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1.
Anal Chem ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32003219

RESUMO

Noble metal nanoparticles (NPs) have enabled surface-enhanced Raman scattering (SERS) for in situ monitoring of NPs-catalyzed reactions. However, it still remains a great challenge to ensure that analytes without plasmonic metal surface-affinity groups (such as thiol and amino groups) can be located into hotspots and detected by SERS. Here, we report a novel sacrificial template method for the fabrication of "pomegranate-like" plasmonic nanoreactors (PPNs), in which high-density embedded AuNPs simultaneously generated SERS enhancement and catalytic performance. Once the analytes entering PPNs are catalyzed and meanwhile located into the hotspots, in situ SERS monitoring of catalytic reactions can be achieved. The intense hotspots of localized electric fields of PPNs were evaluated by finite-difference time-domain simulation. By using PPNs as a substrate, SERS signals of molecules without Au surface-affinity groups were obtained, such as p-naphthoquinone and 4-nitrophenol. The PPNs showed high catalytic activities in the reduction of 4-nitrothiophenol to 4-aminothiophenol and 4-nitrophenol to 4-aminophenol, respectively. Besides, the SERS spectra of both 4-nitrophenol and 4-aminophenol during the reduction reaction of 4-nitrophenol with NaBH4 were first obtained, demonstrating their utilization in the detection of catalytic reactions.

2.
J Clin Pharm Ther ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985852

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Teicoplanin is widely used for the treatment of infections caused by drug-resistant Gram-positive bacteria. Since there is a good correlation between trough levels and clinical outcome, therapeutic drug monitoring (TDM) is recommended to achieve better clinical curative effects. However, TDM of teicoplanin is not routine in China. So, a programme was initiated in 2017, including both HPLC method establishment and interlaboratory quality assessment, for the measurement of teicoplanin. METHODS: A main centre and a quality control centre were set up in the study. An HPLC-based method of teicoplanin determination in plasma was developed by the main centre. Analysis was performed using a Waters Symmetry C18 column (250 mm × 4.6 mm, 5 µm). The mobile phase was NaH2 PO4 (0.01 mol/L) and acetonitrile (75:25 v/v; pH 3.3), with a flow rate of 1.0 mL/min and a detection wavelength of 215 nm. Piperacillin sodium was selected as an internal standard (IS). Twenty-six additional TDM centres were then recruited to adopt this method. Then, all the centres were asked to take part in a quality control assessment evaluated by the quality control centre. RESULTS: For all TDM centres, linearity of teicoplanin concentration ranges was between 3.125 and 100 µg/mL. Intraday and interday accuracies ranged from 87.1% to 118.4%. Intraday and interday precision ranged from 0.3% to 13.8%. Therapeutic drug monitoring centres all passed inter-room quality assessment. All samples tested met the acceptance criteria. Then, 542 samples were collected. Patients with sub-optimal (≤10 mg/L) plasma teicoplanin concentrations constituted 42% of the total study population. WHAT IS NEW AND CONCLUSIONS: For the first time, a simple, rapid and accurate HPLC method for determining teicoplanin levels was successfully applied to therapeutic drug monitoring in clinical practice for twenty-seven TDM centres in China. The results demonstrated excellent interlaboratory agreement for teicoplanin testing and provide support for clinical laboratory quality management and results inter-accreditation.

3.
Clin Exp Allergy ; 50(2): 231-243, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31715648

RESUMO

BACKGROUND: The on-purpose-modulated dendritic cells (DCs) have shown charming effects on restoring immune regulatory functions in subjects with immune diseases. OBJECTIVE: This study aims to construct DCs carrying chimerical antigen (Ag) peptides (CAP-DCs) to induce interleukin (IL)-17+ inducible Tregs (iTregs) to alleviate food allergy (FA) in a murine model. METHODS: In this study, we constructed CAP-DCs. The CAP is a fusion protein, consisting of a segment of recombinant scFv of anti-DEC205 antibody and an ovalbumin (OVA) epitope (IC). A murine OVA-FA model was developed to test the effects of CAP-DCs on suppressing the allergic response in the intestine. RESULTS: The CAP-DCs are characterized as that a complex of scFv-IC is presented on the surface of the cells, moderately express CD80 and CD86 as well as IL-6, IL-23, transforming growth factor (TGF)-ß and CCR9. After being passively transferred with CAP-DCs or injection of scFv-IC, Ag-specific IL-17+ Foxp3+ iTregs were induced in the intestinal lamina propria of FA mice. The iTregs showed immune suppressive effects on Ag-specific Th2 response. FA mice were adoptively transferred with the CAP-DCs or scFv-IC injection, which resulted in a significant decrease in the number of Ag-specific Th2 cells and suppression of FA response in an Ag-specific manner. CONCLUSIONS AND CLINICAL RELEVANCE: CAP-DCs can ameliorate FA response by inducing Ag-specific IL-17+ Foxp3+ iTregs and suppressing Ag-specific Th2 response. To generate CAP-DCs has the translational potential in the treatment of FA.

4.
Appetite ; 144: 104462, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539578

RESUMO

INTRODUCTION: Food portion size (PS) and energy density (ED) are the two primary determinants of total energy intake. While emerging neuroscientific data indicate judgments of PS and ED involve distinct brain regions, it is not understood how these judgements interact with each other to influence an individual's energy consumption. The present study investigated these cognitive interactions against body-mass-index (BMI) and sex. METHODS: We tested 70 participants (including 34 overweight individuals) for cognitive biases when judging PS and ED, using the Garner task paradigm. Participants were asked to discriminate PS and ED, following pre-determined cognitive rules. Reaction time and correctness of their responses were recorded and analysed against the testing conditions across sexes and BMI groups. RESULTS: We detected a significant 3-way interaction between BMI, Task, and Condition (F(3, 67) = 4.1, p = 0.047, ƞ2 = 0.06). Post-hoc tests suggested that, in the PS task, both weight groups experienced the Garner Interference effect introduced by variations of ED. That is, when making judgments concerning PS, participants were unable to ignore information relating to ED. Results from the ED task differed across weight groups, with only the overweight group being susceptible to the Garner Interference introduced by variations of PS. Additionally, both Sex and BMI were significant factors moderating reaction time when judging PS. Significantly longer reaction time was observed in female versus male comparisons, and for overweight versus healthy-weight participants (p < 0.05). CONCLUSION: Overall, the results confirmed cognitive interactions involving PS and ED, although these interactions were asymmetric across BMI groups. These findings provide new insights into the cognitive processes underpinning individual dietary decision-making, and are potentially important for developing targeted intervention strategies for effective management of unhealthy eating behaviour.

5.
Bioorg Med Chem ; 28(2): 115258, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31864776

RESUMO

Proguanil, a member of biguanide family, has excellent anti-proliferative activities. Fluorine-containing compounds have been demonstrated to have super biological activities including enhanced binding interactions, metabolic stability, and reduced toxicity. In this study, based on the intermediate derivatization methods, we synthesized 13 new fluorine-containing proguanil derivatives, and found that 7a,7d and 8e had much lower IC50 than proguanil in 5 human cancerous cell lines. The results of clonogenic and scratch wound healing assays revealed that the inhibitory effects of derivatives 7a,7d and 8e on proliferation and migration of human cancer cell lines were much better than proguanil as well. Mechanistic study based on representative derivative 7a indicated that this compound up-regulates AMPK signal pathway and downregulates mTOR/4EBP1/p70S6K. In conclusion, these new fluorine-containing derivatives show potential for the development of cancer chemotherapeutic drugs.

6.
Oncol Lett ; 18(6): 5663-5672, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788038

RESUMO

Cancer cells are characterized by a high glycolytic rate, which leads to energy regeneration and anabolic metabolism; a consequence of this is the abnormal expression of pyruvate kinase isoenzyme M2 (PKM2). Multiple studies have demonstrated that the expression levels of PKM2 are upregulated in numerous cancer types. Consequently, the mechanism of action of certain anticancer drugs is to downregulate PKM2 expression, indicating the significance of PKM2 in a chemotherapeutic setting. Furthermore, it has previously been highlighted that the downregulation of PKM2 expression, using either inhibitors or short interfering RNA, enhances the anticancer effect exerted by THP treatment on bladder cancer cells, both in vitro and in vivo. The present review summarizes the detailed mechanisms and therapeutic relevance of anticancer drugs that inhibit PKM2 expression. In addition, the relationship between PKM2 expression levels and drug resistance were explored. Finally, future directions, such as the targeting of PKM2 as a strategy to explore novel anticancer agents, were suggested. The current review explored and highlighted the important role of PKM2 in anticancer treatments.

7.
Hum Mutat ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680349

RESUMO

Whole-exome sequencing (WES) is widely used to detect genetic mutations that cause Mendelian diseases, and has been successfully applied in combination with preimplantation genetic diagnosis (PGD) to avoid the transmission of genetic defects. We investigated 40 nonconsanguineous families with unexplained, recurrent fetal malformations (two or more malformed fetuses) from May 2016 to December 2018. Using Trio-WES, we identified 32 disease-associated variants in 40 families (80% positive rate), which were subsequently verified. Known Mendelian diseases were identified in 12 families (30%), highly suspected Mendelian diseases in 12 families (30%), variants with uncertain significance in 8 families (20%), and no noticeable variants for 8 families (20%). Further analysis showed variants in 22 genes may cause fetal malformations. Four gene variants were detected in fetuses for the first time, which expanded the spectrum of the disease phenotype. Two novel candidate genes may be related to fetal malformations. Of 26 couples receiving PGD on disease-associated genes, 3 healthy newborns were delivered, and 4 couples are undergoing pregnancies. We reported the fetal data and developed an optimized genetic testing strategy. Our finding strongly suggests the presence of single gene Mendelian disorders in 60% of those families, and PGD services for couples to have healthy babies.

8.
Front Pharmacol ; 10: 1159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649535

RESUMO

Activations of Akt or ERK pathway induced by clinical drugs promote therapeutic failure due to decrease of drug response, and no available strategies have been developed to solve these problems. In this study, we found that pirarubicin (THP), one important chemotherapeutic drug for treating bladder cancer intravesically, dramatically elevated phosphorylations of both Akt and Erk1/2 in addition to inducing DNA damage. MK2206 or AZD6244, representative Akt and Erk1/2 inhibitors, respectively, profoundly sensitized bladder cancer cells to THP treatment. Interestingly, we found that inhibition of a single arm of either Akt or Erk1/2 pathway would induce the increase of another arm, indicating the existence of the crosstalk between these two pathways. Thus, simultaneous suppression of both signals may be needed for increasing the sensitivity of THP. On the other hand, we revealed that phenformin efficiently inhibited both Akt and Erk1/2 phosphorylation in a dose-dependent manner. Furthermore, we demonstrated that phenformin, mimicking dual inhibitors, plays dramatically synergistic action with THP both in vitro and in vivo. Our findings suggest that combination therapy of THP with dual inhibitors may constitute a successful strategy for improving chemotherapy response.

9.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31654067

RESUMO

Reprogrammed metabolism is an important hallmark of cancer cells. Pyruvate kinase (PK) is one of the major rate-limiting enzymes in glucose metabolism. The M2 isoform of PK (PKM2), is considered to be an important marker of metabolic reprogramming and one of the key enzymes. Recently, through the continuous development of genome-wide analysis and functional studies, accumulating evidence has demonstrated that long non-coding RNAs (LncRNAs) play vital regulatory roles in cancer progression by acting as either potential oncogenes or tumor suppressors. Furthermore, several studies have shown that up-regulation of PKM2 in cancer tissues is associated with LncRNAs expression and patient survival. Thus, scientists have begun to unveil the mechanism of LncRNA-associated PKM2 in cancer metabolic progression. Based on these novel findings, in this mini-review, we summarize the detailed molecular mechanisms of LncRNA related to PKM2 in cancer metabolism. We expect that this work will promote a better understanding of the molecular mechanisms of PKM2, and provide a profound potential for targeting PKM2 to treat tumors.

10.
Parasit Vectors ; 12(1): 457, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547847

RESUMO

BACKGROUND: Potent granulomatous inflammation responses induced by schistosome eggs and resultant fibrosis are the primary causes of morbidity in schistosomiasis. Recombinant Sj16 (rSj16), a 16-kDa protein of Schistosoma japonicum produced in Escherichia coli, has been demonstrated to have novel immunoregulatory effects in vivo and in vitro. Thus, this study investigated the anti-inflammatory and anti-fibrotic effects of rSj16 treatment in S. japonicum-infected mice and demonstrated the immune modulation between the schistosome and the host. METHODS: Schistosoma japonicum infected mice were treated with the rSj16 protein and Sj16 peptide at different time points post-infection to assess their efficacy at the optimal time point. Sj16 peptide and/or Praziquantel (PZQ) treatments were initiated at week 5 post-infection to compare the therapeutic efficacy of each regimen. Hepatic granulomatous inflammation, fibrosis and cytokine production (pro-inflammatory, Th1, Th2, Th17 and regulatory cytokines IL-10) were detected. Moreover, M2 macrophages were measured to illuminate the mechanisms of Sj16. RESULTS: The rSj16 protein and Sj16 peptide had significant protective effects in S. japonicum-infected mice, as shown by decreased granuloma formation, areas of collagen deposition and inhibition of pro-inflammatory Th1, Th2 and Th17 cytokine production. These protective activities were more obvious when animals were treated with either the Sj16 protein or peptide at early stages post-infection. Interestingly, the combined treatment of PZQ and Sj16 was more effective and upregulated IL-10 production than administration of PZQ alone in infected mice. Furthermore, the Sj16 treatment alleviated the pathological effects associated with activated M2 macrophages. CONCLUSIONS: This study demonstrates the anti-inflammatory and anti-fibrotic effects of rSj16 in schistosomiasis. Therefore, the combination of rSj16 with PZQ could be a viable and promising therapeutic strategy for schistosomiasis. In addition, this investigation provides additional information on schistosome-mediated immune modulation and host-parasite interactions.


Assuntos
Granuloma/prevenção & controle , Proteínas de Helminto/metabolismo , Fatores Imunológicos/metabolismo , Fígado/patologia , Macrófagos/imunologia , Esquistossomose Japônica/patologia , Animais , Anti-Helmínticos/administração & dosagem , Modelos Animais de Doenças , Fibrose/patologia , Fibrose/prevenção & controle , Granuloma/patologia , Proteínas de Helminto/administração & dosagem , Fatores Imunológicos/administração & dosagem , Inflamação/patologia , Inflamação/prevenção & controle , Camundongos , Praziquantel/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Resultado do Tratamento
11.
Libyan J Med ; 14(1): 1648963, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31357919

RESUMO

The use of health information technology (HIT) is expected to deliver benefits for patients, nurses, physicians, and organizations, but the benefits of HIT can only be attained if nurses accept and intend to use it as they are the leading user-group. The use of the tablet is becoming commonplace in healthcare organizations to improve patient care. The current study incorporates Technology Acceptance Model2 (TAM2) with two antecedents, facilitating condition and personal, to identify and understand the factors that influence nurses' intention to use the Tablet PC. The survey methodology was used to collect data from the nurses working in a regional healthcare center in Taiwan. The structural equation modeling (SEM) technique was employed to analyze the research framework. A total of 110 valid responses for analysis. The results suggest that the modified proposed research framework explains about 41.7% of the variance of nurses' behavioral intention. The partial least squares (PLS) regression indicated that perceived usefulness, subjective norm, and personal a positive and significant influence on nurses' intention to use the Tablet PC. But concerning the perceived ease of use, the insignificant path coefficient was reported. The finding also indicated that personal on the research model is much stronger than the subjective norm on Tablet PC performance. The proposed research framework contributes to the conclusive explanation for understanding nurses' intention to use. The current study brings perspectives from the technological and attitudinal differences that have largely been missing in the existing literature of the nurses' intention to use HIT. Thus, health care providers must take these factors into consideration as the findings of the current study advance theory and contribute to the basis for future study intended for enhancing our understanding of nurses' adoption behavior regarding HIT.

12.
World J Gastroenterol ; 25(17): 2099-2109, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31114136

RESUMO

BACKGROUND: The methylated septin 9 (mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test. However, the diagnostic and prognostic role of preoperative mSEPT9 for colorectal cancer (CRC) in Chinese patients is still unknown. AIM: To improve the understanding of diagnostic and prognostic factors, serum mSEPT9 was detected in Chinese CRC patients. METHODS: A retrospective analysis of 354 cases, of which 300 had CRC and 54 were normal, was performed in China. Patients' characteristics, treatments, and laboratory data, including age, the date of surgery, Union for International Cancer Control (UICC) stages, distant metastasis (M), and so on, were collected. Methylation levels of SEPT9 were quantified by quantitative, methylation-specific polymerase chain reaction before surgery. In addition, the effects of mSEPT9 on the occurrence and prognosis of 330 CRC cases from The Cancer Genome Atlas (TCGA) database were evaluated using bioinformatics analyses. Potential prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier univariate analysis. RESULTS: In Chinese CRC patients, positive mSEPT9 was strongly associated with advanced UICC stages, deeper invasion by the primary tumor, and more distant metastasis. Methylation levels of SEPT9 were stage-dependent and showed a stepwise increase in UICC stages (I-IV), primary tumor categories (T1-T4), regional node categories (N0-N2), and distant metastasis categories (M0-M1). The patients with positive mSEPT9 showed a tendency toward lower PFS. After analyzing TCGA clinical data, the high mSEPT9 group was found to be obviously correlated only with more distant metastasis. The patients with high mSEPT9 levels showed a tendency toward lower OS. Besides, nine meaningful mSEPT9 sites were found to provide guidance for the follow-up studies. CONCLUSION: MSEPT9 analysis may add valuable information to current tumor staging. Serum mSEPT9 in Chinese CRC patients appears to offer promising novel prognostic markers and might be considered for monitoring CRC recurrence.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Septinas/metabolismo , Adenoma/sangue , Adenoma/diagnóstico , Adenoma/cirurgia , Idoso , China , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Biologia Computacional , Metilação de DNA , Detecção Precoce de Câncer , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
13.
Cancer Manag Res ; 11: 2405-2414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114318

RESUMO

Clusterin is a conserved glycoprotein that has been characterized from almost all human tissues and fluids and plays a key role in cellular stress response and survival. Recently, research efforts have been contributed to explore the function of Clusterin in cancer metastasis, which is particularly important to design the strategies for treating metastatic patients. Evidence collected has demonstrated that Clusterin is overexpressed in tumor metastatic patients and experimental metastasis models. Specifically, Clusterin has been shown to have the role in anti-apoptotic capacities, development of therapy resistance and induction of epithelial-mesenchymal transition, all associated with cancer metastasis. Inhibition of Clusterin is known to increase the cytotoxic effects of chemotherapeutic agents and improves advanced cancer patients survival in clinical trials. Our unpublished data have demonstrated that Clusterin is overexpressed in bladder cancer and metformin, a well-known metabolism modulator specifically targets Clusterin by inhibiting migration of bladder cancer cells. In this review, we provide a general view of how Clusterin modulates cancer metastasis and update current understanding of detailed molecular mechanisms underlying of Clusterin for developing cancer management in future.

14.
Hu Li Za Zhi ; 66(2): 93-100, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30924519

RESUMO

The sustainable development goals (SDGs), announced by the United Nations in 2016, now help guide public policy in many nations around the world. The United Nations has appealed to all governments and citizens worldwide to align together, taking action in each of the SDG dimensions of people, planet, prosperity, peace, and partnership in order to eradicate extreme poverty, inequality, and injustice; to slow / stop climate change; and to ensure sustainable development for humanity and the earth. Nursing is critical to achieving SDG3 (Health and Welfare) and has a significant impact on each of the other 16 SDGs. However, many nurses are unfamiliar or inadequately acquainted with SDGs. Therefore, this article introduces the content of the SDGs and the role of nurses in achieving each. In addition, we encourage nurses to exert their professionalism and compassion in realizing the pledge of the SDGs -- No one is left behind.


Assuntos
Papel do Profissional de Enfermagem , Desenvolvimento Sustentável , Humanos , Nações Unidas
15.
Food Funct ; 10(2): 1235-1242, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30747184

RESUMO

Inflammation caused by either intrinsic or extrinsic toxins results in intestinal barrier dysfunction, contributing to inflammatory bowel disease (IBD) and other diseases. Vitamin A is a widely used food supplement although its mechanistic effect on intestinal structures is largely unknown. The goal of this study was to explore the mechanism by investigating the influence of vitamin A on the intestinal barrier function, represented by tight junctions. IPEC-J2 cells were differentiated on transwell inserts and used as a model of intestinal barrier permeability. Transepithelial electrical resistance (TEER) was used as an indicator of monolayer integrity and paracellular permeability. Western blot and the reverse transcriptase-polymerase chain reaction were used to assess the protein and mRNA expression of tight junction proteins. Immunofluorescence microscopy was used to evaluate the localization and expression of tight junctions. Differentiated cells were treated with a vehicle control (Ctrl), inflammatory stimulus (1 µg mL-1 LPS), LPS co-treatment with 0.1 µmol L-1 Vitamin A (1 µg mL-1 LPS + 0.1 µmol L-1 VA) and 0.1 µmol L-1 Vitamin A. LPS significantly decreased TEER by 24 hours, continuing this effect to 48 hours after application. Vitamin A alleviated the LPS-induced decrease of TEER from 12 hours to 48 hours, while Vitamin A alone enhanced TEER, indicating that Vitamin A attenuated LPS-induced intestinal epithelium permeability. Mechanistically, different concentrations of Vitamin A (0-20 µmol L-1) enhanced tight junction protein markers including Zo-1, Occludin and Claudin-1 both at protein and mRNA levels with an optimized dose of 0.1 µmol L-1. Immunofluorescence results demonstrated that majority of Zo-1 and Claudin-1 is located at the tight junctions, as we expected. LPS reduced the expression of these proteins and Vitamin A reversed LPS-reduced expression of these proteins, consistent with the results of western blot. In conclusion, Vitamin A improves the intestinal barrier function and reverses LPS-induced intestinal barrier damage via enhancing the expression of tight junction proteins.


Assuntos
Células Epiteliais/efeitos dos fármacos , Mucosa Intestinal/citologia , Lipopolissacarídeos/toxicidade , Proteínas de Junções Íntimas/metabolismo , Vitamina A/farmacologia , Animais , Linhagem Celular , Suínos , Proteínas de Junções Íntimas/genética
16.
J Med Internet Res ; 21(2): e10816, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30758289

RESUMO

BACKGROUND: Transitioning into parenthood can be stressful for new parents, especially with the lack of continuity of care from health care professionals during the postpartum period. Short hospital stays limit the availability of support and time parents need to be well equipped with parenting and infant care skills. Poor parental adjustment may, in turn, lead to negative parental outcomes and adversely affect the child's development. For the family's future well-being, and to facilitate a smoother transition into parenthood, there is a need for easily accessible, technology-based educational programs to support parents during the crucial perinatal period. OBJECTIVE: This study aimed to examine the effectiveness of a technology-based supportive educational parenting program (SEPP) on parenting outcomes during the perinatal period in couples. METHODS: A randomized, single-blinded, parallel-armed, controlled trial was conducted. The study recruited 236 parents (118 couples) from an antenatal clinic of a tertiary hospital in Singapore. Eligible parents were randomly assigned to the intervention group (n=118) or the control group (n=118). The SEPP is based on Bandura's self-efficacy theory and Bowlby's theory of attachment. Components of the intervention include 2 telephone-based educational sessions (1 antenatal and 1 immediately postnatal) and a mobile health app follow-up for 1 month. The control group only received routine perinatal care provided by the hospital. Outcome measures including parenting self-efficacy (PSE), parental bonding, perceived social support, parenting satisfaction, postnatal depression (PND), and anxiety were measured using reliable and valid instruments. Data were collected over 6 months at 4 time points: during pregnancy (third trimester), 2 days postpartum, 1 month postpartum, and 3 months postpartum. Outcomes were standardized using baseline means and SDs. Linear mixed models were used to compare the groups for postpartum changes in the outcome variables. RESULTS: The intervention group showed significantly better outcome scores than the control group from baseline to 3 months postpartum for PSE (mean difference, MD, 0.37; 95% CI 0.06 to 0.68; P=.02), parental bonding (MD -1.32; 95% CI -1.89 to -0.75; P<.001), self-perceived social support (MD 0.69; 95% CI 0.18 to 1.19; P=.01), parenting satisfaction (MD 1.40; 95% CI 0.86 to 1.93; P<.001), and PND (MD -0.91; 95% CI -1.34 to -0.49; P<.001). Postnatal anxiety (PNA) scores of the intervention group were only significantly better after adjusting for covariates (MD -0.82; 95% CI -1.15 to -0.49; P<.001). CONCLUSIONS: The technology-based SEPP is effective in enhancing parental bonding, PSE, perceived social support and parental satisfaction, and in reducing PND and PNA. Health care professionals could incorporate it with existing hands-on infant care classes and routine care to better meet parents' needs and create positive childbirth experiences, which may in turn encourage parents to have more children. TRIAL REGISTRATION: ISRCTN Registry ISRCTN48536064; http://www.isrctn.com/ISRCTN48536064 (Archived by WebCite at http://www.webcitation.org/6wMuEysiO).


Assuntos
Poder Familiar/psicologia , Pais/educação , Avaliação de Programas e Projetos de Saúde/métodos , Apoio Social , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Appetite ; 135: 108-114, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30639843

RESUMO

Research on eating behaviour has confirmed that portion size can substantially influence intake, a phenomenon known as the Portion-Size-Effect (PSE). Despite extensive research interest, there is limited understanding about the PSE on intended consumption (often measured by Expected Intake). It also remains unclear whether the presentation of food cues (e.g., Word Descriptors; Food Images) can modulate PSE during pre-meal planning. The current study addressed these questions by comparing PSE on intended versus actual consumption, with 62 participants based on a within-subject design. Participants firstly rated Expected Intake for a pasta dish of three sizes (400, 600, and 800 g), with each size presented in three different formats of food cues. The participants' actual pasta intake with the three portion sizes was tested in three ad libitum sessions over 7 weeks. The results suggested that Expected Intake increases as portion size becomes larger, following a nearly linear relationship. In comparison, the Actual Intake had a smaller increment after the presented portion size exceeded the 'appropriate' range. Relating to these results, the pre-meal PSE was found to be comparable to the actual PSE with moderate portion sizes (i.e., 600 g-400 g), but significantly stronger than the actual effect with large portion sizes. Overall, our data support the hypothesis that portion size can have a stronger influence on meal planning than actual food intake, and show that the format of food cues has considerable influence on Expected Intake. Studies of pre-meal planning should carefully consider the role of portion sizes and food cues on Expected Intake.

18.
J Cell Physiol ; 234(3): 3088-3104, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30221356

RESUMO

Fatty acid synthase (FASN) catalyzing the terminal steps in the de novo biogenesis of fatty acids is correlated with low survival and high disease recurrence in patients with bladder cancer. Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels and provides a growth advantage to tumors. However, it is unclear whether the change of PKM2 has an effect on FASN and what is the mechanisms underlying. Here we describe a novel function of PKM2 in control of lipid metabolism by mediating transcriptional activation of FASN, showing the reduced expression of sterol regulatory element binding protein 1c (SREBP-1c). We first discovered that PKM2 physically interacts with the SREBP-1c using biochemical approaches, and downregulation of PKM2 reduced the expression of SREBP-1c by inactivating the AKT/mTOR signaling pathway, which in turn directly suppressed the transcription of major lipogenic genes FASN to reduce tumor growths. Furthermore, either PKM2 inhibitor-Shikonin or FASN inhibitor-TVB-3166 alone induced a strong antiproliferative and anticolony forming effect in bladder cancer cell line. The combination of both inhibitors exhibits a super synergistic effect on blocking the bladder cancer cells growth. It provides a new target and scientific basis for the treatment of bladder cancer.


Assuntos
Proteínas de Transporte/genética , Proliferação de Células/genética , Ácido Graxo Sintase Tipo I/genética , Proteínas de Membrana/genética , Hormônios Tireóideos/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Azetidinas/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Linhagem Celular Tumoral , Sinergismo Farmacológico , Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lipogênese/genética , Proteínas de Membrana/antagonistas & inibidores , Naftoquinonas/farmacologia , Nitrilos/farmacologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Pirazóis/farmacologia , Transdução de Sinais/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Serina-Treonina Quinases TOR/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
19.
Obes Rev ; 20(2): 325-338, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30450791

RESUMO

OBJECTIVE: The modern food environment is a key driver of rising levels of obesity. While olfaction is known to play a major role in food choice; however, its relationship to obesity is yet to be understood. This review assesses current knowledge of the interaction between obesity and olfaction. METHODS: This review is based on observational studies comparing olfactory abilities across weight groups (N = 10) and clinical studies evaluating olfactory changes following bariatric surgery (N = 9). Meta-analyses were performed on data collected by a standard olfactory assessment tool (Sniffin΄ Sticks), to test whether olfaction has any association with body weight or bariatric surgery. RESULTS: This review synthesizes findings derived from 38 datasets, with a total of 1432 individual olfactory assessments. The meta-analyses suggest that olfactory function is negatively correlated with body weight. In addition, Roux-en-Y gastric bypass patients frequently report olfactory changes, yet more pronounced and immediate shifts have been observed among sleeve gastrectomy recipients. CONCLUSIONS: Our review finds strong evidence for the link between olfaction and obesity and indicates that bariatric surgery (particularly the sleeve gastrectomy) is effective in reversing olfactory decline associated with obesity. In conclusion, we present mechanistic models to underpin the observed relationship between olfaction and obesity.


Assuntos
Índice de Massa Corporal , Obesidade/fisiopatologia , Percepção Olfatória/fisiologia , Olfato/fisiologia , Derivação Gástrica , Humanos , Obesidade/cirurgia
20.
Cancer Sci ; 110(1): 23-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30358009

RESUMO

The success of targeted drug therapies for treating cancer patients has attracted broad attention both in the academic community and social society. However, rapidly developed acquired resistance is becoming a newly recognized major challenge to the continuing efficiency of these therapies. Metformin is a well-known natural compound with low toxicity derived from the plant French lilac. Our previous work has highlighted research progress of the combination of clinically applied chemotherapies and metformin by different mechanisms. We have also launched a study to combine metformin with the small molecule targeted drug gefitinib to treat bladder cancer using intravesical administration. Thus, in this minireview, we summarize recent achievements combining metformin with various targeted therapies. This work directs the potential clinical future by selecting available cancer patients and providing precise medicine by the combination of metformin and targeted drugs to overcome resistance and enhance therapeutic efficacies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Terapia de Alvo Molecular/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Gefitinibe/administração & dosagem , Humanos , Metformina/administração & dosagem , Resultado do Tratamento
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