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1.
Int J Surg Pathol ; : 10668969231188910, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488488

RESUMO

Ectopic/accessory liver tissue is a rare developmental anomaly thought to be due to abnormal development of the liver during embryogenesis. Most patients with ectopic liver tissue are asymptomatic, and the condition is usually discovered incidentally during intraabdominal surgery or autopsy. In rare symptomatic cases, patients' presentations can range from mild liver function test abnormalities to severe abdominal pain or discomfort secondary to torsion and ischemia. Here, we report 2 patients with ectopic liver tissue identified incidentally during cholecystectomy: one with histologic manifestations of sickle cell congestion and the other with steatohepatitis. A possible relationship between ectopic liver tissue and gallbladder and biliary diseases, such as cholecystitis, has been proposed. To the best of our knowledge, ectopic liver tissue with sickle cell congestion has not been reported previously.

2.
Gynecol Oncol Rep ; 47: 101188, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37122437

RESUMO

•Dedifferentiated endometrial carcinoma arising from serous carcinoma (null-type P53).•Differential diagnosis including carcinosarcoma, FIGO grade 3 endometrioid carcinoma.•Also need to rule out SMARCA4-deficient uterine sarcoma and other sarcomas.

3.
J Environ Manage ; 342: 118088, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37201389

RESUMO

Nano zero-valent manganese (nZVMn) is theoretically expected to exhibit high reducibility and adsorption capacity, yet its feasibility, performance, and mechanism for reducing and adsorbing hexavalent uranium (U(VI)) from wastewater remain unclear. In this study, nZVMn was prepared via borohydride reduction, and its behaviors about reduction and adsorption of U(VI), as well as the underlying mechanism, were investigated. Results indicated that nZVMn exhibited a maximum U(VI) adsorption capacity of 625.3 mg/g at a pH of 6 and an adsorbent dosage of 1 g/L, and the co-existing ions (K+, Na+, Mg2+, Cd2+, Pb2+, Tl+, Cl-) at studied range had little interference on U(VI) adsorption. Furthermore, nZVMn effectively removed U(VI) from rare-earth ore leachate at a dosage of 1.5 g/L, resulting in a U(VI) concentration of lower than 0.017 mg/L in the effluent. Comparative tests demonstrated the superiority of nZVMn over other manganese oxides (Mn2O3 and Mn3O4). Characterization analyses, including X-ray diffraction and depth profiling X-ray photoelectron spectroscopy, combined with density functional theory calculation revealed that the reaction mechanism of U(VI) using nZVMn involved reduction, surface complexation, hydrolysis precipitation, and electrostatic attraction. This study provides a new alternative for efficient removal of U(VI) from wastewater and improves the understanding of the interaction between nZVMn and U(VI).


Assuntos
Manganês , Urânio , Manganês/análise , Urânio/análise , Águas Residuárias , Adsorção , Água/química , Íons , Concentração de Íons de Hidrogênio , Cinética
4.
Transfusion ; 62(11): 2409-2413, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36082758

RESUMO

BACKGROUND: Graft-versus-host-disease (GVHD) is one of the rare complications following liver transplantation. We report on the efficacy and safety of extracorporeal photopheresis (ECP) in managing GVHD and hemophagocytic lymphohistiocytosis (HLH) after liver transplantation. CASE REPORT: The patient is a 63-year-old male with hepatitis B cirrhosis who underwent liver transplantation. Three weeks after transplant, he presented with fever, diarrhea, and poor appetite. The patient also had bilateral blanchable erythematous patches on his palms, biopsy of which was suggestive of GVHD. The patient continued to have high-grade fever with altered mental status. CBC showed pancytopenia. Liver function examination was normal. Patient was started on methylprednisolone. Additional laboratory analysis showed high ferritin (>15000 ug/L), triglycerides (280 mg/dl), and low fibrinogen (80 mg/dl). Chimerism analysis using short tandem repeat (STR) PCR confirmed the diagnosis of GVHD. Marrow biopsy showed hemophagocytosis. The patient fulfilled the HLH-2004 diagnostic criteria. He was kept on tacrolimus and steroids and was started on etanercept and ECP. After the first two cycles of ECP (one cycle defined as the weekly two procedures of ECP), the patient reported improvement of symptoms. He tolerated ECP well. His labs improved during the course of treatment, until his peripheral blood STR showed 100% recipient DNA. He was discharged after the fourth cycle of ECP to receive the remaining treatments as outpatient. At one year follow-up, the patient is asymptomatic with no evidence of GVHD or HLH. DISCUSSION: ECP in combination with immunosuppressive therapy and etanercept was safe and efficient in managing GVHD and HLH following liver transplantation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Fígado , Linfo-Histiocitose Hemofagocítica , Fotoferese , Masculino , Humanos , Pessoa de Meia-Idade , Fotoferese/métodos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/terapia , Transplante de Fígado/efeitos adversos , Etanercepte , Febre
5.
J Environ Radioact ; 241: 106771, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34775288

RESUMO

Natural radium isotopes have been widely used to study groundwater discharge in different systems. Therefore, it is of great significance to understand the desorption behavior of radium isotopes on sediments to trace water-land exchange processes. However, there is very limited studies observing the desorption Ra isotopes to lake water of the brine lake. 224Ra desorption experiments with different salinities and particle sizes were carried out by collecting samples of brackish water from Qinghai Lake, brine from Dabuxun Lake and river sediments entering the lakes. The results show that the desorption activity of 224Ra from the river sediments to lake water of Qinghai Lake is 0.2 dpm/g when the salinity is 10.07‰. The maximum desorption activity of 224Ra from river sediments to lake water of Dabuxun Lake is 0.195 dpm/g at a salinity of 40.81‰. A salinity of 41.81‰ and particle size of 16.28 µm are the threshold points affecting the desorption behavior of Ra. When the salinity is less than 40.81‰, the desorption activity of Ra increases linearly with increasing salinity. When the salinity is greater than 40.81‰, the desorption activity of Ra decreases nonlinearly with increasing salinity and tends toward a stable low value. When the particle size is larger than 16.28 µm, the small particle size promotes desorption. The smaller the particle size is, the greater the desorption activity is. When the particle size is less than 16.28 µm, the small particle size inhibits desorption. The smaller the particle size is, the smaller the desorption activity. The co-precipitation of Ra2+ with supersaturated Ca2+, SO42- and other ions may be the main reason for the threshold point of salinity and particle size in Ra desorption process in salt lake system.


Assuntos
Monitoramento de Radiação , Rádio (Elemento) , Monitoramento Ambiental , Sedimentos Geológicos , Lagos , Tamanho da Partícula , Rádio (Elemento)/análise , Rios , Salinidade , Tibet
6.
Sci Total Environ ; 805: 150237, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34818805

RESUMO

Water pollution caused by the release of manganese (Mn2+) and ammonia nitrogen (NH4+-N) from electrolytic manganese residue (EMR) generated from industrial activities poses a serious threat to ecosystems and human health. In this study, an integrated process consisting sequentially of hydroxide sedimentation, struvite precipitation, breakpoint chlorination, and ferric chloride coagulation was optimized to remove Mn2+ and NH4+-N from EMR leachate, and to address the issue of residual orthophosphate caused by struvite precipitation. The precipitates were characterized using X-ray diffraction, scanning electron microscopy, and thermogravimetric analyses. Results show that Mn2+ ions and the resulting chemical oxygen demand (COD) were mainly removed using hydroxide precipitation at a sedimentation pH of 10.2, with poor-crystalline manganese hydroxide as the main precipitate. NH4+-N was primarily removed and recovered using struvite precipitation with well crystalline struvite as the main product, and then further eliminated using breakpoint chlorination. The residual orthophosphate introduced by struvite precipitation is successfully removed with ferric coagulation, and the effluent pH (7.5) is also lowered to discharge limits by means of hydrolysis of ferric coagulant. The concentration of COD, Mn2+, NH4+-N, and orthophosphate concentrations in the final effluent were 30.52 ± 9.38, 0.026 ± 0.013, 0.87 ± 0.01, and 0.06 ± 0.002 mg/L, respectively, meeting all local discharge standards. This combined process has robust pollutant removal efficiency, high resource recovery potential and few environmental constraints; thus, it is recommended as a potential solution for the treatment of Mn2+- and NH4+-N-rich acid mine drainage.


Assuntos
Compostos de Amônio , Fosfatos , Ecossistema , Halogenação , Humanos , Hidróxidos , Manganês , Estruvita
7.
Clin Cancer Res ; 27(8): 2301-2313, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33419778

RESUMO

PURPOSE: On the basis of the recent discovery of mutations in Bruton tyrosine kinase (BTK) in follicular lymphoma, we studied their functional properties. EXPERIMENTAL DESIGN: We identified novel somatic BTK mutations in 7% of a combined total of 139 follicular lymphoma and 11 transformed follicular lymphoma cases, none of which had received prior treatment with B-cell receptor (BCR) targeted drugs. We reconstituted wild-type (WT) and mutant BTK into various engineered lymphoma cell lines. We measured BCR-induced signal transduction events in engineered cell lines and primary human follicular lymphoma B cells. RESULTS: We uncovered that all BTK mutants destabilized the BTK protein and some created BTK kinase-dead mutants. The phospholipase C gamma 2 (PLCγ2) is a substrate of BTK but the BTK mutants did not alter PLCγ2 phosphorylation. Instead, we discovered that BTK mutants induced an exaggerated AKT phosphorylation phenotype in anti-Ig-treated recombinant lymphoma cell lines. The short hairpin RNA-mediated knockdown of BTK expression in primary human nonmalignant lymph node-derived B cells resulted in strong anti-Ig-induced AKT activation, as did the degradation of BTK protein in cell lines using ibrutinib-based proteolysis targeting chimera. Finally, through analyses of primary human follicular lymphoma B cells carrying WT or mutant BTK, we detected elevated AKT phosphorylation following surface Ig crosslinking in all follicular lymphoma B cells, including all BTK-mutant follicular lymphoma. The augmented AKT phosphorylation following BCR crosslinking could be abrogated by pretreatment with a PI3Kδ inhibitor. CONCLUSIONS: Altogether, our data uncover novel unexpected properties of follicular lymphoma-associated BTK mutations with direct implications for targeted therapy development in follicular lymphoma.See related commentary by Afaghani and Taylor, p. 2123.


Assuntos
Tirosina Quinase da Agamaglobulinemia/genética , Linfoma Folicular/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tirosina Quinase da Agamaglobulinemia/metabolismo , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Análise Mutacional de DNA , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Mutação com Perda de Função , Linfoma Folicular/patologia , Mutagênese Sítio-Dirigida , Fosfolipase C gama/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Cultura Primária de Células , Estabilidade Proteica
9.
Oncotarget ; 9(81): 35286, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30443298

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.1795.].

10.
Sci Rep ; 8(1): 3294, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29459640

RESUMO

Efforts for tissue engineering vascular grafts focuses on the tunica media and intima, although the tunica adventitia serves as the primary structural support for blood vessels. In surgery, during endarterectomies, surgeons can strip the vessel, leaving the adventitia as the main strength layer to close the vessel. Here, we adapted our recently developed technique of forming vascular tissue rings then stacking the rings into a tubular structure, to accommodate human fibroblasts to create adventitia vessels in 8 days. Collagen production and fibril cross-linking was augmented with TGF-ß and ascorbic acid, significantly increasing tensile strength to 57.8 ± 3.07 kPa (p = 0.008). Collagen type I gel was added to the base fibrin hydrogel to further increase strength. Groups were: Fibrin only; 0.7 mg/ml COL; 1.7 mg/ml COL; and 2.2 mg/ml COL. The 0.7 mg/ml collagen rings resulted in the highest tensile strength at 77.0 ± 18.1 kPa (p = 0.015). Culture periods of 1-2 weeks resulted in an increase in extracellular matrix deposition and significantly higher failure strength but not ultimate tensile strength. Histological analysis showed the 0.7 mg/ml COL group had significantly more, mature collagen. Thus, a hydrogel of 0.7 mg/ml collagen in fibrin was ideal for creating and strengthening engineered adventitia vessels.


Assuntos
Túnica Adventícia/crescimento & desenvolvimento , Prótese Vascular , Fibroblastos/efeitos dos fármacos , Alicerces Teciduais/química , Túnica Adventícia/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , Vasos Coronários , Fibrina/química , Fibrina/farmacologia , Fibroblastos/metabolismo , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Fator de Crescimento Transformador beta/genética , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/crescimento & desenvolvimento , Túnica Média/efeitos dos fármacos , Túnica Média/crescimento & desenvolvimento
11.
J Vis Exp ; (121)2017 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-28447994

RESUMO

Coronary artery disease remains a leading cause of death, affecting millions of Americans. With the lack of autologous vascular grafts available, engineered grafts offer great potential for patient treatment. However, engineered vascular grafts are generally not easily scalable, requiring manufacture of custom molds or polymer tubes in order to customize to different sizes, constituting a time-consuming and costly practice. Human arteries range in lumen diameter from about 2.0-38 mm and in wall thickness from about 0.5-2.5 mm. We have created a method, termed the "Ring Stacking Method," in which variable size rings of tissue of the desired cell type, demonstrated here with vascular smooth muscle cells (SMCs), can be created using guides of center posts to control lumen diameter and outer shells to dictate vessel wall thickness. These tissue rings are then stacked to create a tubular construct, mimicking the natural form of a blood vessel. The vessel length can be tailored by simply stacking the number of rings required to constitute the length needed. With our technique, tissues of tubular forms, similar to a blood vessel, can be readily manufactured in a variety of dimensions and lengths to meet the needs of the clinic and patient.


Assuntos
Prótese Vascular , Impressão Tridimensional , Engenharia Tecidual , Enxerto Vascular/métodos , Animais , Vasos Coronários/cirurgia , Humanos
12.
Oncotarget ; 5(4): 1101-10, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24658355

RESUMO

Increased activation of ERK signaling has been reported in breast cancer models of acquired tamoxifen resistance. Here, we examined the expression of Mitogen-Activated Protein Kinase Phosphatases (MKPs) 1 and 2 following tamoxifen treatment and the effects of MKP-1/MKP-2 overexpression on tamoxifen sensitivity. Treatment of MCF7 breast cancer cells with tamoxifen increased MKP-2, but not MKP-1, protein levels. Overexpression of MKP-1 or MKP-2 inhibited estrogen-induced MCF7 cell proliferation compared to vector controls. MCF7-MKP-2 cells displayed significantly increased sensitivity to tamoxifen as compared to vector control or MCF7-MKP-1 cells. MKP-1 or MKP-2 overexpression eliminated ERK1/2 phosphorylation, suggesting that decreases in estrogen-induced proliferation of MKP-1 and MKP-2 overexpressing cells are due to ERK1/2 dephosphorylation. JNK1/2 activation was not detectable in any of these cells. These data suggest that tamoxifen-induced death of these cells is not dependent upon JNK signaling, but rather that ERK is the major MAPK driving their proliferation. MCF7-TAMR cells express higher levels of MKP-2 mRNA and protein than MCF7 cells. MKP-2 and phospho-ERK1/2 proteins are constitutively expressed in MCF7-TAMR cells, and activated JNK1/2 is not detectable. These data suggest that MKP-2 rather than MKP-1 is tamoxifen-regulated and that the elevated expression of MKP-2 in MCF7-TAMR cells potentially functions to restore tamoxifen sensitivity.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Fosfatase 1 de Especificidade Dupla/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Tamoxifeno/farmacologia , Fosfatases de Especificidade Dupla/genética , Feminino , Humanos , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética
13.
Cell Cycle ; 13(23): 3750-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25551360

RESUMO

Protein phosphatase 2A (PP2A) is the major serine-threonine phosphatase that regulates a number of cell signaling pathways. PP2A activity is controlled partially through protein degradation; however, the underlying mechanism is not fully understood. Here we show that PP2A/C, a catalytic subunit of PP2A, is degraded by the Cullin3 (Cul3) ligase-mediated ubiquitin-proteasome pathway. In response to death receptor signaling by tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL), PP2A/C, caspase-8 and Cul3, a subunit of the cullin family of E3 ligases, are recruited into the death-inducing signaling complex (DISC) where the Cul3 ligase targets PP2A/C for ubiquitination and subsequent degradation. Functionally, knockdown of PP2A/C expression by siRNA or pharmacological inhibition of PP2A activity increases TRAIL-induced apoptosis. In cancer cells that have developed acquired TRAIL resistance, PP2A phosphatase activity is increased, and PP2A/C protein is resistant to TRAIL-induced degradation. Thus, this work identifies a new mechanism by which PP2A/C is regulated by Cul3 ligase-mediated degradation in response to death receptor signaling and suggests that inhibition of PP2A/C degradation may contribute to resistance of cancer cells to death receptor-induced apoptosis.


Assuntos
Domínio Catalítico/fisiologia , Proteínas Culina/fisiologia , Proteína Fosfatase 2/metabolismo , Transdução de Sinais/fisiologia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ubiquitinação/fisiologia , Linhagem Celular Tumoral , Células HEK293 , Humanos
14.
J Biol Chem ; 288(46): 33263-71, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24100030

RESUMO

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in transformed and tumor cells but not in normal cells, making it a promising agent for cancer therapy. However, many cancer cells are resistant to TRAIL, and the underlying mechanisms are not fully understood. Here, we show that the regulation of the PP2A and Src interaction plays a critical role in TRAIL resistance. Specifically, we show that TRAIL treatment activates the tyrosine kinase Src, which subsequently phosphorylates caspase-8 at tyrosine 380, leading to the inhibition of caspase-8 activation. We also show that upon TRAIL treatment, Src, caspase-8, and PP2A/C (a catalytic subunit of the PP2A phosphatase) are redistributed into lipid rafts, a microdomain of the plasma membrane enriched with cholesterol, where PP2A dephosphorylates Src at tyrosine 418 and in turn inhibits caspase-8 phosphorylation. Furthermore, we find that TRAIL treatment causes PP2A/C degradation. These data suggest that the balance between Src-mediated caspase-8 phosphorylation and the inactivation of Src-mediated caspase-8 phosphorylation by PP2A determines the outcome of TRAIL treatment in breast cancer cells. Therefore, this work identifies a novel mechanism by which the interaction between PP2A and Src in the context of caspase-8 activation modulates TRAIL sensitivity in cancer cells.


Assuntos
Apoptose , Caspase 8/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Proteína Fosfatase 2/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Quinases da Família src/metabolismo , Caspase 8/genética , Linhagem Celular Tumoral , Humanos , Microdomínios da Membrana/genética , Microdomínios da Membrana/metabolismo , Proteínas de Neoplasias/genética , Neoplasias/genética , Fosforilação/genética , Proteína Fosfatase 2/genética , Proteólise , Ligante Indutor de Apoptose Relacionado a TNF/genética , Quinases da Família src/genética
15.
BMC Cancer ; 13: 368, 2013 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-23915259

RESUMO

BACKGROUND: We previously reported that Axin1 (Axin) is down-regulated in many cases of lung cancer, and X-ray irradiation increased Axin expression and inhibited lung cancer cells. The mechanisms, however, were not clear. METHODS: Four lung cancer cell lines were used to detect the methylation status of Axin with or without X-ray treatment. Real-time PCR was used to quantify the expression of Axin, and western blot analysis was applied to measure protein levels of Axin, ß-catenin, Cyclin D1, MMP-7, DNMTS, MeCP2 and acetylated histones. Flow cytometric analysis, colony formation assay, transwell assay and xenograft growth experiment were used to study the biological behavior of the cells with hypermethylated or unmethylated Axin gene after X-ray treatment. RESULTS: Hypermethylated Axin gene was detected in 2 of 4 cell lines, and it correlated inversely with Axin expression. X-ray treatment significantly up-regulated Axin expression in H446 and H157 cells, which possess intrinsic hypermethylation of the Axin gene (P<0.01), but did not show up-regulation in LTE and H460 cells, which have unmethylated Axin gene. 2Gy X-ray significantly reduced colony formation (from 71% to 10.5%) in H157 cells, while the reduction was lower in LTE cells (from 71% to 20%). After X-ray irradiation, xenograft growth was significantly decreased in H157 cells (from 1.15 g to 0.28 g) in comparison with LTE cells (from 1.06 g to 0.65 g). Significantly decreased cell invasiveness and increased apoptosis were also observed in H157 cells treated with X-ray irradiation (P<0.01). Down-regulation of DNMTs and MeCP2 and up-regulation of acetylated histones could be detected in lung cancer cells. CONCLUSIONS: X-ray-induced inhibition of lung cancer cells may be mediated by enhanced expression of Axin via genomic DNA demethylation and histone acetylation. Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor to predict radiosensitivity of the tumor.


Assuntos
Proteína Axina/genética , Metilação de DNA/genética , Neoplasias Pulmonares/genética , Tolerância a Radiação/genética , Animais , Proteína Axina/metabolismo , Western Blotting , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo
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