RESUMO
INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.
Assuntos
Doença de Alzheimer , População do Leste Asiático , Predisposição Genética para Doença , População Branca , Idoso , Feminino , Humanos , Masculino , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Receptores ErbB/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , População Branca/genética , População do Leste Asiático/genéticaRESUMO
BACKGROUND: Holistic health care considers all aspects of patient care, namely the physical, psychological, spiritual, and social aspects. To assess which patient needs are unmet, a screening questionnaire covering the four aforementioned aspects is required. Therefore, the Sheffield Profile for Assessment and Referral for Care (SPARC), a multidimensional, self-reported questionnaire designed to screen patients regardless of diagnosis, was developed. This study developed a translated and validated traditional Chinese version of the SPARC for patients in Taiwan. METHODS: The original English version of the SPARC was translated into a traditional Chinese version (SPARC-T) through forward-backward translation. Semistructured debriefing interviews were conducted with participants to evaluate the SPARC-T. The reliability and validity of the SPARC-T were assessed through Cronbach's alpha coefficients and a correlation analysis conducted using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. RESULTS: Fifty-three patients were enrolled from our hospital: 22 had cancer but the majority had nonmalignant chronic conditions. About internal consistency, the Cronbach's alpha values for all domains of the SPARC-T were favorable. A correlation analysis of the SPARC-T and FACT-G revealed significant correlations for the domains of physical symptoms, independence and activity, family and social issues, sleep, and treatment issues; no significant correlation was identified for the "psychological issues" domain. CONCLUSION: This study revealed that the SPARC-T is an effective tool for screening Mandarin-speaking patients. Thus, it can be used in hospitals to holistically screen and identify the needs of patients to ensure they can receive appropriate professional support and holistic health care.
Assuntos
Neoplasias , Humanos , Reprodutibilidade dos Testes , Cuidados Paliativos , Inquéritos e Questionários , Encaminhamento e Consulta , Psicometria/métodos , China , Qualidade de Vida/psicologiaRESUMO
BACKGROUND: Early dietary intake enhanced recovery after surgery (ERAS). There remains a gap in the recognition and implementation of early diet after surgery in medical institutions in Taiwan. This study aimed to investigate whether early oral intake after benign gynecologic surgery results in favorable outcomes in Taiwanese patients. METHODS: This was a prospective controlled nonrandomized cohort study. Patients who underwent benign gynecological surgery were included in the early- and conventional-diet groups. The primary outcome was length of hospital stay, and the secondary outcome was postoperative complications. RESULTS: Forty and 38 patients were included in the early and conventional-diet groups, respectively. The early-diet group demonstrated significantly reduced length of hospital stay (the early-diet group, 2.58 ± 0.93 days; conventional-diet group, 4.16 ± 1.13 days; p < 0.001). No increase in postoperative complications was observed in the early-diet group. Laparoscopic surgery reduced the length of hospital stay (ß, -0.65; 95% confidence interval [CI], -1.22 to -0.08; p = 0.027), while an increased length of hospital stay was associated with higher visual analog scales (VAS, ß, 0.21; 95% CI, 0.03-0.39; p = 0.026) and the conventional-diet group (ß, 1.13; 95% CI, 0.65-1.61; p < 0.001) as assessed by multivariate regression analysis. CONCLUSION: Patients who underwent benign gynecologic surgery tolerated an early oral diet well without an increase in complications. Laparoscopic surgery and lower pain scores also enhanced postoperative recovery.
Assuntos
Dieta , Procedimentos Cirúrgicos em Ginecologia , Humanos , Feminino , Estudos Prospectivos , Estudos de Coortes , Procedimentos Cirúrgicos em Ginecologia/métodos , Tempo de Internação , Complicações Pós-OperatóriasRESUMO
Establishing apicobasal polarity, involving intricate interactions among polarity regulators, is key for epithelial cell function. Though phosphatase of regenerating liver (PRL) proteins are implicated in diverse biological processes, including cancer, their developmental role remains unclear. In this study, we explore the role of Drosophila PRL (dPRL) in photoreceptor cell development. We reveal that dPRL, requiring a C-terminal prenylation motif, is highly enriched in the apical membrane of developing photoreceptor cells. Moreover, dPRL knockdown during retinal development results in adult Drosophila retinal degeneration, caused by hid-induced apoptosis. dPRL depletion also mislocalizes cell adhesion and polarity proteins like Armadillo, Crumbs, and DaPKC and relocates the basolateral protein, alpha subunit of Na+/K+-ATPase, to the presumed apical membrane. Importantly, this polarity disruption is not secondary to apoptosis, as suppressing hid expression does not rescue the polarity defect in dPRL-depleted photoreceptor cells. These findings underscore dPRL's crucial role in photoreceptor cell polarity and emphasize PRL's importance in establishing epithelial polarity and maintaining cell survival during retinal development, offering new insights into PRL's role in normal epithelium.
Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Células Fotorreceptoras de Invertebrados/metabolismo , Fígado/metabolismo , Polaridade Celular/genéticaRESUMO
AIM: To evaluate a mobile e-learning program for nurses caring for women with gynecologic cancer and explore the effect of personal involvement and motivation on self-learning. BACKGROUND: Cancer care has gradually come to be regarded as chronic disease management. In this context, nurses require health education skills to impart cancer-related knowledge and teach patients the relevant practices to enhance their adaptation to the illness. Thus, nurses would benefit from a mobile program to facilitate learning educational skills efficiently as it allows learners to learn at their own pace and convenience. METHODS: A cross-sectional study design was used. A mobile e-learning program with interactive tasks was designed to function as supplementary education for nurses. The program comprised four topics including exercise, illness representations based on the Common Sense Model, caring principles associated with chemotherapy and radiation therapy in caring for women with gynecologic cancer. In total, 84 purposively sampled nurses completed the program successfully. Data were collected via structured questionnaire from March to August 2021. Partial least squares structural equation modeling was used to examine the proposed hypotheses regarding the effects of involvement and motivation on learning outcomes. RESULTS: The results showed that cognitive involvement had significant effects on learning motivation. However, no significant effects were found for affective involvement. Furthermore, cognitive involvement was indirectly associated with learning effects via motivational components. The strongest associations between motivational factors and learning effects were found for perceived attention, followed by perceived relevance. CONCLUSIONS: The results suggest that motivation is a proximal influencing factor for learning effects. However, the effects of perceived attention and relevance were stronger than those of perceived confidence and satisfaction. Furthermore, the authors identified the different aspects of involvement and found that cognitive involvement had significant effects on learning motivation, while no effects were observed for affective involvement.
Assuntos
Instrução por Computador , Neoplasias , Humanos , Feminino , Motivação , Estudos Transversais , Aprendizagem , Satisfação PessoalAssuntos
Displasia Broncopulmonar , Enterocolite Necrosante , Doenças do Prematuro , Lactente , Recém-Nascido , Humanos , Enterocolite Necrosante/induzido quimicamente , Enterocolite Necrosante/complicações , Displasia Broncopulmonar/etiologia , Antibacterianos/efeitos adversos , Recém-Nascido de muito Baixo Peso , Peso ao NascerRESUMO
BACKGROUND: The incidence of metabolic syndrome (MetS) is increasing, and n-3 polyunsaturated fatty acids (PUFAs) in salmon (Oncorhynchus) phospholipids can effectively reduce the risk of MetS. RESULTS: Under the intervention of 4% salmon phospholipid, the levels of fasting blood glucose (FBG), insulin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly reduced in the plasma of MetS mice, whereas adiponectin was significantly increased. By screening, we found that the 18 differential metabolites, consisting of seven triglycerides (TGs), six diglycerides (DGs), one phosphatidylethanolamine (PE), three sphingomyelins (SMs) and one eicosanoid, could be the key differential metabolites, and two metabolic pathways were significantly affected: glycerolipid metabolism and glycerophospholipid metabolism. CONCLUSION: 4% salmon phospholipids could affect MetS by inhibiting insulin resistance, reducing inflammatory factors and promoting the synthesis of PE, yet the mechanism required further study. Our results could help in the treatment of MetS. © 2021 Society of Chemical Industry.
Assuntos
Resistência à Insulina , Síndrome Metabólica , Animais , Lipidômica , Síndrome Metabólica/tratamento farmacológico , Camundongos , Fosfolipídeos , SalmãoRESUMO
Patients undergoing gynecological surgery commonly receive indwelling transurethral Foley catheters, however duration of catheterization is associated with risk of urinary tract infections and other adverse effects. Early removal of catheters is encouraged, however optimal timing postsurgery remains unclear. This quasi-experimental study compared outcomes for women after removal of a Foley catheter at two different times following benign gynecological surgery. Participants received either early catheter removal, within 6 hours of surgery (n = 38) or standard catheter removal, within 12 to 24 hours of surgery (n = 45). There were no significant differences in outcomes for discomfort scores or re-catheterization rates between groups. However, the early removal group had a significantly shorter time to first ambulation and shorter hospital stays. Early removal of Foley catheters in patients who underwent gynecological surgery did not increase adverse events. Early removal of catheters after gynecological surgery may decrease re-catheterization rates and increase patient satisfaction.
Assuntos
Cateteres Urinários , Infecções Urinárias , Cateteres de Demora/efeitos adversos , Remoção de Dispositivo , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Cateterismo Urinário/efeitos adversos , Cateteres Urinários/efeitos adversos , Infecções Urinárias/etiologiaAssuntos
Adenomiose , Procedimentos Cirúrgicos em Ginecologia/métodos , Laparoscopia , Resultado da Gravidez , Miomectomia Uterina/métodos , Adenomiose/patologia , Adenomiose/cirurgia , Parto Obstétrico , Dismenorreia , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Gravidez , Complicações na Gravidez/etiologia , Nascimento Prematuro , Resultado do TratamentoRESUMO
BACKGROUND: CSF1R-related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown. METHODS: In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations, we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases. Next generation sequencing was conducted for 10 probands to confirm the diagnosis. Sanger sequencing, segregation analysis and phenotypic reevaluation were utilized to substantiate findings. Functional examination of identified mutations was further explored. RESULTS: Clinical and neuroimaging characteristics were summarized. The average age at onset was 35.9 ± 6.4 years (range 24-46 years old). Younger age of onset was observed in female than male (34.2 vs. 39.2 years). The most common initial symptoms were speech dysfunction, cognitive decline and parkinsonian symptoms. One patient also had marked peripheral neuropathy. Brain biopsy of two cases showed typical pathological changes, including myelin loss, axonal spheroids, phosphorylated neurofilament and activated macrophages. Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons. A total of 7 pathogenic variants (4 novel, 3 documented) were identified with autophosphorylation deficiency, among which c.2342C > T remained partial function of autophosphorylation. Western blotting disclosed the significantly lower level of c.2026C > T (p.R676*) than wild type. The level of microtubule associated protein 1 light chain 3-II (LC3-II), a classical marker of autophagy, was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining. CONCLUSIONS: Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis. Autophagy abnormality may play a role in the disease. Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future. However, whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled. TRIAL REGISTRATION: ChiCTR, ChiCTR1800015295. Registered 21 March 2018.
RESUMO
OBJECTIVE: Stress urinary incontinence (SUI) is a common disease in aged women, and some of them need surgical correction. Recently, the mid-urethral sling is an accepted surgical approach for SUI. However, complication may occur in this surgery, and some of them are needle-related. Therefore, the needleless system may diminish this-type complication. MATERIALS AND METHODS: We conducted a retrospective study to evaluate the feasibility of women with SUI undergoing needleless sling surgery in 2017. Assessments were performed by two independent special urogynecologists before, during and post operation periods. We used a category-time-site-pain code following the International Continence Society and International Urogynecological Association (ICS/IUGA) Complication Classification Code (CCC) guidelines. RESULTS: Thirty-eight women were analyzed. The characteristics of the patients were 66.3 ± 12.8 years old (mean ± standard deviation) of age, 2.8 ± 1.2 of parity, and 25.6 ± 4.2 kg/m2 of body mass index. All had history of vaginal delivery for term. The objective cure rate at 2- and 4-week follow-up was 97.4% (n = 37) and 94.7% (n = 36), respectively. The subjective cure rate at 2- and 4-week follow-up was both 89.5% (n = 34). Both objective and subjective cure rates remained constant and similar to the end of 4 weeks. There were 6 patients (15.8%) who had complications according to ICS/IUGA CCC guidelines. CONCLUSION: This needleless mid-urethral sling procedure seemed to be feasible in the management of women with SUI in this small series and short-term follow-up study, suggesting that a further prospective, randomized, comparative study with other tension-free procedures and mini-sling systems can be conducted.
Assuntos
Slings Suburetrais , Âncoras de Sutura , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Idoso , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Desenho de Prótese , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Incontinência Urinária por Estresse/fisiopatologia , Micção/fisiologiaRESUMO
Acute hepatic injury caused by inflammatory liver disease is associated with high mortality. This study examined the role of caveolin-1 (Cav-1) in lipopolysaccharide (LPS) and D-galactosamine (GalN)-induced fulminant hepatic injury in wild type and Cav-1-null (Cav-1-/- ) mice. Hepatic Cav-1 expression was induced post-LPS/GalN treatment in wild-type mice. LPS/GalN-treated Cav-1-/- mice showed reduced lethality and markedly attenuated liver damage, neutrophil infiltration and hepatocyte apoptosis as compared to wild-type mice. Cav-1 deletion significantly reduced LPS/GalN-induced caspase-3, caspase-8 and caspase-9 activation and pro-inflammatory cytokine and chemokine expression. Additionally, Cav-1-/- mice showed suppressed expression of Toll-like receptor 4 (TLR4) and CD14 in Kupffer cells and reduced expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 in liver cells. Cav-1 deletion impeded LPS/GalN-induced inducible nitric oxide synthase expression and nitric oxide production and hindered nuclear factor-κB (NF-κB) activation. Taken together, Cav-1 regulated the expression of mediators that govern LPS-induced inflammatory signalling in mouse liver. Thus, deletion of Cav-1 suppressed the inflammatory response mediated by the LPS-CD14-TLR4-NF-κb pathway and alleviated acute liver injury in mice.
Assuntos
Caveolina 1/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Inflamação/genética , Fígado/efeitos dos fármacos , Animais , Apoptose/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Molécula 1 de Adesão Intercelular/genética , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Receptores de Lipopolissacarídeos/genética , Lipopolissacarídeos/toxicidade , Fígado/lesões , Fígado/metabolismo , Fígado/patologia , Camundongos , NF-kappa B/genética , Infiltração de Neutrófilos/genética , Óxido Nítrico Sintase Tipo II/genética , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Fator de Transcrição RelA/genéticaRESUMO
It was demonstrated that isoflavones can cross the blood-brain barrier, making them desirable candidate agents for the prevention of neurological symptoms. 8-Hydroxydaidzein (8-OHD, 4',7,8-trihydoxyisoflavone) is an isoflavone found only in fermented soy food. Current results showed that 8-OHD inhibited LPS-stimulated production of nitric oxide (NO) and proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, by inhibiting gene expression in BV2 microglial cells. Moreover, 8-OHD markedly quenched reactive oxygen species (ROS) and activated NF-E2-related factor 2 (Nrf2) so as to upregulate expression of Phase II enzymes, including heme oxygenase (HO)-1, NAD(P)H quinone dehydrogenase 1 (NQO1), and the modifier subunit of glutamate cysteine ligase (GCLM). 8-OHD also suppressed LPS-stimulated phosphorylation of Akt and NF-κB-p65. The anti-inflammatory activity of 8-OHD was attenuated by the HO-1 inhibitor zinc protoporphyrin (Znpp) but augmented by the PI3K/Akt inhibitor LY294002. 8-OHD also diminished LPS-induced prostaglandin E2 (PGE2) production without affecting cyclooxygenase (COX)-2 expression. In vitro assay shows that 8-OHD displayed mixed-type inhibition of COX-2 with an IC50 of 8.9 ± 1.2 µM. These data suggest that the anti-inflammatory activity of 8-OHD may be associated with the activation of Nrf2/HO-1 and attenuation of Akt/NF-κB signaling pathways as well as inhibition of COX-2 enzyme activity. In conclusion, 8-OHD, a potent Nrf2 activator, Akt/NF-κB activation suppressor, and COX-2 enzyme inhibitor, may have health-promoting effects for mitigating microglia activation and preventing neuroinflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Isoflavonas/farmacologia , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes , Linhagem Celular Transformada , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desintoxicação Metabólica Fase II , Camundongos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de OxigênioRESUMO
BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells. METHODS: Cell viability was assayed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptotic and autophagic markers were analyzed by Western blot. Gene expression of unfolded protein response (UPR) and Phase II enzymes was further investigated using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) by a fluorometer. The effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1 (Sirtuin 1) signaling pathways were examined using Western blotting and specific inhibitors. RESULTS: Fisetin (<20 µM) restored cell viability and repressed apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2-targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38 MAPK. Addition of JNK and p38 MAPK inhibitor significantly antagonized its cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm-inhibited SIRT1 expression and addition of sirtinol (SIRT1 activation inhibitor) significantly blocked fisetin-mediated cytoprotection. In conclusion, this result shows that fisetin activates Nrf2, MAPK and SIRT1, which may elicit adaptive cellular stress response pathways so as to protect cells from Tm-induced cytotoxicity.
Assuntos
Antioxidantes/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Flavonóis , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/genética , Células PC12 , Ratos , Sirtuína 1/genéticaRESUMO
BACKGROUND: Adenoviral vector is an efficient tool for gene transfer. Protein expression is regulated by a number of factors, but the regulation by gene copy number remains to be investigated further. RESULTS: Assessed by flow cytometry, we demonstrated a significant linear correlation between average fluorescence intensity of green fluorescent protein (GFP) and a wide range of multiplicity of infection (MOI), spanning from 0.01 to 200. Average GFP intensity was calculated by mean fluorescence intensity (MFI) × percentage of infection (POI) (MFI × POI) and the correlation was observed in cells transduced with GFP-expressing adenoviral vector driven either by a cytomegalovirus (CMV) promoter for 3 to 6 h or by a human phosphoglycerate kinase (PGK) promoter for 18 to 24 h. Factors impacting this linear correlation include MOI of viral vector, strength of promoter driving GFP expression, cell type transduced and incubation time after gene transfer. We also found that weak GFP signals could be interfered by background signals, whereas strong GFP signals could overshot the detection limitation of the flow cytometer and resulted in a deviation from linearity which was prevented by adjusting the setting in flow cytometer. Moreover, we compared promoter strength as measured by MFI × POI and found that the relative activity of CMV promoter to PGK promoter was 20 to 47 folds in A549 cells and 32 to > 100 folds in H1299 cells. CONCLUSIONS: The linear correlation between MFI × POI and a wide range of adenoviral MOI provides an efficient method to investigate factors regulating protein expression and to estimate virus titers.
Assuntos
Infecções por Adenoviridae/virologia , Adenoviridae/fisiologia , Fluorescência , Proteínas de Fluorescência Verde/metabolismo , Regiões Promotoras Genéticas , Linhagem Celular Tumoral , Citomegalovirus/fisiologia , Citometria de Fluxo , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Humanos , Fosfoglicerato Quinase/metabolismoRESUMO
The chronic effects of carboxyl-terminal polypeptide of Cardiotrophin-1 (CT-1-CP) on ventricular electrical remodeling were investigated. CT-1-CP, which contains 16 amino acids in sequence of the C-terminal of Cardiotrophin-1, was selected and synthesized, and then administered to Kunming mice (aged 5 weeks) by intraperitoneal injection (500 ng·g⻹·day⻹) (4 groups, n=10 and female: male=1:1 in each group) for 1, 2, 3 and 4 weeks, respectively. The control group (n=10, female: male=1:1) was injected by physiological saline for 4 weeks. The epicardial monophasic action potential (MAP) was recorded by using a contact-type MAP electrode placed vertically on the left ventricular (LV) epicardium surface, and the electrocardiogram (ECG) signal in lead II was monitored synchronously. ECG intervals (RR, PR, QRS and QT) and the amplitude of MAP (Am), the maximum upstroke velocity (Vmax), as well as action potential durations (APDs) at different repolarization levels (APD30, APD50, APD70, and APD90) of MAP were determined and analyzed in detail. There were no significant differences in RR and P intervals between CT-1-CP-treated groups and control group, but the PR segment and the QRS complex were greater in the former than in the latter (F=2.681 and 5.462 respectively, P<0.05). Though QT interval and the corrected QT interval (QTc) were shorter in CT-1-CP-treated groups than in control group, the QT dispersion (QTd) of them was greater in the latter than in the former (F=3.090, P<0.05) and increased with the time. The ECG monitoring synchronously with the MAP showed that the compression of MAP electrode on the left ventricular epicardium induced performance similar to myocardium ischemia. As compared with those before chest-opening, the PR segment and QT intervals remained basically unchanged in control group, but prolonged significantly in all CT-1-CP-treated groups and the prolongation of QT intervals increased gradually along with the time of exposure to CT-1-CP. The QRS complex had no significant change in control group, one-week and three-week CT-1-CP-treated groups, but prolonged significantly in two-week and four-week CT-1-CP-treated groups. Interestingly, the QTd after chest-opening was significantly greater than that before chest-opening in control group (t=5.242, P<0.01), but decreased along with the time in CT-1-CP-treated groups. The mean MAP amplitude, Vmax and APD were greater in CT-1-CP-treated groups than those in control group, and became more obvious along with the time. The APD in four CT-1-CP-treat groups was prolonged mainly in middle to final repolarization phase. The difference among these groups became significant in middle phase (APD50) (F=6.076, P<0.01) and increased furthermore in late and final phases (APD70: F=10.054; APD90: F=18.691, P<0.01) along with the time of injection of CT-1-CP. The chronic action of CT-1-CP might induce the adapting alteration in cardiac conductivity and ventricular repolarization. The amplitude and the Vmax of the anterior LV epicardial MAP increased obviously, and the APD prolonged mainly in late and final phase of repolarization.
Assuntos
Citocinas/fisiologia , Ventrículos do Coração/metabolismo , Fragmentos de Peptídeos/fisiologia , Função Ventricular , Animais , Citocinas/química , Eletrocardiografia , CamundongosRESUMO
BACKGROUND: Breast cancer patients frequently experience psychological distress during the chemotherapy period. OBJECTIVES: This study aimed to evaluate the effect of relaxation with guided imagery on patients with breast cancer. PATIENTS AND METHODS: A two-group, pretest-posttest, quasi-experimental design with a randomized controlled trial was conducted. Sixty-five breast cancer patients from one medical center in Taiwan were enrolled in the study. These patients were randomly assigned to the experimental group (n = 32) or to the control group (n = 33). Both groups received chemotherapy self-care education, but the experimental group also received relaxation with guided imagery training. The training on relaxation with guided imagery was conducted before chemotherapy, and the patients were supplied with a compact disc detailing the performance of relaxation with guided imagery for 20 minutes daily at home for 7 days after chemotherapy. RESULTS: The experimental group showed significant decreases in insomnia (-0.34 ± 0.83, P < 0.05), pain (-0.28 ± 0.58, P < 0.05), anxiety (-3.56 ± 2.94, P < 0.00), and depression (-2.38 ± 2.70, P < 0.00) between the pretest and the posttest. Comparing the two groups, statistically significant differences were found in the overall symptom distress (B = 0.11, P < 0.05), insomnia (B = 0.50, P <0.05), depression (B = 0.38, P < 0.05), and numbness in physical symptoms (B = 0.38, P < 0.05), as well as in anxiety (B = 3.08, P < 0.00) and depression (B = 1.86, P < 0.00) in psychological distress. One week of relaxation with guided imagery can significantly improve the overall symptoms of distress, insomnia, depression, physical symptoms, and anxiety, and can decrease psychological distress. CONCLUSIONS: Relaxation with guided imagery had a positive effect on mediating anxiety and depression in breast cancer patients.