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1.
J Colloid Interface Sci ; 630(Pt B): 235-248, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36327726

RESUMO

Hexavalent chromium (VI) heavy metal contamination is considered a serious threat to human health and the environment. The photocatalytic reduction of Cr(VI) basically occurs in the acidic environment, severely limiting the application of photocatalysts for the reduction of Cr(VI). Therefore, we designed a microenvironment strategy to achieve efficient reduction of Cr (VI) under neutral conditions by introducing sulfonic acid onto the aromatic conjugated skeleton. A series of characterizations and experiments have shown that the sulfonated aromatic ring conjugated polymer (Arcp-SO3H) can efficiently remove Cr(VI) under neutral or even alkaline conditions. In neutral solutions, Arcp-SO3H has a rate constant of 0.054 min-1 within 90 min and has an efficiency of nearly 100 %, which is 16 times faster than before sulfonation (k = 0.0316 min-1). the Arcp-SO3H surpasses all organic polymers and most metal-based photocatalysts in the related field. The capture experiments have proved that •O2- is the main role of reducing Cr(VI), and e- is secondary, which is quite different from the mechanism reported in the previous literature. The efficiency of reducing Cr (VI) in the four-cycle experiment is still 96 %, which also proves that Arcp-SO3H has strong stability and reproducibility. Thus, Arcp-SO3H has great practical application potential in the treatment of wastewater, and microenvironmental strategies also offer new possibilities in the field of environmental remediation.


Assuntos
Recuperação e Remediação Ambiental , Polímeros , Humanos , Reprodutibilidade dos Testes , Cromo
2.
China Pharmacy ; (12): 1142-1146, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-972962

RESUMO

OBJECTIVE To establish a drug batch number traceability management mode in intelligent anesthesia pharmacy of operating room, improve the management level of batch number traceability in anesthesia pharmacy of operating room and ensure the safety of surgical medication. METHODS The problems encountered in the application of batch number traceability management mode in intelligent anesthesia pharmacy of operating room were analyzed to implement the optimization measure and summarize the optimization effect. RESULTS In view of the incompatibility of multiple batch numbers on the dosing track, the insufficient number of drugs in the automated dispensing cabinet, the long replenishment time, the low stability of the automated dispensing cabinet, and the tedious management of drugs with a near-expiration period, the following measures were implemented, including changing the minimum unit of dosing, adjusting the drug base number and surgery schedule, optimizing the supplementary drug delivery order, repairing dosing tracks of the automated dispensing cabinet, adding the batch number correction function, improving the screening function of drugs with a near-expiration period, and configuring the automated dispensing cabinet in the recovery room. It realized the coexistence of multiple batch numbers on the dosing track, the sufficient number of drugs in the automated dispensing cabinet, the shortening of the replenishment time, the improvement in the stability of the automated dispensing cabinet, and the efficient management of drugs with a near-expiration period. CONCLUSIONS The batch number traceability management mode is established in intelligent anesthesia pharmacy of operating room in our hospital, which improves the system function module, optimizes the work process, increases the stability of the automated dispensing cabinet, improves the work efficiency, and realizes the refined management of surgical medication.

3.
J Med Case Rep ; 16(1): 459, 2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-36496425

RESUMO

BACKGROUND: Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi'an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6-31.0) and 36.1 (26.4-not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi'an site); he had received five prior lines of treatment and had extensive extramedullary lesions. CASE PRESENTATION: The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10-4) complete response status for 52 months. CONCLUSIONS: This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Masculino , Humanos , Pessoa de Meia-Idade , Receptores de Antígenos Quiméricos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Antígeno de Maturação de Linfócitos B , Linfócitos T/patologia , Progressão da Doença
4.
Chin J Integr Med ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35947230

RESUMO

OBJECTIVE: To investigate the effects of Pien Tze Huang (PZH) on the migration and invasion of HCC cells and underlying molecular mechanism. METHODS: Cell counting kit-8 (CCK-8) was applied to evaluate the cell viabilities of SMMC-7721, SK-Hep-1, C3A and HL-7702 (6 × 103 cells/well) co-incubated with different concentrations of PZH (0, 0.2, 0.4, 0.6, 0.8 mg/mL) for 24 h. Transwell, wound healing assay, CCK-8 and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration, invasion, proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells (650 µ g/mL for SK-Hep-1 cells and 330 µ g/mL for SMMC-7721 cells), respectively. In vivo, lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH. SK-Hep-1 cells (106 cells/200 µ L per mice) were injected into B-NDG mice via tail vein. Totally 8 mice were randomly divided into PZH and control groups, 4 mice in each group. After 2-d inoculation, mice in the PZH group were administered with PZH (250 mg/kg, daily) and mice in the control group received only vehicle (PBS) from the 2nd day after xenograft to day 17. Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to verify RNA-seq results. Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein (YAP). RESULTS: PZH treatment significantly inhibited the migration, invasion, proliferation and promoted the apoptosis of HCC cells in vitro and in vivo (P<0.01). Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH. Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta (PDGFRB), YAP, connective tissue growth factor (CCN2), N-cadherin, vimentin and matrix metallopeptidase 2 (MMP2, P<0.01). Meanwhile, the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo. Furthermore, PZH played roles in inhibiting the transcriptional activity of YAP. CONCLUSION: PZH restrained migration, invasion and epithelial-mesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.

5.
J Hazard Mater ; 434: 128938, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35452994

RESUMO

The conversion of hexavalent chromium (Cr(VI)), a highly poisonous heavy metal found in natural environment, to less poisonous trivalent chromium (Cr(III)) has attracted a lot of interest. However, little interest has been paid to the development of metal-free catalysts. Here, we demonstrate for the first time a molecular engineering strategy to synthesize a range of donor-acceptor conjugated polymer photocatalysts, which can significantly increase the reduction efficiency of Cr(VI) by a factor of 5.2, corresponding to a significant change in the reduction reaction rate constant (from 0.0337 to 0.1740 min-1). In addition, the apparent quantum efficiency (AQE) of Cr(VI) removal was obtained, and the optimized photocatalyst (Py-SO1) could achieve the highest apparent quantum efficiency at wavelength of 420 nm in those samples. Despite the narrow light absorption of Py-SO1 polymer, its excellent exciton separation efficiency and efficient electron output enabled it to achieve excellent performance in photoreduction of Cr(VI), surpassing that of the reported metal-free photocatalysts. The results show that the present work provides a new perspective for designing suitable environmental remediation catalysts based on molecular engineering strategies.

6.
Sci Total Environ ; 810: 151182, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34710406

RESUMO

Fenton-like catalysts represent a family of promising materials to degrade micropollutants from contaminated water. However, the practical applications of Fenton-like catalysts are mainly limited by low catalytic degradation efficiency and stability. Herein, for the first time, rapid fabrication of Ag-decorated Fe3O4/polydopamine (FPA) microspheres was achieved via the help of UV irradiation, and the designed FPA microspheres were employed as Fenton-like catalysts to degrade micropollutants. Results showed that UV irradiation could activate the generation of the polydopamine shell and accelerate the Ag deposition, which played a crucial role in the rapid synthesis of highly active and stable FPA catalysts. Relative to reported catalysts, these FPA microspheres exhibited outstanding catalytic degradation performance, achieving 94.38% removal of tetracycline within 60 min. This work will provide a convenient strategy in the sustainable and efficient purification of wastewater to improve the quality of human life.


Assuntos
Peróxido de Hidrogênio , Polímeros , Catálise , Humanos , Indóis
7.
Small ; 18(2): e2105308, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34741427

RESUMO

The ever-increasing development of flexible and wearable electronics has imposed unprecedented demand on flexible batteries of high energy density and excellent mechanical stability. Rechargeable lithium (Li) metal battery shows great advantages in terms of its high theoretical energy density. However, the use of Li metal anode for flexible batteries faces huge challenges in terms of its undesirable dendrite growth, poor mechanical flexibility, and slow fabrication speed. Here, a highly scalable Li-wicking strategy is reported that allows ultrafast fabrication of mechanically flexible and electrochemically stable Li metal anodes. Through the rational design of the interface and structure of the wicking host, the mean speed of Li-wicking reaches 10 m2 min-1 , which is 1000 to 100 000 fold faster than the reported electrochemical deposition or thermal infusion methods and meets the industrial fabrication speed. Importantly, the Li-wicking process results in a unique 3D Li metal structure, which not only offers remarkable flexibility but also suppresses the dendrite formation. Paring the Li metal anode with lithium-iron phosphate or sulfur cathode yields flexible full cells that possess a high charging rate (8.0 mA cm-2 ), high energy density (300-380 Wh kg-1 ), long cycling stability (over 550 cycles), and excellent mechanical robustness (500 bending cycles).


Assuntos
Eletrônica , Lítio , Ação Capilar , Eletrodos
8.
Anal Chim Acta ; 1190: 339236, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34857140

RESUMO

The antibiotic tetracycline (Tc) is a major contaminant in food and water, with adverse effects on both ecosystems and human health. The development of novel sensors for tetracycline detection is of great importance. In this work, we develop a novel heteroatom-free conjugated tetraphenylethylene polymer (TPE-CMP) fluorescence sensor for the detection of tetracycline. In the presence of Tc, the emission fluorescence of TPE-CMP was quenched by the photoinduced electron transfer mechanism to achieve high sensitivity. The polymers can detect tetracycline at a concentration of 0-100 µg/mL with a good linear correlation (0.99), and the limit of detection (LOD) is 1.23 µg/mL. Furthermore, TPE-CMP has excellent selectivity in detecting Tc in the presence of various anti-interference analytes, including ions and antibiotics. In addition, the practical feasibilities of TPE-CMP for Tc sensing were further investigated in milk, urine and wastewater samples with satisfactory recoveries (from 94.96% to 112.53% for milk, from 96.41% to 99.31% for urine and from 98.54% to 100.52% for wastewater). We have designed and synthesized TPE-CMP based on heteroatom-free for the specific fluorescence detection of tetracycline, expanding the range of fluorescence detection sensors and offering great promise for practical applications.


Assuntos
Ecossistema , Polímeros , Antibacterianos , Corantes Fluorescentes , Humanos , Espectrometria de Fluorescência , Estilbenos , Tetraciclina
9.
Front Oncol ; 11: 712348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422665

RESUMO

ARTEMIN (ARTN), one of the glial-cell derived neurotrophic factor family of ligands, has been reported to be associated with a number of human malignancies. In this study, the enhanced expression of ARTN in colorectal carcinoma (CRC) was observed; the expression of ARTN positively correlated with lymph node metastases and advanced tumor stages and predicted poor prognosis. Forced expression of ARTN in CRC cells enhanced oncogenic behavior, mesenchymal phenotype, stem cell-like properties and tumor growth and metastasis in a xenograft model. These functions were conversely inhibited by depletion of endogenous ARTN. Forced expression of ARTN reduced the sensitivity of CRC cells to 5-FU treatment; and 5-FU resistant CRC cells harbored enhanced expression of ARTN. The oncogenic functions of ARTN were demonstrated to be mediated by p44/42 MAP kinase dependent expression of CDH2 (CADHERIN 2, also known as N-CADHERIN). Inhibition of p44/42 MAP kinase activity or siRNA mediated depletion of endogenous CDH2 reduced the enhanced oncogenicity and chemoresistance consequent to forced expression of ARTN induced cell functions; and forced expression of CDH2 rescued the reduced mesenchymal properties and resistance to 5-FU after ARTN depletion. In conclusion, ARTN may be of prognostic and theranostic utility in CRC.

10.
J Cancer Res Ther ; 15(4): 882-888, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436247

RESUMO

OBJECTIVE: T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) has been widely recognized as a negative regulator of antitumor immunity. However, the mechanism by which Tim-3 suppresses antitumor treatment in gliomas remains unclear. This study aims to explore whether Tim-3 is expressed and to evaluate its effect in drug-fasted glioma cells. SUBJECTS AND METHODS: U87 and U251 glioma cell lines were tested. Cell proliferation activity, cell viability, and the protein and mRNA levels of Tim-3 were detected using CCK-8, flow cytometry, Western blotting, and reverse transcription-quantitative polymerase chain reaction, respectively. Enhancement of the sensitivity of glioma cells to chemotherapeutic agents was tested after inhibiting Tim-3 expression using Tim-3 small interfering RNAs (siRNA). RESULTS: As temozolomide (TMZ) concentration increased, the ratio of apoptotic cells also increased accordingly. However, the level of Tim-3 expression in living cells from the high-dose group was higher than in the low- and middle-dose groups. After interfering with the expression of Tim-3 using siRNA against Tim-3, the killing effect of TMZ rose through an increase in apoptosis. CONCLUSIONS: The presence of Tim-3 mRNA and protein in glioma cells was detected. Significantly, knocking down Tim-3 expression improved the potential of TMZ treatment.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/patologia , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Temozolomida/farmacologia , Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Proliferação de Células/efeitos dos fármacos , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/antagonistas & inibidores , Receptor Celular 2 do Vírus da Hepatite A/genética , Humanos , RNA Interferente Pequeno/genética , Células Tumorais Cultivadas
11.
J Hematol Oncol ; 11(1): 141, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572922

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. RESULTS: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. CONCLUSIONS: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.


Assuntos
Antígeno de Maturação de Linfócitos B/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Receptores de Antígenos Quiméricos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Indução de Remissão , Adulto Jovem
12.
Oncotarget ; 8(61): 103900-103918, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29262609

RESUMO

Tumor derived human growth hormone (hGH) has been implicated in cancer development and progression. However, the specific functional role of autocrine/paracrine hGH in colorectal cancer (CRC) remains largely to be determined. Herein, we demonstrated a crucial oncogenic role of autocrine hGH in CRC progression. Elevated hGH expression was detected in CRC compared to normal colorectal tissue, and hGH expression in CRC was positively associated with tumor size and lymph node metastasis. Forced expression of hGH stimulated cell proliferation, survival, oncogenicity and epithelial to mesenchymal transition (EMT) of CRC cells, and promoted xenograft growth and local invasion in vivo. Autocrine hGH expression in CRC cells stimulated the activation of the ERK1/2 pathway, which in turn resulted in increased transcription of the mesenchymal marker FIBRONECTIN 1 and transcriptional repression of the epithelial marker E-CADHERIN. The autocrine hGH-stimulated increase in CRC cell proliferation, cell survival and EMT was abrogated upon ERK1/2 inhibition. Furthermore, autocrine hGH-stimulated CRC cell migration and invasion was dependent on the ERK1/2-mediated increase in FIBRONECTIN 1 expression and decrease in E-CADHERIN expression. Forced expression of hGH also enhanced CSC-like behavior of CRC cells, as characterized by increased colonosphere formation, ALDH-positive population and CSC marker expression. Autocrine hGH-enhanced cancer stem cell (CSC)-like behavior in CRC cells was also observed to be E-CADHERIN-dependent. Thus, autocrine hGH plays a critical role in CRC progression, and inhibition of hGH could be a promising targeted therapeutic approach to limit disease progression in metastatic CRC patients.

13.
Int J Mol Sci ; 18(6)2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28617312

RESUMO

Despite progress in diagnosis and treatment of hepatocellular carcinoma (HCC), the clinical outcome is still unsatisfactory. Increased expression of human growth hormone (hGH) in HCC has been reported and is associated with poor survival outcome in HCC patients. Herein, we investigated the mechanism of the oncogenic effects of hGH in HCC cell lines. In vitro functional assays demonstrated that forced expression of hGH in these HCC cell lines promoted cell proliferation, cell survival, anchorage-independent growth, cell migration, and invasion, as previously reported. In addition, forced expression of hGH promoted cancer stem cell (CSC)-like properties of HCC cells. The increased invasive and CSC-like properties of HCC cells with forced expression of hGH were mediated by inhibition of the expression of the tight junction component CLAUDIN-1. Consistently, depletion of CLAUDIN-1 expression increased the invasive and CSC-like properties of HCC cell lines. Moreover, forced expression of CLAUDIN-1 abrogated the acquired invasive and CSC-like properties of HCC cell lines with forced expression of hGH. We further demonstrated that forced expression of hGH inhibited CLAUDIN-1 expression in HCC cell lines via signal transducer and activator of transcription 3 (STAT3) mediated inhibition of CLAUDIN-1 transcription. Hence, we have elucidated a novel hGH-STAT3-CLAUDIN-1 axis responsible for invasive and CSC-like properties in HCC. Inhibition of hGH should be considered as a therapeutic option to hinder progression and relapse of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Claudina-1/genética , Regulação Neoplásica da Expressão Gênica , Hormônio do Crescimento Humano/metabolismo , Neoplasias Hepáticas/genética , Fator de Transcrição STAT3/metabolismo , Apoptose , Comunicação Autócrina , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Células Hep G2 , Hormônio do Crescimento Humano/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
14.
Oncol Lett ; 12(5): 4013-4020, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27895764

RESUMO

Cancer cachexia remains a leading cause of morbidity and mortality worldwide, despite extensive research and clinical trials. The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, and that leads to progressive functional impairment. The mechanism underlying muscle loss in patients with cachexia is poorly understood. The present study analyzed 21 cancer patients with or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated in the rectus abdominis of patients with cachexia, which was associated with body weight loss. In vitro cell experiments indicated that loss of Mfn2 was associated with atrophy of the C2C12 mouse myoblast cell line. Furthermore, in vivo animal experiments demonstrated that cachexia decreased gastrocnemius muscle mass and Mfn2 expression, and overexpression of Mfn2 in gastrocnemius muscle was able to partially attenuate cachexia-induced gastrocnemius muscle loss. The results of the present study suggested that Mfn2 is involved in cachexia-induced muscle loss and may serve as a potential target for therapy of cachexia.

15.
Nutr Cancer ; 67(8): 1314-23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26576476

RESUMO

Hypoxia has been proved to be a typical character of solid tumors. Tumor cells prefer to use glucose through the glycolysis pathway instead of aerobic respiration. However, the precise molecular mechanism underlying this so-called Warburg effect remains elusive. In the current study, siRNA was synthesized and transfected into BxPC-3 cell line to silence the expression of HIF-1α gene. It was found that hypoxia induced hypoxia-inducible factor 1α (HIF-1α) overexpression in BxPC-3 cells, enhanced the expression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A, thus facilitating glycolysis and making tumor cells more tolerant to hypoxic stress. The silencing of HIF-1α gene significantly attenuated glycolysis under hypoxic conditions, inhibited the growth and invasion ability of BxPC-3 cells, and enhanced hypoxia-induced cell apoptosis.


Assuntos
Inativação Gênica , Glicólise/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Animais , Apoptose , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Isoenzimas/genética , L-Lactato Desidrogenase/genética , Lactato Desidrogenase 5 , Ácido Láctico/biossíntese , Camundongos , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Proteínas Serina-Treonina Quinases/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil , RNA Interferente Pequeno/genética , Transfecção
16.
Clinicoecon Outcomes Res ; 7: 369-75, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26170701

RESUMO

BACKGROUND AND OBJECTIVES: Clinical evidence supports the use of omega-3 polyunsaturated fatty acid (PUFA)-enriched lipid emulsions in place of standard lipid emulsions in parenteral nutrition (PN) for intensive care unit (ICU) patients, but uptake may be limited by higher costs. We compared clinical and economic outcomes for these two types of lipid emulsion in the Chinese ICU setting. METHODS: We developed a pharmacoeconomic discrete event simulation model, based on efficacy data from an international meta-analysis and patient characteristics, resource consumption, and unit costs from a Chinese institutional setting. Probabilistic sensitivity analyses were undertaken to assess the effects of uncertainty around input parameters. Model predictive validity was assessed by comparing results with data observed in a patient subset not used in the modeling. RESULTS: The model predicted that omega-3 PUFA-enriched emulsion (Omegaven(®) 10% fish oil emulsion) would dominate standard lipid emulsions, with better clinical outcomes and lower overall health care costs (mean savings ~10,000 RMB), mainly as a result of faster recovery and shorter hospital stay (by ~6.5 days). The external validation process confirmed the reliability of the model predictions. CONCLUSION: Omega-3 PUFA-enriched lipid emulsions improved clinical outcome and decreased overall costs in Chinese ICU patients requiring PN.

17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(2): 315-9, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25970884

RESUMO

The present manuscript researches the near infrared quantum cutting luminescence phenomena of Yb3+ ion in YVO4 crystal matrix The luminescence spectra, excitation spectra and fluorescence lifetimes were measured. It was found that the excitation of YVO4 crystal matrix energy band by 322.0 nm light can result in the effective secondary cooperative energy transfer of Yba+ ion from the YVO4 crystal matrix It results in the intense 985.5 nm 2F(5/2)-->2F(7/2) near infrared quantum cutting luminescence of Yb3+ ion. Meanwhile, the 430.O nm luminescence intensity of YVO4 crystal matrix decreases greatly. From the experimental measurements, it was found that the lifetime of 430.0 nm fluorescence of (A) Yb(1.5) : YVO4 crystal is tauA = 3.785 s and that of (B) YVO4 crystal is tauB=22.72 s. It was found also that the theoretical efficiency up limit of quantum cutting of (A) Yb(1.5) : YVO4 crystal is about eta1.5%=183-3%.

18.
Asian Pac J Cancer Prev ; 15(14): 5551-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25081663

RESUMO

BACKGROUND: The prognostic value of human epidermal growth factor receptor-2 (HER-2/neu) for survival of patients with colorectal cancer (CRC) is still ambiguous. We therefore performed a meta-analysis to evaluate its prognostic significance. MATERIALS AND METHODS: We searched the MEDLINE and EMBASE databases for published literature investigating associations between HER-2/neu status and overall survival of patients with CRC. A meta-analysis was performed using a DerSimonian-Laird model and publication bias was investigated by Begg's and Egger's tests. Subgroup analysis was also conducted according to the study design type, study quality score, cut-off value for HER-2/neu overexpression, publication region, patient number and publication year. RESULTS: A total of 17 eligible studies involving 2,347 patients were identified for this meta-analysis. The combined hazard ratio (HR) was 1.31 (95% confidence interval (CI): 0.96-1.79), suggesting that HER-2/neu overexpression was not significantly associated with overall survival of patients with CRC. However, subgroup analysis revealed that HER-2/neu overexpression had an unfavorable impact on survival when the analysis was restricted to subgroups of study quality score ≤ 5 (HR=1.56, 95%CI: 1.17-2.10), Asian patients (HR=1.74, 95%CI: 1.22-2.49), patient number ≤ 106 (HR=1.57, 95%CI: 1.01-2.44), publication year before 2003 (HR=1.59, 95%CI: 1.02-2.49), and prospectively designed study (HR=3.62, 95%CI: 1.42-9.24). The effect disappeared in subgroups of study quality scores > 5 (HR=0.69, 95%CI: 0.33-1.44), non Asian patients (HR=1.14, 95%CI: 0.77-1.70), patients' number > 106 (HR=1.07, 95%CI: 0.67-1.72), publication year after 2003 (HR=1.13, 95%CI: 0.76-1.69), and retrospectively designed study (HR=1.22, 95%CI: 0.89-1.67). CONCLUSIONS: Our meta-analysis suggests that HER-2/neu overexpression might not be a significantly prognostic indicator for patients with CRC. Further studies are required to confirm these results.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Receptor ErbB-2/metabolismo , Povo Asiático , Neoplasias Colorretais/genética , Humanos , Prognóstico , Receptor ErbB-2/biossíntese , População Branca
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 15(12): 1287-90, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23268279

RESUMO

OBJECTIVE: To demonstrate the expression of proteolysis induce factor(PIF) in the gastrointestinal(GI) cancer cachexia patients and evaluate its role in cancer cachexia. METHODS: Examination of PIF was performed in urine samples from 28 GI cancer cachexia patients, 13 GI cancer patients without cachexia, and 12 weight loss patients with benign disease. PIF was added to the mice cultured C2C12 muscle cells, then the protein kinase B(Akt) phosphorylation and morphological change were measured. RESULTS: The positive rate of PIF in urine of 28 cancer cachexia patients was 53.6%(15/28). In the other two groups, no positive result was detected. PIF could successfully induce Akt phosphorylation, cell atrophy, metamorphosis, and death. The peak of this phosphorylation could be detected after half an hour of the initiation of PIF at a concentration of 4 nmol/L. CONCLUSIONS: PIF is specifically and highly expressed in GI cancer cachexia patients' urine. PIF can induce cancer cachexia possibly by activating Akt phosphorylation and inducing downstream proteolysis.


Assuntos
Caquexia/etiologia , Caquexia/metabolismo , Neoplasias Gastrointestinais/complicações , Animais , Linhagem Celular , Humanos , Camundongos , Proteoglicanas , Proteólise
20.
IUBMB Life ; 64(9): 775-82, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22807066

RESUMO

Pyruvate kinase type M2 (PKM2) has been reported to be involved in aerobic glycolysis and cell growth in various tumors. However, the expression pattern of PKM2 in colorectal cancer (CRC) and the correlation between PKM2 expression and CRC remains unclear. The aim of this study is to investigate PKM2 expression and its possible role in CRC. We found that expression of PKM2 was increased in CRC and the increased PKM2 expression was associated with later stage and lymph metastasis of the tumors. Knockdown of PKM2 suppressed the aerobic glycolysis and decreased lactate production of colon cancer RKO cells. Knockdown of PKM2 repressed proliferation and migration of the cells. Inhibition of PKM2 suppressed xenograft tumor growth of RKO cells in vivo. These results suggest that the expression of PKM2 plays a critical role in development of CRC, and it may provide a growth advantage for colon cancer cells. Thus, PKM2 might be a potential therapeutic target for CRC.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais/enzimologia , Piruvato Quinase/genética , Regulação para Cima , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Expressão Gênica , Glicólise , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Piruvato Quinase/metabolismo , Carga Tumoral
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