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1.
J Pediatr ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061408

RESUMO

OBJECTIVE: To identify distinct body mass index (BMI) trajectories across the life-course and explore the effects of BMI trajectories on the adult cardiovascular disease outcomes using a dataset with 30 years of follow-up in northern China. STUDY DESIGN: A total of 2839 participants aged 6-18 years whose BMIs were measured 3-6 times during the Hanzhong Adolescent Hypertension Study were included in our analysis. Latent mixture modeling was used to clarify distinct BMI trajectories in longitudinal analyses. RESULTS: Three groups with distinct trajectories in BMI were identified by the latent mixed models: a low-increasing group (n = 1324 [36.64%]), a moderate-increasing group (n = 1178 [16.89%]), and a high-increasing group (n = 337 [39.46%]). Compared with the participants in the low-increasing group, the risk ratios of hypertension, type 2 diabetes mellitus, high-risk triglycerides, and high-risk high-density lipoprotein cholesterol were more than 3.0 in the high-increasing group (all P < .001) after being fully adjusted. Increased risks existed in high brachial-ankle pulse wave velocity for the high-increasing group compared with the low-increasing group (RR, 2.75; 95% CI, 1.94-3.91; P < .001). Additionally, participants in the moderate-increasing group had a 2.31-fold increased risks of left ventricular hypertrophy (95% CI, 1.25-4.30; P = .008). CONCLUSIONS: Our study indicates that BMI trajectories from childhood to adulthood vary and that an elevated BMI trajectory in early life is predictive of an increased the risk of developing cardiovascular disease risks. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02734472.

2.
Scand J Trauma Resusc Emerg Med ; 28(1): 3, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937354

RESUMO

BACKGROUND: Therapeutic hypothermia has been recommended for eligible patients after cardiac arrest (CA) in order to improve outcomes. Up to now, several comparative observational studies have evaluated the combined use of extracorporeal cardiopulmonary resuscitation (ECPR) and therapeutic hypothermia in adult patients with CA. However, the effects of therapeutic hypothermia in adult CA patients receiving ECPR are inconsistent. METHODS: Relevant studies in English databases (PubMed, ISI web of science, OVID, and Embase) were systematically searched up to September 2019. Odds ratios (ORs) from eligible studies were extracted and pooled to summarize the associations of therapeutic hypothermia with favorable neurological outcomes and survival in adult CA patients receiving ECPR. RESULTS: 13 articles were included in the present meta-analysis study. There were nine studies with a total of 806 cases reporting the association of therapeutic hypothermia with neurological outcomes in CA patients receiving ECPR. Pooling analysis suggested that therapeutic hypothermia was significantly associated with favorable neurological outcomes in overall (N = 9, OR = 3.507, 95%CI = 2.194-5.607, P < 0.001, fixed-effects model) and in all subgroups according to control type, regions, sample size, CA location, ORs obtained methods, follow-up period, and modified Newcastle Ottawa Scale (mNOS) scores. There were nine studies with a total of 806 cases assessing the association of therapeutic hypothermia with survival in CA patients receiving ECPR. After pooling the ORs, therapeutic hypothermia was found to be significantly associated with survival in overall (N = 9, OR = 2.540, 95%CI = 1.245-5.180, P = 0.010, random-effects model) and in some subgroups. Publication bias was found when evaluating the association of therapeutic hypothermia with neurological outcomes in CA patients receiving ECPR. Additional trim-and-fill analysis estimated four "missing" studies, which adjusted the effect size to 2.800 (95%CI = 1.842-4.526, P < 0.001, fixed-effects model) for neurological outcomes. CONCLUSIONS: Therapeutic hypothermia may be associated with favorable neurological outcomes and survival in adult CA patients undergoing ECPR. However, the result should be treated carefully because it is a synthesis of low-level evidence and other limitations exist in present study. It is necessary to perform randomized controlled trials to validate our result before considering the result in clinical practices.

3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 74-80, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950793

RESUMO

Objective: To develop an assay for determination of 8-oxo-2'-deoxyguanosine and cotinine in human urine by hydrophilic chromatography tandem mass spectrometry (HILIC-MS/MS) with isotope dilution. Methods: The urine supernatant was 1∶5 diluted with 3 mmol/L ammonium formate aqueous solution containing 15N 5-8-OHdG and D 3-cotinine as internal standard. After being filtered through a 0.22 µm water filter, the sample solution was injected into ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for analysis. Separation was performed on ACQUITY UPLC® BEH HILIC column (50 mm×3.0 mm, 1.7 µm) with isocratic elution (A∶B=10∶90) at 40 ℃. The mobile phase was composed with acetonitrile (B) and 3 mmol/L ammonium formate water soulution (A). The flow rate was 0.3 mL/min. Positive ion scan-multiple reaction monitoring (MRM) mode were used for monitoring and internal standard curves were applied for quantification. Results: Good linearity was obtained under the optimal conditions. Detection limits for 8-OHdG and cotinine were 0.064 µg/L and 0.035 µg/L respectively, the quantitation limits were 0.21 µg/L and 0.12 µg/L respectively, and the recoveries of the spiked urine samples were 92.6%-102% and 102%-106% respectively. Statistical analysis of 40 urine sample determination results obtained by using the above assay showed that there were significant differences in tobacco smoke exposure and tobacco-specific nitrosamine intake between active and passive smoker ( P<0.05). The concentration of NNAL and cotinine were higher in urine samples of active smoker. Tobacco smoke exposure was positively correlated with tobacco specific nitrosamine intake in both active and passive smokers (the correlation coefficients were 0.487 and 0.786 respectively, P<0.05). Conclusion: We successfully established a simple and fast assay for simultaneously detecting 8-oxo-2'-deoxyguanosine and cotinine in human urine. It was sensitive and accurate for quntification via the calibration by the isotope internal standards, and can meet the needs of batch analysis.


Assuntos
Cromatografia Líquida de Alta Pressão , Cotinina , Espectrometria de Massas em Tandem , Urinálise , /urina , Cotinina/urina , Humanos , Isótopos/química , Urinálise/métodos
4.
FASEB J ; 34(2): 2524-2540, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31908026

RESUMO

The main mechanism of hyaluronidase 1(HYAL-1) in the development of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) was unknown. In this study, a comprehensive inventory of pre-, intra-, and postoperative clinical and biological data of two cohorts (62 pancreatic cancer [PCa] and 111 pancreatic ductal adenocarcinoma [PDAC]) which could induce POPF were retrospectively analyzed. Then, a total of 7644 genes correlated with HYAL-1 was predicted in PDAC tissues and the enriched pathway, kinase targets and biological process of those correlated genes were evaluated. Finally, a mouse pancreatic fistula (PF) model was first built and in vitro studies were performed to investigate the effects of HYAL-1 on PF progression. Our data indicated that preoperative serum HYAL-1 level, pancreatic fibrosis score, and pancreatic duct size were valuable factors for detecting POPF of Grade B and C. The serum HYAL-1 level of 2.07 mg/ml and pancreatic fibrosis score of 2.5 were proposed as the cutoff values for indicating POPF. The bioinformatic analysis and in vitro and in vivo studies demonstrated that HYAL-1 facilitates pancreatic acinar cell autophagy via the dephosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and signal transducers and activators of transcription 3 (STAT3) signaling pathways, which exacerbate pancreatic secretion and inflammation. In summary, the preoperative serum HYAL-1 was a significant predictor for POPF in patients who underwent PD. Tumor-induced HYAL-1 is one of core risk in accelerating PF and then promoting pancreatic secretion and acute inflammation response through the AMPK and STAT3-induced autophagy.

5.
World Neurosurg ; 133: e62-e67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31442648

RESUMO

OBJECTIVE: Microvascular decompression (MVD) has been widely accepted for treating hemifacial spasm (HFS) and glossopharyngeal neuralgia (GN); an effective surgical treatment of coexistent HFS and GN still remains to be determined, however. In this paper we discuss the operative strategy of MVD for patients with coexistent HFS and GN. METHODS: This was a retrospective study. All cases of HFS with or without GN at China-Japan Friendship Hospital from January 2014 to June 2016 have been included. All patients underwent MVD and have been followed up for an average of 1.5 years. RESULTS: A total of 5375 cases of HFS were included, wherein 8 cases coexist with GN. Eight patients had same offending vessel(s) compressing the root entry zone of glossopharyngeal nerve and facial nerve. Posterior inferior cerebellar artery was identified as at least 1 of the offending arteries in all 8 patients. After MVD, spasm ceased in all 8 cases, with 7 cases ceasing immediately and 1 within 2 months. Pain disappeared also in all cases, with 7 cases immediately and 1 case after 4 days. No recurrence or complication was observed during the follow-ups. CONCLUSIONS: HFS combined with ipsilateral GN was rare. MVD could be performed to effectively relieve nerve root compression and associated symptoms for coexistent HFS and GN. Sufficient exposure of root entry zones of both nerves and fully decompression of offending blood vessels and exploratory sequences of different nerve roots are critical points for improving operative effect and reducing complications.


Assuntos
Doenças do Nervo Glossofaríngeo/cirurgia , Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular , Síndromes de Compressão Nervosa/cirurgia , Adulto , Nervo Facial/fisiopatologia , Feminino , Seguimentos , Nervo Glossofaríngeo/fisiopatologia , Doenças do Nervo Glossofaríngeo/fisiopatologia , Espasmo Hemifacial/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
6.
Acta Paediatr ; 109(2): 258-265, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31472095

RESUMO

AIM: Epidemiological studies on associations between Caesarean sections (C-sections) and attention-deficit hyperactivity disorder (ADHD) have been inconsistent, and we performed a meta-analysis. METHODS: We systematically searched PubMed and Embase to December 2018 and included nine hospital-based and population registry studies published in 2011-2018. These covered a total study cohort of more than 2.5 million people in eight countries: Australia, Brazil, Denmark, Finland, Germany, Sweden, Turkey and the UK. The analysis provided summary odds ratios (ORs) and 95% confidence intervals (CI) while taking heterogeneity into account. RESULTS: We found that that C-sections were associated with a small increase in the risk of ADHD (OR 1.14, 95% CI 1.11, 1.17, I2 0%) in offspring. In subgroup analyses, the association remained for both infants born after elective C-sections (OR, 1.15, 1.11, 1.19, I2 0%) and emergency C-sections (OR, 1.13, 1.1, 1.17, I2 45.4%). However, these were only marginally significant when we pooled data from siblings from other pregnancies (OR, 1.06, 1.00-1.13, I2 0%), implying that the association was due to confounding. CONCLUSION: The statistically significant association between C-sections and ADHD in children can be partially explained by unmeasured confounding. Further research controlling for important confounders is required before firm conclusions can be drawn.

7.
Behav Brain Res ; 379: 112374, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31759045

RESUMO

BACKGROUND: Accumulating evidence has focused on elucidating the bacterial component of the gut microbiota in patients with schizophrenia (SC); however, the fungal composition in the gut has not been investigated, although previous studies have suggested that gut mycobiota may be intricately linked to this disorder. The purpose of this analysis was to examine gut bacterial and fungi in first-episode, drug- naïve adult SC patients in relation to age- and sex-matched healthy controls (HC). METHODS: Ten SC patients and 16 HCs were enrolled in this cross-sectional study, and their gut microbiota and mycobiota were systematically characterized using 16S rRNA gene- and ITS1-based DNA sequencing. RESULTS: The microbiota of the SC patients were characterized by increased abundance of harmful bacterial (Proteobacteria) and decreased short-chain fatty acid (SCFA)-producing bacteria, such as the Faecalibacterium and Lachnospiraceae genera. The gut mycobiota were characterized by a relative reduction in alpha diversity and altered composition. Most notably, the SC group had a higher level of Chaetomium and a lower level of Trichoderma than the HC group. Furthermore, the gut microbiota in patients with SC displayed a significant enhancement in the bacteria-fungi correlation network, suggestive of altered interkingdom interactions. CONCLUSIONS: Both the bacterial gut microbiota as well as the gut mycobiota contributed to gut dysbiosis in patients with SC. However, our study was limited by sample size, and additional studies involving larger cohorts characterizing the gut mycobiome in SC patients are needed to form a foundation for research into the relationship between mycobiota, dysbiosis, and SC development.

8.
Huan Jing Ke Xue ; 40(7): 3216-3222, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854721

RESUMO

Mechanical, chemical, and biological methods are always used to pretreat sewage sludge. To determine which pretreatment can release more organic matter from sewage sludge, and therefore, make it more economical, mechanical pretreatment (ultrasonic treatment at 20 kHz), chemical pretreatment (pH 10), and biological pretreatment (anaerobic conditions at 70℃) were compared. Results showed that all three pretreatments increased the organic matter release of sewage sludge; the initial total soluble protein and carbohydrate concentration of which was only 418.9 mg·L-1 (cal. as COD) and the DNA content was 18.1 mg·L-1. However, the pH 10 and anaerobic (70℃) pretreatments resulted in a greater organic release than the ultrasonic (20 kHz) pretreatment, with total soluble protein and carbohydrate concentrations of 7516.0 mg·L-1 and 7892.5 mg·L-1, and DNA contents of 1343.3 mg·L-1 and 1766.1 mg·L-1, respectively. Flow cytometry was adopted to assess cell morphology. The cell mortality rates of sludge after pretreatment accounted for 61.6%, 59.9%, and 34.5% respectively, which was improved by 45.6% (at pH 10), 43.9% (under anaerobic conditions at 70℃), and 18.5% (with ultrasonic pretreatment at 20 kHz) compared with raw sewage sludge. At the same time, organic matter removal ratios of sludge after pretreatment were 19.1% (at pH 10), 13.8% (under anaerobic conditions at 70℃), and 7.6% (with ultrasonic pretreatment at 20 kHz). Moreover, the pretreatment of per liter sludge at pH 10 saved 28.5% and 124.1% more than ultrasonic pretreatment (20 kHz) and anaerobic (70℃) pretreatment. Taking both organic matter release and economic analysis into consideration, the chemical method of pretreatment (at pH 10) was identified as the best option.

9.
Front Psychol ; 10: 2310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681104

RESUMO

To address the need for a valid and reliable scale of youth leadership potential based on the development theory of leadership, the current study developed the Youth Leadership Potential Scale (YLPS) and investigated its factor structure and psychometric properties in a sample of 696 students (grades 7-9) in China. Exploratory structural equation modeling (ESEM) identified a five-factor solution comprising leadership information, leadership attitude, communication skills, decision-making skills, and stress management skills. ESEM within confirmatory factor analysis demonstrated an adequate fit for this structure. The scale showed good composite reliability and measurement invariance across different gender and grade/age groups. The scale also showed sufficient concurrent validity with the Coping Self-Efficacy Scale, the Chinese Roets Rating Scale for Leadership, and the Leadership Skills Inventory. Furthermore, criterion-related validity was supported by the relationship between YLPS scores and the length of student leadership positions. The results suggest that the YLPS is a valid and pragmatic measure for assessing youth leadership potential. The current study is the first to develop a youth leadership potential scale based on the development theory of leadership.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31733109

RESUMO

BACKGROUND AND AIM: There is evidence of a relationship between infection (and the associated antibiotic exposure) and the risk of celiac disease (CD). This study performed a meta-analysis to investigate this relationship. METHODS: To identify relevant studies, we conducted systematic searches of the PubMed, Embase, and Cochrane databases for articles published up to April 2019. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: The meta-analysis included 19 observational studies (15 on infection and six on antibiotic exposure). Our results showed that any infection was associated with an increased risk of CD later in life (odds ratio, 1.37; 95% CI: 1.2-1.56; P < 0.001). The I2 was 94% (high heterogeneity among studies). Subgroup analyses suggested that the risk of CD is not affected by the type of infectious agent, timing of exposure, and site of infection. Exposure to antibiotics was also associated with new-onset CD (odds ratio, 1.2; 95% CI: 1.04-1.39; P < 0.001). CONCLUSION: Exposure to early infection or antibiotic appears to increase the odds of developing CD, suggesting that intestinal immune or microbiota dysbiosis may play a role in the pathogenesis of CD. These findings may influence clinical management and primary prevention of CD. However, noncausal explanations for these positive associations cannot be excluded.

11.
Eur J Clin Nutr ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728032

RESUMO

BACKGROUND: A high atherogenic index of plasma (AIP) is associated with increased cardiovascular risk and higher serum uric acid levels, but whether AIP is a strong risk factor for developing subclinical renal damage (SRD) is unknown. This study aimed to explore the effect of AIP variations on the prevalence of SRD in a 12-year follow-up study. METHODS: (1) The cross-sectional study enrolled 2485 participants from the Hanzhong cohort in 2017; (2) A total of 202 participants were included in the small longitudinal cohort from 2005 to 2017. Longitudinal analysis was used to determine whether an elevated AIP predicts the development of SRD. RESULTS: In the cross-sectional analysis, the AIP level was correlated with the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (uACR) (P < 0.05). The age-adjusted odds ratio (OR) for prevalent SRD in men in the high AIP group was 1.924 (1.355-2.732) (P < 0.001), while in women, the OR was 1.616 (1.049-2.490) (P = 0.030) in the high AIP group. In the longitudinal analysis, significantly higher uACR levels were found in participants with normal AIP at baseline and elevated AIP in 2013 (P < 0.05). The adjusted OR for prevalent SRD in the incident AIP group was 4.741 (1.668-13.472) (P = 0.003) compared with the control group. CONCLUSIONS: Our study indicates that elevated AIP increased the risk of developing SRD and was associated with uACR and eGFR. As a simple marker of CVD risk, AIP may emerge as a novel and reliable indicator of SRD.

12.
PLoS One ; 14(11): e0224680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31730636

RESUMO

BACKGROUND AND OBJECTIVES: The aim of the study was to examine the associations of uric acid (UA) in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort. METHODS: 1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD. 2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline. RESULTS: In cross-sectional analysis, higher levels of uACR were associated with higher levels of serum uric acid (SUA) and urinary uric acid/creatinine ratio (uUA/Cre). Lower eGFR was associated with higher levels of SUA and fractional excretion of uric acid (FEUA) but lower uUA/Cre levels in all subjects. In addition, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255-5.664) for uUA/Cre. Increasing uUA/Cre levels were associated with higher risk of SRD. In longitudinal analysis, 4-year changes of uUA/Cre and SUA were significantly associated with eGFR decline. CONCLUSIONS: This study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects.

13.
Radiol Oncol ; 53(4): 434-442, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747378

RESUMO

Background Endometrial cancer (EC) is one of the most common gynaecological tumours in the worldwide. Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) promotes cell proliferation, migration and invasion in EC cells. However, the molecular mechanisms of NEAT1 in EC have not been fully clarified. We conducted this study to reveal the function of NEAT1 in EC tissues and cell lines. Materials and methods Cancer and adjacent tissues were collected from EC patients. HEC-1A and Ishikawa cells were cultured in vitro. NEAT1 expression was downregulated by transfecting small hairpin RNA (shRNA) and miR-144-3p was overexpressed by transfecting miR-144-3p mimics. Cell proliferation was detected by MTT assay and colony formation assay. Cell migration and invasion abilities were assessed by transwell assay. A dual-luciferase reporter assay was used to verify the relationship among NEAT1, EZH2, and miR-144-3p. The expression level of EZH2 was measured by Western blot and qPCR. Results NEAT1 was highly expressed in EC tissues and cells. Knockdown of NEAT1 inhibited the proliferation, migration and invasion of EC cells. Additionally, NEAT1 acted as a ceRNA of miR-144-3p, leading to EZH2 upregulation. Overexpression of miR-144-3p suppressed the proliferation and invasion of EC cells. Conclusions NEAT1 promotes EC cells proliferation and invasion by regulating the miR-144-3p/EZH2 axis.

14.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(4): 404-409, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31612676

RESUMO

OBJECTIVE: To investigate the expression of some genes in Pomacea canaliculata infected with Angiostrongylus cantonensis, so as to provide insight into the preliminary understanding of the interactions between Angiostrongylus cantonensis and its intermediate host Pomacea canaliculata. METHODS: P. canaliculata was fed with rat faces containing the first-stage larvae of A. cantonensis. Three to five P. canaliculata was sampled 1, 10 days and 20 days after feeding, and the hemolymph, hepatopancreas, kidney, intestinal tract, head-foot and gill tissues were collected, while uninfected P. canaliculata served as controls. Total RNA was extracted from various tissues of P. canaliculata at different time points post-infection, and transcribed reversely into cDNA. Based on previous transcriptome sequencing results, 10 genes associated with immune defense, signal transduction, cell growth and metabolism, stress response were selected, and the gene expression was determined in the hemolymph tissues of P. canaliculata 1, 10 days and 20 days post-infection with A. cantonensis using real-time fluorescent quantitative PCR assay, and the α-tubulin gene expression was quantified in the hepatopancreas, kidney, head-foot, intestinal tract and gill tissues of P. canaliculata infected with A. cantonensis. RESULTS: Higher CELA1 gene expression was detected in the infection group than in the control group 1 (t = 12.32, P < 0.05), 10 days (t = 23.51, P < 0.05) and 20 days post-infection (t = 34.92, P < 0.05), and the CELA1 expression increased with the time of infection. The GST gene expression was (7.26 ± 1.80) times higher in the infection group than in the control group 1 day post-infection, and was significantly lower in the infection group than in the control group 10 days (t = 23.89, P < 0.05) and 20 days post-infection (t = 19.83, P < 0.05). Higher ferritin gene expression was found in the infection group than in the control group 10 days post-infection (t = 32.76, P < 0.05), and higher CRT gene expression was seen in the infection group than in the control group 1 (t = 7.23, P < 0.05), 10 days (t = 5.78, P < 0.05) and 20 days post-infection (t = 6.32, P < 0.05). In addition, the greatest α-tubulin gene expression was observed in the the hepatopancreatic tissues of P. canaliculata (F = 17.58, P < 0.05), and the α-tubulin gene expression altered in various tissues of P. canaliculata post-infection with A. cantonensis, with the most remarkable reduction of α - tubulin gene expression seen in the hepatopancreatic tissues (P < 0.05). CONCLUSIONS: Following A. cantonensis infection in P. canaliculata, the expression of multiple genes is altered, and the expression of α-tubulin gene is inhibited in multiple tissues. The findings provide a basis for the further elucidation of the interactions between P. canaliculata and A. cantonensis.


Assuntos
Angiostrongylus cantonensis , Gastrópodes , Interações Hospedeiro-Parasita , Infecções por Strongylida , Tubulina (Proteína) , Angiostrongylus cantonensis/fisiologia , Animais , Gastrópodes/genética , Gastrópodes/parasitologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Interações Hospedeiro-Parasita/genética , Larva , Ratos , Tubulina (Proteína)/genética
15.
Nat Mater ; 18(12): 1376-1383, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31636420

RESUMO

Among the strategies used for enhancement of tumour retention of imaging agents or anticancer drugs is the rational design of probes that undergo a tumour-specific enzymatic reaction preventing them from being pumped out of the cell. Here, the anticancer agent olsalazine (Olsa) was conjugated to the cell-penetrating peptide RVRR. Taking advantage of a biologically compatible condensation reaction, single Olsa-RVRR molecules were self-assembled into large intracellular nanoparticles by the tumour-associated enzyme furin. Both Olsa-RVRR and Olsa nanoparticles were readily detected with chemical exchange saturation transfer magnetic resonance imaging by virtue of exchangeable Olsa hydroxyl protons. In vivo studies using HCT116 and LoVo murine xenografts showed that the OlsaCEST signal and anti-tumour therapeutic effect were 6.5- and 5.2-fold increased, respectively, compared to Olsa without RVRR, with an excellent 'theranostic correlation' (R2 = 0.97) between the imaging signal and therapeutic response (normalized tumour size). This furin-targeted, magnetic resonance imaging-detectable platform has potential for imaging tumour aggressiveness, drug accumulation and therapeutic response.

16.
Plant Cell Physiol ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642503

RESUMO

Anthocyanins are preferentially accumulated in certain tissues of particular species in citrus. A R2R3-MYB transcription factor (named as Ruby1) has been well documented as an activator of citrus anthocyanin biosynthesis. Here, we characterized CsMYB3, a transcriptional repressor that regulates anthocyanin biosynthesis in citrus. CsMYB3 was expressed in anthocyanin pigmented tissues and the expression was closely associated with that of Ruby1, which is a key anthocyanin activator. Overexpression of CsMYB3 in Arabidopsis resulted in a decrease in anthocyanins under nitrogen stress. Overexpression of CsMYB3 in the background of CsRuby1-overexpressing strawberry and Arabidopsis reduced the anthocyanin accumulation level. Transient promoter activation assays revealed that CsMYB3 could repress the activation capacity of the complex formed by CsRuby1/CsbHLH1 for the anthocyanin biosynthetic genes. Moreover, CsMYB3 could be transcriptionally activated by CsRuby1 via promoter binding, thus forming an 'activator-and-repressor' loop to regulate anthocyanin biosynthesis in citrus. This work shows that CsMYB3 plays a repressor role in the regulation of anthocyanin biosynthesis, and proposes an 'activator-and-repressor' loop model constituted by CsRuby1 and CsMYB3 in the regulation of anthocyanin biosynthesis in citrus.

17.
J Cancer Res Clin Oncol ; 145(12): 2951-2967, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31654121

RESUMO

PURPOSE: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide and new improvements are urgently needed. Several miRNA-targeted therapeutics have reached clinical development. MicroRNA-143 (miR-143) was found to significantly suppress the migration and invasion of NSCLC. It might be of great potential for NSCLC treatment. However, the therapeutic effect of miR-143 against NSCLC in vivo has not been explored until now. METHODS: The cationic liposome/pVAX-miR-143 complex (CL-pVAX-miR-143) was prepared and its biodistribution was assessed. The tumor suppression effects of CL-pVAX-miR-143 were evaluated in early-stage and advanced experimental lung cancer metastasis mice models by systemic delivery, respectively, and also in subcutaneous tumor models by intratumoral injection. The toxicity of CL-pVAX-miR-143 was assessed by H&E analysis and biochemical measurements. The preliminary mechanism of CL-pVAX-miR-143 on tumor suppression was explored by immunochemistry and western blotting. RESULTS: The assays on the stability and safety of CL-pVAX-miR-143 showed that it mainly accumulated in the lung after systemic administration. The intratumoral delivery of CL-pVAX-miR-143 effectively inhibited A549 subcutaneous tumor growth. Notably, systemic delivery of CL-pVAX-miR-143 significantly inhibited tumor metastasis and prolonged survival dose dependently in early-stage experimental lung cancer metastasis models. More importantly, same results were shown in advanced mice models with metastasis. CL-pVAX-miR-143 treatment did not induce obvious acute toxicity. The preliminary mechanism on inhibiting tumor metastasis might be induced by targeting CD44v3. CONCLUSIONS: Our results suggested that CL-pVAX-miR-143 might be a promising strategy for clinical treatment of non-small cell lung cancer, especially for advanced NSCLC with metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cátions/administração & dosagem , Lipossomos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/administração & dosagem , Células A549 , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Tecidual
18.
Chin J Integr Med ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31630361

RESUMO

OBJECTIVE: To analyze the effective components of Chinese medicine (CM) contained in Chaihu Shugan Powder (, CSP) in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology. METHODS: Absorption, distribution, metabolism, excretion, and toxicity calculation method was used to screen the active components of CSP. Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool (GoPuMed database) were used to predict and screen the active ingredients of CSP and anti-depressive targets. Through Genetic Association Database, Therapeutic Target Database, and PharmGkb database targets for depression were obtained. Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP, and to analyze gene function and metabolic pathways through Database for Annotation, Visualization and Integrated Discovery and the Omicshare database. RESULTS: The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity, growth, transfer condition and gene expression of neuronal cell, and the raise of the expression of gap junction protein. The 15 targets passed 14 metabolic pathways, mainly involved in the regulation of neurotransmitters (5-hydroxytryptamine, dopamine and epinephrine), inflammatory mediator regulation of TRP channels, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects. CONCLUSION: This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research, and lays a foundation for further target studies.

19.
J Org Chem ; 84(22): 14911-14918, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31621323

RESUMO

A one-pot novel strategy is described for the construction of various oxazolo[4,5-c]quinoline derivatives starting from the isocyano(triphenylphosphoranylidene)acetates, aldehydes, amines, and 2-azidobenzoic acids. The reactions generated the target products directly in moderate to good yields via a sequential Ugi/Wittig/aza-Wittig cyclization process. The salient features of the method are that all three groups of the multifunctional isocyanides were involved in the reaction with broad substituent scopes and mild reaction conditions, making the protocol a useful contribution to the synthesis of oxazolo[4,5-c]quinoline heterocycles.

20.
AAPS PharmSciTech ; 20(7): 305, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506831

RESUMO

The aim of this study was to prepare a 20(S)-protopanaxadiol nanocrystalline suspension and enhance the bioavailability of 20(S)-protopanaxadiol by intramuscular injection. 20(S)-Protopanaxadiol nanocrystalline suspension was prepared using an anti-solvent combined with ultrasonic approach, in which meglumine and bovine serum albumin were screened as the optimized stabilizer and the coating agent during spray drying process, respectively. The optimal nanocrystallines were nearly spherical with a uniform particle size distribution, the mean particle size, polydispersity index, and drug loading of which were 151.20 ± 2.54 nm, 0.11 ± 0.01, and 47.15% (w/w), respectively. Sterile 20(S)-protopanaxadiol nanocrystalline suspension was obtained by passing through a 0.22-µm membrane, and the average filtration efficiency (FE%) was 99.96%. The cumulative release percentage of 20(S)-protopanaxadiol nanocrystalline suspension was 92.36% 20(S)-protopanaxadiol within 60 min in vitro, which was relatively rapid compared with that of the physical mixture for 12.51% and the 20(S)-protopanaxadiol bulk powder for 9.71% during the same time interval. The sterile 20(S)-protopanaxadiol nanocrystalline suspension caused minimal irritation responses by histological examination, indicating a good biocompatibility between the 20(S)-protopanaxadiol nanocrystalline suspension and muscle tissues. In pharmacokinetic study, the absolute bioavailability of 20(S)-protopanaxadiol nanocrystalline suspension for intramuscular injection and for oral gavage was 5.99 and 0.03, respectively. In summary, the 20(S)-protopanaxadiol nanocrystalline via intramuscular injection is an efficient drug delivery system to improve its bioavailability.


Assuntos
Sistemas de Liberação de Medicamentos , Sapogeninas/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Injeções Intramusculares , Masculino , Nanopartículas/química , Ratos , Ratos Sprague-Dawley , Sapogeninas/administração & dosagem , Sapogeninas/química , Soroalbumina Bovina/química , Suspensões
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