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2.
Biochem Genet ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34327615

RESUMO

The present study established a necroptosis model in vitro and investigated the role of HMGB1 in cell necroptosis. A combination of tumor necrosis factor-α and z-VAD-fmk was used to induce necroptosis in L929 cells with necroptosis inhibitor necrostatin-1 applied as an intervention. Flow cytometry and transmission electron microscopy (TEM) were used to measure cell necroptosis. Western blotting assay was applied to detect the expression of receptor-interacting serine/threonine-protein kinase 3 (RIPK3), mixed lineage kinase domain-like pseudokinase (MLKL) and HMGB1. Co-immunoprecipitation (Co-IP) assay was used to confirm the interaction between HMGB1 and RIPK3. Our study demonstrated that HMGB1 migrated from the nucleus to the cytoplasm at the onset of necroptosis and was subsequently released passively to the extracellular matrix. Further experiments determined that the binding of HMGB1 with RIPK3 in the cytoplasm was loose during necroptosis. By contrast, when necroptosis was inhibited, the interaction in the cytoplasm was tight suggesting that this association between HMGB1 and RIPK3 might affect its occurrence. In conclusion, the transfer of HMGB1 from nucleus to cytoplasm, and its interaction with RIPK3 might be potentially involved in necroptosis.

3.
Bioorg Med Chem Lett ; 41: 127993, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33775841

RESUMO

Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.


Assuntos
Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Tranilcipromina/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Tranilcipromina/análogos & derivados , Tranilcipromina/química
5.
Taiwan J Obstet Gynecol ; 60(1): 78-83, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33495013

RESUMO

OBJECTIVE: To evaluate the short-term effect of routine early postpartum electromyographic biofeedback assisted pelvic floor muscle training on sexual function and lower urinary tract symptoms. MATERIALS AND METHODS: From December 2016 to November 2017, primiparous women with vaginal delivery, who experienced non-extended second-degree perineal laceration were invited to participate. Seventy-five participants were assigned into a pelvic floor muscle training (PFMT) group or control group. Women in the PFMT group received supervised biofeedback-assisted pelvic floor muscle training at the 1st week and 4th week postpartum. Exercises were performed at home with the same protocol until 6 weeks postpartum. The Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire (PISQ-12) and the Urinary Distress Inventory short form questionnaire (UDI-6) were used to evaluate sexual function and lower urinary tract symptoms respectively at immediate postpartum, 6 weeks, 3 months, and 6 months postpartum. RESULTS: Forty-five women (23 in PFMT group,22 in control group) completed all questionnaires at 6 months postpartum. For overall sexual function and the three sexual functional domains, no statistically significant difference was found in PISQ scores from baseline to 6 weeks, 3 months, and 6 months postpartum between the PFMT and control groups. For postpartum lower urinary tract symptoms, all symptoms gradually improved over time for both groups without a statistically significant difference between groups. CONCLUSION: Our study showed that supervised biofeedback-assisted pelvic floor muscle training started routinely at one week postpartum did not provide additional improvement in postpartum sexual function and lower urinary tract symptoms.


Assuntos
Sintomas do Trato Urinário Inferior/terapia , Neurorretroalimentação/métodos , Complicações do Trabalho de Parto/terapia , Períneo/lesões , Disfunções Sexuais Fisiológicas/terapia , Adulto , Feminino , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Complicações do Trabalho de Parto/fisiopatologia , Paridade , Diafragma da Pelve/fisiopatologia , Período Pós-Parto , Gravidez , Disfunções Sexuais Fisiológicas/etiologia , Resultado do Tratamento
6.
BMC Med Genomics ; 14(1): 21, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468134

RESUMO

BACKGROUND: Hirschsprung disease (HSCR) is a hereditary defect, which is characterized by the absence of enteric ganglia and is frequently concurrent with Hirschsprung-associated enterocolitis (HAEC). However, the pathogenesis for HSCR is complicated and remains unclear. Recent studies have shown that pro-inflammatory cytokines such as interleukin-11 (IL-11) are involved in the enteric nervous system's progress. It was found that IL-11 SNPs (rs8104023 and rs4252546) are associated with HSCR in the Korean population waiting for replication in an independent cohort. This study evaluated the relationship between IL-11 and the susceptibility of patients to HSCR by performing subphenotype interaction examination, HAEC pre-/post-surgical patient-only association analysis, and independence testing. METHODS: In this study, a cohort consisting of children from Southern China, comprising 1470 cases and 1473 controls, was chosen to examine the relationship between two polymorphisms (rs8104023 and rs4252546 in IL-11) and susceptibility to HSCR by replication research, subphenotype association analysis, and independence testing. RESULTS: The results showed that IL-11 gene polymorphisms (rs8104023 and rs4252546) are not associated with the risk of HSCR in the Chinese population. The results of both short-segment and long-segment (S-HSCR and L-HSCR) surgery (3.34 ≤ OR ≤ 4.05, 0.02 ≤ P ≤ 0.04) showed that single nucleotide polymorphisms (SNP) rs8104023 is associated with susceptibility to HAEC. CONCLUSIONS: This study explored the relationship between genetic polymorphisms and susceptibility to HAEC in HSCR subtypes for the first time. These findings should be replicated in a larger and multicentre study.

7.
Psychol Health Med ; 26(5): 607-620, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33227216

RESUMO

Screen time is becoming increasingly common in daily life. Early and excessive screen use has raised growing concerns for children's neuropsychological development. The purpose of this study was to evaluate the association between exposure to screen time in early life and the presence of autistic-like behaviors among preschool children. 29,461 child-caregiver dyads at kindergartens in Longhua New District of Shenzhen, China, were enrolled in this cross-sectional study. Information concerning socio-demographic characteristics, frequency and duration of children's electronic screen exposure for each year since birth, and autistic-like behaviors (measured by the Autism Behavior Checklist) were collected using a self-administered structured questionnaire completed by the primary caregivers. A series of logistic regression models assessed the association between screen time and autistic-like behaviors. Results indicated that younger initial age, longer daily screen time and longer cumulative years of screen exposure since birth were associated with the presence of autistic-like behaviors at preschool age. The risk was enhanced with the increase of both daily screen time and cumulative years of screen exposure during preschool period. Moreover, the cross-over analysis indicated that the first three years following birth might be a sensitive period for children when screen exposure increases the risk of experiencing autistic-like behaviors. In conclusion, our study implied that screen exposure in early life might increase the occurrence of autistic-like behaviors among preschoolers. These findings support the need for early interventions into preschoolers' screen use, however longitudinal studies are necessary to further confirm the causal relationship between early screen time and the incidence of later autistic-like behaviors among preschool children.

8.
In Vivo ; 34(6): 3407-3412, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144448

RESUMO

BACKGROUND/AIM: Incisional hernia is a complication that occurs occasionally, and surgical intervention is required to prevent more severe sequela. While there are several options for management, robotic-assisted incisional repair has not been well discussed yet. We herein report a case series of 10 patients who underwent robotic-assisted incisional hernia repair (RIHR) after robotic-assisted radical prostatectomy (RARP). The aim of the study was to examine the feasibility of incisional hernia repair with da Vinci® robotics. PATIENTS AND METHODS: We recruited patients from a group of 2,000 consecutive patients who underwent RARP from December, 2005 to June, 2020 by a single surgeon. Patient characteristics included age, body mass index (BMI), PSA level, pathology Gleason score, and pathology TNM staging. The variants regarding the patients' incisional hernia included incisional hernia occurrence time after RARP, defect size, operation time, console time, blood loss, and follow-up time after the herniation occurrence. Furthermore, we established a defect size of 3x2 cm2 as the cutoff value for using mesh reinforcement or not. RESULTS: The mean defect area was 27.7 cm2, and the average operative time was 114.8 min, with a mean console time of 87 min. Blood loss was 32.5 ml, and the hospital stay for all patients was 3 days without complications. The mean follow-up period was 29.5 months, with no recurrence. CONCLUSION: RIHR is a feasible surgical method that is not inferior to the traditional open or laparoscopic repair. Furthermore, RIHR can possibly lessen the burden of both the surgeon and patient.


Assuntos
Hérnia Ventral , Hérnia Incisional , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Hérnia Ventral/cirurgia , Herniorrafia , Humanos , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Masculino , Próstata , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Telas Cirúrgicas
9.
Stress Health ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33251689

RESUMO

Exposure to prenatal maternal stress (PNMS) has been implicated as a risk factor for a range of psychiatric disorders in children. However, there have been a few studies showing inconsistent associations between PNMS and offspring autistic-like behaviours. We therefore aimed to examine whether trimester-specific PNMS exposure might be related to an increased risk of autistic-like behaviours among preschoolers. Using data from Longhua Children Cohort Study, mothers of 65,931 preschool children were asked to recall their level of PNMS in each of the three trimesters of pregnancy, while children's current autistic-like behaviours were assessed using the Autism Behaviour Checklist. A series of Cox regression models were fitted to assess the association between PNMS exposure and autistic-like behaviours. After adjusting for potential confounders, the Cox regression models showed that PNMS exposure, especially during the second pregnant trimester, was significantly and positively associated with the presence of children's autistic-like behaviours. The strength of these associations was enhanced with the increase of PNMS exposure level. Furthermore, based on different permutations of exposure versus no exposure in each trimester, the participants were divided into eight groups. A cross-over analysis confirmed the aforementioned finding that the second pregnant trimester might be the sensitive period for PNMS exposure increasing the risk of autistic-like behaviours. Our findings supported the hypothesis of an association between PNMS exposure and autistic-like behaviours among preschoolers. Preventive interventions should be trialled to examine whether minimizing maternal psychological stress during pregnancy, especially the second trimester, may reduce the risk of offspring autistic-like behaviours.

10.
Children (Basel) ; 7(11)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126543

RESUMO

Research into early screen exposure has raised growing concerns about its impact upon children's neuropsychological well-being. However, possible pathways remain unclear. This study therefore aimed not only to evaluate the association between screen exposure during the ages of 0-3 years and preschoolers' autistic-like behaviors, but also the mediating roles of the frequency of caregiver-child interaction, sleep duration and level of participation in outdoor activities. Based on the 2017 survey of the Longhua Child Cohort Study, data of 29,595 child-caregiver dyads were obtained via a caregiver-reported questionnaire, with the data from 29,461 dyads included in the data analysis. Multiple linear and logistic regression models were employed to estimate the associations between screen exposure, caregiver-child interaction, sleep duration, outdoor activities, and children's autistic-like behaviors. The results indicated that screen exposure during 0-3 years of age was associated with the presence of autistic-like behaviors at preschool age, and the strength of the association was enhanced with the increase of average daily screen time (Odds Ratios (ORs) ranging from 1.358 to 4.026). The frequency of caregiver-child interaction and sleep duration mediated 5.32% and 1.19% of the variance of the association respectively, but outdoor activities did not mediate the association. Our findings indicate that preschoolers who are exposed to screens at aged 0-3 years might have an increased risk of autistic-like behaviors, and that, the frequency of caregiver-child interaction and sleep duration might function as potential mediators of this association.

11.
Eur J Med Chem ; 208: 112760, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32883639

RESUMO

KDM5B (Lysine-Specific Demethylase 5B) erases the methyl group from H3K4me2/3, which performs wide regulatory effects on chromatin structure, and represses the transcriptional function of genes. KDM5B functions as an oncogene and associates with human cancers closely. Targeting KDM5B has been a promising direction for curing cancer since the emergence of potent KDM5B inhibitor CPI-455. In this area, most reported KDM5B inhibitors are Fe (Ⅱ) chelators, which also compete with the cofactor 2-OG in the active pockets. Besides, Some KDM5B inhibitors have been identified through high throughput screening or biochemical screening. In this reviewing article, we summarized the pioneering progress in KDM5B to provide a comprehensive realization, including crystal structure, transcriptional regulation function, cancer-related functions, development of inhibitors, and SAR studies. We hope to provide a comprehensive overview of KDM5B and the development of KDM5B inhibitors.


Assuntos
Antineoplásicos/farmacologia , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias/tratamento farmacológico , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Compostos Orgânicos/farmacologia , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Histona Desmetilases com o Domínio Jumonji/química , Estrutura Molecular , Neoplasias/metabolismo , Proteínas Nucleares/química , Compostos Orgânicos/química , Compostos Orgânicos/uso terapêutico , Proteínas Repressoras/química , Relação Estrutura-Atividade
12.
J Contin Educ Nurs ; 51(10): 457-464, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32976614

RESUMO

BACKGROUND: This study aimed to evaluate correlations between female nurses' needs satisfaction and behavioral intentions for providing sexual health care and to assess moderating effects of learning needs on that correlation. METHOD: A total of 300 female RNs were enrolled. Two validated instruments were used to collect information on participants' learning needs, needs satisfaction, and behavioral intentions for providing sexual health care. RESULTS: Adjusted multivariable regression analysis revealed significant moderating effects of medium and low learning needs on correlations between needs satisfaction and behavioral intentions (medium learning needs: ß = 0.282, 95% CI = 0.075, 0.490; p = .008; low learning needs: ß = 0.293, 95% CI = 0.033, 0.553; p = .027), while no moderating effect was observed in those with high learning needs. CONCLUSION: Needs satisfaction was significantly correlated with behavioral intentions of sexual health care in medium and low learning needs groups. [J Contin Educ Nurs. 2020;51(10):457-464.].

13.
Anticancer Res ; 40(5): 2995-3002, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366454

RESUMO

BACKGROUND/AIM: Expanded indications for patients with preoperatively suspected prostate cancer (PC) undergoing theranostic robotic-assisted laparoscopic radical prostatectomy (T-RARP) are reported. We aimed to build a nomogram of T-RARP to predict final pathologically proven PC. This study reviewed data of 153 patients that underwent T-RARP for suspected PC performed by the same surgeon. PATIENTS AND METHODS: Patients' preoperative demographic and clinical characteristics included age, prostate-specific antigen (PSA) level, PSA density (PSAD), history of acute urinary retention (AUR), abnormal digital rectal examination (DRE) of the prostate, and Prostate Imaging Reporting and Data System (PI-RADS) classification at 3-T multiparametric magnetic resonance imaging (MRI). Logistic regression with backward elimination was used to select potential risk factors. RESULTS: Based on Harrell's guidelines, we chose seven variables for our final model: Age, DRE corresponding with MRI, AUR, PSAD, prostate-specific antigen velocity (PSAV), PI-RADS, and biopsy pathology. A nomogram for prediction of adenocarcinoma was developed. The original C-index for the nomogram was 0.80 (95% confidence interval=0.74-0.89). The cut-off of the nomogram score for predicting PC was 50 (sensitivity=55.4%; specificity=91.9%). The receiver operating characteristic curve of the model analysis showed an area under the curve of 0.801. CONCLUSION: A nomogram was produced using age, DRE-corresponding MRI, AUR, PSAD, PSAV, PI-RADS, and biopsy pathology. A preoperative nomogram prediction of prostate adenocarcinoma can help the patient and his family understand the possibility of PC and assist them in their decision-making.


Assuntos
Nomogramas , Cuidados Pré-Operatórios/métodos , Neoplasias da Próstata/diagnóstico , Humanos , Masculino , Neoplasias da Próstata/patologia , Estudos Retrospectivos
14.
Urol Case Rep ; 31: 101154, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32292700

RESUMO

Xanthogranulomatous prostatitis is a rare occasion that mimics the prostate cancer in every aspect of clinical diagnosis. These two occasions require totally diverse therapeutics principles. Thus, emphasis should be exerted to distinguish them. The most precise tool to distinguish them is tissues' evidence. However, another possible overlooking occasion is successive xanthogranulomatous prostatitis after complete remission under androgen deprivation therapy. This case demonstrated one metastatic prostate cancer with initial treatment of androgen deprivation therapy. PSA was suppressed to the lowest and then radical prostatectomy was performed. Hints from the specimen gave complete remission of cancer cell and development of xanthogranulomatous prostatitis.

15.
Horm Metab Res ; 52(11): 788-795, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32299109

RESUMO

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited endocrine tumor syndrome caused by inactivating variants of the MEN1 gene. The aim of this study is to explore the clinical and genetic characteristics of four MEN1 patients. We isolated genomic deoxyribonucleic acid from lymphocytes, parathyroid, and thymic tumoral tissue specimens from the MEN1 patients. All exons of the MEN1 and CDNK1B genes and adjacent exon-intron sequences were amplified by polymerase chain reaction and subsequently sequenced. Further, the splice alterations were studied by sequencing the amplified RT-PCR products for MEN1 cDNA. We identified four heterozygous MEN1 germline variants: c.564delC, c.1268G>A, IVS5+5delG, and c.1546_1547insC. Both c.564delC and IVS5+5delG were novel variants. The impact of the MEN1 splice variant, IVS5+5delG, was evaluated using bioinformatics and in vitro analyses. The analyses indicated that this variant resulted in skipping of the neighboring exon and was disease-causing. Two novel somatic variants, c.249_252delGTCT and c.313_314insC, were found. Additionally, loss of heterozygosity (LOH) for the MEN1 locus (IVS5+5delG and c.564delC) was found in tumor tissue samples from the MEN1 patients, consistent with Knudson's two-hit mechanism. We identified four MEN1 germline variants and two novel somatic variants. Early recognition of the phenotype coupled with variant screening of the MEN1 gene is the key to diagnosing and treating MEN1 effectively at an early stage.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32046062

RESUMO

This study aimed to explore the association between screen exposure in early life and preschool myopia. During the baseline survey of the Longhua Child Cohort Study (LCCS), data of 29,595 preschoolers were collected via a caregiver-reported questionnaire regarding children's socio-demographic characteristics, visual status, screen exposure and relevant parental information. Data of 26,433 preschoolers with normal eyesight or myopia were included in the analysis and cox regression modelling was employed to assess the associations. Results suggested the hypothesis that screen exposure in early life could be significantly and positively associated with preschool myopia, and in agreement with this hypothesis was the association being strengthened with the increasing daily exposure duration and total years of exposure; in the stratification analysis based on the presence of parental myopia, these associations still existed, and the strength of associations was stronger in preschoolers with myopic parents than those without. Moreover, a statistically significant association was only observed between initial screen exposure that occurred during 0-1-years old and myopia for preschoolers without myopic parents, while the significant associations were observed between initial screen exposure that occurred during 0-1, 1-2, 2-3, and after 3 years old and myopia for preschoolers who had myopic parents, with the strongest association found in the group of children initially exposed to electronic screens during 0-1 year old. Thus our findings indicated the hypothesis that screen exposure in early life might be associated with the occurrence of preschool myopia, and that the postnatal first year might be the sensitive period for the association. However, it is premature to conclude that early screen time leads to myopia with current data. Further longitudinal studies performed with cycloplegia are necessary to verify the hypothesis and shed light on the more urgent question whether early screen exposure contributes to the later myopia epidemic of school-aged children.


Assuntos
Miopia/etiologia , Tempo de Tela , Grupo com Ancestrais do Continente Asiático , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Miopia/epidemiologia , Inquéritos e Questionários
18.
Insect Sci ; 27(6): 1208-1223, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31840397

RESUMO

Metamorphosis is one of the most important physiological processes in insects. It is regulated by a serial of ecdysone cascade genes. Recently, lots of microRNAs (miRNAs) were investigated in insects; however, their function in metamorphosis is largely unknown. In the present study, the dynamics of a small RNA population was investigated by RNA sequencing from the midgut of a lepidopteran pest Spodoptera litura during larval-pupal metamorphosis. A total of 101 miRNAs were identified, and 75 miRNAs were differentially expressed during the metamorphic process. The relationship between these differentially expressed miRNAs and 12 ecdysone cascade genes was analyzed by four classical software programs, and a multiple-to-multiple regulatory network was found to exist between these miRNAs and their targets. Among them, miR-14-3p and its two targets (EcR and E75) were chosen for further validation. MiR-14-3p had higher expression level in the 6th instar larvae as compared with either the prepupae or pupae, which was opposite to that of both EcR and E75, two ecdysone cascade genes. Luciferase reporter assay confirmed that both EcR and E75 were regulated by miR-14-3p. Interestingly, the 3' untranslated regions are nearly identical to each other among different transcript variants of the ecdysone cascade genes, including EcR, USP, E75, E74, E78, E93, Hr3, Hr4, Hr39, Krh1 and Ftzf1. Thus, different transcript variants of one ecdysone cascade gene could be regulated by the same miRNA. The above data suggest that the ecdysone signaling pathway is under the tight control of miRNA. These findings expand our understanding of the mechanism of insect metamorphosis and may also provide a novel possibility for the control of pest insects in the future.


Assuntos
Ecdisona/metabolismo , Metamorfose Biológica/genética , MicroRNAs/genética , Transdução de Sinais/genética , Spodoptera/fisiologia , Animais , Sistema Digestório/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Larva/genética , Larva/crescimento & desenvolvimento , Larva/fisiologia , MicroRNAs/metabolismo , Pupa/genética , Pupa/crescimento & desenvolvimento , Pupa/fisiologia , Spodoptera/genética , Spodoptera/crescimento & desenvolvimento , Transcriptoma
19.
Mol Med Rep ; 21(1): 485-492, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746415

RESUMO

Individual differences in the response to fentanyl, which may be caused by different concentrations of the drug in the central nervous system, can complicate analgesic treatment. It has been reported that the organic anion transporting polypeptide (OATP) at the blood­brain barrier (BBB) in Sprague­Dawley rats may serve an important role in the transport of fentanyl across the BBB. However, whether human OATP can transport fentanyl has thus far not been reported. The present study aimed to establish a 293 cell line stably overexpressing OATP1A2, and to determine whether OATP1A2 is able to transport fentanyl across the plasma membrane. Initially, 293 cells were transfected with an OATP1A2­expressing plasmid (referred to as 293­OATP1A2 cells), and single colonies were selected and characterized following geneticin treatment. Subsequently, reverse transcription­quantitative polymerase chain reaction and western blot analyses were conducted to verify the transfection efficiency. Furthermore, treatment of 293­OATP1A2 cells with different concentrations of fexofenadine (FEX) and fentanyl was performed to investigate the transport function of OATP1A2 in 293 cells. FEX and fentanyl uptake experiments were also performed with naringenin, an inhibitor of OATP1A2. The results indicated that FEX and fentanyl uptake was significantly increased in 293­OATP1A2 cells compared with that in the control­transfected cells. The 293­OATP1A2­mediated uptake of FEX at concentration of 100 nM FEX was ~10­fold higher than that of 293­VC cells. The 293­OATP1A2­mediated uptake of fentanyl (100 nM) was 5.1­fold higher compared with that in 293­VC cells. In 293­OATP1A2 cells, the uptake of FEX without OATP1A2 inhibitor naringenin (100 µg/ml) was 2.8­fold higher compared with that in the presence of naringenin, and the uptake of fentanyl without naringenin was 7.3­fold higher compared with that in the presence of naringenin (100 µg/ml). In conclusion, 293 cells that overexpressed OATP1A2 were successfully constructed, and OATP1A2 was revealed to mediate fentanyl uptake in the cultured cells.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Fentanila/farmacologia , Transportadores de Ânions Orgânicos/genética , Animais , Transporte Biológico/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Sistema Nervoso Central/metabolismo , Células HEK293 , Humanos , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
20.
Artigo em Inglês | MEDLINE | ID: mdl-31623306

RESUMO

This study aimed to investigate the association between environmental exposure to tobacco smoke (ETS) during early life and astigmatism in Chinese preschool children. In this cross-sectional study, information concerning prenatal and postnatal ETS exposure at three stages of early life (during pregnancy, from birth to one year and from one to three years), visual problems of children and parents (including a confirmed diagnosis of astigmatism), socio-demographics and perinatal characteristics were obtained from 27,890 parent-reported questionnaires. Logistic regression analyses were undertaken to yield adjusted odds ratios (OR) for assessing their associations. After adjusting for the potential confounders, children were more likely to exhibit astigmatism when they were exposed to ETS during pregnancy + from one to three years [OR (95% CI) = 1.37 (1.02, 1.84)], or from birth to one year + from one to three years [OR (95% CI) = 1.36 (1.11, 1.66)], or during pregnancy + from birth to one year + from one to three years old [OR (95% CI) = 1.29 (1.16, 1.45)], compared to children without ETS exposure at any stage of early life. In Chinese preschool children, prenatal and postnatal astigmatism was associated with ETS exposure; the greater the ETS dose, the greater the astigmatism risk.


Assuntos
Astigmatismo/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Astigmatismo/epidemiologia , Astigmatismo/fisiopatologia , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos
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