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1.
Clin Rheumatol ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31760539

RESUMO

In this study, we aimed to explore the expression levels of JAK2 and PTPRC in peripheral blood mononuclear cells (PBMCs) from SLE patients and controls, detect the effects of SLE activity on genes mRNA expression, and find the association between genes mRNA expression and clinical manifestations of patients. We performed quantitative real-time PCR (qRT-PCR) to test differences in the expression levels of JAK2 and PTPRC in PBMCs extracted from 135 patients with SLE and 130 healthy controls. Furthermore, we detected the regulatory effect of SNPs on gene expression by expression quantitative trait loci (eQTL). We also tested whether the genes mRNA expression was affected with the SLE activity and analyzed the relationship between genes mRNA expression and clinical manifestations of patients. The mRNA expression levels of JAK2 in SLE patients were significantly higher than those in healthy controls (P = 0.005), and PTPRC mRNA expression levels were significantly decreased (P < 0.001). However, no other statistical significance was detected. We found that the elevated JAK2 mRNA expression and the decreased PTPRC mRNA expression may play suggestive roles in the pathogenesis of SLE.Key Points• The JAK2 mRNA expression levels in SLE patients were significantly higher than those in healthy controls.• The PTPRC mRNA expression levels in SLE were decreased.• JAK2 and PTPRC mRNA expression may play suggestive roles in the pathogenesis of SLE.

2.
Epigenomics ; 11(14): 1613-1625, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31701765

RESUMO

Aim: To understand whether the anatomical location of origin plays a role in shaping the DNA methylation (DNAm) landscape of psoriatic skins. Patients & methods: A number of 108 psoriatic and 57 control skin samples were grouped based on their anatomical locations. Two group t-tests were used to identify those differentially methylated sites and regions. Target region methylation loci were validated by bisulfate conversion sequencing. The correlations of DNAm with pathological features, DNAm and gene expression were also interrogated. Results: Our analysis revealed 315 location-specific differentially methylated sites for back, 291 for the extremities and 801 for abdomen. Moreover, we observed that the extremity-specific loci cg21942490 located on HOXA9 is associated with hyperkeratosis. We further observed that HOXA5 and KIAA1949 are differential methylation regions. Conclusion: Our study shown evidence of anatomical location-dependent DNAm pattern in psoriasis skins, and thus provided new insights into the pathogenesis of this disease.

3.
J Formos Med Assoc ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31395463

RESUMO

The incidence of acute pancreatitis and related health care utilization are increasing. Acute pancreatitis may result in organ failure and various local complications with risks of morbidity and even mortality. Recent advances in research have provided novel insights into the assessment and management for acute pancreatitis. This consensus is developed by Taiwan Pancreas Society to provide an updated, evidence-based framework for managing acute pancreatitis.

4.
BMC Med Educ ; 19(1): 183, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159798

RESUMO

BACKGROUND: Early clinical exposure (ECE) is viewed as a way to provide contexts of basic science and highlight its relevance to medical practice. However, very few studies have specifically looked into how the ECE experience contributes to students' academic performance. The purpose of this study was to investigate whether ECE experiences (external cause) or students' learning attitudes (internal cause) more closely correlated with medical students' academic performance. METHODS: Subjects who participated in the study comprised 109 s-year students at Taipei Medical University. Fifty of the 109 study participants were enrolled in an elective ECE program. The dependent variable in this study was the test score of a systems-based basic sciences (SBBS) course. Independent variables of the study included students' attitudes and test anxiety towards the SBBS course, engagement/length of time spent in ECE, and the ECE learning environment. Data of students' engagement in ECE, levels of their motivational beliefs and test anxiety, differences in the ECE learning environment, and the SBBS final test scores of these 109 respondents were collected for hierarchical multiple regression (HMR) analyses. RESULTS: Results of the HMR analyses revealed that students' test anxiety towards basic science and also the learning environment of the ECE had significant positive predictive power on their SBBS test scores. CONCULSION: This study discovers that medical students' academic performance in basic science correlates not only with their anxiety to testing, but even more so with the clinical environment they are exposed to. Hence we suggest including further investigations about different learning environments on ECE experiences in future studies.

5.
J Cell Mol Med ; 23(8): 5692-5704, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199053

RESUMO

Several biological effects of haem oxygenase (HO)-1, including anti-inflammatory, antiapoptotic and antioxidative properties were reported; however, the role of HO-1 in apoptosis is still unclear. In the presence of stimulation by cobalt protoporphyrin (CoPP), an HO-1 inducer, apoptotic characteristics were observed, including DNA laddering, hypodiploid cells, and cleavages of caspase (Casp)-3 and poly(ADP) ribose polymerase (PARP) proteins in human colon carcinoma COLO205, HCT-15, LOVO and HT-29 cells in serum-free (SF) conditions with increased HO-1, but not heat shock protein 70 (HSP70) or HSP90. The addition of 10% foetal bovine serum (FBS) or 1% bovine serum albumin accordingly inhibited CoPP-induced apoptosis and HO-1 protein expression in human colon cancer cells. CoPP-induced apoptosis of colon cancer cells was prevented by the addition of the pan-caspase inhibitor, Z-VAD-FMK (VAD), and the Casp-3 inhibitor, Z-DEVD-FMK (DEVD). N-Acetyl cysteine inhibited reactive oxygen species-generated H2 O2 -induced cell death with reduced intracellular peroxide production, but did not affect CoPP-induced apoptosis in human colorectal carcinoma (CRC) cells. Two CoPP analogs, ferric protoporphyrin and tin protoporphyrin, did not affect the viability of human CRC cells or HO-1 expression by those cells, and knockdown of HO-1 protein expression by HO-1 small interfering (si)RNA reversed the cytotoxic effect elicited by CoPP. Furthermore, the carbon monoxide (CO) donor, CORM, but not FeSO4 or biliverdin, induced DNA ladders, and cleavage of Casp-3 and PARP proteins in human CRC cells. Increased phosphorylated levels of the endoplasmic reticular (ER) stress proteins, protein kinase R-like ER kinase (PERK), and eukaryotic initiation factor 2α (eIF2α) by CORM and CoPP were identified, and the addition of the PERK inhibitor, GSK2606414, inhibited CORM- and CoPP-induced apoptosis. Increased GRP78 level and formation of the HO-1/GRP78 complex were detected in CORM- and CoPP-treated human CRC cells. A pro-apoptotic role of HO-1 against the viability of human CRC cells via induction of CO and ER stress was firstly demonstrated herein.

7.
JAMA Dermatol ; 155(3): 327-334, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698628

RESUMO

Importance: It is necessary to determine whether psoriasis responds to methotrexate in the same manner in patients with and without psoriatic arthritis. Objective: To evaluate the effectiveness and safety of methotrexate in treating patients with psoriasis with and without psoriatic arthritis. Design, Setting, and Participants: In this prospective, single-arm, interventional study, a total of 235 patients with psoriasis, 107 without psoriatic arthritis and 128 with psoriatic arthritis who were receiving methotrexate therapy from April 1, 2015, to December 31, 2017, were recruited from the outpatient department of a hospital at a large Chinese university. There were no significant demographic or clinical differences between the subgroups with the exception of diabetes. Interventions: A 12-week course of low-dosage oral methotrexate (7.5-15 mg weekly). Main Outcomes and Measures: Changes in disease severity, adverse events, blood cell counts, and liver and renal function. Results: A total of 235 patients with psoriasis (166 male [66.0%]; mean [SD] age, 49.6 [15.1] years) received methotrexate treatment for 12 weeks. The 90% reduction from baseline Psoriasis Area Severity Index response was significantly lower in patients with psoriatic arthritis than in patients without psoriatic arthritis at week 8 (4 0f 128 [3.1%] vs 12 of 107 [11.2%]; P = .02) and week 12 (19 of 128 [14.8%] vs 27 of 107 [25.2%]; P = .049). Furthermore, the incidence of adverse events, including dizziness (12 of 128 [9.4%] vs 1 of 107 [0.9%]; P = .007), gastrointestinal symptoms (32 of 128 [25.0%] vs 13 of 107 [12.1%]; P = .01), and hepatoxicity (34 of 128 [26.6%] vs 16 of 107 [15.0%]; P = .04), was significantly higher in patients with psoriatic arthritis than in patients without psoriatic arthritis. Methotrexate-induced elevation of alanine aminotransferase levels was associated with body mass index (mean [SD] body mass index, 26 [4] in patients with [P = .04] vs 26 [4] in those without [P = .005] psoriatic arthritis) and smoking (17 of 34 [50.0%] in patients with [P = .02] vs 9 of 16 [56.3%] in those without [P = .04] psoriatic arthritis). Conclusions and Relevance: In this study, methotrexate was well tolerated and effective in treating psoriasis. It was more effective, with fewer adverse effects, in patients with psoriasis who did not have psoriatic arthritis than in patients who presented with both psoriasis and psoriatic arthritis. Therefore, methotrexate can be recommended as first-line treatment for psoriasis without arthritis.

8.
Skin Res Technol ; 25(4): 424-433, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30657212

RESUMO

OBJECTIVE: The objective of this study was to perform noninvasive analysis of skin proteins in a healthy Chinese population using label-free nanoflow liquid chromatography-mass spectrometry (nLC-MS). MATERIALS AND METHODS: Five consecutive tape strippings were obtained from the volar forearm skin of healthy Chinese subjects. Proteins were extracted, and trypsin-digested peptides were analyzed by a nanochromatography instrument coupled to an Orbitrap Fusion Tribrid mass spectrometer. Data-dependent acquisition allowed protein identification, which was performed by using Proteome Discoverer software (v2.2). RESULTS: In this study, we identified 80 common proteins that were expressed in the skin of healthy Chinese volunteers and divided these proteins into 16 categories, including keratins, cornified envelope proteins, and enzymes associated with substance metabolism. These proteins were closely associated with multiple functions of the skin barrier. CONCLUSION: This study provides a noninvasive method to analyze healthy human epidermal proteins, which are closely associated with the skin barrier. In addition, this study provides a reference for further studies on the application of proteomic technologies to investigate the role of human epidermal proteins in health and disease.

9.
Surg Endosc ; 32(4): 1937-1944, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29071416

RESUMO

BACKGROUND AND STUDY AIM: Current capsule endoscopy procedures are ineffective for upper gastrointestinal (GI) tract examination because they do not allow for operator-controlled navigation of the capsule. External controllability of a capsule endoscope with an applied magnetic field is a possible solution to this problem. We developed a novel magnetic-assisted capsule endoscope (MACE) system to visualize the entire upper GI tract. The present study evaluated the safety and feasibility of the MACE system for the examination of the upper GI tract, including the esophagus, stomach, and duodenum. METHODS: The present open clinical study enrolled ten healthy volunteers. All participants swallowed a MACE, and an external magnetic field navigator was used for magnetic capsule manipulation in the upper GI tract. We assessed the maneuverability of the magnetic capsule and completeness of the MACE examination as well as the safety and tolerability of the procedure. RESULTS: The present study enrolled ten healthy volunteers with a mean age and body mass index of 47.7 years and 25.6 kg/m2, respectively. One volunteer withdrew because of difficulty in swallowing the capsule. In total, nine volunteers underwent the MACE examination. The average examination time was 27.1 min. The maneuverability of the capsule was assessed as good and fair in 55.6 and 44.4% of the participants, respectively. The overall completeness of the examination in the esophagus, stomach, and duodenum was 100, 85.2, and 86.1%, respectively. No severe adverse events occurred during this study. All participants exhibited satisfactory tolerance of the MACE examination. CONCLUSION: The MACE system has satisfactory maneuverability and visualization completeness with excellent acceptance and tolerance.

10.
Am J Chin Med ; 45(8): 1649-1666, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29121802

RESUMO

Hispolon (HIS) is an active polyphenol compound derived from Phellinus linteus (Berkeley & Curtis), and our previous study showed that HIS effectively inhibited inflammatory responses in macrophages [Yang, L.Y., S.C. Shen, K.T. Cheng, G.V. Subbaraju, C.C. Chien and Y.C. Chen. Hispolon inhibition of inflammatory apoptosis through reduction of iNOS/NO production via HO-1 induction in macrophages. J. Ethnopharmacol. 156: 61-72, 2014]; however, its effect on neuronal inflammation is still undefined. In this study, HIS concentration- and time-dependently inhibited lipopolysaccharide (LPS)- and lipoteichoic acid (LTA)-induced inducible nitric oxide (NO) synthase (iNOS)/NO production with increased heme oxygenase (HO)-1 proteins in BV-2 microglial cells. Accordingly, HIS protected BV-2 cells from LPS- or LTA-induced apoptosis, characterized by decreased DNA ladder formation, and caspase-3 and poly(ADP ribose) polymerase (PARP) protein cleavage in BV-2 cells. Similarly, the NOS inhibitor, N-nitro-L-arginine methyl ester (NAME), inhibited LPS- or LTA-induced apoptosis of BV-2 cells, but neither NAME nor HIS showed any inhibition of NO production or cell death induced by the NO donor, sodium nitroprusside (SNP), indicating the involvement of NO in the inflammatory apoptosis of microglial cells. Activation of c-Jun N-terminal kinase (JNK) and nuclear factor (NF)-[Formula: see text]B contributed to LPS- or LTA-induced iNOS/NO production and apoptosis of BV-2 cells, and that was suppressed by HIS. Additionally, HIS possesses activity to induce HO-1 protein expression via activation of extracellular signal-regulated kinase (ERK) in BV-2 cells, and application of the HO inhibitor, tin protoporphyrin (SnPP), or knockdown of HO-1 protein by HO-1 small interfering (si)RNA significantly reversed HIS inhibition of NO production and cell death in BV-2 cells stimulated by LPS. Results of an analysis of the effects of HIS and two structurally related chemicals, i.e. dehydroxy-HIS (D-HIS) and HIS-methyl ester (HIS-ME), showed that HIS expressed the most potent inhibitory effects on iNOS/NO production, JNK activation, and apoptosis in BV-2 microglial cells activated by LPS with increased HO-1 protein expression. Overall these results suggested that HIS possesses inhibitory activity against LPS- or LTA-induced inflammatory responses including iNOS/NO production and apoptosis in BV-2 microglial cells and that the mechanisms involve upregulation of the HO-1 protein and downregulation of JNK/NF-[Formula: see text]B activation. A critical role of hydroxyl at position C3 in the anti-inflammatory actions of HIS against activated BV-2 microglial cells was suggested.


Assuntos
Anti-Inflamatórios , Apoptose/efeitos dos fármacos , Catecóis/farmacologia , Lipopolissacarídeos/efeitos adversos , Microglia/metabolismo , Microglia/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Ácidos Teicoicos/efeitos adversos , Caspase 3/metabolismo , Catecóis/isolamento & purificação , Células Cultivadas , Relação Dose-Resposta a Droga , Heme Oxigenase-1/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/isolamento & purificação , Poli(ADP-Ribose) Polimerases/metabolismo , Fatores de Tempo
11.
PLoS One ; 11(3): e0150367, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26959661

RESUMO

BACKGROUND: Postoperative pain resulting from surgical trauma is a significant challenge for healthcare providers. Opioid analgesics are commonly used to treat postoperative pain; however, these drugs are associated with a number of undesirable side effects. OBJECTIVE: This systematic review and meta-analysis evaluated the effectiveness of acupuncture and acupuncture-related techniques in treating postoperative pain. DATA SOURCE: MEDLINE, Cochrane Library, and EMBASE databases were searched until Sep 30, 2014. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials of adult subjects (≥ 18 years) who had undergone surgery and who had received acupuncture, electroacupuncture, or acupoint electrical stimulation for managing acute post-operative pain were included. RESULTS: We found that patients treated with acupuncture or related techniques had less pain and used less opioid analgesics on Day 1 after surgery compared with those treated with control (P < 0.001). Sensitivity analysis using the leave-one-out approach indicated the findings are reliable and are not dependent on any one study. In addition, no publication bias was detected. Subgroup analysis indicated that conventional acupuncture and transcutaneous electric acupoint stimulation (TEAS) were associated with less postoperative pain one day following surgery than control treatment, while electroacupuncture was similar to control (P = 0.116). TEAS was associated with significantly greater reduction in opioid analgesic use on Day 1 post surgery than control (P < 0.001); however conventional acupuncture and electroacupuncture showed no benefit in reducing opioid analgesic use compared with control (P ≥ 0.142). CONCLUSION: Our findings indicate that certain modes of acupuncture improved postoperative pain on the first day after surgery and reduced opioid use. Our findings support the use of acupuncture as adjuvant therapy in treating postoperative pain.


Assuntos
Terapia por Acupuntura/normas , Manejo da Dor/métodos , Dor Pós-Operatória/terapia , Humanos , Resultado do Tratamento
12.
Eur J Pharmacol ; 776: 124-31, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-26879868

RESUMO

Colon cancer is the third most common malignancy worldwide. Recently, some interesting associations between ghrelin and cancer were reported, and it may participate in colon cancer development. In the present report, we explored the role of the growth hormone secretagogue receptor (GHS-R), Ras, phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) pathways in the ghrelin-induced proliferation of human colon cancer cells. Ghrelin-caused HT-29 proliferation was reduced by [D-Lys3]-GHRP-6 (a GHS-R inhibitor). We also found that a dominant negative mutant of Ras (Ras DN), a PI3K inhibitor (LY 294002), an Akt DN, and an mTOR inhibitor (rapamycin) attenuated ghrelin-caused colon cancer cell proliferation. We found that ghrelin induced time-dependent increases in Ras activity. Moreover, ghrelin-mediated Akt Ser473 phosphorylation was attenuated by a Ras DN and LY 294002. Furthermore, a Ras DN, LY 294002, and an Akt DN all inhibited ghrelin-caused mTOR Ser2448 phosphorylation. These results indicate that the Ras/PI3K/Akt/mTOR cascade plays a critical role in ghrelin-induced colon cancer cell proliferation.


Assuntos
Neoplasias do Colo/patologia , Grelina/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Grelina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas ras/metabolismo , Proliferação de Células/efeitos dos fármacos , Células HT29 , Humanos , Mutação , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/química , Serina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas ras/genética
13.
Phytomedicine ; 23(1): 68-78, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26902409

RESUMO

BACKGROUND: Evodiamine (EVO; 8,13,13b,14-tetrahydro-14-methylindolo[2'3'-3,4]pyrido[2,1-b]quinazolin-5-[7H]-one derived from the traditional herbal medicine Evodia rutaecarpa was reported to possess anticancer activity; however, the anticancer mechanism of EVO against the viability of human ovarian cancer cells is still unclear. PURPOSE: A number of studies showed that chemotherapeutic benefits may result from targeting the endoplasmic reticular (ER) stress signaling pathway. The objective of the study is to investigate the mechanism by which ER stress protein PERK plays in EVO-induced apoptosis of human ovarian cancer cells. METHODS: Cell death analysis was performed by MTT assay, DNA fragmentation assay, and Giemsa staining. DiOC6 staining was used for mitochondrial membrane potential measurement. Protein levels were analyzed by Western blotting. Pharmacological studies using MAPK inhibitors and PERK inhibitor GSK2606414 were involved. RESULTS: The viability of human ovarian cancer cells A2780, A2780CP, ES-2, and SKOV-3 was inhibited by EVO at various concentrations in accordance with increases in the percentage of apoptotic cells, DNA ladders, and cleavage of caspase 3 and poly(ADP ribose) polymerase (PARP) proteins. Decreased viability of cells was reversed by adding caspase inhibitors VAD and DEVD in SKOV-3 and A2780CP cells, and incubation of cells with JNK inhibitor SP600125 (SP) and JNKI, but not other MAPK and AKT inhibitors including PD98059, SB203580, significantly prevented the apoptosis elicited by EVO in human ovarian cancer cells. Furthermore, increased expression of phospho-eIF2α (peIF2α) and phospho-PERK (pPERK) proteins was detected in EVO-treated human ovarian cancer cells, and that was inhibited by adding JNK inhibitors SP600125 and JNKI. Application of a PERK inhibitor GSK2606414 showed a significant protection of human ovarian cancer cells A2780 and A2780CP from EVO-induced apoptosis. EVO disruption of mitochondrial membrane potential (MMP) was also inhibited by adding JNK or PERK inhibitors. The structure-activity relationship study indicated that the alkyl group at position 14 in EVO is important for apoptosis induction via activation of JNK and PERK in human ovarian cancer cells. CONCLUSION: Evidence supporting EVO induction of apoptosis via activation of JNK and PERK to disrupt MMP in human ovarian cancer cells is provided, and the alkyl at position 14 is a critical substitution for the apoptotic actions of EVO.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Ovarianas/patologia , Quinazolinas/farmacologia , eIF-2 Quinase/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Antracenos/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Evodia/química , Feminino , Humanos , Indóis/farmacologia , Potencial da Membrana Mitocondrial , Poli(ADP-Ribose) Polimerases/metabolismo , Transdução de Sinais , Relação Estrutura-Atividade
14.
Toxicol In Vitro ; 31: 1-11, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26549707

RESUMO

Nilotinib (AMN) induces apoptosis in various cancer cells; however the effect of AMN on human ovarian cancer cells is still unclear. A reduction in cell viability associated with the occurrence of apoptotic characteristics was observed in human SKOV-3 ovarian cancer cells under AMN but not sorafenib (SORA) or imatinib (STI) stimulation. Activation of apoptotic pathway including increased caspase (Casp)-3 and poly(ADP-ribose) polymerase 1 (PARP1) protein cleavage by AMN was detected with disrupted mitochondrial membrane potential (MMP) accompanied by decreased Bcl-2 protein and increased cytosolic cytochrome (Cyt) c/cleaved Casp-9 protein expressions was found, and AMN-induced cell death was inhibited by peptidyl Casp inhibitors, VAD, DEVD and LEHD. Increased phosphorylated c-Jun N-terminal kinase (JNK) protein expression was detected in AMN- but not SORA- or STI-treated SKOV-3 cells, and the JNK inhibitors, SP600125 and JNKI, showed slight but significant enhancement of AMN-induced cell death in SKOV-3 cells. The intracellular peroxide level was elevated by AMN and H2O2, and N-acetylcysteine (NAC) prevented H2O2- but not AMN-induced peroxide production and apoptosis in SKOV-3 cells. AMN induction of apoptosis with increased intracellular peroxide production and JNK protein phosphorylation was also identified in human A2780 ovarian cancer cells, cisplatin-resistant A2780CP cells, and clear ES-2 cells. The evidence supporting AMN effectively reducing the viability of human ovarian cancer cells via mitochondrion-dependent apoptosis is provided.


Assuntos
Antineoplásicos/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Fragmentação do DNA , Feminino , Humanos , Mesilato de Imatinib/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Neoplasias Ovarianas/metabolismo , Compostos de Fenilureia/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sorafenibe
15.
Chin J Physiol ; 57(5): 286-94, 2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25241989

RESUMO

Body iron levels have recently been shown to be a strong predictor for non-alcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence of NAFLD in a general adult population, and to investigate the relationship between body iron levels, NAFLD and the metabolic syndrome (MetS). 2186 adults participated in the third National Nutrition and Health Survey in Taiwan (NAHSIT, 2005-2008). The participants underwent anthropometry measurements and phlebotomy after an overnight fast, and those with excessive alcohol intake, iron overload of serum ferritin > 600 ng/ml, hepatitis viral infection and hepatocellular carcinoma were excluded. Suspected NAFLD was diagnosed by three alanine transaminase (ALT) cut-points: cut-point 1: serum ALT > 40 U/l; cut-point 2: ALT ≥ 25 U/l for male and ALT ≥ 17 U/l for female; and cut-point 3: ALT ≥ 35 U/l for male and ALT ≥ 26 U/l for female. The prevalence proportion of suspected NAFLD among Taiwanese adults was 6.6% (cut-point 1), 36% (cut-point 2); and 14.3% (cut-point 3). Body iron levels were significantly higher in individuals with suspected NAFLD compared with those without. Distribution of hemoglobin levels, but not serum ferritin levels, by decade of age showed strong correlation with the prevalence of suspected NAFLD in individuals with MetS. Multivariate adjusted odds ratio (OR) showed that the best predictors for suspected NAFLD with the MetS were hemoglobin [OR 1.43 (1.21-1.68); P < 0.0001] and hyperlipidemia [OR 1.52 (1.19-1.94); P = 0.0007]. In individuals without MetS, the adjusted OR of suspected NAFLD was markedly higher for hemoglobin [OR 1.25 (1.12-1.41); P < 0.0001]. In conclusion, adults with high hemoglobin levels (14.4 µg/dl for male and 13.2 µg/dl for female) are at the greatest risk for developing abnormal liver function. Hemoglobin test should be considered as a part of clinical evaluation for patients with NAFLD.


Assuntos
Hemoglobinas/metabolismo , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/epidemiologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Distribuição por Idade , Idoso , Alanina Transaminase/sangue , Feminino , Ferritinas/sangue , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/epidemiologia , Sobrecarga de Ferro/diagnóstico , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Razão de Chances , Prevalência , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por Sexo , Taiwan/epidemiologia
16.
PLoS One ; 9(8): e104891, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25122478

RESUMO

Previous report showed that epidermal growth factor (EGF) promotes tumor progression. Several studies demonstrated that growth factors can induce heme oxygenase (HO)-1 expression, protect against cellular injury and cancer cell proliferation. In this study, we investigated the involvement of the c-Src, NADPH oxidase, reactive oxygen species (ROS), PI3K/Akt, and NF-κB signaling pathways in EGF-induced HO-1 expression in human HT-29 colon cancer cells. Treatment of HT-29 cells with EGF caused HO-1 to be expressed in concentration- and time-dependent manners. Treatment of HT-29 cells with AG1478 (an EGF receptor (EGFR) inhibitor), small interfering RNA of EGFR (EGFR siRNA), a dominant negative mutant of c-Src (c-Src DN), DPI (an NADPH oxidase inhibitor), glutathione (an ROS inhibitor), LY294002 (a PI3K inhibitor), and an Akt DN inhibited EGF-induced HO-1 expression. Stimulation of cells with EGF caused an increase in c-Src phosphorylation at Tyr406 in a time-dependent manner. Treatment of HT-29 cells with EGF induced an increase in p47(phox) translocation from the cytosol to membranes. The EGF-induced ROS production was inhibited by DPI. Stimulation of cells with EGF resulted in an increase in Akt phosphorylation at Ser473, which was inhibited by c-Src DN, DPI, and LY 294002. Moreover, treatment of HT-29 cells with a dominant negative mutant of IκB (IκBαM) inhibited EGF-induced HO-1 expression. Stimulation of cells with EGF induced p65 translocation from the cytosol to nuclei. Treatment of HT-29 cells with EGF induced an increase in κB-luciferase activity, which was inhibited by a c-Src DN, LY 294002, and an Akt DN. Furthermore, EGF-induced colon cancer cell proliferation was inhibited by Sn(IV)protoporphyrin-IX (snPP, an HO-1 inhibitor). Taken together, these results suggest that the c-Src, NADPH oxidase, PI3K, and Akt signaling pathways play important roles in EGF-induced NF-κB activation and HO-1 expression in HT-29 cells. Moreover, overexpression of HO-1 mediates EGF-induced colon cancer cell proliferation.


Assuntos
Neoplasias do Colo/metabolismo , Fator de Crescimento Epidérmico/fisiologia , Heme Oxigenase-1/metabolismo , NF-kappa B/metabolismo , Sequência de Bases , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Primers do DNA , Células HT29 , Humanos , NADPH Oxidases/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
17.
Biomed Res Int ; 2014: 195097, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25013762

RESUMO

OBJECTIVE: Chronic hepatitis C virus (HCV) infection is a serious health problem in Taiwan. The high dropout rate due to side effects limits the efficacy of treatment. The objective of this study is to investigate the effectiveness of telecare for the treatment of chronic hepatitis. MATERIAL AND METHODS: Two hundred and ninety-eight patients randomly chose either of the two support programs. Group 1 was offered public health nurse consultation at outpatient clinic. Group 2 was offered telecare program with 24 hours of consultation services via a health communication center. All patients were treated with standard therapy and followed up for 72 weeks. RESULTS: Normalization of serum biochemistry was noted in both Group 1 (150 patients) and Group 2 (148 patients). The most common types of side effect in both groups were influenza-like symptoms. Patient compliance was 88% (Group 1) and 94.6% (Group 2). Total dropout cases were 18 (12%) in Group 1 and 8 (5.4%) in Group 2. The program costs were 232,632 USD (Group 1) and 112,500 USD (Group 2). CONCLUSION: Telecare system with health care communication center model is significant in reducing dropout rate and is more effective with easy access.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Telemedicina , Pesquisa Médica Translacional , Adulto , Aspartato Aminotransferases/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan
18.
PLoS One ; 9(6): e99729, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24959718

RESUMO

Evodiamine (EVO; 8,13,13b,14-tetrahydro-14-methylindolo[2'3'-3,4]pyrido[2,1-b]quinazolin-5-[7H]-one derived from the traditional herbal medicine Evodia rutaecarpa was reported to possess anticancer activity; however, the anticancer mechanism is still unclear. In this study, we investigated the anticancer effects of EVO on human colon COLO205 and HT-29 cells and their potential mechanisms. MTT and lactate dehydrogenase (LDH) release assays showed that the viability of COLOL205 and HT-29 cells was inhibited by EVO at various concentrations in accordance with increases in the percentage of apoptotic cells and cleavage of caspase-3 and poly(ADP ribose) polymerase (PARP) proteins. Disruption of the mitochondrial membrane potential by EVO was accompanied by increased Bax, caspase-9 protein cleavage, and cytochrome (Cyt) c protein translocation in COLO205 and HT-29 cells. Application of the antioxidant N-acetyl-L-cysteine (NAC) inhibited H2O2-induced reactive oxygen species (ROS) production and apoptosis, but did not affect EVO-induced apoptosis of COLO205 or HT-29 cells. Significant increases in the G2/M ratio and cyclinB1/cdc25c protein expression by EVO were respectively identified in colon carcinoma cells via a flow cytometric analysis and Western blotting. Induction of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) protein phosphorylation was detected in EVO-treated cells, and the JNK inhibitor, SP600125, but not the ERK inhibitor, U0126, inhibited EVO-induced phosphorylated JNK protein expression, apoptosis, and G2/M arrest of colon carcinoma cells. Data of the structure-activity analysis showed that EVO-related chemicals containing an alkyl group at position 14 were able to induce apoptosis, G2/M arrest associated with increased DNA ladder formation, cleavage of caspase-3 and PARP, and elevated cycB1 and cdc25c protein expressions in COLO205 and HT-29 cells. Evidence supporting JNK activation leading to EVO-induced apoptosis and G2/M arrest in colon carcinoma cells is provided, and alkylation at position 14 of EVO is a critical substitution for treatment of colonic cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/metabolismo , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinazolinas/farmacologia , Alquilação , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Células HT29 , Humanos , Camundongos , Células NIH 3T3 , Relação Estrutura-Atividade
19.
J Cell Physiol ; 229(12): 2015-26, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24777714

RESUMO

Conditioned mediums (CMs) from glioma cells U87, GBM-8401, and C6 significantly induced iNOS protein and NO production by microglial cells BV-2 but without altering the cell viability or cell-cycle progression of BV2 microglia. Significant increases in intracellular peroxide by U87-CM and C6-CM were detected by a DCHF-DA assay, and vitamin (Vit) C and N-acetyl cysteine (NAC)-reduced intracellular peroxide levels elicited by CMs lead to inhibition of iNOS/NO production The extracellular signal-regulated kinase (ERK) inhibitor, U0126, and c-Jun N-terminal kinase (JNK) inhibitor, SP600125, suppressed U87-CM- and C6-CM-induced iNOS/NO production by respectively blocking phosphorylated ERK (pERK) and JNK (pJNK) protein expressions stimulated by U87-CM and C6-CM. Increased migration of U87 and C6 glioma cells by a co-culture with BV-2 microglial cells or adding the nitric oxide (NO) donor, sodium nitroprusside (SNP) was observed, and that was blocked by adding an NO synthase (NOS) inhibitor, N-nitro L-arginine methyl ester (NAME). Contributions of ROS, pERK, and pJNK to the migration of glioma cells was further demonstrated in a transwell coculture system of U87 and C6 gliomas with BV-2 microglial cells. Furthermore, expressions of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 messenger (m)RNA in U87 and C6 cells were detected by an RT-PCR, and TNF-α and MCP-1 induced iNOS protein expression in time- and concentration-dependent manners. Neutralization of TNF-α or MCP-1 in U87-CM and C6-CM using a TNF-α or MCP-1 antibody inhibited iNOS protein expression, and increased intracellular peroxide by TNF-α or MCP-1 was identified in BV-2 cells. The reciprocal activation of glioma cells and microglia via ROS-dependent iNOS/NO elevation at least partially mediated by TNF-α and MCP-1 is elucidated.


Assuntos
Glioma/metabolismo , Microglia/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antracenos/administração & dosagem , Butadienos/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Técnicas de Cocultura , Meios de Cultivo Condicionados , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/patologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Microglia/patologia , NF-kappa B/biossíntese , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitrilos/administração & dosagem , Fator de Necrose Tumoral alfa/biossíntese
20.
Mol Carcinog ; 53 Suppl 1: E119-29, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24019108

RESUMO

Oxidative stress or excessive antioxidant levels-caused redox imbalance can alter apoptotic responses, and N-acetyl-L-cysteine (NAC) was able to inhibit H2 O2 -mediated cell death, but unable to prevent apoptosis induced by other chemicals such as etoposide. We now demonstrate that 10 and 20 mM NAC, non-toxic concentrations, can enhance fisetin (FIS)-mediated apoptosis in colon cancer cells COLO205. Compared to treatment with FIS alone, combination treatment with NAC increased the expression of cleaved caspase-3 and PAPR protein, and produced greater density of DNA ladders. NAC reduced the mitochondrial membrane potential of FIS-treated COLO205 cells with induction of caspase 9 protein cleavage. DNA ladders induced by FIS + NAC were diminished by adding the caspase 3 inhibitor, DEVD-FMK, and the caspase 9 inhibitor, YVAD-FMK. Combinatorial treatment COLO205 cells with NAC and FIS showed potent inhibition on ERK protein phosphorylation, compared with those from FIS or NAC-treated groups by Western blotting using specific antibodies. Addition of the chemical ERK inhibitors, PD98059 and U0126, significantly inhibited ERK protein phosphorylation, accompanied by induced DNA ladder formation, cleavage of caspase 3 and PARP protein in COLO205 cells. Furthermore, NAC showed an enhancement on a FIS-related chemical chrysin-induced apoptosis of COLO205 cells, and NAC sensitization of colon cancer cells to FIS-induced apoptosis was also identify in colonic cancer cells HCT-116, HT-29, and HCT-15 cells. The evidence to support NAC sensitizing human colon cancer cells to FIS-induced apoptosis was provided, and application of NAC and FIS as a strategy to treat colonic cancer deserved for further in vivo study.


Assuntos
Acetilcisteína/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Flavonoides/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Western Blotting , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Sinergismo Farmacológico , Depuradores de Radicais Livres/farmacologia , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Células Tumorais Cultivadas
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