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1.
Mol Diagn Ther ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919754

RESUMO

The global liquid biopsy industry is expected to exceed $US5 billion by 2023. One application of liquid biopsy technology is the diagnosis of disease using biomarkers found in blood, urine, stool, saliva, and other biological samples from patients. These biomarkers could be DNA, RNA, protein, or even a cell. More recently, the use of cell-free DNA from plasma is emerging as an important minimally invasive tool for clinical diagnosis. The development of technology has increased the diversity of its application. Here, we discuss how liquid biopsies have been used in the clinic, and how personalized medicine are likely to use liquid biopsies in the near future.

2.
Biochem Pharmacol ; : 113797, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926936

RESUMO

BX795, a small molecule with an aminopyrimidine backbone, is a potent ATP-competitive inhibitor of phosphoinositide-dependent kinase 1 (PDK1) and TANK-binding kinase 1 (TBK1). BX795 has significant functions in various immune responses and cancer. Few reports on the anti-inflammatory effect of BX795 are available, and its molecular mechanisms have not been fully elucidated. In this study, lipopolysaccharide (LPS)-treated macrophages (RAW264.7 cells), luciferase reporter gene assay, knock-down and overexpression strategies, kinase assay, protein chip, immunoprecipitation, and immunoblotting analyses were employed to clarify the anti-inflammatory mechanism of BX795. BX795 was found to dose-dependently inhibit the production of pro-inflammatory mediators without exhibiting cytotoxicity. Luciferase assay and immunoblotting analysis with nuclear fractions showed that activator protein-1 (AP-1), signal transducer and activator of transcription 1 (STAT1), and interferon regulatory factor 3 (IRF3) are targeted by BX795 rather than nuclear factor (NF)-κB. Moreover, TBK1 and AKT, transforming growth factor activated kinase (TAK)-1/c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase kinase 4 (MKK4) for AP-1 activation, and Janus kinase 2 (JAK2)/STAT1 were inhibited by BX795. Consistent with these findings, BX795 strongly ameliorated inflammatory symptoms in colitis models. These results suggest that BX795 can suppress inflammatory responses triggered by Gram-positive bacteria by suppressing multiple pathways.

3.
Chemosphere ; 242: 125237, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896179

RESUMO

The presence of surfactants in biofilters could enhance hydrophobic VOC removal. In this study, blood agar plate, methylene blue agar plate and a culture with n-hexane as the only carbon source were used to screen strains that could biodegrade n-hexane and produce biosurfactants simultaneously. The effects of n-hexane concentration on n-hexane removal and biosurfactant production were also investigated. Results showed that such a strain identified to be Pseudomonas sp. Strain NEE2 was successfully isolated from oil-polluted soils. The biosurfactants production by this strain were dependent on the initial concentration of n-hexane (132-2640 mg/L). At the concentration of 2640 mg/L of n-hexane, the biosurfactants promoted n-hexane removal. At 132 mg/L of n-hexane, n-hexane removal efficiency on day 2 exceeded 60%. The synergistic mechanisms of n-hexane removal and biosurfactant production by Pseudomonas sp. Strain NEE2 were discussed including the enhanced mass transfer from gas to liquid phase, within the biofilm phase and biodegradation at the presence of biosurfactants as well as the consequently enhanced production of the biosurfactants. These results in this study proved that it is possible for microorganisms utilizing the synergistic effect of hydrophobic VOC degradation and biosurfactant production for cost-effective hydrophobic VOC removal in biofilters.

4.
Chemistry ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916323

RESUMO

The increased demand for more efficient, safe and green production in fine chemical and pharmaceutical industry calls for the development of continuous-flow manufacturing, and for chiral chemicals in particular, enantioselective catalytic processes. In recent years, this emerging direction has received considerable attention and gained rapid progress. In most cases, catalytic enantioselective flow processes using homogeneous, heterogeneous or enzymatic catalysts have shown significant advantages over the conventional batch mode, such as shortened reaction times, lower catalysts loadings, higher selectivities other than common merits in non-enantioselective flow operations. In this review, the advancements, key strategies, methods and technologies in the last six years as well as remaining challenges are summarized.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31905143

RESUMO

This study aims to build deep learning-based radiomic methods in differentiating vessel invasion from non-vessel invasion in cervical cancer with multi-parametric MRI data. A set of 1,070 dynamic T1 contrast-enhanced (DCE-T1) and 986 T2 weighted imaging (T2WI) MRI images from 167 early-stage cervical cancer patients (January 2014 - August 2018) were used to train and validate deep learning models. Predictive performances were evaluated using receiver operating characteristic (ROC) curve and confusion matrix analysis, with the DCE-T1 showing more discriminative results than T2WI MRI. By adopting an attention ensemble learning strategy that integrates both MRI sequences, the highest average area was obtained under the ROC curve (AUC) of 0.911 (Sensitivity = 0.881 and Specificity = 0.752). The superior performances in this study, when compared to existing radiomic methods, indicate that a wealth of deep learning-based radiomics could be developed to aid radiologists in preoperatively predicting vessel invasion in cervical cancer patients.

6.
Nat Commun ; 11(1): 262, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937768

RESUMO

Navigation requires not only the execution of locomotor programs but also high arousal and real-time retrieval of spatial memory that is often associated with hippocampal theta oscillations. However, the neural circuits for coordinately controlling these important processes remain to be fully dissected. Here we show that the activity of the neuromedin B (NMB) neurons in the nucleus incertus (NI) is tightly correlated with mouse locomotor speed, arousal level, and hippocampal theta power. These processes are reversibly suppressed by optogenetic inhibition and rapidly promoted by optogenetic stimulation of NI NMB neurons. These neurons form reciprocal connections with several subcortical areas associated with arousal, theta oscillation, and premotor processing. Their projections to multiple downstream stations regulate locomotion and hippocampal theta, with the projection to the medial septum being particularly important for promoting arousal. Therefore, NI NMB neurons functionally impact the neural circuit for navigation control according to particular brains states.

7.
J Colloid Interface Sci ; 565: 110-118, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31935584

RESUMO

Solid-state electrolytes with high ionic conductivity, large electrochemical window, and excellent stability with lithium electrode are needed for high-energy solid-state lithium batteries. In this work, a novel polyethylene oxide (PEO)-Lithium bis(trifluoromethylsulphonyl)imide (LiTFSI)-nanocomposite-based polymer electrolyte was prepared by using nickel phosphate (VSB-5) nanorods as the filler. The ionic conductivity of the obtained PEO-LiTFSI-3%VSB-5 solid polymer electrolyte was found to be as high as 4.83 × 10-5 S·cm-1 at 30 °C and electrochemically stable up to about 4.13 V versus Li/Li+. The enhanced ionic conductivity was attributed to the reduced crystallinity of the PEO and the interaction between VSB and 5 and PEO-LiTFSI. In addition, the solid polymer electrolyte exhibited improved compatibility to the lithium metal anode with excellent suppression of lithium dendrites. The assembled LiFePO4/Li battery with the PEO-LiTFSI-3%VSB-5 solid polymer electrolyte showed better rate performance and higher cyclic stability than the PEO-LiTFSI electrolyte. It is demonstrated that this new solid polymer hybrid should be a promising electrolyte applied in solid state batteries with lithium metal electrode.

8.
J Affect Disord ; 265: 63-70, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31957693

RESUMO

OBJECTIVES: This is a meta-analysis of randomized double-blind controlled-placebo trials (RCTs) examining the effectiveness, tolerability, and safety of intranasal esketamine in treating major depressive disorder (MDD). METHODS: Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were calculated using RevMan version 5.3. RESULTS: Four RCTs with 7 active arms covering 708 patients with MDD on intranasal esketamine (n = 419) and placebo (n = 289) were included. Compared with placebo, adjunctive intranasal esketamine was associated with significantly greater study-defined response (RR=1.39, 95%CI: 1.18 to 1.64, P<0.0001) and remission (RR=1.42, 95%CI: 1.17 to 1.72, P = 0.0004) at endpoint assessment. Intranasal esketamine had greater study-defined response starting at 2 h (RR= 2.77, 95%CI: 1.62 to 4.76, P = 0.0002), peaking at 24 h (RR=5.42, 95%CI: 1.38 to 21.20, P = 0.02), and at least lasting for 28 days (RR=1.36, 95%CI: 1.16 to 1.58, P = 0.0001). Similarly, intranasal esketamine had significantly greater study-defined remission starting at 2 h (RR=7.71, 95%CI: 2.16 to 27.55, P = 0.002), peaking at 24 h (RR=6.87, 95%CI: 1.55 to 30.35, P = 0.01), and lasting for 28 days (RR=1.38, 95%CI: 1.11 to 1.72, P = 0.004). Intranasal esketamine had a significantly higher rate of discontinuation due to intolerability (RR=3.50, 95%CI: 1.38 to 8.86, P = 0.008). Discontinuation due to any reasons and inefficacy were similar between the two groups. CONCLUSION: Intranasal esketamine appears to have an ultra-rapid antidepressant effect for MDD, at least lasting for 28 days. The long-term therapeutic effect and safety of intranasal esketamine need to be further examined in large-scale RCTs.

9.
Brain ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31953931

RESUMO

At least 50% of patients with tuberous sclerosis complex present with intractable epilepsy; for these patients, resective surgery is a treatment option. Here, we report a nationwide multicentre retrospective study and analyse the long-term seizure and neuropsychological outcomes of epilepsy surgery in patients with tuberous sclerosis complex. There were 364 patients who underwent epilepsy surgery in the study. Patients' clinical data, postoperative seizure outcomes at 1-, 4-, and 10-year follow-ups, preoperative and postoperative intelligence quotients, and quality of life at 1-year follow-up were collected. The patients' ages at surgery were 10.35 ± 7.70 years (range: 0.5-47). The percentage of postoperative seizure freedom was 71% (258/364) at 1-year, 60% (118/196) at 4-year, and 51% (36/71) at 10-year follow-up. Influence factors of postoperative seizure freedom were the total removal of epileptogenic tubers and the presence of outstanding tuber on MRI at 1- and 4-year follow-ups. Furthermore, monthly seizure (versus daily seizure) was also a positive influence factor for postoperative seizure freedom at 1-year follow-up. The presence of an outstanding tuber on MRI was the only factor influencing seizure freedom at 10-year follow-up. Postoperative quality of life and intelligence quotient improvements were found in 43% (112/262) and 28% (67/242) of patients, respectively. Influence factors of postoperative quality of life and intelligence quotient improvement were postoperative seizure freedom and preoperative low intelligence quotient. The percentage of seizure freedom in the tuberectomy group was significantly lower compared to the tuberectomy plus and lobectomy groups at 1- and 4-year follow-ups. In conclusion, this study, the largest nationwide multi-centre study on resective epilepsy surgery, resulted in improved seizure outcomes and quality of life and intelligence quotient improvements in patients with tuberous sclerosis complex. Seizure freedom was often achieved in patients with an outstanding tuber on MRI, total removal of epileptogenic tubers, and tuberectomy plus. Quality of life and intelligence quotient improvements were frequently observed in patients with postoperative seizure freedom and preoperative low intelligence quotient.

10.
J Food Prot ; : 204-210, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917614

RESUMO

The milk bar is an emerging style of retail business that mainly produces pasteurized milk (PM) and other dairy products on-site in many large cities of the People's Republic of China. To date, no data about veterinary drug residues in PM samples produced from milk bars have been reported. The objective of this study was to investigate the safety of PM from a total of 182 PM samples collected from milk bars from 10 provincial capital cities and to analyze the residues of seven classes of 61 veterinary drugs. First, the chemical components were screened with test kits, and then the positive samples were further confirmed by ultraperformance liquid chromatography-tandem mass spectrometry. The results showed that 15 (8.24%) samples were screened positive for veterinary drugs, and six drugs in 11 (6.04%) samples were confirmed. The veterinary drugs detected were penicillin G (2.20%), tetracycline (1.10%), tylosin (1.10%), amoxicillin (0.55%), oxytetracycline (0.55%), and gentamicin (0.55%), with maximum residue levels of 3.4, 11.9, 28.2, 3.0, 26.9, and 63.5 µg kg-1, respectively. Veterinary drug residues were detected as positive in 7 of 10 cities, with the highest detection rate as 14.29% in Urumqi. No positive samples were found in the cities of Nanjing, Tianjin, and Nanning. All detected drug levels were far below the maximum residue levels regulated by China, the European Union, and the Codex Alimentarius Commission. This suggests that the overall veterinary drug residues in PM in milk bars reached the safety code of the country. However, potential risks still exist, and continuous attention should be paid to guarantee the safety of this milk product in the future.

11.
Brain Behav ; : e01523, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917897

RESUMO

BACKGROUND: Genetic factors have been suggested to affect the efficacy of working memory training. However, few studies have attempted to identify the relevant genes. METHODS: In this study, we first performed a randomized controlled trial (RCT) to identify brain regions that were specifically affected by working memory training. Sixty undergraduate students were randomly assigned to either the adaptive training group (N = 30) or the active control group (N = 30). Both groups were trained for 20 sessions during 4 weeks and received fMRI scans before and after the training. Afterward, we combined the data from the 30 participants in the RCT study who received adaptive training with data from 71 additional participants who also received the same adaptive training but were not part of the RCT study (total N = 101) to test the contribution of the COMT Val158/108Met polymorphism to the interindividual difference in the training effect within the identified brain regions. RESULTS: In the RCT study, we found that the adaptive training significantly decreased brain activation in the left prefrontal cortex (TFCE-FWE corrected p = .030). In the genetic study, we found that compared with the Val allele homozygotes, the Met allele carriers' brain activation decreased more after the training at the left prefrontal cortex (TFCE-FWE corrected p = .025). CONCLUSIONS: This study provided evidence for the neural effect of a visual-spatial span training and suggested that genetic factors such as the COMT Val158/108Met polymorphism may have to be considered in future studies of such training.

12.
Mol Cancer ; 19(1): 6, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924214

RESUMO

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. METHODS: LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. RESULTS: It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. CONCLUSIONS: Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

13.
Sci Total Environ ; 698: 134106, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505350

RESUMO

Chronic exposure to cadmium (Cd) can cause renal dysfunction. Studies of animals, cell cultures, and plants have found that selenium (Se) can effectively alleviate the hazard generated by Cd, but there has been little study of this in general human populations. This study recruited 313 subjects from China's Hubei Province, including 160 living in areas with high soil Cd and Se (exposure group) and 153 living in clean areas (control group). The levels of the following were detected: Cd and Se in blood (B-Cd and B-Se), urine (U-Cd and U-Se), and hair (H-Cd and H-Se); N-acetyl-ß-D-glucosaminidase (U-NAG), ß2-microglobulin (U-ß2-MG), and albumin (U-ALB) in urine; and malondialdehyde (S-MDA), superoxide dismutase (S-SOD), and glutathione peroxidase (S-GSH-Px) in serum. In addition, the interactions between Cd and Se were assessed. The median levels of B-Cd, B-Se, U-Cd, U-Se, H-Cd, H-Se, S-MDA, and S-GSH-Px of exposure group (2.60 ng/mL, 238.90 ng/mL, 3.13 µg/g Cr, 45.43 µg/g Cr, 0.06 µg/g, 0.70 µg/g, 5.22 nmol/mL, and 308.89 U, respectively) were significantly higher than of controls (0.95 ng/mL, 130.50 ng/mL, 1.08 µg/g Cr, 30.51 µg/g Cr, 0.04 µg/g, 0.49 µg/g, 4.71 nmol/mL, and 267.54 U, respectively), but there were no significant differences in U-NAG, U-ß2-MG, U-ALB, or S-SOD between the two groups. U-NAG levels were significantly negatively associated with the interaction between Cd and Se (B: -0.511, 95% CI: -0.886, -0.136). Additionally, changes in the direction of the estimated regression coefficient in the low and high H-Se groups were observed for U-Cd and S-MDA (from 0.018 to -0.090), U-Cd and S-GSH-Px (from -0.039 to 0.101). This study found that populations living in areas with high levels of soil Cd and Se did not show greater Cd-induced renal tubular and glomerular injuries than the control population, which could attribute to the protective effects of Se. The protective effects may be related to the peculiar function of Se that Se can combine with free Cd to activate the antioxidant enzyme system.


Assuntos
Cádmio/análise , Exposição Ambiental/estatística & dados numéricos , Nefropatias/epidemiologia , Selênio/análise , Poluentes do Solo/análise , Acetilglucosaminidase/metabolismo , Antioxidantes , Cádmio/metabolismo , China/epidemiologia , Glutationa Peroxidase/metabolismo , Humanos , Nefropatias/metabolismo , Malondialdeído/metabolismo , Substâncias Protetoras/metabolismo , Selênio/metabolismo , Poluentes do Solo/metabolismo , Superóxido Dismutase/metabolismo , Microglobulina beta-2/metabolismo
14.
Behav Sleep Med ; 18(1): 1-9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30380915

RESUMO

Objective: Mindfulness-based interventions (MBIs) are clinically effective for insomnia, but the research findings have been mixed. This meta-analysis of randomized controlled trials (RCTs) examined the effect of MBIs on insomnia. Method: Both English (PubMed, PsycINFO, Embase, and Cochrane Library databases) and Chinese (WanFang and CNKI) databases were systematically and independently searched. Standardized mean differences (SMDs) and risk ratio (RR) with their 95% confidence intervals (CIs) were calculated using the random effects model. Results: Five RCTs (n = 520) comparing MBIs (n = 279) and control (n = 241) groups were identified and analyzed. Compared to the control group, participants in the MBIs group showed significant improvement in insomnia as measured by the Pittsburgh Sleep Quality Index (n = 247; SMD: -1.01, 95% CI: -1.28 to -0.75, I2 = 0%, p < 0.00001) at post-MBIs assessment. Conclusion: In this comprehensive meta-analysis, MBIs appear to be effective in the treatment of insomnia. Further studies to examine the long-term effects of MBIs for insomnia are needed.

15.
J Pharm Biomed Anal ; 179: 112963, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31848079

RESUMO

9-Nitrocamptothecin-20-O-propionate (CZ112) and 9-Nitrocamptothecin (9NC) are the bioactive derivatives of camptothecin (CPT), an alkaloid isolated from Camptotheca acuminata, and have been confirmed to possess high anti-cancer properties. In the present study, 9NC was identified as the major metabolite of CZ112 in rat plasma through HPLC/photodiode array detection (PDA) and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. A highly sensitive LC-MS/MS method was developed and validated for the simultaneous analysis of CZ112 and 9NC in rat plasma, and camptothecin-20-O-acetate (CZ44) was used as an internal standard (IS). The calibration curves were linear (r2 > 0.999) over concentrations from 2.5 to 320 ng/mL for both CZ112 and 9NC. The method had an accuracy of 96.7-109.6%, and the intra- and inter-day precision (RSD%) were 10.9% or less for CZ112 and 9NC. The stability data showed no significant degradation occurred under the experimental conditions. This method was successfully applied to the pharmacokinetic study of CZ112 and its metabolite 9NC in rat plasma after intravenous and intragastric administration. The oral bioavailability of CZ112 was 6.2 ±â€¯3.3% (n = 6).

16.
Psychiatr Genet ; 30(1): 30-33, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31842058

RESUMO

OBJECTIVE: Major depressive disorder (MDD) is a global mental health problem. As a serotonin-noradrenaline reuptake inhibitor (SNRI), the antidepressant venlafaxine is used to alleviate MDD clinically. Recent research has shown that Cytochrome P450 (CYP) enzymes affect venlafaxine efficacy by mediating its metabolism. The present study investigates genetic polymorphisms of cytochrome P450 family 2 subfamily C member 19 (CYP2C19) are associated with remission after venlafaxine treatment for MDD. METHODS: A total of 175 Han Chinese patients with depression were recruited to accept a 6-week treatment with venlafaxine. Three single-nucleotide polymorphisms of CYP2C19 were selected from dbSNP and previous literature to compare the allele and genotype frequencies between patients in remission and nonremission. Seventeen items Hamilton Depression Scale (17-HAMD) was used to access the outcomes of patients' depressive symptoms through the study. Our results denied the role of CYP2C19 polymorphisms for remission after venlafaxine treatment in MDD patients. RESULT & CONCLUSION: CYP2C19 genetic polymorphism may not have association with SNRI venlafaxine treatment remission in the Han Chinese population.

17.
Pathol Res Pract ; : 152766, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31796334

RESUMO

OBJECTIVES: The aim of this study was to investigate the effect of Toll like receptor 4 (TLR4) on fracture healing. METHODS: The open tibial fracture models in TLR4 knockout (TLR4-/-) and wild type (WT) C57BL-6 J mice were established. The radiological examination, tartrate-resistant acid phosphatase (TRAP) staining, Micro-CT scan and biological torsion test were performed on 7, 14 and 21 days after operation. Enzyme Linked Immunosorbent Assay (ELISA) kit was used to detect the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß) and interleukin 6 (IL-6). Western blotting was used to detect the expression of ß-catenin, Wingless-type MMTV integration site family, member 4 and 5B (Wnt4 and Wnt5B), proliferating cell nuclear antigen (PCNA) and bone morphogenetic protein-2 (BMP-2) of the callus tissue obtained from mice. RESULTS: TLR4 knockout promoted fracture healing, reduced the number of osteoclasts, increased bone callus volume (BV) and callus mineralized volume fraction (BV/TV%) (P < 0.05), increased the maximum torque and torsional stiffness of callus (P < 0.05), reduced TNF-α, IL-1ß and IL-6 expression (P < 0.01), and increased the expression levels of ß-catenin, Wnt4, Wnt5B, PCNA and BMP-2 (P < 0.01). CONCLUSION: TLR4 knockout reduced inflammatory and promoted fracture healing by activating Wnt/ß-catenin signaling pathway.

18.
J Steroid Biochem Mol Biol ; 198: 105564, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31809868

RESUMO

Obesity is associated with low serum 25-hydroxyvitamin D [s25(OH)D], high serum leptin, and generally high bone mineral density (BMD). Human Marrow Stromal Cells (hMSCs) differentiate to osteoblasts and are both a target and source of vitamin D metabolites in bone marrow. There is no information about the influence of obesity on vitamin D metabolism and osteoblastogenesis in hMSCs and little about direct effects of leptin on hMSCs. In this study, we tested the hypotheses that 1) obesity has an influence on the ex vivo constitutive expression of vitamin D-hydroxylase genes in hMSCs, and 2) recombinant human (rh) Leptin regulates the D-hydroxylases and promotes osteoblastogenesis in hMSCs. In a cohort of female subjects undergoing joint replacement surgery, the effects of Body Mass Index (BMI) and Fat Mass Index (FMI) on BMD T-scores and s25(OH)D were evaluated. hMSCs were isolated from bone tissues discarded during surgery. The direct effects of rh-Leptin on osteoblast differentiation and D-related genes in hMSCs were examined in vitro. There were positive correlations for BMD T-score of femoral neck and spine with BMI and FMI. Serum 25(OH)D levels in obese subjects were 71% of that in non-obese counterparts (p = 0.001). hMSCs from obese women had higher constitutive expression of CYP27A1/25-hydroxylase and vitamin D receptor. Those findings raised the mechanistic question of how obesity could influence vitamin D metabolism and osteoblast differentiation in hMSCs. Treating hMSCs with rh-Leptin in vitro significantly stimulated osteoblastogenesis. In addition, leptin downregulated CYP24A1 and upregulated CYP27B1, CYP27A1 and VDR, which play vital roles in vitamin D metabolism. Furthermore, co-treatment with leptin and vitamin D3 metabolites promoted ALP activity compared with either alone. This research demonstrates links between obesity, vitamin D metabolism, and osteoblastogenesis by which leptin's direct effects on D-metabolism and osteoblast differentiation in hMSCs may protect bone from low s25(OH)D in obese subjects.

19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(12): 1230-1234, 2019 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-31813155

RESUMO

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) CHRNA4 gene with response to selective serotonin re-uptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD). METHODS: For 304 patients receiving drug treatment for major depression, 2 SNPs, namely rs4522666 and rs4603829, of the CHRNA4 gene were determined by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th and 6th weeks treatment. RESULTS: The frequency of GG genotype/G allele for rs4522666 differed significantly from that of TT and GT genotypes/T allele between responders and non-responders (P=0.015 and P=0.006, respectively). No significant difference was found in genotypic and allelic frequencies of rs4603829 between the two groups (P> 0.05). CONCLUSION: SNPs of the CHRNA4 gene may play an important role in the response to antidepressant drugs among ethnic Han Chinese with MDD.

20.
J Affect Disord ; 263: 129-133, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31818768

RESUMO

BACKGROUND: Few studies have estimated the prevalence and correlates of bipolar disorder (BP) in agricultural areas of China. This study examined the one-month and lifetime prevalence of BP, its subtypes and socio-demographic factors in the adult population of Hebei province, a predominantly agricultural area of China. METHODS: A multistage, stratified, cluster random sampling method was used to estimate the prevalence and correlates of BP in adults in Hebei province, China. The expanded version of the 12-item General Health Questionnaire (GHQ-12) and the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID-I/P/C) were administered to establish the diagnosis of BP. RESULTS: A total of 20,884 participants were screened. The weighted lifetime prevalence of BP, BP type I (BP-I), type II (BP-II), and BP not otherwise specified (BP-NOS) were 0.20% (95% CI: 0.14-0.26%), 0.13% (95% CI: 0.08-0.18%), 0.03% (95% CI: 0.009-0.06%) and 0.03% (95% CI: 0.009-0.06%), respectively. The weighted one-month prevalence estimates were 0.12% (95% CI: 0.08-0.17%) for BP, 0.07% (95% CI: 0.04-0.11%) for BP-I, 0.03% (95% CI: 0.006-0.05%) for BP-II, and 0.02% (95% CI: 0.003-0.04%) for BP-NOS. Multiple Poisson regression analysis revealed that positive family history of any psychiatric disorder (P<0.001, OR=6.48, 95% CI: 2.53-16.56) was significantly associated with greater risk of BP. CONCLUSION: The prevalence of BP in Hebei province appears lower than in most areas of China and other countries. Continued surveillance of BP in China along with the development of primary and tertiary preventative interventions for psychiatric disorders is indicated.

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