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1.
Cytopathology ; 35(3): 398-403, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441189

RESUMO

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.


Assuntos
Segunda Neoplasia Primária , Neurofibrossarcoma , Derrame Pleural Maligno , Derrame Pleural , Humanos , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia
2.
Sci Total Environ ; 914: 169927, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38199345

RESUMO

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.


Assuntos
Ferroptose , Glifosato , Masculino , Animais , Camundongos , Células Intersticiais do Testículo , Autofagia , Ferro , Testosterona
3.
J Biochem Mol Toxicol ; 37(12): e23508, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37623816

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo
4.
Phys Rev Lett ; 130(21): 216702, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37295086

RESUMO

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.

5.
Environ Int ; 178: 108054, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37354883

RESUMO

Microbial degradation has been confirmed as effective and environmentally friendly approach to remediate phthalates from the environment, and hydrolase is an effective element for contaminant degradation. In the present study, a novel dibutyl phthalate (DBP)-hydrolyzing carboxylesterase (named PS06828) from Pseudomonas sp. PS1 was heterogeneously expressed in E. coli, which was identified as a new member of the lipolytic family VI. Purified PS06828 could efficiently degrade DBP with a wide range of temperature (25-37 °C) and pH (6.5-9.0). Multi-spectroscopy methods combined with molecular docking were employed to study the interaction of PS06828 with DBP. Fluorescence and UV-visible absorption spectra revealed the simultaneous presence of static and dynamic component in the fluorescence quenching of PS06828 by DBP. Synchronous fluorescence and circular dichroism spectra showed inconspicuous alteration in micro-environmental polarity around amino acid residues but obvious increasing of α-helix and reducing of ß-sheet and random coil in protein conformation. Based on the information on exact binding sites of DBP on PS06828 provided by molecular docking, the catalytic mechanism mediated by key residues (Ser113, Asp166, and His197) was proposed and subsequently confirmed by site-directed mutagenesis. The results can strengthen our mechanistic understanding of family VI esterase involved in hydrolysis of phthalic acid esters, and provide a solid foundation for further enzymatic modification.


Assuntos
Esterases , Ácidos Ftálicos , Esterases/genética , Esterases/metabolismo , Dibutilftalato , Simulação de Acoplamento Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Ácidos Ftálicos/metabolismo
6.
Environ Pollut ; 324: 121394, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36906059

RESUMO

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.


Assuntos
Fígado Gorduroso , PPAR alfa , Embrião de Galinha , Masculino , Animais , PPAR alfa/genética , PPAR alfa/metabolismo , Galinhas/metabolismo , Fígado Gorduroso/induzido quimicamente , Fígado/metabolismo , Metabolismo dos Lipídeos , Ácidos Graxos/metabolismo , Autofagia , Epigênese Genética , Glifosato
7.
Phys Rev Lett ; 131(24): 246301, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38181146

RESUMO

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.

8.
Ann Med ; 55(2): 2247004, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38232757

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Animais , Humanos , Scutellaria baicalensis , Carcinoma Hepatocelular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Neoplasias Hepáticas/tratamento farmacológico
9.
Neurotoxicol Teratol ; 93: 107123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36150581

RESUMO

Propionate is an effective mould inhibitor widely used as a food preservative. In this study, we used zebrafish to explore the adverse effects of long-term exposure to low concentrations of sodium propionate and the underlying molecular mechanisms (from larvae to adult). When exposed for 3 months, we found that blood glucose, total cholesterol, and triglyceride levels increased, and zebrafish developed a hyperglycaemic state. New tank test results showed depression in zebrafish reduced 5-hydroxytryptamine levels in the brain and damaged the dopamine system. At the same time, the results of the color preference test showed that zebrafish had cognitive impairments. In addition, Hypothalamic-Pituitary-Adrenal axis analysis revealed abnormal gene expression, increased cortisol levels, and reduced glucocorticoid receptor mRNA levels, which were consistent with depressive behavior. We also observed abnormal transcription of inflammatory and apoptotic factors. Overall, we found that chronic exposure to sodium propionate induces depressive symptoms. This may be related to the activation of the HPA axis by the hyperglycaemic state, thereby inducing inflammation and disrupting the dopaminergic system. In summary, this study provides theoretical and technical support for the overlap of the emotional pathogenesis associated with diabetes.


Assuntos
Hiperglicemia , Doenças do Sistema Nervoso , Animais , Glicemia/metabolismo , Colesterol , Dopamina/metabolismo , Conservantes de Alimentos/metabolismo , Conservantes de Alimentos/farmacologia , Hidrocortisona/metabolismo , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Propionatos/metabolismo , Propionatos/toxicidade , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/metabolismo , Serotonina/metabolismo , Triglicerídeos/metabolismo , Triglicerídeos/farmacologia , Peixe-Zebra/metabolismo
10.
Diagn Cytopathol ; 50(10): 471-481, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35838168

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) represents the most common primary pancreatic malignancy. An understanding of the cytomorphologic features of conventional ductal adenocarcinoma and its variants is important to ensure accurate diagnoses. METHODS: The clinicopathological and cytological data of serous fluids in PDAC patients were obtained from the electronic medical records and pathology database. All samples were analyzed and reclassified according to the "The International System for Reporting Serous Fluid Cytopathology" guidelines. Cytomorphologic features were examined with SurePath automatically prepared slides and stained using the Pap method in malignant (MAL) effusion specimens from 21 patients with PDAC. Immunocytochemical staining was conducted on 12 cell blocks from MAL PDAC effusion. RESULTS: A total of 137 serous fluids specimens of PDACs were included, among which 61 (44.5%), 9 (6.6%), 13 (9.5%), 52 (38.0%), and 2 (1.5%) patients were classified into malignancy, suspicious for malignancy, atypia of undetermined significance, negative for malignancy and nondiagnostic groups, respectively. The key cytologic features for the conventional type of PDAC included cohesive clusters of ductal cells in glandular crowding and disorganized "drunken honeycomb" pattern or intercalated duct-like structure with anisonucleosis, cytoplasmic vacuoles, and concomitant "Indian-file" configuration. Undifferentiated carcinoma was comprised of enlarged, undifferentiated, pleomorphic MAL cells. Adenosquamous carcinoma could show glandular and/or squamous differentiation. Colloid carcinoma was composed of three-dimensional cancer cell clusters floating in thick mucin. CONCLUSION: Crowding and disorganized "drunken honeycomb" pattern or intercalated duct-like structure with anisonucleosis, may represent an important clue for diagnosing PDAC in serous fluids. Immunocytochemical staining in combination with review of medical records and cytomorphological data can serve as useful adjuncts for distinguishing between PDAC and its variants.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Derrame Pleural Maligno , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Humanos , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas
11.
Ecotoxicol Environ Saf ; 241: 113791, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35753272

RESUMO

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.


Assuntos
Resistência à Insulina , Peixe-Zebra , Animais , Ritmo Circadiano , Glucose/metabolismo , Propionatos/toxicidade , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
12.
Nat Commun ; 12(1): 7061, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862380

RESUMO

Electric currents carrying a net spin polarization are widely used in spintronics, whereas globally spin-neutral currents are expected to play no role in spin-dependent phenomena. Here we show that, in contrast to this common expectation, spin-independent conductance in compensated antiferromagnets and normal metals can be efficiently exploited in spintronics, provided their magnetic space group symmetry supports a non-spin-degenerate Fermi surface. Due to their momentum-dependent spin polarization, such antiferromagnets can be used as active elements in antiferromagnetic tunnel junctions (AFMTJs) and produce a giant tunneling magnetoresistance (TMR) effect. Using RuO2 as a representative compensated antiferromagnet exhibiting spin-independent conductance along the [001] direction but a non-spin-degenerate Fermi surface, we design a RuO2/TiO2/RuO2 (001) AFMTJ, where a globally spin-neutral charge current is controlled by the relative orientation of the Néel vectors of the two RuO2 electrodes, resulting in the TMR effect as large as ~500%. These results are expanded to normal metals which can be used as a counter electrode in AFMTJs with a single antiferromagnetic layer or other elements in spintronic devices. Our work uncovers an unexplored potential of the materials with no global spin polarization for utilizing them in spintronics.

13.
Ann Diagn Pathol ; 55: 151828, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34571341

RESUMO

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.


Assuntos
Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Adulto , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Carcinogênese , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Molécula de Adesão da Célula Epitelial/metabolismo , Feminino , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Imuno-Histoquímica , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
14.
Nanomaterials (Basel) ; 11(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34073150

RESUMO

The tunneling of electrons and holes in quantum structures plays a crucial role in studying the transport properties of materials and the related devices. 8-Pmmn borophene is a new two-dimensional Dirac material that hosts tilted Dirac cone and chiral, anisotropic massless Dirac fermions. We adopt the transfer matrix method to investigate the Klein tunneling of massless fermions across the smooth NP junctions and NPN junctions of 8-Pmmn borophene. Like the sharp NP junctions of 8-Pmmn borophene, the tilted Dirac cones induce the oblique Klein tunneling. The angle of perfect transmission to the normal incidence is 20.4∘, a constant determined by the Hamiltonian of 8-Pmmn borophene. For the NPN junction, there are branches of the Klein tunneling in the phase diagram. We find that the asymmetric Klein tunneling is induced by the chirality and anisotropy of the carriers. Furthermore, we show the oscillation of electrical resistance related to the Klein tunneling in the NPN junctions. One may analyze the pattern of electrical resistance and verify the existence of asymmetric Klein tunneling experimentally.

15.
Front Oncol ; 11: 657665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959508

RESUMO

BACKGROUND: Apigenin, as a natural flavonoid, has low intrinsic toxicity and has potential pharmacological effects against hepatocellular carcinoma (HCC). However, the molecular mechanisms involving microRNAs (miRNAs) and their target genes regulated by apigenin in the treatment of HCC have not been addressed. OBJECTIVE: In this study, the molecular mechanisms of apigenin involved in the prevention and treatment of HCC were explored in vivo and in vitro using miRNA transcriptomic sequencing to determine the basis for the clinical applications of apigenin in the treatment of HCC. METHODS: The effects of apigenin on the proliferation, cell cycle progression, apoptosis, and invasion of human hepatoma cell line Huh7 and Hep3B were studied in vitro, and the effects on the tumorigenicity of Huh7 cells were assessed in vivo. Then, a differential expression analysis of miRNAs regulated by apigenin in Huh7 cells was performed using next-generation RNA sequencing and further validated by qRT-PCR. The potential genes targeted by the differentially expressed miRNAs were identified using a curated miRTarBase miRNA database and their molecular functions were predicted using Gene Ontology and KEGG signaling pathway analysis. RESULTS: Compared with the control treatment group, apigenin significantly inhibited Huh7 cell proliferation, cell cycle, colony formation, and cell invasion in a concentration-dependent manner. Moreover, apigenin reduced tumor growth, promoted tumor cell necrosis, reduced the expression of Ki67, and increased the expression of Bax and Bcl-2 in the xenograft tumors of Huh7 cells. Bioinformatics analysis of the miRNA transcriptome showed that hsa-miR-24, hsa-miR-6769b-3p, hsa-miR-6836-3p, hsa-miR-199a-3p, hsa-miR-663a, hsa-miR-4739, hsa-miR-6892-3p, hsa-miR-7107-5p, hsa-miR-1273g-3p, hsa-miR-1343, and hsa-miR-6089 were the most significantly up-regulated miRNAs, and their key gene targets were MAPK1, PIK3CD, HRAS, CCND1, CDKN1A, E2F2, etc. The core regulatory pathways of the up-regulated miRNAs were associated with the hepatocellular carcinoma pathway. The down-regulated miRNAs were hsa-miR-181a-5p and hsa-miR-148a-3p, and the key target genes were MAPK1, HRAS, STAT3, FOS, BCL2, SMAD2, PPP3CA, IFNG, MET, and VAV2, with the core regulatory pathways identified as proteoglycans in cancer pathway. CONCLUSION: Apigenin can inhibit the growth of HCC cells, which may be mediated by up-regulation or down-regulation of miRNA molecules and their related target genes.

16.
BMC Plant Biol ; 21(1): 209, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964877

RESUMO

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.


Assuntos
Frutas/crescimento & desenvolvimento , Frutas/genética , Frutas/metabolismo , Malus/crescimento & desenvolvimento , Malus/genética , Malus/metabolismo , China , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Variação Genética , Genótipo , Reação de Maillard , Metaboloma
17.
Diagn Cytopathol ; 49(9): 997-1007, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34019334

RESUMO

BACKGROUND: Recently, the International System for Reporting Serous Fluid Cytopathology (TIS) has been established, with an aim to standardize reporting and guide clinical decision making. METHODS: The cytological and clinicopathological data of pleural effusions were retrieved from the pathology database and electronic medical records. All specimens were evaluated and reclassified in accordance with the TIS recommendations. Finally, the risk of malignancy (ROM) and performance parameters were measured. RESULTS: A total of 2454 pleural effusion specimens were included, among which 30 (1.2%), 1670 (68.1%), 151 (6.2%), 54 (2.2%) and 549 (22.4%) patients were classified into non-diagnostic (ND), negative for malignancy (NFM), atypia of undetermined significance (AUS), suspicious for malignancy (SFM) and malignancy (MAL) groups, respectively. The most commonly diagnosed malignancies were lung cancer (48.4%), ovary cancer (10.2%), breast cancer (7.5%), and 21.3% unknown primary site (UPS). Among the 36 UPS patients, the most common site of origin was lung (36.1%), followed by ovary (13.9%) and breast (11.1%) via immunocytochemistry of cell block. The calculated ROM values were 26.7%, 12%, 62.3%, 77.8% and 100% for ND, NFM, AUS, SFM and MAL groups, respectively. When considering MAL as the only positive group, the diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were determined to be 95.2%, 81.9%, 100%, 100% and 93.6%, respectively. CONCLUSION: The newly proposed TIS is an easy-to-master, user-friendly, and standardized classification system, especially when applying on pleural effusions. An adequate serous sample, application of immunocytochemistry, review of cytomorphological data and past medical history could enhance the accuracy of cytological diagnosis.


Assuntos
Neoplasias da Mama/patologia , Neoplasias Pulmonares/patologia , Neoplasias Ovarianas/patologia , Derrame Pleural Maligno/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Citodiagnóstico/normas , Citodiagnóstico/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Derrame Pleural Maligno/classificação
18.
J Ethnopharmacol ; 275: 114110, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33864890

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria barbata D.Don (SB) and Oldenlandia diffusa (Willd.) Roxb are commonly known as Ban Zhi Lian and Bai Hua She Cao in Chinese herbal medicines, respectively. As a pair of herbs, they have traditionally been used as ethnomedicines for clearing away heat and toxins, removing blood stasis, and promoting blood circulation, diuresis, and detumescence. AIM OF THE STUDY: The aim of the present study was to determine the active ingredients in SB and OD extracts and to investigate whether these extracts can inhibit the growth of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) cell lines (HepG2.2.15 and Hep3B) in vitro and in vivo, as well as to explore their mechanisms of action. MATERIALS AND METHODS: We determined the levels of total flavonoids, luteolin, and apigenin in SB and OD extracts via ultraviolet-visible spectrophotometry and high-performance liquid chromatography. The effects of SB and OD extracts on HBV-associated HCC cell growth were assessed by HepG2.2.15 and Hep3B cells phenotype and RNA sequencing of Hep3B cells in vitro, and xenograft models in vivo. RESULTS: The extracts of SB and OD contained total flavonoids. There were active ingredients of luteolin and apigenin in SB, but not in OD. The extracts of SB and OD significantly inhibited HCC growth, migration, invasion, and HBV activity in vitro and in vivo, as well as altered circRNA expression in Hep3B cells. Moreover, we constructed a circRNA-miRNA-mRNA co-expression network. CONCLUSIONS: The extracts of SB and OD may inhibit HCC cell growth and HBV activity in vitro and in vivo through altering circRNA-miRNA-gene expression and that the efficacies of these extracts may be related to the presence of luteolin and apigenin.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Oldenlandia/química , RNA Circular/metabolismo , Scutellaria/química , Animais , Apigenina/análise , Apoptose/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/análise , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Hepatite B/complicações , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Luteolina/análise , Camundongos Nus , RNA Circular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Phys Rev Lett ; 124(6): 067203, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32109084

RESUMO

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.

20.
Bioorg Med Chem ; 28(5): 115325, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982241

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , DNA/química , Corantes Fluorescentes/farmacologia , Naftalimidas/farmacologia , Estirenos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Bovinos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Quadruplex G/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Naftalimidas/síntese química , Naftalimidas/química , Relação Estrutura-Atividade , Estirenos/síntese química , Estirenos/química
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