;1 aquaporin was transformed into Kitaake rice, and three transgenic lines were evaluated by profiling the changes of the physiological metabolism, osmotic potential, and differentially expressed genes under salt stress. The TsPIP1;1 protein contains six transmembrane domains and is localized in the cytoplasm membrane. Overexpression of the TsPIP1;1 gene not only increased the accumulation of prolines, soluble sugars and chlorophyll, but also lowered the osmotic potential and malondialdehyde content in rice under salt stress, and alleviated the amount of salt damage done to rice organs by regulating the distribution of Na/K ions, thereby promoting photosynthetic rates. Transcriptome sequencing confirmed that the differentially expressed genes that are up-regulated in rice positively respond to salt stimulus, the photosynthetic metabolic process, and the accumulation profiles of small molecules and Na/K ions. The co-expressed Rubisco and LHCA4 genes in rice were remarkably up-regulated under salt stress. This data suggests that overexpression of the TsPIP1;1 gene is involved in the regulation of water transport, the accumulation of Na/K ions, and the translocation of photosynthetic metabolites, thus conferring enhanced salt tolerance to rice.


Asunto(s)
Acuaporinas/genética , Expresión Génica Ectópica , Oryza/genética , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente/genética , Tolerancia a la Sal , Acuaporinas/metabolismo , Brassicaceae/genética , Brassicaceae/fisiología , Regulación de la Expresión Génica de las Plantas , Oryza/fisiología , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/fisiología , Transformación Genética , Regulación hacia Arriba
13.
Tumour Biol ; 37(8): 11457-67, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27010469

RESUMEN

Our previous study has reported that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) regulates the growth and survival of hepatocellular carcinoma (HCC) cells. This study was undertaken to explore the roles of MAP4K4 in the epithelial-mesenchymal transition (EMT) and metastasis in HCC. Effects of overexpression and knockdown of MAP4K4 on the migration, invasion, and EMT of HCC cells were examined. The in vivo role of MAP4K4 in lung metastasis of HCC was determined in nude mice. The relationship between MAP4K4 expression and EMT in human HCC specimens was determined by immunohistochemistry. MAP4K4 overexpression significantly enhanced the migration and invasion of MHCC-97L HCC cells, whereas MAP4K4 silencing hindered the migration and invasion of MHCC-97H HCC cells. MAP4K4-overexpressing cells undergo EMT, which was accompanied by downregulation of E-cadherin and upregulation of vimentin. In contrast, MAP4K4 silencing caused a reversion from a spindle morphology to cobblestone-like morphology and induction of E-cadherin and reduction of vimentin. Pretreatment with chemical inhibitors of JNK and NF-κB abolished MAP4K4-mediated migration, invasion, and regulation of EMT markers in MHCC-97L cells. Ectopic expression of MAP4K4 promoted and knockdown of MAP4K4 inhibited lung metastasis of HCC, which was associated with regulation of JNK and NF-κB signaling and EMT markers. High MAP4K4 immunoreactivity was inversely correlated with E-cadherin and was positively correlated with vimentin, phospho-JNK, and phospho-NF-κB in HCC specimens. Taken together, MAP4K4 promotes the EMT and invasiveness of HCC cells largely via activation of JNK and NF-κB signaling.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundario , Transición Epitelial-Mesenquimal/fisiología , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Neoplasias Hepáticas/patología , Proteínas Serina-Treonina Quinasas/biosíntesis , Animales , Western Blotting , Carcinoma Hepatocelular/genética , Femenino , Técnica del Anticuerpo Fluorescente , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FN-kappa B/metabolismo , Invasividad Neoplásica/genética , Reacción en Cadena de la Polimerasa , Proteínas Serina-Treonina Quinasas/genética
14.
Angew Chem Int Ed Engl ; 54(32): 9313-8, 2015 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-26079517

RESUMEN

Chemical synaptic transmission is central to the brain functions. In this regard, real-time monitoring of chemical synaptic transmission during neuronal communication remains a great challenge. In this work, in vivo-like oriented neural networks between superior cervical ganglion (SCG) neurons and their effector smooth muscle cells (SMC) were assembled in a microfluidic device. This allowed amperometric detection of individual neurotransmitter release events inside functional SCG-SMC synapse with carbon fiber nanoelectrodes as well as recording of postsynaptic potential using glass nanopipette electrodes. The high vesicular release activities essentially involved complex events arising from flickering fusion pores as quantitatively established based on simulations. This work allowed for the first time monitoring in situ chemical synaptic transmission under conditions close to those found in vivo, which may yield important and new insights into the nature of neuronal communications.


Asunto(s)
Potenciales Postsinápticos Excitadores/fisiología , Unión Neuromuscular/metabolismo , Sinapsis/metabolismo , Animales , Células Cultivadas , Técnicas de Cocultivo , Técnicas Electroquímicas , Electrodos , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Microscopía Fluorescente , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Nanoestructuras/química , Unión Neuromuscular/química , Neurotransmisores/metabolismo , Ganglio Cervical Superior/citología , Ganglio Cervical Superior/metabolismo , Transmisión Sináptica
15.
Angew Chem Int Ed Engl ; 53(46): 12456-60, 2014 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-25060546

RESUMEN

Chemical neurotransmission occurs at chemical synapses and endocrine glands, but up to now there was no means for direct monitoring of neurotransmitter exocytosis fluxes and their precise kinetics from inside an individual synapse. The fabrication of a novel finite conical nanoelectrode is reported perfectly suited in size and electrochemical properties for probing amperometrically inside what appears to be single synapses and monitoring individual vesicular exocytotic events in real time. This allowed obtaining direct and important physiological evidences which may yield important and new insights into the nature of synaptic communications.


Asunto(s)
Técnicas Electroquímicas/instrumentación , Exocitosis , Neuronas/citología , Sinapsis/metabolismo , Animales , Células Cultivadas , Diseño de Equipo , Microelectrodos , Nanotecnología , Neuronas/metabolismo , Neurotransmisores/metabolismo , Ganglio Cervical Superior/citología
16.
Sci Total Environ ; 914: 169927, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38199345

RESUMEN

Glyphosate (GLY), a widely used herbicide, can adversely affect the male reproductive health by inhibiting testosterone synthesis. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to inhibition of testosterone secretion. However, it still remains unclear whether ferroptosis is involved in GLY-inhibited testosterone synthesis. Hereby, an in vitro model of 1 mM GLY-exposed testicular Leydig (TM3) cells was established to elucidate this issue. Data firstly showed that GLY causes cytotoxicity and testosterone synthesis inhibition via ferroptosis, while accumulation of lipid peroxides due to intracellular ferrous ion (Fe2+) overload and glutathione depletion is confirmed as a determinant of ferroptosis. Blockage of ferroptosis via chelation of Fe2+ or inhibition of lipid peroxidation can markedly mitigate GLY-induced testosterone synthesis inhibition. Also, autophagy activation is revealed in GLY-treated TM3 cells and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is involved in ferroptosis through the release of excess Fe2+. GLY-induced cytotoxicity and testosterone synthesis inhibition are significantly alleviated by NCOA4 knockdown, demonstrating the crucial role of NCOA4-mediated ferritinophagy in GLY-inhibited testosterone synthesis. In summary, this study provides solid evidence that NCOA4-mediated ferritinophagy promotes ferroptosis to inhibit testosterone synthesis, highlighting that targeting NCOA4 may be a potential therapeutic approach in GLY-induced male reproductive toxicity.


Asunto(s)
Ferroptosis , Glifosato , Masculino , Animales , Ratones , Células Intersticiales del Testículo , Autofagia , Hierro , Testosterona
17.
World J Clin Cases ; 12(16): 2831-2836, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38899307

RESUMEN

BACKGROUND: Computed tomography (CT) small bowel three-dimensional (3D) reconstruction is a powerful tool for the diagnosis of small bowel disease and can clearly show the intestinal lumen and wall as well as the outside structure of the wall. The horizontal axis position can show the best adjacent intestinal tube and the lesion between the intestinal tubes, while the coronal position can show the overall view of the small bowel. The ileal end of the localization of the display of excellent, and easy to quantitative measurement of the affected intestinal segments, the sagittal position for the rectum and the pre-sacral lesions show the best, for the discovery of fistulae is also helpful. Sagittal view can show rectal and presacral lesions and is useful for fistula detection. It is suitable for the assessment of inflammatory bowel disease, such as assessment of disease severity and diagnosis and differential diagnosis of the small bowel and mesenteric space-occupying lesions as well as the judgment of small bowel obstruction points. CASE SUMMARY: Bleeding caused by small intestinal polyps is often difficult to diagnose in clinical practice. This study reports a 29-year-old male patient who was admitted to the hospital with black stool and abdominal pain for 3 months. Using the combination of CT-3D reconstruction and capsule endoscopy, the condition was diagnosed correctly, and the polyps were removed using single-balloon enteroscopy-endoscopic retrograde cholangiopancreatography without postoperative complications. CONCLUSION: The role of CT-3D in gastrointestinal diseases was confirmed. CT-3D can assist in the diagnosis and treatment of gastrointestinal diseases in combination with capsule endoscopy and small intestinal microscopy.

18.
Cell Biol Int ; 37(9): 929-39, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23589395

RESUMEN

Carboxypeptidase D (CPD), a membrane-bound metallocarboxypeptidase that functions as a docking receptor for duck hepatitis B virus, is frequently overexpressed in human cancers. We have explored its expression pattern, clinical significance, and biological function of CPD in hepatocellular carcinoma (HCC). CPD expression was markedly elevated in HCCs relative to adjacent non-tumor liver tissues, as determined by quantitative real-time polymerase chain reaction and Western blot analysis. Immunohistochemistry showed that 164 of 400 (41%) HCCs had high expression of CPD. CPD overexpression was significantly associated with serum levels of hepatitis B surface antigen and hepatitis B e antigen, liver cirrhosis, pathological grade, and intrahepatic metastasis. Knockdown of endogenous CPD expression in Huh7 HCC cells by RNA interference reduced cell proliferation, blocked the cell cycle at G1 phase, and increased apoptosis. Many genes implicated in cell-cycle regulation, including P21waf1, P27 Kip1, SKP2, and CDC2, were deregulated by CPD downregulation. Thus CPD is frequently upregulated in HCC, and targeting CPD inhibits HCC cell proliferation through induction of G1 cell-cycle arrest and apoptosis, thereby providing a potential therapeutic target for this malignancy.


Asunto(s)
Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Hepatitis B/genética , Neoplasias Hepáticas/genética , Neoplasias Primarias Secundarias/genética , Proteínas/genética , ARN Interferente Pequeño/genética , Adulto , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular , Hepatitis B/complicaciones , Hepatitis B/patología , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos e de la Hepatitis B/genética , Antígenos e de la Hepatitis B/metabolismo , Virus de la Hepatitis B/fisiología , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/complicaciones , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/virología , Proteínas/antagonistas & inhibidores , Proteínas/metabolismo , ARN Interferente Pequeño/metabolismo
19.
Environ Pollut ; 324: 121394, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36906059

RESUMEN

Glyphosate (Gly) is the most widely used herbicide with well-defined hepatotoxic effects, but the underlying mechanisms of Gly-induced hepatic steatosis remain largely unknown. In this study, a rooster model combined with primary chicken embryo hepatocytes was established to dissect the progresses and mechanisms of Gly-induced hepatic steatosis. Data showed that Gly exposure caused liver injury with disrupted lipid metabolism in roosters, manifested by significant serum lipid profile disorder and hepatic lipid accumulation. Transcriptomic analysis revealed that PPARα and autophagy-related pathways played important roles in Gly-induced hepatic lipid metabolism disorders. Further experimental results suggested that autophagy inhibition was involved in Gly-induced hepatic lipid accumulation, which was confirmed by the effect of classic autophagy inducer rapamycin (Rapa). Moreover, data substantiated that Gly-mediated autophagy inhibition caused nuclear increase of HDAC3, which altered epigenetic modification of PPARα, leading to fatty acid oxidation (FAO) inhibition and subsequently lipid accumulation in the hepatocytes. In summary, this study provides novel evidence that Gly-induced autophagy inhibition evokes the inactivation of PPARα-mediated FAO and concomitant hepatic steatosis in roosters by mediating epigenetic reprogramming of PPARα.


Asunto(s)
Hígado Graso , PPAR alfa , Embrión de Pollo , Masculino , Animales , PPAR alfa/genética , PPAR alfa/metabolismo , Pollos/metabolismo , Hígado Graso/inducido químicamente , Hígado/metabolismo , Metabolismo de los Lípidos , Ácidos Grasos/metabolismo , Autofagia , Epigénesis Genética , Glifosato
20.
Ann Med ; 55(2): 2247004, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38232757

RESUMEN

BACKGROUND: Traditional Chinese medicines have been reported to have outstanding effects in the treating of hepatocellular carcinoma. Scutellaria baicalensis (S. baicalensis) has demonstrated anti-tumor, anti-angiogenic, and anti-inflammatory properties. Baicalein, wogonin, and baicalin are the main pharmacologically bioactive compounds of S. baicalensis. METHODS: Eight electronic databases were searched to select articles published from their inception to 30 May 2022. For selected articles, clinical and preclinical data was obtained on the use of S. baicalensis and its bioactive compounds in hepatocellular carcinoma therapy. Statistical analyses were performed using RevMan version 5.3 and Stata software. Quality assessment of the studies was performed using Cochrane and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tools. RESULTS: Seven clinical and 17 preclinical in vivo studies along with 31 in vitro studies were included in this research. Meta-analysis showed that a Chinese herbal medicine preparation, with S. baicalensis as the sovereign herb, combined with Transcatheter arterial chemoembolization (TACE) or primary treatment, could lead to a significantly improved tumor objective response rate (Risk ratio (RR) = 1.57, 95% confidence interval (CI): [1.30, 1.90], p < 0.00001). Scutellaria baicalensis-based extracts (standard mean difference (SMD) = -0.86, 95%CI: [-1.20, -0.53], p < 0.00001), baicalein (SMD = -4.80, 95%CI: [-6.66, - 2.95], p < 0.00001), baicalin (SMD = -2.28, 95%CI [-3.26, -1.30], p < 0.00001) and wogonin (SMD = -1.41, 95%CI [-2.26, -0.57], p < 0.00001) slowed tumor growth in vivo. These outcomes might be linked to the mechanism by which S. baicalensis promotes apoptosis, induces autophagy, and blocks the expression of vascular endothelial growth factor (p < 0.05). CONCLUSION: Based on experimental and clinical evidence, we believe that S. baicalensis and its bioactive compounds have therapeutic potential and plausible mechanisms of action against hepatocellular carcinoma, in terms of efficacy and safety.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Animales , Humanos , Scutellaria baicalensis , Carcinoma Hepatocelular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular , Neoplasias Hepáticas/tratamiento farmacológico
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