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1.
Sci Rep ; 14(1): 2942, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316853

RESUMO

To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor.


Assuntos
Neoplasias Pancreáticas , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Metástase Linfática , Prognóstico , Neoplasias Pancreáticas/patologia , Quimioterapia Adjuvante , Biomarcadores , Recidiva Local de Neoplasia/patologia
2.
Gastroenterology ; 165(1): 133-148.e17, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36907523

RESUMO

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA), with its highly metastatic propensity, is one of the most lethal subtypes of pancreatic cancer. Although recent large-scale transcriptomic studies have demonstrated that heterogeneous gene expressions play an essential role in determining molecular phenotypes of PDA, biological cues for and consequences of distinct transcriptional programs remain unclear. METHODS: We developed an experimental model that enforces the transition of PDA cells toward a basal-like subtype. We combined epigenome and transcriptome analyses with extensive in vitro and in vivo evaluations of tumorigenicity to demonstrate the validity of basal-like subtype differentiation in association with endothelial-like enhancer landscapes via TEA domain transcription factor 2 (TEAD2). Finally, we used loss-of-function experiments to investigate the importance of TEAD2 in regulating reprogrammed enhancer landscape and metastasis in basal-like PDA cells. RESULTS: Aggressive characteristics of the basal-like subtype are faithfully recapitulated in vitro and in vivo, demonstrating the physiological relevance of our model. Further, we showed that basal-like subtype PDA cells acquire a TEAD2-dependent proangiogenic enhancer landscape. Genetic and pharmacologic inhibitions of TEAD2 in basal-like subtype PDA cells impair their proangiogenic phenotypes in vitro and cancer progression in vivo. Last, we identify CD109 as a critical TEAD2 downstream mediator that maintains constitutively activated JAK-STAT signaling in basal-like PDA cells and tumors. CONCLUSIONS: Our findings implicate a TEAD2-CD109-JAK/STAT axis in the basal-like differentiated pancreatic cancer cells and as a potential therapeutic vulnerability.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição de Domínio TEA , Neoplasias Pancreáticas
3.
Adv Sci (Weinh) ; 10(8): e2205148, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36698298

RESUMO

Cholangiocarcinoma (CCA) is a fatal disease often detected late in unresectable stages. Currently, there are no effective diagnostic methods or biomarkers to detect CCA early with high confidence. Analysis of tumor-derived extracellular vesicles (tEVs) harvested from liquid biopsies can provide a new opportunity to achieve this goal. Here, an advanced nanoplasmonic sensing technology is reported, termed FLEX (fluorescence-amplified extracellular vesicle sensing technology), for sensitive and robust single EV analysis. In the FLEX assay, EVs are captured on a plasmonic gold nanowell surface and immunolabeled for cancer-associated biomarkers to identify tEVs. The underlying plasmonic gold nanowell structures then amplify EVs' fluorescence signals, an effective amplification process at the single EV level. The FLEX EV analysis revealed a wide heterogeneity of tEVs and their marker levels. FLEX also detected small tEVs not detected by conventional EV fluorescence imaging due to weak signals. Tumor markers (MUC1, EGFR, and EPCAM) are identified in CCA, and this marker combination is applied to detect tEVs in clinical bile samples. The FLEX assay detected CCA with an area under the curve of 0.93, significantly better than current clinical markers. The sensitive and accurate nanoplasmonic EV sensing technology can aid in early CCA diagnosis.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Vesículas Extracelulares , Humanos , Colangiocarcinoma/diagnóstico , Biomarcadores Tumorais , Vesículas Extracelulares/química , Ductos Biliares Intra-Hepáticos/química , Neoplasias dos Ductos Biliares/diagnóstico
4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-897012

RESUMO

Purpose@#This study aims to evaluate the effect of different pneumoperitoneum pressures on postoperative pain, especially by subcategorizing the pressures into 3 groups during laparoscopic cholecystectomy (LC). @*Methods@#We conducted a prospective randomized, double-blinded study of 150 patients with benign and uncomplicated gallbladder disease. They were categorized into 3 groups. Each group (50 patients) underwent LC with different pneumoperitoneum methods: group VLP, very-low pressure (6–8 mmHg); group LP, low pressure (9–11 mmHg); and group SP, standard pressure (12–14 mmHg). The 3 groups were compared for pain intensity, duration, analgesic requirement, and complications. @*Results@#The characteristics of the patients were similar among all groups. Postoperative pain scores at each time point (1, 2, 4, 6, 12, 24, and 48 hours) were not significantly different among the 3 groups. Further, operation time, hospital stay, the number of analgesic consumption doses, and postoperative complications were not significantly different among the 3 groups. @*Conclusion@#This study demonstrates no difference in postoperative pain among various pneumoperitoneum pressures during LC. Therefore, routine use of lower-pressure pneumoperitoneum is not recommended unless in selected patients who require low-pressure pneumoperitoneum surgery.

5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-889308

RESUMO

Purpose@#This study aims to evaluate the effect of different pneumoperitoneum pressures on postoperative pain, especially by subcategorizing the pressures into 3 groups during laparoscopic cholecystectomy (LC). @*Methods@#We conducted a prospective randomized, double-blinded study of 150 patients with benign and uncomplicated gallbladder disease. They were categorized into 3 groups. Each group (50 patients) underwent LC with different pneumoperitoneum methods: group VLP, very-low pressure (6–8 mmHg); group LP, low pressure (9–11 mmHg); and group SP, standard pressure (12–14 mmHg). The 3 groups were compared for pain intensity, duration, analgesic requirement, and complications. @*Results@#The characteristics of the patients were similar among all groups. Postoperative pain scores at each time point (1, 2, 4, 6, 12, 24, and 48 hours) were not significantly different among the 3 groups. Further, operation time, hospital stay, the number of analgesic consumption doses, and postoperative complications were not significantly different among the 3 groups. @*Conclusion@#This study demonstrates no difference in postoperative pain among various pneumoperitoneum pressures during LC. Therefore, routine use of lower-pressure pneumoperitoneum is not recommended unless in selected patients who require low-pressure pneumoperitoneum surgery.

6.
J Hazard Mater ; 388: 121739, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31796361

RESUMO

Mechanisms involved in an electrochemically assisted oxidation process using persulfate and nanosized zero-valent iron (NZVI) were elucidated. Initially, Fe0 acted as a source of Fe2+ to activate the persulfate, then Fe2+/Fe3+ redox mediation between cathode and persulfate played a decisive role in persulfate activation at a current density low enough not to inhibit Fe0 corrosion. An excessive current density which resulted in a low cathodic potential limited Fe0 corrosion and therefore limited the supply of dissolved Fe to activate the persulfate. Direct oxidation of phenol at the anode therefore became more important under the excessive current density than oxidation by sulfate radicals. At a low current density, Fe0 in the NZVI particles was completely transformed into iron (oxyhydr)oxides such as ferrihydrite, lepidocrocite, and magnetite. Fe0 was transformed into Fe2+ little when the current density was high. Increasing the current density increased the energy cost by increasing the amount of electrical energy dissipated in side reactions that decreased sulfate radical formation. The results indicated that a low current density can generally be used to give a high reaction rate and a high energy efficiency and that a high current density can be used when the NZVI particles need to be preserved.

7.
J Hazard Mater ; 378: 120760, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31228709

RESUMO

A carbonation/granulation process for treating mine tailings using a MgO/ground-granule blast-furnace-slag (GGBS) binder was developed. The materials were mixed and granules produced using a granulator, then the granules were cured in a CO2 atmosphere. The optimum granulator rotation speed and retention time were 60 rpm and 7 min, respectively. The binder composition MgO0.5GGBS0.5 and binder: mine tailings ratio 3:10 gave the strongest granules. Carbonation generally increased the granule strength, but different CO2 concentrations, between 0.04% and 100%, changed the granule strength to different degrees. Granules cured in 20% CO2 for 28 d had a strength of 4.71 MPa, which was higher than the strengths of granules cured in other CO2 concentrations and of granules produced using Portland cement. The granules had relatively high CO2 storage capacities of 0.157-0.167 kg CO2/kg binder and good acid-neutralizing capacities (higher than the acid-neutralizing capacity of granules produced using Portland cement). The strength of the granules cured in 20% CO2 for 28 d was probably mainly attributed to the formation of hydromagnesite during carbonation. The hydromagnesite contributed dense and connected structures within the granules. The granules produced show great potential for use as aggregates for reclamation work and backfilling in mining areas.

8.
Environ Sci Pollut Res Int ; 25(23): 22552-22560, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29808408

RESUMO

We previously described a MgO-based binder for treating fine sediment and simultaneously store CO2. Here, we describe a study of the physical/mechanical characteristics and carbonation reactions of the MgO-based binder used to solidify/stabilize fine sediment in atmospheres containing different CO2 concentrations. Carbonation of the sediment treated with the MgO-based binder at the atmospheric CO2 concentration markedly improved the compressive strength of the product. The compressive strength was 4.78 MPa after 365 days of curing, 1.3 times higher than the compressive strength of sediment treated with portland cement. This improvement was caused by the formation of carbonation products, such as hydromagnesite, nesquehonite, and lansfordite, and the constant high pH (~ 12) of the specimen, which favored the growth of hydration products such as calcium silicate hydrates and portlandite. Very low compressive strengths were found when 50 and 100% CO2 atmospheres were used because of excessive formation of carbonation products, which occupied 78% of the specimen depth. Abundant carbonation products increased the specimen volume and decreased the pH to 10.2, slowing the growth of hydration products. The absence of brucite in specimens produced in a 100% CO2 atmosphere indicated that MgO carbonation is favored over hydration at high CO2 concentrations.


Assuntos
Dióxido de Carbono/química , Materiais de Construção , Óxido de Magnésio/química , Atmosfera , Compostos de Cálcio/química , Carbonatos , Força Compressiva , Concentração de Íons de Hidrogênio , Hidróxido de Magnésio , Microscopia Eletrônica de Varredura , Silicatos/química , Termogravimetria , Difração de Raios X
9.
Environ Sci Technol ; 52(6): 3625-3633, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29432692

RESUMO

The mechanisms involved in the activation of persulfate by nanosized zero-valent iron (NZVI) were elucidated and the NZVI transformation products identified. Two distinct reaction stages, in terms of the kinetics and radical formation mechanism, were found when phenol was oxidized by the persulfate/NZVI system. In the initial stage, lasting 10 min, Fe0(s) was consumed rapidly and sulfate radicals were produced through activation by aqueous Fe2+. The second stage was governed by Fe catalyzed activation in the presence of aqueous Fe3+ and iron (oxyhydr)oxides in the NZVI shells. The second stage was 3 orders of magnitude slower than the initial stage. An electron balance showed that the sulfate radical yield per mole of persulfate was more than two times higher in the persulfate/NZVI system than in the persulfate/Fe2+ system. Radicals were believed to be produced more efficiently in the persulfate/NZVI system because aqueous Fe2+ was supplied slowly, preventing sulfate radicals being scavenged by excess aqueous Fe2+. In the second stage, the multilayered shell conducted electrons, and magnetite in the shell provided electrons for the activation of persulfate. Iron speciation analysis (including X-ray absorption spectroscopy) results indicated that a shrinking core/growing shell model explained NZVI transformation during the persulfate/NZVI process.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Ferro , Oxirredução , Água
10.
Cancer Research and Treatment ; : 1106-1113, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-717756

RESUMO

PURPOSE: Even though the therapeutic gold standard of hilar cholangiocarcinoma (HCCA) resection is cancer-free resection margin (RM), surgical treatment still remains challenging. This study evaluated the prognostic significance of RM status in resected HCCA patients and identified survival prognostic factors. MATERIALS AND METHODS: We reviewed records of 96 HCCA patients who underwent surgery from 2001 to 2012 and analyzed the RM status and prognostic factors that affecting survival. RESULTS: Negative RM (n=31, 33%) was significantly associated with better survival vs. positive RM (n=65, 67%) (mean survival time [MST], 33 months vs. 21 months; p=0.011). Margins with histological findings of non-dysplastic epithelium, low-grade dysplasia, and carcinoma in situ were not associated with survival differences (MST, 33 months vs. 33 months vs. 30 months; p=0.452), whereas positive margins were associated with poorer survival relative to carcinoma in situ (MST, 30 months vs. 21 months; p=0.050). Among patients with R0 resection, narrow (≤ 5 mm) and wide (> 5 mm) margins were not associated with survival differences (MST, 33 months vs. 30 months; p=0.234). Although positive proximal RM was associated with poorer survival compared to negative RM (MST, 19 vs. 33; p=0.002), no survival difference was observed between positive and negative distal RMs (MST, 30 vs. 33; p=0.628). Proximal RM positivity (hazard ratio [HR], 2.688; p=0.007) and nodal involvement (HR, 3.293; p < 0.001) were independent survival prognostic factors. CONCLUSION: A clear RM, especially proximal RM status, was significant prognosticator, and proximal bile duct resection to the greatest technically feasible extent may be necessary, with careful consideration of the potential morbidity and oncologic outcomes after resection. However, an aggressive approach to obtain a negative distal RM might be controversial and should be considered carefully, depending on the patient's status.


Assuntos
Humanos , Ductos Biliares , Carcinoma in Situ , Epitélio , Tumor de Klatskin
11.
Biochem Biophys Res Commun ; 482(4): 1407-1412, 2017 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-27965092

RESUMO

Clusterin is a secretory glycoprotein that is up-regulated in areas of inflammation and under increased levels of oxidative stress. Previously, we demonstrated that clusterin activates NF-κB, and up-regulates the expression of MMP-9 and TNF-α. In this research, we extend our previous findings by reporting that such clusterin-induced macrophage response is mediated via TLR4 signaling. Specifically, we found that TNF-α induced by clusterin was significantly abrogated by pretreatment of TLR4-signaling inhibitors and anti-TLR4 neutralizing antibody. Additionally, a primary culture of macrophages derived from TLR4-signal defective and knockout mice were unresponsive to clusterin, resulting in no TNF-α secretion, whereas macrophages carrying wild-type TLR4 responded to clusterin and induced TNF-α. Moreover, clusterin increased NF-κB promoter activity in HEK-Blue hTLR4 cells, but not in HEK-Blue Null2 cells. To confirm that clusterin elicits TLR4 signal transduction, recombinant clusterin was generated and purified from cell culture. Interestingly, we found that the recombinant clusterin with C-terminal HA-tag induces TNF-α secretion at a significantly lower level compared to an intact form of clusterin without C-terminal HA-tag. Removal of HA-tag from the recombinant clusterin restored its activity, suggesting that C-terminal HA-tag partially masks the domain involved in TLR4 signaling. Furthermore, clusterin enhanced TLR4 mobilization into lipid raft of plasma membrane, and TNF-α and MMP-9 secretion stimulated by clusterin was diminished by pretreatment with methyl-ß-cyclodextrin (MßCD), which was used to disrupt lipid raft. In conclusion, clusterin-induced TNF-α and MMP-9 up-regulation is most likely mediated via TLR4 recruitment into lipid rafts, and these data describe a novel role of clusterin as an endogenous regulator for TLR4 signaling.


Assuntos
Clusterina/metabolismo , Macrófagos/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Humanos , Inflamação , Macrófagos/citologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Microdomínios da Membrana/química , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , NF-kappa B/metabolismo , Estresse Oxidativo , Domínios Proteicos , Células RAW 264.7
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-13359

RESUMO

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.


Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/sangue , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Transplante de Fígado , Análise Multivariada , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , alfa-Fetoproteínas/análise
13.
J Nanosci Nanotechnol ; 15(11): 9014-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26726634

RESUMO

We report a simple approach for the production of copper nanoparticles by a wire explosion process that creates different structures in deionized (DI) water versus isopropyl alcohol (IPA) liquid media. In DI water, copper nanoparticles (CNs) are formed, while multi-layer graphene-synthesized copper nanoparticles (MGCNs) with a high degree of graphitization are formed in the IPA liquid media. The nanoparticles have an average diameter ranging from 10 nm to 300 nm and a quasi-spherical morphology. The morphologies and sizes of nanoparticles formed via this method were characterized by high-resolution transmission electron microscopy (HRTEM), field-emission scattering electron microscopy (FESEM), and analysis of dynamic light scattering (DLS). The microstructures and chemical bonding of the nanoparticles were studied by X-ray diffraction (XRD), Raman spectra measurement, and X-ray photoelectron spectroscopy (XPS). This results show an easily reproducible way to synthesize metal-core nanoparticles with multi-layer graphene shells based onto the liquid media used during synthesis. These materials can be used in the field of energy storage and as additives in the near future.

14.
J Nanosci Nanotechnol ; 15(11): 9034-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26726638

RESUMO

We achieved a method for power enhancement of heavy-duty lithium-ion batteries (LIBs) by synthesizing a graphene interfacial layer onto the anode copper current collector (ACCC). We tested fabricated coin cells, which used either 35-µm-thick rolled pristine copper foil or graphene synthesized onto the pristine copper foil for power output estimation of the LIBs. We observed the copper surface morphology with a scanning electron microscope (SEM). Raman spectroscopy was used to measure the bonding characteristics and estimate the layers of graphene films. In addition, transmittance and electrical resistance were measured by ultra-violet visible near-infrared spectroscopy (UV-Vis IR) and 4 point probe surface resistance measurement. The graphene films on polyethylene terephthalate (PET) substrate obtained a transmittance of 97.5% and sheet resistance of 429 Ω/square. Power enhancement performances was evaluated using LIB coin cells. After 5C current discharge rate of -1.7 A/g reversible capacity of 293 mAh/g and 326 mAh/g were obtained for pristine and synthesized graphene anode current collectors, respectively. The graphene synthesized onto the ACCC showed superior power performance. The results presented herein demonstrate a power enhancement of LIBs by a decrease in electron flow resistivity between active materials and the ACCC and removal of the native oxide layer on the anode copper surface using high quality graphene synthesized onto the ACCC.

15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-57050

RESUMO

PURPOSE: We evaluated the heterogeneity of steatosis in living donor livers to determine its regional differences. METHODS: Between June 2011 and February 2012, 81 liver donors were selected. Fat fraction was estimated using magnetic resonance triple-echo chemical shifting gradient imaging in 13 different regions: segment 1 (S1), S2, S3, and each peripheral and deep region of S4, S5, S6, S7, and S8. RESULTS: There were differences (range, 3.2%-5.3%) in fat fractions between each peripheral and deep region of S4, S6, S7, and S8 (P < 0.001, P = 0.004, P < 0.001, and P = 0.006). Fat deposit amount in S1, S2, S3 and deep regions of S4-S8 were significantly different from one another (F [4.003, 58.032] = 8.684, P < 0.001), while there were no differences among the peripheral regions of S4-S8 (F [2.9, 5.3] = 1.3, P = 0.272) by repeated measure analysis of variance method. And regional differences of the amount of fat deposit in the whole liver increased as a peripheral fat fraction of S5 increased (R2 = 0.428, P < 0.001). CONCLUSION: Multifocal fat measurements for the whole liver are needed because a small regional evaluation might not represent the remaining liver completely, especially in patients with severe hepatic steatosis.


Assuntos
Humanos , Fígado Gorduroso , Fígado , Transplante de Fígado , Doadores Vivos , Imageamento por Ressonância Magnética , Características da População , Doadores de Tecidos , Sítio Doador de Transplante
16.
Biochem Biophys Res Commun ; 445(3): 645-50, 2014 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-24569077

RESUMO

Clusterin induces the expression of various chemotactic cytokines including tumor necrosis factor-α (TNF-α) in macrophages and is involved in the cell migration. According to the results of this study, clusterin induced the directional migration (chemotaxis) of macrophages based on a checkerboard analysis. The chemotactic activity of clusterin was prevented by pretreatment with pertussis toxin (PTX), indicating that the Gαi/o-protein coupled receptor (GPCR) was involved in the chemotactic response of clusterin. Clusterin-stimulated chemotaxis was abrogated in a dose-dependent manner by pretreatment with gallein (a Gßγ inhibitor), indicating the involvement of Gßγ released from the GPCR. In addition, inhibitors of phospholipase C (PLC, U73122) and phosphoinositide 3-kinase (PI3K, LY294002), the key targets of Gßγ binding and activation, suppressed chemotactic migration by clusterin. The phosphorylation of Akt induced by clusterin was blocked by pretreatment with gallein or LY294002 but not with U73122, indicating that Gßγ released from the PTX-sensitive Gi protein complex activated PLC and PI3K/Akt signaling pathways separately. The activation of cellular MAP kinases was essential in that their inhibitors blocked clusterin-induced chemotaxis, and Gßγ was required for the activation of MAP kinases because gallein reduced their phosphorylations induced by clusterin. In addition, the inflammation-induced migration of macrophages was greatly reduced in clusterin-deficient mice based on a thioglycollate-induced peritonitis model system. These results suggest that clusterin stimulates the chemotactic migration of macrophages through a PTX-sensitive GPCR and Gßγ-dependent pathways and describe a novel role of clusterin as a chemoattractant of monocytes/macrophages, suggesting that clusterin may serve as a molecular bridge between inflammation and its remodeling of related tissue by recruiting immune cells.


Assuntos
Quimiotaxia , Clusterina/metabolismo , Macrófagos/citologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Quimiotaxia/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Toxina Pertussis/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Transdução de Sinais , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismo
17.
J Nanosci Nanotechnol ; 14(12): 9515-24, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25971093

RESUMO

Electroless Ni-P films were investigated with the aim of application as barrier and seed layers in 3D interconnect technology. Different shapes of blind-via holes were fabricated with a deep reactive ion etcher and SiO2 formed on these holes as an insulating layer. The surface of the substrate has been made hydrophilic by O2 plasma treatment with 100 W of power for 20 min. Electroless Ni-P films were deposited as both a diffusion barrier and a seed layer for Cu filling process. Prior to plating, substrates were activated in a palladium chloride solution after sensitization in a tin chloride solution with various conditions in order to deposit uniform films in TSV. After the formation of the electroless barrier layer, electro Cu was plated directly on the barrier layer. Ni-P films fabricated in blind-via holes were observed by scanning electron microscope. Energy dispersive spectroscopy line scanning was carried out for evaluating the diffusion barrier properties of the Ni-P films. The electroless Ni-P layer worked well as a Cu diffusion barrier until 300 degrees C. However, Cu ions diffused into barrier layer when the annealing temperature increases over 400 degrees C.

18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-111999

RESUMO

Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by bone fragility and connective tissue manifestations. We report a successful liver transplantation (LT) in an 8-month-old boy with OI and cholestatic biliary cirrhosis. After 4 cycles of intravenous pamidronate, LT was performed under intravenous anesthesia using a left lateral section from his mother without mechanical retractors. The operation time was 420 min and estimated blood loss was 520 mL requiring one unit of RBC transfusion. He was discharged without surgical complications. Therefore, LT should be considered for patients with end stage liver disease and OI under organic multidisciplinary cooperation.


Assuntos
Humanos , Lactente , Masculino , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Colestase Intra-Hepática/diagnóstico , Difosfonatos/uso terapêutico , Fraturas Ósseas/tratamento farmacológico , Transplante de Fígado , Doadores Vivos , Osteogênese Imperfeita/complicações
19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-124862

RESUMO

Liver transplantation (LT) has been the key therapy for end stage liver diseases. However, LT in infancy is still understudied. From 1992 to 2010, 152 children had undergone LT in Seoul National University Hospital. Operations were performed on 43 patients aged less than 12 months (Group A) and 109 patients aged over 12 months (Group B). The mean age of the recipients was 7 months in Group A and 74 months in Group B. The patients' survival rates and post-LT complications were analyzed. The mean Pediatric End-stage Liver Disease score was higher in Group A (21.8) than in Group B (13.4) (P = 0.049). Fulminant hepatitis was less common in Group A (4.8%) than in Group B (13.8%) (P = 0.021). The post-transplant lymphoproliferative disorder and portal vein complication were more common in Group A (14.0%, 18.6%) than in Group B (1.8%, 3.7%) (P = 0.005). However, the 1, 5, and 10 yr patient survival rates were 93%, 93%, and 93%, in Group A and 92%, 90%, and 88% in Group B (P = 0.212). The survival outcome of pediatric LT is excellent and similar regardless of age. LTs in infancy are not riskier than those of children.


Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Fatores Etários , Doença Hepática Terminal/mortalidade , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Infecções por Herpesviridae/etiologia , Transplante de Fígado/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Doenças Vasculares/etiologia
20.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-193464

RESUMO

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema ABO de Grupos Sanguíneos/imunologia , Anticorpos Monoclonais Murinos/uso terapêutico , Dessensibilização Imunológica/métodos , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Teste de Histocompatibilidade , Fígado/cirurgia , Transplante de Fígado , Doadores Vivos , Plasmaferese , Cuidados Pré-Operatórios , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Linfócitos T/imunologia , Transplantados
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