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1.
Sensors (Basel) ; 20(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054134

RESUMO

The incidence of oral squamous cell carcinoma (OSCC), which is one of the most common cancers worldwide, has been increasing. Serum anti-p53 autoantibody is one of the most sensitive biomarkers for OSCC. Currently, the most commonly used method on clinical screening platforms is the enzyme-linked immunosorbent assay, owing to its high specificity and repeatability. However, conducting immunoassays on 96-well plates is typically time consuming, thereby limiting its clinical applications for fast diagnosis and immediate prognosis of rapidly progressive diseases. The present study performed immunoassays in glass capillaries of 1-mm internal diameter, which increases the surface to volume ratio of the reaction, to shorten the time needed for immunoassay. The immunoassay was automated while using linear motorized stages and a syringe pump. The results indicated that, when compared with the 96-well plate immunoassay, the glass capillary immunoassay decreased the reaction time from typical 120 min to 45 min, reduced the amount of reagent from typical 50 µL to 15 µL, and required only simple equipment setup. Moreover, the limit of detection for glass capillary anti-p53 autoantibody immunoassay was 0.46 ng mL-1, which is close to the 0.19 ng mL-1 value of the conventional 96-well plate assay, and the glass capillary method had a broader detection range. The apparatus was used to detect the serum anti-p53 autoantibody concentration in clinical patients and compare its results with the conventional 96-well plate method results, which suggested that both of the methods detect the same trend in the relative concentration of serum anti-p53 autoantibody in healthy individuals or patients with OSCC.

2.
J Asian Nat Prod Res ; : 1-6, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30982343

RESUMO

A new isoflavone glycoside named as 8-O-methylrelusin-7-O-ß-D-apifuranosyl-(1→2)-ß-D-glucopyranoside (1), together with two known compounds, 8-O-methylrelusin-7-O-ß-D-glucopyranoside (2) and isobiflorin (3), were isolated from Abrus cantoniensis. The structure of the new compound was elucidated on the basis of spectroscopic methods including extensive 1D NMR, 2D NMR, and HRESIMS. This is the first report of isoflavone from Abrus cantoniensis. Moreover, all isolated compounds were evaluated for their cytotoxicity against SMMC-7721 and MHCC97-H cell lines.

3.
Aging (Albany NY) ; 11(3): 986-1007, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760647

RESUMO

Spinocerebellar ataxia (SCA) type 17 is an autosomal dominant ataxia caused by expanded polyglutamine (polyQ) tract in the TATA-box binding protein (TBP). Substantial studies have shown involvement of compromised mitochondria biogenesis regulator peroxisome proliferator-activated receptor gamma-coactivator 1 alpha (PGC-1α), nuclear factor erythroid 2-related factor 2 (NRF2), nuclear factor-Y subunit A (NFYA), and their downstream target genes in the pathogenesis of polyQ-expansion diseases. The extracts of Paeonia lactiflora (P. lactiflora) and Glycyrrhiza uralensis (G. uralensis) have long been used as a Chinese herbal medicine (CHM). Shaoyao Gancao Tang (SG-Tang) is a formulated CHM made of P. lactiflora and G. uralensis at a 1:1 ratio. In the present study, we demonstrated the aggregate-inhibitory and anti-oxidative effect of SG-Tang in 293 TBP/Q79 cells. We then showed that SG-Tang reduced the aggregates and ameliorated the neurite outgrowth deficits in TBP/Q79 SH-SY5Y cells. SG-Tang upregulated expression levels of NFYA, PGC-1α, NRF2, and their downstream target genes in TBP/Q79 SH-SY5Y cells. Knock down of NFYA, PGC-1α, and NRF2 attenuated the neurite outgrowth promoting effect of SG-Tang on TBP/Q79 SH-SY5Y cells. Furthermore, SG-Tang inhibited aggregation and rescued motor-deficits in SCA17 mouse model. The study results suggest the potential of SG-Tang in treating SCA17 and probable other polyQ diseases.

4.
J Clin Med ; 8(2)2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30744214

RESUMO

Since the clinical benefit of lung recruitment maneuvers (LRMs) is still conflicting, we performed this prospective, randomized, controlled study to investigate whether LRMs should be used in the routine management of acute respiratory distress syndrome (ARDS). This trial was conducted in four intensive care units (ICUs) to compare application of a modified stepwise LRMs with solely lung-protective ventilation in patients with moderate to severe ARDS within 72 h from the onset. The primary outcome was 28-day mortality, and the secondary outcomes were ventilator-free days and ICU-free days. We collected data on 120 ARDS patients from 2009 to 2012, and there was no difference in 28-day mortality between the two groups (28.3% vs. 30.0%, p = 0.84). However, among survivors, patients in the LRM group had a significant longer median duration of ventilator-free days (18 vs. 13 days; p = 0.04) and ICU-free days (16 vs. 11 days; p = 0.03) at 28 days than in the control group. The respiratory system compliance was significantly higher in the LRM group from day 1 to day 7. The occurrence rate of barotrauma was similar in both groups. We concluded that LRMs combined with lung-protective ventilation in early ARDS may improve patient outcomes.

5.
Complement Ther Med ; 42: 248-254, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30670249

RESUMO

OBJECTIVES: Little information is available about the impact of Chinese herbal medicine (CHM) treatment on acute exacerbation of hepatitis. This study aimed to assess the risk of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma in HBV patients with and without CHM use. DESIGN AND SETTING: This population-based case-control study used data from the Taiwan Longitudinal Health Insurance Database from 2000 to 2013. Newly diagnosed HBV patients had acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma as the case group, while another patients had no acute exacerbation of hepatitis and cirrhosis and hepatoma as the control group. To correct the differences in sociodemographic factors and Western medication use between the two groups, propensity score matching was used at a 1:1 ratio, and resulted in a comparison of 1306 and 805 patients per group, respectively. MAIN OUTCOME MEASURES: Occurrence of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma. RESULTS: Overall rate of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma was 7.9% and 4.8%, respectively. Patients receiving CHM had a significantly lower risk of acute exacerbation of hepatitis (adjusted odds ratio [aOR] =0.20, 95% confidence interval [95%CI]: 0.13-0.31) and subsequent cirrhosis and hepatoma (aOR = 0.29, 95%CI: 0.18-0.49) than those not receiving CHM after adjusting for relevant covariates. However, no dose-dependent relationship was exhibited for either incidence of acute exacerbation of hepatitis and cirrhosis and hepatoma. CONCLUSION: These findings highlight that the use of CHM was associated with a significantly reduced risk of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma in patients with HBV. Future research could further explore the benefit of CHM therapies for treatment of acute hepatitis exacerbation.


Assuntos
Doença Aguda/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Hepatite/tratamento farmacológico , Hepatite/virologia , Adulto , Idoso , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Hepatite/prevenção & controle , Hepatite B/virologia , Humanos , Incidência , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Taiwan , Adulto Jovem
6.
Am J Chin Med ; 47(1): 63-95, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30612452

RESUMO

Nine autosomal dominant spinocerebellar ataxias (SCAs) are caused by an abnormal expansion of CAG trinucleotide repeats that encodes a polyglutamine (polyQ) tract within different genes. Accumulation of aggregated mutant proteins is a common feature of polyQ diseases, leading to progressive neuronal dysfunction and degeneration. SCA type 3 (SCA3), the most common form of SCA worldwide, is characterized by a CAG triplet expansion in chromosome 14q32.1 ATXN3 gene. As accumulation of the mutated polyQ protein is a possible initial event in the pathogenic cascade, clearance of aggregated protein by ubiquitin proteasome system (UPS) has been proposed to inhibit downstream detrimental events and suppress neuronal cell death. In this study, Chinese herbal medicine (CHM) extracts were studied for their proteasome-activating, polyQ aggregation-inhibitory and neuroprotective effects in GFPu and ATXN3/Q 75 -GFP 293/SH-SY5Y cells. Among the 14 tested extracts, 8 displayed increased proteasome activity, which was confirmed by 20S proteasome activity assay and analysis of ubiquitinated and fused GFP proteins in GFPu cells. All the eight extracts displayed good aggregation-inhibitory potential when tested in ATXN3/Q 75 -GFP 293 cells. Among them, neuroprotective effects of five selected extracts were shown by analyses of polyQ aggregation, neurite outgrowth, caspase 3 and proteasome activities, and ATXN3-GFP, ubiquitin, BCL2 and BAX protein levels in neuronal differentiated ATXN3/Q 75 -GFP SH-SY5Y cells. Finally, enhanced proteasome function, anti-oxidative activity and neuroprotection of catalpol, puerarin and daidzein (active constituents of Rehmannia glutinosa and Pueraria lobata) were demonstrated in GFPu and/or ATXN3/Q 75 -GFP 293/SH-SY5Y cells. This study may have therapeutic implication in polyQ-mediated disorders.


Assuntos
Antioxidantes , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doença de Machado-Joseph/tratamento farmacológico , Doença de Machado-Joseph/genética , Fármacos Neuroprotetores , Peptídeos/genética , Peptídeos/metabolismo , Fitoterapia , Complexo de Endopeptidases do Proteassoma/metabolismo , Agregação Patológica de Proteínas/metabolismo , Ubiquitina/metabolismo , Células Cultivadas , Células HEK293 , Humanos , Glucosídeos Iridoides/farmacologia , Glucosídeos Iridoides/uso terapêutico , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Terapia de Alvo Molecular , Mutação , Agregação Patológica de Proteínas/prevenção & controle , Pueraria/química , Rehmannia/química , Expansão das Repetições de Trinucleotídeos/genética
7.
Mol Cell Endocrinol ; 480: 74-82, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30339820

RESUMO

Diabetes-induced neutrophil NETosis impairs wound healing through neutrophil extracellular traps (NETs). Reactive oxygen species (ROS)-triggered activation of mitogen-activated protein kinase (MAPK) ERK1/2 and p38 is involved in NETosis. Hydrogen sulfide (H2S), an endogenous signaling molecule, accelerates diabetic wound healing (DWH), and inhibits ROS production, ERK1/2 and p38 activation, while its level is decreased in diabetes. However, it remains unknown whether H2S could accelerate DWH through inhibition of NETosis, and whether this inhibitory effect was associated with blockage of ROS-induced ERK1/2 and p38 activation. In order to solve these problems, serum NETs content was measured in diabetic foot patients and healthy individuals. Wound was created in dorsal skin of LepRdb/db and control mice and NETs content in wound tissues was tested. An in vitro NETosis model was induced by phorbol 12-myristate 13-acetate (PMA) in isolated neutrophils. Effects of H2S in form of Na2S on skin wound healing and NETosis were investigated both in vivo and in vitro. It was found that NETs level was highly increased in diabetic foot patients. Comparing with LepRm+/db mice, DWH was delayed in LepRdb/db mice, accompanied with high NETs level. In PMA-induced NETosis model, peptidylarginine deiminase (PAD)-4 and citrullinated histone H3, as well as NETs components dsDNA framework, myeloperoxidase and neutrophil elastase, were significantly increased. PMA-induced neutrophil NETosis and NETs formation were abolished by treatment with H2S. The delayed DWH of diabetic mice was partially restored by intraperitoneal injection of H2S, meanwhile, the highly expressed NETosis and NETs release were also down-regulated. The treatment with H2S not only attenuated ROS production but also abolished MAPK ERK1/2 and p38 activation. Like the effects of H2S, inhibition of MAPK ERK1/2 or p38 could decrease NETs release. These findings suggests that H2S attenuates NETosis and primes diabetic wound to heal through blockage of ROS-mediated MAPK ERK1/2 and p38 activation.


Assuntos
Diabetes Mellitus Experimental/patologia , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Sulfeto de Hidrogênio/farmacologia , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Animais , Diabetes Mellitus Experimental/sangue , Pé Diabético/sangue , Pé Diabético/patologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Adulto Jovem
8.
J Clin Med ; 7(8)2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30096809

RESUMO

This study aims to investigate the association between oxygenation saturation index (OSI) and the outcome of acute respiratory distress syndrome (ARDS) patients, and assess the predictive performance of OSI for ARDS patients' mortality. This study was conducted at one regional hospital with 66 adult intensive care unit (ICU) beds. All patients with ARDS were identified between November 1 2016 and May 31 2018, and their clinical information was retrospectively collected. The lowest PaO2/FiO2 ratio and SpO2/FiO2 ratio and highest mean airway pressure (MAP) were recorded on the first day of ARDS; and oxygen index (OI) and OSI were calculated as (FiO2 × MAP × 100)/PaO2, and (FiO2 × MAP × 100) /SpO2 accordingly. During the study period, a total of 101 patients with ARDS were enrolled, and their mean age was 69.2 years. The overall in-ICU and in-hospital mortality rate was 57.4% and 61.4%, respectively. The patients with in-ICU mortality had higher APACHE II score than the survivors (31.6 ± 9.8 vs. 23.0 ± 9.1, p < 0.001). In addition, mortalities had lower SpO2, and SpO2/FiO2 ratios than the survivors (both p < 0.05). In contrast, survivors had lower OI, and OSI than the mortalities (both p = 0.008). Both OSI (area under curve (AUC) = 0.656, p = 0.008) and OI (AUC = 0.654, p = 0.008) had good predictive performance of mortality among ARDS patients using receiver-operating characteristics (ROC) curves analysis. In addition, the AUC of SpO2/FiO2 (AUC = 0.616, p = 0.046) had better performance for mortality prediction than PaO2/FiO2 (AUC = 0.603, p = 0.08). The patients with OSI greater than 12 had a higher risk of mortality than OSI < 12 (adjusted OR, 5.22, 95% CI, 1.31⁻20.76, p = 0.019). In contrast, OI, PaO2/FiO2, and SpO2/FiO2 were not found to be significantly associated with increased mortality. OSI is significantly associated with the increased mortality of ARDS patients and can also be a good outcome predictor.

9.
Neurotoxicology ; 67: 259-269, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29936316

RESUMO

Spinocerebellar ataxia type 17 (SCA17) is caused by the expansion of translated CAG repeat in the TATA box binding protein (TBP) gene encoding a long polyglutamine (polyQ) tract in the TBP protein, which leads to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On cells with inducible SCA17 TBP/Q79-GFP expression to test five in-house NC009 indole compounds for neuroprotection. We found that both aggregation and polyQ-induced reactive oxygen species can be significantly prohibited by the tested NC009 compounds in Tet-On TBP/Q79 293 cells. Among the five indole compounds, NC009-1 up-regulated expression of heat shock protein family B (small) member 1 (HSPB1) chaperone to reduce polyQ aggregation and promote neurite outgrowth in neuronal differentiated TBP/Q79 SH-SY5Y cells. The increased HSPB1 thus ameliorated the increased BH3 interacting domain death agonist (BID), cytochrome c (CYCS) release, and caspase 3 (CASP3) activation which result in apoptosis. Knock down of HSPB1 attenuated the effects of NC009-1 on TBP/Q79 SH-SY5Y cells, suggesting that HSPB1 might be one of the major pathways involved for NC009-1 effects. NC009-1 further reduced polyQ aggregation in Purkinje cells and ameliorated behavioral deficits in SCA17 TBP/Q109 transgenic mice. Our results suggest that NC009-1 has a neuroprotective effect on SCA17 cell and mouse models to support its therapeutic potential in SCA17 treatment.


Assuntos
Proteínas de Choque Térmico/metabolismo , Indóis/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/metabolismo , Proteínas de Neoplasias/metabolismo , Crescimento Neuronal/efeitos dos fármacos , Proteína de Ligação a TATA-Box/metabolismo , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Proteínas de Choque Térmico/agonistas , Humanos , Indóis/química , Indóis/farmacologia , Camundongos , Camundongos Transgênicos , Proteínas de Neoplasias/agonistas , Crescimento Neuronal/fisiologia , Proteína de Ligação a TATA-Box/genética
10.
Medicine (Baltimore) ; 97(26): e11124, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29952954

RESUMO

This retrospective cohort study investigated the outcomes of patients with unplanned intensive care unit (ICU) readmission.All of the patients readmitted to ICU within 48 hours between 2010 and 2016 were enrolled.A total of 99 patients early readmitted to ICU were identified and their mean age of the patients was 68.8 ± 14.8 years. Respiratory failure was the most common cause of ICU readmission (n = 48, 48.5%), followed by acute myocardial ischemia or worsening heart failure (n = 25, 25.3%), sepsis (n = 22, 22.2%), gastrointestinal disease (n = 16, 16.2%), and neurologic disease (n = 11, 11.1%). The median length of stay in the ICU and hospital was 7 (IQR, 4-11.5) and 32 (IQR, 15.5-48.5) days, respectively. A total of 34 patients died during the hospital stay and the rate of in-hospital mortality was 34.3%. Patients with higher APACHE II scores (adjusted odds ratio [OR], 1.17; 95% CI, 1.02-1.33), underlying malignancy (adjusted OR, 4.70; 95% CI, 1.19-18.57), and cardiovascular organ dysfunction (adjusted OR, 5.14; 95% CI, 1.24-21.38) were more likely to die.The mortality rate of ICU readmission patients was high, especially for those with higher APACHE II score, underlying malignancy and cardiovascular organ dysfunction.


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Prognóstico , APACHE , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastroenteropatias/epidemiologia , Gastroenteropatias/mortalidade , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Mortalidade Hospitalar/tendências , Humanos , Unidades de Terapia Intensiva/tendências , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/mortalidade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/mortalidade , Readmissão do Paciente/tendências , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Fatores de Risco , Sepse/epidemiologia , Sepse/mortalidade , Índice de Gravidade de Doença
11.
Oncotarget ; 9(21): 15817, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29645015

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.24051.].

12.
Oncotarget ; 9(6): 7197-7203, 2018 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-29467961

RESUMO

This retrospective cohort study investigated the outcomes and prognostic factors in nonagenarians (patients 90 years old or older) with acute respiratory failure. Between 2006 and 2016, all nonagenarians with acute respiratory failure requiring invasive mechanical ventilation (MV) were enrolled. Outcomes including in-hospital mortality and ventilator dependency were measured. A total of 173 nonagenarians with acute respiratory failure were admitted to the intensive care unit (ICU). A total of 56 patients died during the hospital stay and the rate of in-hospital mortality was 32.4%. Patients with higher APACHE (Acute Physiology and Chronic Health Evaluation) II scores (adjusted odds ratio [OR], 5.91; 95 % CI, 1.55-22.45; p = 0.009, APACHE II scores ≥ 25 vs APACHE II scores < 15), use of vasoactive agent (adjust OR, 2.67; 95% CI, 1.12-6.37; p = 0.03) and more organ dysfunction (adjusted OR, 11.13; 95% CI, 3.38-36.36, p < 0.001; ≥ 3 organ dysfunction vs ≤ 1 organ dysfunction) were more likely to die. Among the 117 survivors, 25 (21.4%) patients became dependent on MV. Female gender (adjusted OR, 3.53; 95% CI, 1.16-10.76, p = 0.027) and poor consciousness level (adjusted OR, 4.98; 95% CI, 1.41-17.58, p = 0.013) were associated with MV dependency. In conclusion, the mortality rate of nonagenarians with acute respiratory failure was high, especially for those with higher APACHE II scores or more organ dysfunction.

13.
Oncotarget ; 8(60): 101372-101382, 2017 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-29254171

RESUMO

Genetic heterogeneity is the basis of clinical heterogeneity among different subtypes of AML. We have successfully cloned a gene related to AML termed FAMLF from a FAB-M2 patient's sample of a second largest AML pedigree. Then we revealed at least three splice variants, named as FAMLF-1, FAMLF-2 and FAMLF-3, and found miR181a1/b1 in the second intron of FAMLF gene family. Higher expression of FAMLF-1 was related to a higher complete remission (CR) rate, but shorter relapse free survival (RFS) in AML. We further found that the FAMLF-1 single nucleotide polymorphism (SNP) haplotype and its expression were positively correlated to clinical parameters of acute myeloid leukemia partially differentiated (FAB-M2) patients, but not FAB non-M2 patients or Acute Monocytic Leukemia (FAB-M5) patients. GTAGG SNP haplotype of FAMLF gene might increase FAB-M2 susceptibility in Han population and act as a useful candidate biomarker for FAB-M2 screening. We also demonstrated that FAMLF-1 gene silencing in FAB-M2 cells could lead to proliferation inhibition, cell cycle G0/G1 phase arrest, and differentiation promotion independent of its intronic miR-181a1, which might be related to Akt/c-Myc pathway. These findings reveal a role of FAMLF-1 as a potential pathogenic gene for FAB-M2.

14.
Oncotarget ; 8(52): 89643-89654, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-29163777

RESUMO

The role of DHX15, a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in DHX15 (NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally, DHX15 was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of DHX15. DHX15 was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells. DHX15 was down-regulated when AML patients achieved disease remission or when leukemia cell lines were induced to differentiate. DHX15 silencing greatly inhibited leukemia cell proliferation and induced cell apoptosis and G1-phase arrest. In contrast, the restoration of DHX15 expression rescued cell viability and reduced cell apoptosis. In addition, we found that DHX15 was down-regulated when cell apoptosis was induced by ATO (arsenic trioxide); overexpression of DHX15 caused dramatic resistance to ATO-induced cell apoptosis, suggesting an important role for DHX15 in cell apoptosis. We further explored the mechanism of DHX15 in apoptosis and found that overexpression of DHX15 activated NF-kB transcription. Knockdown of DHX15 inhibited the nuclear translocation and activation of the NF-kB subunit P65 in leukemia cells. Several downstream targets of the NF-kB pathway were also down-regulated, and apoptosis-associated genes CASP3 and PARP were activated. In conclusion, this study represents the first demonstration that DHX15 plays an important role in leukemogenesis via the NF-kB signaling pathway and may serve as an independent prognostic marker for AML.

15.
Eur J Appl Physiol ; 117(12): 2445-2455, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28988307

RESUMO

PURPOSE: Oxidative stress-induced lymphocyte apoptosis is linked to hypoxemic individuals suffering from cardiopulmonary disorders or exposed to hypoxic environments. What kind of the exercise strategy under hypoxic condition improves exercise performance and simultaneously minimizes lymphocyte dysfunction caused by oxidative stress has not yet been established. This study elucidates how various exercises regimens with/without hypoxia affect lymphocyte apoptosis induced by oxidative stress. METHODS: A total of 60 sedentary males were randomly divided into five groups. Each group (n = 12) received one of the five interventions: hypoxic-absolute exercise (HAT, 50%W max under 15%O2), hypoxic-relative exercise (HRT, 50% heart rate reserve under 15%O2), normoxic exercise (NT, 50%W max under 21%O2), hypoxic control (HC, resting under 15%O2), or normoxic control (NC, resting under 21%O2) for 30 min/day, 5 days/week for 4 weeks. RESULTS: Before the intervention, the graded exercise test (GXT, progressive exercise up to VO2max) decreased the surface thiol level on lymphocytes and subsequently augmented the extents of H2O2-induced mitochondria transmembrane potential (MTP) diminishing, caspase 3/8/9 activations, and phosphotidyl serine (PS) exposure in lymphocytes. However, 4 weeks of NT, HRT, or HAT reduced the extents of surface thiol decreasing on lymphocytes and H2O2-induced MTP diminishing, caspase 3/8/9 activations, and PS exposure in lymphocytes following GXT. Moreover, the HAT group exhibited greater improvements in pulmonary ventilation and VO2max than either NT or HRT group did. CONCLUSIONS: Exercise training with/without hypoxic exposure effectively alleviates lymphocyte apoptosis induced by oxidative stress following strenuous exercise. However, the HAT is superior to the NT or HRT for enhancing aerobic capacity.


Assuntos
Apoptose , Hipóxia/sangue , Linfócitos/metabolismo , Estresse Oxidativo , Condicionamento Físico Humano/métodos , Adulto , Humanos , Masculino , Oxigênio/metabolismo , Condicionamento Físico Humano/efeitos adversos , Comportamento Sedentário
16.
Clin Chim Acta ; 474: 120-123, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28919492

RESUMO

BACKGROUND: Febrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reactions, and it could be reduced by transfusing patients with leukocyte-poor blood products. However, FNHTR still occur in certain patients transfused with leukocyte-poor red blood cell (LPR) products. It is examined whether human platelet antigen (HPA) could be a potential membrane antigen that plays a role in FNHTR. METHODS: A total of 120 inpatient subjects who transfused with LPR (60 in FNHTR group, 60 in control group) were typed for HPA-2, HPA-3, and HPA-15 using sequence specific primer-polymerase chain reaction (SSP-PCR) and electrophoresis. RESULTS: HPA-2 unmatched rate between donors and patients in FNHTR group was 18%, and only 3% unmatched rate was observed in control group (p=0.0082). FNHTR group was further classified according to the imputability. There was a significant difference (p=0.0041) between FNHTR (probable imputability, infection) group and control group, and more significant difference (p=0.0008) was seen between FNHTR (probable imputability, febrile neutropenia) group and control group. CONCLUSIONS: Those results indicated that HPA-2 might play roles on inducing FNHTR in patients suffering from infectious diseases and febrile neutropenia. HPA-2 genotyping between donors and recipients might be worth integrating in pre-transfusion testing to increase transfusion safety.


Assuntos
Antígenos de Plaquetas Humanas/genética , Febre/complicações , Reação Transfusional/complicações , Reação Transfusional/genética , Genótipo , Humanos
17.
Phytomedicine ; 23(12): 1422-1433, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27765362

RESUMO

BACKGROUND: The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. PURPOSE: We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP+-treated cells. METHODS: Promoter reporter assay in HEK-293 cells was used to examine the cis/trans elements controlling FBXO7 expression and to screen extracts of medicinal herbs enhancing FBXO7 expression. MTT assay was performed to assess cell viability of MPP+-treated HEK-293/SH-SY5Y cells. In addition, proteasome activity, mitochondrial membrane potential and FBXO7/TRAF2/GATA2 protein expression were evaluated. RESULTS: We demonstrated that -202--57 region of the FBXO7 promoter is likely to contain sequences that are bound by positive trans protein factors to activate FBXO7 expression and GATA2 is the main trans protein factor enhancing FBXO7 expression. Extracts of medicinal herbs Oenanthe javanica (Blume) DC. (Umbelliferae), Casuarina equisetifolia L. (Casuarinaceae), and Sorghum bicolor (L.) Moench (Gramineae) improved cell viability of both MPP+-treated HEK-293 and SH-SY5Y cells, rescued proteasome activity in MPP+-treated HEK-293 cells, and restored mitochondrial membrane potential in MPP+-treated SH-SY5Y cells. These protection effects of herbal extracts are acting through enhancing FBXO7 and decreasing TRAF2 expression, which is probably mediated by GATA2 induction. CONCLUSION: Collectively, our study provides new targets, FBXO7 and its regulator GATA2, for the development of potential treatments of PD.


Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Proteínas F-Box/metabolismo , Fármacos Neuroprotetores/farmacologia , Oenanthe , Doença de Parkinson/metabolismo , Extratos Vegetais/farmacologia , Sorghum , Sobrevivência Celular/efeitos dos fármacos , Proteínas F-Box/genética , Fator de Transcrição GATA2/metabolismo , Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Herbicidas/toxicidade , Humanos , Magnoliopsida , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mutação , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Regiões Promotoras Genéticas , Complexo de Endopeptidases do Proteassoma/metabolismo , Fator 2 Associado a Receptor de TNF/metabolismo
19.
Pediatr Nephrol ; 31(8): 1305-12, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26975387

RESUMO

BACKGROUND: Community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging problem. Compared with urban infants, rural infants may encounter different distributions of community-acquired resistant strains and various barriers to efficient management. METHODS: A retrospective survey and comparison was conducted for infants with UTI caused by ESBL-producing E. coli admitted to an urban hospital (n = 111) and a rural hospital (n = 48) in southern Taiwan from 2009 to 2012. RESULTS: Compared with 2009 and 2010, the total number of cases at both hospitals significantly increased in 2011 and 2012 (p < 0.001). Compared with the rural patients, the urban patients were significantly younger, and they had fewer days of fever before and after admission, fewer presentations of poor activity and poor appetite, and a lower serum creatinine level. Most of the patients had no prior history of illness, and we could not identify any significant different risk factors for acquiring ESBL-producing E. coli, such as past antimicrobial use, hospitalization, UTI, and underlying renal diseases, between the urban and rural populations. CONCLUSIONS: The increase in community-acquired UTI in infants caused by ESBL-producing E. coli was similar between the urban and rural populations. Our preliminary data suggest that the rural-urban disparities were probably related to easy access to health care by the urban population. ESBL complicates disease management, and the increase in the prevalence of ESBL producers is a major health concern and requires further healthy carrier and environmental surveillance.


Assuntos
Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções Urinárias/microbiologia , Resistência beta-Lactâmica , Estudos Transversais , Escherichia coli , Feminino , Hospitais Rurais , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Prevalência , Estudos Retrospectivos , Saúde da População Rural , Saúde da População Urbana , Infecções Urinárias/epidemiologia
20.
Appl Environ Microbiol ; 82(6): 1889-1897, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26773082

RESUMO

Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli sequence type ST131 has emerged as the leading cause of community-acquired urinary tract infections and bacteremia worldwide. Whether environmental water is a potential reservoir of these strains remains unclear. River water samples were collected from 40 stations in southern Taiwan from February to August 2014. PCR assay and multilocus sequence typing (MLST) analysis were conducted to determine the CTX-M group and sequence type, respectively. In addition, we identified the seasonal frequency of ESBL-producing E. coli strains and their geographical relationship with runoffs from livestock and poultry farms between February and August 2014. ESBL-producing E. coli accounted for 30% of the 621 E. coli strains isolated from river water in southern Taiwan. ESBL-producing E. coli ST131 was not detected among the isolates. The most commonly detected strain was E. coli CTX-M group 9. Among the 92 isolates selected for MLST analysis, the most common ESBL-producing clonal complexes were ST10 and ST58. The proportion of ESBL-producing E. coli was significantly higher in areas with a lower river pollution index (P = 0.025) and regions with a large number of chickens being raised (P = 0.013). ESBL-producing E. coli strains were commonly isolated from river waters in southern Taiwan. The most commonly isolated ESBL-producing clonal complexes were ST10 and ST58, which were geographically related to chicken farms. ESBL-producing E. coli ST131, the major clone causing community-acquired infections in Taiwan and worldwide, was not detected in river waters.


Assuntos
Escherichia coli/classificação , Escherichia coli/isolamento & purificação , Genótipo , Rios/microbiologia , beta-Lactamases/metabolismo , Criação de Animais Domésticos , Animais , Animais Domésticos , Galinhas , Escherichia coli/enzimologia , Escherichia coli/genética , Tipagem de Sequências Multilocus , Filogeografia , Reação em Cadeia da Polimerase , Estações do Ano , Taiwan , beta-Lactamases/genética
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