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1.
J Pharmacol Exp Ther ; 390(2): 188-195, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38135510

RESUMO

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES. To achieve this, contractions of the clasp and sling strips of the porcine LES, induced by U46619, were measured using isometric transducers. Furthermore, the contractile mechanism of U46619 in the porcine LES was investigated by pretreating the strips with atropine (a muscarinic receptor antagonist), tetrodotoxin (a neuronal sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution. Additionally, reverse transcription polymerase chain reaction (PCR) and immunohistochemistry (IHC) were performed to determine the presence of the TXA2 receptor in porcine LES. The results of this study demonstrated that U46619 caused marked concentration-dependent contractions in both porcine sling and clasp strips. The mechanism of U46619-induced contraction of the porcine LES was found to be related to calcium channels. Furthermore, the reverse transcription PCR analysis and IHC revealed that the TXA2 receptor was expressed in the clasp and sling fibers of porcine LES. Consequently, this study suggests that U46619 mediates the contraction of porcine LES through calcium channels and has potential as a therapeutic approach for treating GERD. SIGNIFICANCE STATEMENT: This study establishes that U46619 induces concentration-dependent contractions in porcine LES, primarily mediated by calcium channels. The presence of the TXA2 receptor in LES clasp and sling fibers is confirmed. These findings highlight U46619's potential as a GERD therapeutic by targeting calcium channels for LES contraction modulation.


Assuntos
Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico , Esfíncter Esofágico Inferior , Contração Muscular , Animais , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Contração Muscular/efeitos dos fármacos , Suínos , Esfíncter Esofágico Inferior/efeitos dos fármacos , Esfíncter Esofágico Inferior/fisiologia , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Masculino , Feminino
2.
BMC Psychiatry ; 23(1): 819, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940885

RESUMO

BACKGROUND: The Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) is a consistent and comprehensive instrument to assess symptoms of specific internet-use disorders including those related to gaming, shopping, pornography use disorder, social networks use and gambling considering criteria in the eleventh revision of the International Classification of Diseases (ICD-11). However, to date, there is little evidence supporting instruments assessing major types of specific internet use disorders in Thailand. The aim of this present study was to assess the psychometric properties of the ACSID-11 among Thai young adults. METHODS: A total of 612 participants were recruited. A confirmatory factor analysis (CFA) examined construct validity of the ACSID-11. Cronbach's α and McDonald's ω were used to assess reliability of the ACSID-11. Pearson correlations examined relationships between ACSID-11 domains and Internet Gaming Disorder Scale-Short Form (IGDS9-SF) scores. RESULTS: The CFA supported validity of the Thai version of the ACSID-11 and a four-factor structure. Specific domains of the Thai ACSID-11, particularly gaming, were positively and significantly correlated with IGDS9-SF scores. CONCLUSIONS: Data indicate that the Thai version of the ACSID-11 is a valid and reliable instrument to assess major types of specific internet use disorders. Additional studies are needed to further examine the validity and reliability of the Thai ACSID-11.


Assuntos
Transtorno de Adição à Internet , Jogos de Vídeo , Humanos , Adulto Jovem , Internet , Uso da Internet , Escalas de Graduação Psiquiátrica , Psicometria , Reprodutibilidade dos Testes , População do Sudeste Asiático , Tailândia , Transtorno de Adição à Internet/diagnóstico
3.
Eur J Pediatr ; 182(1): 343-352, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36352243

RESUMO

Unnecessary radiation exposure (URE) during radiographic examination is an issue among infants in neonatal intensive care units (NICUs). The causes of URE have not been fully explored. This study investigated the incidence and identified the causes of URE in infants during diagnostic radiography in a NICU. This was a retrospective cohort study. We retrieved and analysed requests and radiographs taken at a tertiary NICU between September and November 2018. URE was defined as the rate of discordance between requests and images taken (DisBRI) and unnecessary radiation exposure in irrelevant regions (UREIR) during radiography. We compared the rates of URE between very low-birth-weight (VLBW, birth weight < 1500 g) infants and non-VLBW infants. A total of 306 radiographs from 88 infants were taken. The means ± standard deviations (SDs) of gestational age and birth weight were 35.7 ± 3.6 weeks and 2471 ± 816 g, respectively. Each infant underwent an average of 3.5 radiographs. The DisBRI rate was 1.3% and was mostly related to poor adherence to requests. The UREIR rates in thoraco-abdominal babygrams were 89.6% for the head, 14.8% for the elbows and 18.4% for the knee and were mainly related to improper positioning of and collimation in infants while performing radiography. The UREIR rates for the head, knee and ankle were higher in VLBW infants than in non-VLBW infants (94.6% vs. 85.6%, 27.0% vs. 11.5% and 5.4% vs. 0.7%, respectively, p < 0.05). CONCLUSIONS: URE during diagnostic radiography is common in sick infants and is mainly related to improper positioning and collimation during examinations. Adherence to protocols when performing radiographic examination or using ultrasonography may be a solution to reduce URE in infants in NICUs. WHAT IS KNOWN: • The risk of unnecessary radiation exposure (URE) during radiography has been a common and important issue in sick infants in neonatal intensive care units (NICUs). • The new point-of-care ultrasound (POCUS) technique decreases the need for chest films and prevents radiation exposure in neonates. WHAT IS NEW: • In the NICU, URE is still a common issue in critically ill infants during radiographic examinations. The causes of URE during diagnostic radiography are mainly due to improper positioning and collimation during examinations. • The incidence of URE in irrelevant regions is higher in very low-birth-weight (VLBW) infants than in non-VLBW infants.


Assuntos
Unidades de Terapia Intensiva Neonatal , Exposição à Radiação , Recém-Nascido , Lactente , Humanos , Peso ao Nascer , Estudos Retrospectivos , Recém-Nascido de muito Baixo Peso , Radiografia , Exposição à Radiação/efeitos adversos
4.
J Formos Med Assoc ; 122(12): 1282-1295, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37365099

RESUMO

BACKGROUND/PURPOSE: This study examined the practice rate of Anticipatory Guidance (AG) and the gap between knowledge and practice among caregivers. METHODS: We retrospectively collected data from caregivers who brought their children for seven age-based well-child visits (birth to 7 years old) and seven corresponding AG checklists for practice (each ranged from 16 to 19 guidance items, 118 items in total) between 2015 and 2017. Practice rates of guidance items and their association with children's sex, age, residence, and body mass index were collected and analyzed. RESULTS: We enrolled 2310 caregivers (330 per well-child visit). Average practice rates of guidance items in the seven AG checklists were 77.6%-95.1%, generally without significant differences between urban/rural or male/female children. However, lower (<80%) rates were observed for 32 items, including dental check-ups (38.9%), use of fluoride toothpaste (44.6%), screen time (69.4%), and drinking less sugar-sweetened beverages (SSBs) (75.5%), with corresponding knowledge-to-practice gap rates of 55.5%, 47.9%, 30.3%, and 23.8%, respectively. "Drinking less SSBs" was the only item with a higher obesity rate in the non-achieved group versus the achieved group (16.7% vs. 7.4%, p = 0.036; odds ratio: 3.509, 95% CI: 1.153-10.677, p = 0.027). CONCLUSION: Caregivers in Taiwan practiced most AG recommendations. However, dental check-ups, fluoride toothpaste use, drinking less SSBs, and limiting screen time were less executed items. A higher obesity rate was found among 3-7-year-old children whose caregivers failed to practice the "Drink less SSBs" guidance. Strategies to overcome the gap between knowledge and practice are needed to improve these less-achieved guidance items.


Assuntos
Bebidas , Cuidadores , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Estudos Retrospectivos , Fluoretos , Lacunas da Prática Profissional , Taiwan , Cremes Dentais , Obesidade
5.
Mar Drugs ; 20(8)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-36005485

RESUMO

Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvß3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy.


Assuntos
Neoplasias Colorretais , Tiroxina , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Receptores ErbB/metabolismo , Humanos , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/farmacologia , Transdução de Sinais , Terpenos , Tiroxina/análogos & derivados
6.
Int J Urol ; 29(9): 947-954, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35132699

RESUMO

OBJECTIVE: There is a great interest in determining whether the expression of the programmed cell death ligand 1 is correlated with the efficacy of immune checkpoint inhibitors in patients with clear cell renal cell carcinoma; however, primary tumor biopsies can only provide limited information. Therefore, we explored the expression of programmed cell death ligand 1 on circulating tumor cells, which is a potential predictor of therapeutic response. METHODS: Circulating tumor cells were isolated from 20 clear cell renal cell carcinoma patients based on cell surface markers targeting clear cell renal cell carcinoma using IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. Programmed cell death ligand 1 expression status and clinical correlations were also analyzed. RESULTS: Before treatment with programmed cell death protein 1 inhibitors, circulating tumor cells were detected in all patients, ranging from 1 to 22 (median 7), with 75% (15/20) of the patients having programmed cell death ligand 1 + circulating tumor cells. Circulating tumor cell programmed cell death ligand 1 expression did not correlate with the immunohistochemical staining of programmed cell death ligand 1 in primary tumors. During treatment with programmed cell death protein 1 inhibitors, the disease control rate was much higher in the patients harboring programmed cell death ligand 1 + circulating tumor cells (73%, 11/15) than others (20%, 1/5). We also found that changes in total circulating tumor cell numbers and programmed cell death ligand 1 + circulating tumor cell counts correlated well with the disease outcome. CONCLUSION: We showed that the presence of programmed cell death ligand 1 + circulating tumor cells before programmed cell death protein 1 inhibition treatment could be a prognosis predictive factor and that the dynamic changes in circulating tumor cell numbers may be used to monitor the therapeutic response. Our study confirms the possibility of programmed cell death ligand 1 + circulating tumor cell detection in clear cell renal cell carcinoma patients' blood samples, which can potentially be used as an individualized immunotherapy molecular biomarker for real-time exploration.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Células Neoplásicas Circulantes , Apoptose , Antígeno B7-H1 , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Ligantes
7.
Mediators Inflamm ; 2020: 9694012, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376453

RESUMO

The activation of microglial cells plays an important role in the cascade of events leading to inflammation-mediated neurodegenerative disorders. Precision therapeutics require that adjunctively feasible drugs be found to prevent microglial cell activation and prevent inflammation-mediated neuronal injury. Dextromethorphan (DM) has been reported to possess neuroprotective effects in lipopolysaccharide- (LPS-) stimulated animals; however, it remains unclear whether epigenetic regulatory mechanisms in microglial cells are involved in such DM-mediated neuroprotective effects. In this study, DM simultaneously suppressed LPS-induced activation of tumor necrosis factor- (TNF-) α expression and subsequent caspase-3 signaling in primary microglial cells associated with notable morphological changes. Furthermore, therapeutic action sites of DM involved differential enhanced trimethylation of H3K4 modifications in the promoter region of tnf-α gene locus in primary microglial cells. In summary, DM may exert neuroprotective and anti-inflammatory effects through differential epigenetic histone modifications of TNF-α expression in microglial cells and might therefore raise the possibility of providing an adjunctively beneficial role for a tentative therapeutic strategy in neurodegenerative diseases resulting from inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Dextrometorfano/farmacologia , Epigênese Genética/efeitos dos fármacos , Histonas/metabolismo , Microglia/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Animais , Caspase 3/fisiologia , Células Cultivadas , Lipopolissacarídeos/farmacologia , Microglia/fisiologia , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-Dawley
8.
Mar Drugs ; 16(12)2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30563284

RESUMO

A marine sesterterpenoid-type natural product, heteronemin, retains anticancer effects. In the current study, we investigate the antitumor mechanism of heteronemin in cholangiocarcinoma cells and further explore its molecular targets. Initially, heteronemin exhibited potent cytotoxic effects against cholangiocarcinoma HuccT1 and SSP-25 cells. In vitro, heteronemin altered the abilities of cell adhesion and cell migration in HuccT1 and SSP-25 cell lines. It repressed messenger ribonucleic acid (mRNA) expression levels of transforming growth factor (TGF)-ß, mothers against decapentaplegic homolog (SMAD) and Myc, whose protein products play important roles in regulating cell growth, angiogenesis, and metastasis. In addition, heteronemin altered several signaling pathways. The results indicate that heteronemin was able to modulate cell adhesion, the expression of extracellular matrix (ECM) receptors, the TGF-ß pathway, cell motility, the membrane integration, metastasis response, matrix metalloproteinase (MMP) remodeling, the regulation of metabolism, sprouting angiogenesis, transcription factors, and vasculogenesis in cholangiocarcinoma cell lines. The results also suggest that it activated multiple signal transduction pathways to induce an anti-proliferation effect and anti-metastasis in cholangiocarcinoma. In conclusion, heteronemin may be used as a potential medicine for anticancer therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Terpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Poríferos/química , RNA Mensageiro/metabolismo , Terpenos/uso terapêutico , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
9.
Asian Pac J Allergy Immunol ; 34(3): 206-211, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27001656

RESUMO

BACKGROUND: Asthma is divided into atopic and non-atopic phenotypes. The percentages of atopic asthma and allergen sensitization in patients of different ages have not been well studied. OBJECTIVE: To determine the percentage distribution of atopic and non-atopic phenotypes in different age groups of asthmatic children, and investigate the distribution of specific IgE to different allergens when stratified by age group in southern Taiwan. METHOD: We conducted this hospital-based, retrospective, cross-sectional study in southern Taiwan between 2004 and 2006. Asthmatic children aged 3 to 18 years who were diagnosed according to the Global Initiative for Asthma guidelines were enrolled. The MAST-CLA system was used to detect 36 allergen-specific IgEs. RESULTS: A total of 620 asthmatic children were divided into three groups: preschool (3-6 years old, n=360), school-aged (7-12 years old, n=213), and adolescent (13-18 years old, n=41) children. The atopic and non-atopic phenotypes were observed in 54.8% and 45.2% of the asthmatic children, respectively. The atopic phenotype was observed in 45.6%, 65.7%, and 80.5% of the preschool, school-aged and adolescent groups, respectively. The percentages of the atopic phenotype were significantly different when stratified by age group (p<0.001), and there was a positive trend of percentage distribution. The percentages of sensitization to aeroallergens were significantly different and observed in 44.0%, 65.7%, and 80.5% of the preschool, school-aged and adolescent groups, respectively (p<0.001). There were positive trends between age groups and prevalence rates of sensitization to the main aeroallergen and other aeroallergen groups, but not to each allergen of the seafood or other food allergen group. CONCLUSIONS: A trend of an increasing percentage of the atopic phenotype when stratified by age group was found in asthmatic children in southern Taiwan. Aeroallergens contributed more to pediatric asthma than food allergens. The prevalence of sensitization to aeroallergens increased with increasing age when stratified by age group.


Assuntos
Asma/etiologia , Hipersensibilidade Imediata/complicações , Hipersensibilidade Imediata/epidemiologia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Fenótipo , Prevalência , Estudos Retrospectivos , Taiwan/epidemiologia
10.
Pediatr Int ; 57(4): 746-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26108272

RESUMO

Muscle phosphofructokinase (PFK) deficiency is a rare autosomal recessive disease. We report the case of a preterm female infant who was diagnosed with the infantile form of phosphofructokinase deficiency due to a lack of PFK activity in her muscles, manifesting at a corrected age of 1 month as floppy infant syndrome, congenital joint contracture, cleft palate and duplication of the pelvicalyceal system. She died at a corrected age of 6 months due to respiratory failure. We further reviewed other infantile cases in the literature. Congenital hypotonia (78.6%), arthrogryposis (64.3%) and other systemic involvement including encephalopathy (35.7%) and cardiomyopathy (21.4%) are common presentations of the infantile form of PFK deficiency. The overall survival rate of the infantile form is low. The early recognition of multiple system involvement is essential to provide better clinical care for infants with the infantile form of PFK deficiency.


Assuntos
Doença de Depósito de Glicogênio Tipo VII/diagnóstico , Recém-Nascido Prematuro , Evolução Fatal , Feminino , Doença de Depósito de Glicogênio Tipo VII/complicações , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Insuficiência Respiratória/diagnóstico
11.
Mucosal Immunol ; 17(1): 13-24, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37805143

RESUMO

Air pollution significantly impacts the aggravation of asthma. Exposure to acrylamide, a volatile organic compound in tobacco smoke, is associated with elevated risks of allergy-related outcomes among active smokers. As group 2 innate lymphoid cells (ILC2s) can act as an environmental sensor and significantly contribute to protease allergen-induced lung inflammation, we aimed to elucidate the causal relationship and how inhaled acrylamide worsens allergic lung inflammation via ILC2s. Intranasal acrylamide exposure at nanomolar levels significantly enhanced allergen-induced or recombinant mouse interleukin-33-induced lung inflammation in C57BL/6 mice or Rag1-/- mice, respectively. The cardinal features of lung inflammation included accumulated infiltration of ILC2s and eosinophils. Transcriptomic analysis revealed a gene expression pattern associated with proliferation-related pathways in acrylamide-treated ILC2s. Western blotting revealed significantly higher expression of Ras and phospho-Erk in acrylamide-treated ILC2s than the control, suggesting Ras-Erk signaling pathway involvement. Ex vivo and in vitro analysis showed that acrylamide treatment mainly increased Ki-67+ ILC2s and the cell number of ILC2s whereas PD98059, a highly selective Erk inhibitor, effectively counteracted the acrylamide effect. Intratracheal administration of acrylamide-treated ILC2s significantly enhanced eosinophil infiltration in Rag1-/- mice. This study suggests that airborne acrylamide may enhance the severity of allergen-induced airway eosinophilic inflammation, partly via altering ILC2 proliferative activity.


Assuntos
Poluentes Atmosféricos , Pneumonia , Eosinofilia Pulmonar , Camundongos , Animais , Imunidade Inata , Alérgenos , Linfócitos , Camundongos Endogâmicos C57BL , Acrilamidas , Proteínas de Homeodomínio/genética , Pulmão , Interleucina-33/metabolismo , Citocinas/metabolismo
12.
Heliyon ; 10(13): e34006, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39071644

RESUMO

Progesterone (P4) plays a pivotal role in regulating the cancer progression of various types, including breast cancer, primarily through its interaction with the P4 receptor (PR). In PR-negative breast cancer cells, P4 appears to function in mediating cancer progression, such as cell growth. However, the mechanisms underlying the roles of P4 in PR-negative breast cancer cells remain incompletely understood. This study aimed to investigate the effects of P4 on cell proliferation, gene expression, and signal transduction in PR-negative MDA-MB-231 breast cancer cells. P4-activated genes, associated with proliferation in breast cancer cells, exhibit a stimulating effect on cell growth in PR-negative MDA-MB-231 cells, while demonstrating an inhibitory impact in PR-positive MCF-7 cells. The use of arginine-glycine-aspartate (RGD) peptide successfully blocked P4-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, aligning with computational models of P4 binding to integrin αvß3. Disrupting integrin αvß3 binding with RGD peptide or anti-integrin αvß3 antibody altered P4-induced expression of proliferative genes and modified P4-induced cell growth in breast cancer cells. In conclusion, integrin αvß3 appears to mediate P4-induced ERK1/2 signal pathway to regulate proliferation via alteration of proliferation-related gene expression in PR-negative breast cancer cells.

13.
Anticancer Drugs ; 24(10): 1047-57, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24025560

RESUMO

BPR0C305 is a novel N-substituted indolyl glyoxylamide previously reported with in-vitro cytotoxic activity against a panel of human cancer cells including P-gp-expressing multiple drug-resistant cell sublines. The present study further examined the underlying molecular mechanism of anticancer action and evaluated the in-vivo antitumor activities of BPR0C305. BPR0C305 is a novel synthetic small indole derivative that demonstrates in-vitro activities against human cancer cell growth by inhibiting tubulin polymerization, disrupting cellular microtubule assembly, and causing cell cycle arrest at the G2/M phase. It is also orally active against leukemia and solid tumor growths in mouse models. Findings of these pharmacological and pharmacokinetic studies suggest that BPR0C305 is a promising lead compound for further preclinical developments.


Assuntos
Aminoquinolinas/farmacologia , Antineoplásicos/farmacologia , Indóis/farmacologia , Microtúbulos/efeitos dos fármacos , Administração Oral , Aminoquinolinas/administração & dosagem , Aminoquinolinas/farmacocinética , Aminoquinolinas/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Indóis/administração & dosagem , Indóis/farmacocinética , Indóis/uso terapêutico , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Leucemia/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Camundongos Nus , Microtúbulos/patologia , Tubulina (Proteína)/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Bioorg Med Chem ; 21(11): 2856-67, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23618709

RESUMO

Preclinical investigations and early clinical trials suggest that FLT3 inhibitors are a viable therapy for acute myeloid leukemia. However, early clinical data have been underwhelming due to incomplete inhibition of FLT3. We have developed 3-phenyl-1H-5-pyrazolylamine as an efficient template for kinase inhibitors. Structure-activity relationships led to the discovery of sulfonamide, carbamate and urea series of FLT3 inhibitors. Previous studies showed that the sulfonamide 4 and carbamate 5 series were potent and selective FLT3 inhibitors with good in vivo efficacy. Herein, we describe the urea series, which we found to be potent inhibitors of FLT3 and VEGFR2. Some inhibited growth of FLT3-mutated MOLM-13 cells more strongly than the FLT3 inhibitors sorafenib (2) and ABT-869 (3). In preliminary in vivo toxicity studies of the four most active compounds, 10f was found to be the least toxic. A further in vivo efficacy study demonstrated that 10f achieved complete tumor regression in a higher proportion of MOLM-13 xenograft mice than 4 and 5 (70% vs 10% and 40%). These results show that compound 10f possesses improved pharmacologic and selectivity profiles and could be more effective than previously disclosed FLT3 inhibitors in the treatment of acute myeloid leukemia.


Assuntos
Antineoplásicos/síntese química , Benzamidas/síntese química , Benzamidas/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Inibidores de Proteínas Quinases/síntese química , Ureia/análogos & derivados , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzamidas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Descoberta de Drogas , Humanos , Concentração Inibidora 50 , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/patologia , Camundongos , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Sensibilidade e Especificidade , Relação Estrutura-Atividade , Ureia/síntese química , Ureia/química , Ureia/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Tirosina Quinase 3 Semelhante a fms/química
15.
J Eat Disord ; 11(1): 110, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400881

RESUMO

OBJECTIVES: Most studies of body size perception have been performed in adolescents, and most focus on gender differences in accurate perception of body size. This study investigated misperceptions of body sizes among males and females at different stages of adulthood in Taiwan. DESIGNS: In-person home interviews were used to proportionally and randomly select 2095 adult men and women to answer the East Asian Social Survey. Participants were divided into 18-39, 40-64, and 65 + age groups. The main variables analyzed were self-perceived body size and standardized BMI. RESULTS: Women, unlike men, were more likely to misperceive their body size as being overweight (OR = 2.92; p < .001). People with higher self-perceived social status were less likely to misperceive themselves as overweight (OR = 0.91; p = .01). People with college educations were 2.35 times more likely to overestimate their body size as being heavier than they were (p < .001) and less likely to underestimate it as being thinner than they were (OR = 0.45; p < .001). Women 18-35 and 36-64 years old were 6.96 and 4.31 times more likely (p < .001) to misperceive themselves as being overweight than women 65 or older, who were more likely to misperceive themselves as being too thin. There were no significant differences in body size misperceptions among the three age groups of adult men (p > .05). We found no different significant discrepancies between self-perceived body size and actual BMI between the older men and women (p = .16). However, younger and middle-aged men were 6.67 and 3.1 times more likely to misperceive themselves as being too thin than women in their same age groups (OR = 0.15 and OR = 0.32, respectively). CONCLUSIONS: Age and gender affect self-perceptions of body size in Taiwan. Overall, women are more likely than men to misperceive themselves as being too big, and men are more likely than women to misperceive themselves as too thin. Older women, however, were more likely to misperceive themselves as being too thin. Clinicians and health educators should know that people's perceptions and concerns regarding their body size vary by age and gender.

16.
Heliyon ; 9(3): e14298, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36938463

RESUMO

Background: During the COVID-19 pandemic, physical inactivity and sedentary behaviors (i.e., longer sitting time and excessive gaming) increased because governments across the globe adopted stringent mitigation strategies such as social distancing and lockdowns to curb the spread of the virus. Excessive gaming was one of the coping mechanisms used to deal with the pressure associated with the pandemic. Moreover, perceived weight stigma (PWS) and weight status became more salient concerns among young adults during the COVID-19 pandemic. The current study sought to investigate the relationship between time spent sitting, excessive gaming, weight status, and PWS of Taiwanese Young adults. Additionally, weight status and PWS were examined as mediators between both sedentary behaviors. Methods: This cross-sectional study involved 600 participants who were recruited through Taiwan universities. All participants completed a demographic questionnaire (including weight and height) and self-report measures including the International Physical Activity Questionnaire short form (IPAQ-SF), the Perceived Weight Stigma Scale (PWSS), and the Internet Gaming Disorder Scale-short form (IGDS9-SF). PROCESS model was performed to test the potential mediation roles of weight status and PWS. Moreover, we categorized participants into two groups based on the sitting-time item in the IPAQ-SF: students whose sitting time was less than 8 h daily, and those more than 8 h daily. Results: The group that had less than 8 h had significantly higher PWS and IGDS9-SF scores than the other group. Sitting time was negatively associated with weight status, PWS, and IGDS9-SF. Additionally, we found a significantly direct effect between time spent sitting and excessive gaming. Both weight status and PWS were significant mediators in the association between time spent sitting and excessive gaming.Conclusions: The present study demonstrated important negative correlates of excessive sedentary behaviors. Prevention efforts should focus on promoting physical activity and providing information to decrease sedentary behavior among university students.

17.
Children (Basel) ; 10(11)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38002910

RESUMO

Early-term neonates (with a gestational age (GA) of 37 and 0/7 weeks to 38 and 6/7 weeks) face higher morbidities, including respiratory and neurodevelopmental issues, than full-term (39 and 0/7 weeks to 40 and 6/7 weeks) infants. This study explores whether hyperbilirubinemia necessitating phototherapy also differs between these groups. A retrospective study was conducted on neonates born from January 2021-June 2022, excluding those with specific conditions. Evaluated factors included GA, birth weight, bilirubin levels, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and feeding type, with phototherapy given as per AAP guidelines. Of 1085 neonates, 356 met the criteria. When stratifying the neonates based on the need for phototherapy, a higher proportion of early-term neonates required phototherapy compared to full-term (p < 0.05). After factoring in various risks (GA; birth weight; gender; feeding type; G6PD deficiency; transcutaneous bilirubin levels at 24 h and 24-48 h postpartum; maternal diabetes; and the presence of caput succedaneum or cephalohematoma), early-term neonates were more likely to need phototherapy than full-term babies (OR: 2.15, 95% CI: 1.21 to 3.80). The optimal cut-off for transcutaneous bilirubin levels 24-48 h postpartum that were used to predict phototherapy need was 9.85 mg/dl. In conclusion, early-term neonates are at a greater risk for developing jaundice and requiring phototherapy than full-term neonates. Monitoring bilirubin 24-48 h postpartum enhances early prediction and intervention.

18.
Cells ; 12(17)2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37681860

RESUMO

Androgen has been shown to regulate male physiological activities and cancer proliferation. It is used to antagonize estrogen-induced proliferative effects in breast cancer cells. However, evidence indicates that androgen can stimulate cancer cell growth in estrogen receptor (ER)-positive and ER-negative breast cancer cells via different types of receptors and different mechanisms. Androgen-induced cancer growth and metastasis link with different types of integrins. Integrin αvß3 is predominantly expressed and activated in cancer cells and rapidly dividing endothelial cells. Programmed death-ligand 1 (PD-L1) also plays a vital role in cancer growth. The part of integrins in action with androgen in cancer cells is not fully mechanically understood. To clarify the interactions between androgen and integrin αvß3, we carried out molecular modeling to explain the potential interactions of androgen with integrin αvß3. The androgen-regulated mechanisms on PD-L1 and its effects were also addressed.


Assuntos
Androgênios , Antígeno B7-H1 , Masculino , Humanos , Androgênios/farmacologia , Células Endoteliais , Integrina alfaVbeta3 , Transformação Celular Neoplásica
19.
Heliyon ; 9(12): e22583, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38090014

RESUMO

Aims: The aims of the study were to examine the differential item functioning (DIF) of the Tendency of Avoiding Physical Activity and Sport Scale (TAPAS) among three subgroups (gender, weight status, and region) and to test the construct and concurrent validities of the scale. Methods: Using an online survey, university students (608 Taiwanese and 2319 mainland Chinese) completed the TAPAS. Rasch analysis examined if all the 10 TAPAS items fitted the same construct and displayed no substantial DIF across three subgroups: gender (male vs. female), weight status (overweight vs. non-overweight), and region (Taiwan vs. China). Concurrent validity was examined using the scores on the Weight Self-Stigma Questionnaire (WSSQ) and Weight Bias Internalization Scale (WBIS). Results: All TAPAS items, except for Item 10 ("Prefer to participate in physical activity in a more private setting"), fitted the same construct. None of the TAPAS items displayed DIF in any of the subgroups except for Item 10 across participants from Taiwan and China (DIF contrast = -1.41). Conclusion: The TAPAS can appropriately assess the tendency to avoid physical activity and sport among both Taiwanese and mainland Chinese university students. However, Item 10 may need to be further examined.

20.
Asian J Psychiatr ; 86: 103638, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37285663

RESUMO

Currently, six instruments have been developed using the 11th revision of the International Classification of Diseases (ICD-11) criteria for Gaming Disorder (GD). Two of these are the Gaming Disorder Test (GDT) and Gaming Disorder Scale for Adolescents (GADIS-A). The present study validated both the GDT and GADIS-A among a large sample of Chinese emerging adults. Via an online survey, 3381 participants (56.6% females; mean age = 19.56 years) completed the Chinese versions of the GDT, GADIS-A, Internet Gaming Disorder-Short Form (IGDS9-SF), and Bergen Social Media Addiction Scale (BSMAS). Confirmatory factor analysis was used to examine the factor structure of the Chinese GDT and GADIS-A. Pearson correlations were computed to examine the convergent validity (with IGDS9-SF) and divergent validity (with BSMAS) of the Chinese GDT and Chinese GADIS-A. The GDT had a unidimensional structure, which was invariant across sex and disordered gaming severity subgroups. The GADIS-A had a two-factor structure, which was also invariant across gender and gaming severity subgroups. Both the GDT and GADIS-A had significant associations with both IGDS9-SF and with BSMAS. Both the Chinese GDT and GADIS-A are valid instruments to assess GD among emerging adults in mainland China, enabling healthcare providers to adopt these tools in their efforts to prevent and examine GD severity among Chinese youth.


Assuntos
Comportamento Aditivo , Jogos Recreativos , Escalas de Graduação Psiquiátrica , Humanos , Adolescente , Psicometria , Masculino , Feminino , Adulto Jovem , Adulto , Transtorno de Adição à Internet , Comportamento Aditivo/diagnóstico , China , Idioma , Jogos de Vídeo
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