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1.
Food Chem ; 303: 125363, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472383

RESUMO

Present in many plant foods, biogenic phenolic compounds are important bioactive phytonutrients with high anti-oxidant activity and thereby are praised for their health-promoting properties. However, current food nutrient improvement by high phenolic content in staples is limited by the shortage of genetic resources rich in phenolic compounds. To resolve this obstacle, we developed a non-destructive massive analytical approach to screen wheat phenolic mutants. In grains, multiple mutant lines showed significantly higher contents of flavonoids or cell wall-bound phenolic esters. Moreover, five mutants showed higher anti-oxidant potentials in wall-bound phenolic compounds ranging from 15% to 20%, with the maximal close to natural black wheat. In contrast to black wheat, two mutants accumulated higher phenolic compounds in the endosperm. lrf4 was mapped by BSR to a concentrated genomic region in the short arm of chromosome 1A. The present work represents an efficient high-throughput strategy to increase wheat anti-oxidant potential through traditional mutagenesis.


Assuntos
Antioxidantes/metabolismo , Mutação , Fenóis/metabolismo , Triticum/genética , Triticum/metabolismo , Flavonoides/metabolismo
2.
J Exp Med ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699822

RESUMO

Blood-brain barrier (BBB) dysfunction has been suggested to play an important role in epilepsy. However, the mechanism mediating the transition from cerebrovascular damage to epilepsy remains unknown. Here, we report that endothelial cyclin-dependent kinase 5 (CDK5) is a central regulator of neuronal excitability. Endothelial-specific Cdk5 knockout led to spontaneous seizures in mice. Knockout mice showed increased endothelial chemokine (C-X-C motif) ligand 1 (Cxcl1) expression, decreased astrocytic glutamate reuptake through the glutamate transporter 1 (GLT1), and increased glutamate synaptic function. Ceftriaxone restored astrocytic GLT1 function and inhibited seizures in endothelial Cdk5-deficient mice, and these effects were also reversed after silencing Cxcl1 in endothelial cells and its receptor chemokine (C-X-C motif) receptor 2 (Cxcr2) in astrocytes, respectively, in the CA1 by AAV transfection. These results reveal a previously unknown link between cerebrovascular factors and epileptogenesis and provide a rationale for targeting endothelial signaling as a potential treatment for epilepsy.

3.
Chin Med J (Engl) ; 132(22): 2705-2715, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31725455

RESUMO

BACKGROUND: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. METHODS: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. RESULTS: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. CONCLUSION: Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.

4.
J Nat Prod ; 82(11): 3065-3073, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31718182

RESUMO

Natural triterpenoids, such as oleanolic acid (OA) and hederagenin, display anti-lung cancer effects, and nitric oxide (NO) is associated with some oncogenic signaling pathways. Accordingly, 17 OA/hederagenin-NO donor hybrids were designed, synthesized, and evaluated against tumor cells. The most potent compound, 13, significantly inhibited the proliferation of five tumor cell lines (IC50 4.6-5.2 µM), while hederagenin inhibited the growth of only A549 tumor cells (IC50 > 10 µM). Furthermore, compound 13 showed stronger inhibitory effects on EGFR-LTC kinase activity (IC50 0.01 µM) than hederagenin (IC50 > 20 µM) and inhibited the proliferation of gefitinib-resistant H1975 (IC50 8.1 µM) and osimertinib-resistant H1975-LTC (IC50 7.6 µM) non-small-cell lung cancer (NSCLC) cells. Moreover, compound 13 produced the most NO in H1975 tumor cells, which indicated that NO may play a synergistic role. Collectively, compound 13, a novel hederagenin-NO donor hybrid with a different chemical structure from those of the current FDA-approved EGFR-targeted anti-NSCLC drugs, may be a promising lead compound for the treatment of NSCLC expressing gefitinib-resistant EGFR with a T790 M mutation or osimertinib-resistant EGFR-LTC with an L858R/T790M/C797S mutation. This work should shed light on the discovery of new anti-NSCLC drugs targeting EGFR from natural products.

5.
Cell Death Dis ; 10(12): 879, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754182

RESUMO

Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser473 and Thr308 and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.

6.
Sci Rep ; 9(1): 16758, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728031

RESUMO

Commercial light emitting diode (LED) materials - blue (i.e., InGaN/GaN multiple quantum wells (MQWs) for display and lighting), green (i.e., InGaN/GaN MQWs for display), and red (i.e., Al0.05Ga0.45In0.5P/Al0.4Ga0.1In0.5P for display) are evaluated in range of temperature (77-800) K for future applications in high density power electronic modules. The spontaneous emission quantum efficiency (QE) of blue, green, and red LED materials with different wavelengths was calculated using photoluminescence (PL) spectroscopy. The spontaneous emission QE was obtained based on a known model so-called the ABC model. This model has been recently used extensively to calculate the internal quantum efficiency and its droop in the III-nitride LED. At 800 K, the spontaneous emission quantum efficiencies are around 40% for blue for lighting and blue for display LED materials, and it is about 44.5% for green for display LED materials. The spontaneous emission QE is approximately 30% for red for display LED material at 800 K. The advance reported in this paper evidences the possibility of improving high temperature optocouplers with an operating temperature of 500 K and above.

7.
Curr Neuropharmacol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31744451

RESUMO

Epileptogenesis refers to the process in which a normal brain becomes epileptic, and is characterized by hypersynchronous spontaneous recurrent seizures involving a complex epileptogenic network. Current available pharmacological treatment of epilepsy is generally symptomatic in controlling seizures but is not disease-modifying in epileptogenesis. Cumulative evidence suggests that adult neurogenesis, specifically in the subgranular zone of the hippocampal dentate gyrus, is crucial in epileptogenesis. In this review, we describe the pathological changes that occur in adult neurogenesis in the epileptic brain and how adult neurogenesis is involved in epileptogenesis through different interventions. This is followed by a discussion of some of the molecular signaling pathways involved in regulating adult neurogenesis, which could be potential druggable targets for epileptogenesis. Finally, we provide perspectives on some possible research directions for future studies.

8.
J Phys Chem Lett ; : 7356-7361, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31718190

RESUMO

Liquid NMR spectroscopy generally encounters two major challenges for high-resolution measurements of heterogeneous samples, namely, magnetic field inhomogeneity caused by spatial variations in magnetic susceptibility and spectral congestion induced by crowded NMR resonances. In this study, we demonstrate a spatially selective pure shift NMR approach for high-resolution probing of heterogeneous samples by suppressing effects of field inhomogeneity and J coupling simultaneously. A Fourier phase encoding strategy is proposed and implemented for spatially selective pure shift experiments to enhance signal intensity and further boost the applicability. The spatially selective pure shift method can serve as an effective tool for high-resolution probing of heterogeneous samples, thus presenting interesting prospects for extensive applications in the fields of chemistry, physics, biology, and food science.

9.
Medicine (Baltimore) ; 98(46): e17952, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725653

RESUMO

BACKGROUND: There is no consensus regarding the surgical treatment of humeral shaft fracture. The present meta-analysis was performed to compare the efficacy and safety between antegrade intramedullary nailing (IMN) and plating for humeral shaft fracture. METHODS: PubMed, MEDLINE, Cochrane Library, EMBASE, Clinical Trails, Ovid, ISI Web of Science, and Chinese databases including WanFang Data, China National Knowledge Infrastructure were searched through March 10, 2019. The Review Manager software was adapted to perform statistical analysis and relative risk (RR) were used for the binary variables, and weighted mean difference and standardized mean difference (SMD) were used to measure the continuous variables. Each variable included its 95% confidence interval (CI). RESULTS: A total of 15 trials with 839 patients were included in the analysis. There was significant difference between IMN group and plate group in blood loss (SMD = 3.49, 95% CI: 1.19, 5.79, P = .003) and postoperative infections (RR = 3.04, 95% CI: 1.49, 6.24, P = .002). Additionally, significant difference was observed between minimally invasive plate osteosynthesis (MIPO) group and IMN group in nonunion rate (RR = 3.20, 95% CI: 0.12, 0.84, P = .02). Statistical significance was also observed between the open reduction plate fixation group and IMN group in restriction of shoulder and elbow joints results (RR = 0.49, 95% CI: 0.26, 0.96, P < .05). No significant difference was observed for the operation time, American Shoulder and Elbow Surgeons score, nerve injury, delayed union, reoperation in either group. CONCLUSION: IMN may be superior to plate in reducing blood loss and postoperative infections for the treatment of humeral shaft fracture. However, MIPO was superior to IMN group in nonunion and equal to IMN in other parameters. Further research is required and future studies should include analysis of assessments at different stages and follow-up after removal of the implants.

10.
Spine J ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669615

RESUMO

BACKGROUND CONTEXT: Although the roles of Modic Changes (MCs) and disc degeneration in back pain remain controversial, clues from cadaveric studies suggest that lumbar vertebral endplate lesions may be important in back pain. Endplate lesions can be detected on magnetic resonance (MR) images as various endplate defects, including focal, corner, and erosive defects. Yet, the clinical significance of such endplate defects remains unknown. PURPOSE: To determine the prevalence and distribution patterns of lumbar vertebral endplate defects and their associations with back pain in a population-based sample. STUDY DESIGN: Cross-sectional study. PATIENT SAMPLE: Subjects were randomly selected from a typical community in Hangzhou Eastern China, regardless of back pain status. OUTCOME MEASURES: Each subject underwent a structured interview and lumbar MR imaging. Back pain history, including today, over the past 4 weeks, 12 months, and lifetime, were acquired. Endplate defects, MCs, and disc degeneration were evaluated on MRIs. Age, gender and body mass index (kg/m2), as well as lifetime exposures, including smoking history, riding in motorized vehicles and associated vibration, and occupational physical demands were assessed. METHODS: Descriptive statistics were used to depict prevalence and distribution patterns of endplate defects in the lumbar spine. Logistic regressions were used to examine associations of endplate defects with back pain. The research grant was obtained from the National Natural Science Foundation of China (115,000 USD), Key Platform Project of the Health Department of Zhejiang Province (14,000 USD), Technology Program of Traditional Chinese Medicine Department of Zhejiang Province (21,000 USD), and 2015 Qianjiang Talent Program of Zhejiang Province (7,000 USD) toward this work. There is no conflict to disclose. RESULTS: There were 478 subjects (53.3±14.4 years, range 20-88 years) studied. Endplate defects presented in 301 (63.0%) subjects and 842 (16.0%) endplates. The presence of endplate defects, but not MCs and disc degeneration, was associated with lifetime back pain (odds ratio=1.64, p=.026) in multivariate analyses. Focal and erosive endplate defects were associated with lifetime back pain history (odds ratio=1.74-2.23, p<.05 for both), whereas all three types of defects were associated with intensity of worst back pain over the past 12 months (Coef=5.84-7.19, p<.05 for all). CONCLUSIONS: Endplate defects are common findings on lumbar MRIs in adults. Specific types of endplate defects were associated with back pain history. Endplate defects may be an independent risk factor for back pain.

11.
Anal Chem ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769652

RESUMO

DOSY (Diffusion-ordered NMR spectroscopy) presents an essential tool for the analysis of compound mixtures by revealing intrin-sic diffusion behaviors of mixed components. The applicability of DOSY measurements on complex mixtures is generally limited by the performance of data reconstruction algorithms. Here, based on constraints on low rank and sparsity of DOSY data, we pro-pose a reconstruction method to achieve high-resolution DOSY spectra with excellent peak alignments and accurate diffusion coef-ficients for measurements on complex mixtures, even when component signals are congested and mixed together along the spectral dimension. This proposed method is robust and suitable for DOSY data acquired from common commercial NMR instruments, thus it may broaden the scope of DOSY applications.

12.
Orthop Surg ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773895

RESUMO

OBJECTIVE: To determine the value of Böhler's angle (BA) in a group of Chinese people, analyze possible factors that influence it, and compare BA with that in previous literature. METHODS: A total of 143 cases, aged from 4 to 79 years, were enrolled in the study, including 64 males and 79 females (79 left feet and 64 right feet). Radiographs were independently measured by six observers. Age, sex, body side, subtalar joint congruity (STJC), and X-beam obliquity (TT) were recorded. The database was assessed based on intraobserver agreement, data distribution, the randomness of case selection, and the ratio equality of binomial variables. Then, the normal value of BA was established, as well as the correlation between BA and other parameters. RESULTS: In the present study, the interobserver reliability of BA, STJC, and TT was excellent. The BA data revealed a normal distribution, and the randomness of case selection was verified for age, sex, and body side. The ratio of sex and body side was equal. Homogeneity of variance was observed when comparing the value of BA between different groups. The value of BA was 31.6° ± 5.19° (range, 20.08°-47.19°), which was not related to age, sex, body side, and minor X-ray beam obliquity. BA application was not suitable for individuals younger than 10 years. The mean value of BA in this study was not identical with those in previous reports. This demonstrated that BA varies for different races. CONCLUSION: For Chinese people, 30° to 33° is recommended as the target value of BA for calcaneal fracture reduction, except in children under 10 years of age.

13.
Microb Pathog ; 139: 103866, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715321

RESUMO

PURPOSE: This study aims to evaluate the antimicrobial activities of linezolid and radezolid against Streptococcus agalactiae in vitro and compared for genetic resistance factors. METHOD: Nonduplicate S. agalactiae clinical isolates (n = 136) were collected and the minimal inhibitory concentrations of antimicrobials were determined by agar dilution methodology. The linezolid-resistant mechanism in the clinical linezolid-non-susceptible S. agalactiae isolates and that induced by linezolid pressure in vitro were analyzed by PCR and sequence alignment. Antimicrobial activities and resistance mechanism distinctions between linezolid and radezolid were further investigated in the clinical linezolid-non-susceptible S. agalactiae isolates and that induced by linezolid pressure in vitro. RESULTS: Our data indicated that 17 (13%) of the 136 clinical S. agalactiae isolates were not susceptible to linezolid. For individual S. agalactiae isolates, including linezolid-nonsusceptible isolates with 23S rRNA V domain mutations, radezolid MIC90 values were generally one-half to one-quarter of the linezolid MIC90 values. Radezolid MICs remained low relative to linezolid MICs among linezolid-resistant S. agalactiae isolates, but exhibited the synchronous increases with the increasing copy numbers of 23S rRNA V domain mutations. Overall, 13 optrA-carrying clinical S. agalactiae isolates were found in this study and their MICs all remained sensitive to both linezolid and radezolid. Clinical S. agalactiae isolates with high radezolid MICs showed clonality clustering to sequence type (ST)10. CONCLUSION: Radezolid exhibits stronger potency against S. agalactiae than linezolid and there is a concerning presence of linezolid-nonsusceptible S. agalactiae in clinical samples.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31724840

RESUMO

Bis(diphenylphosphinomethyl)phenylphosphine (dpmp)-supported Pt2Au heterotrinuclear complexes [Pt2Au(dpmp)2(C≡CPh)4](ClO4) (1), [Pt2Au(dpmp)2(DEBf)(C≡CPh)2](ClO4) (2), and [Pt2Au(dpmp)2(DECz)(C≡CPh)2](ClO4) (3) were prepared and used in organic light-emitting diodes (OLEDs) as a new class of light emitters, where DEBf = dibenzofuran-4,6-diacetylide and DECz = 3,6-di-tert-butylcarbazole-1,8-diacetylide. Although the flexible structure of Pt2Au complex 1 (λem = 503 nm, Φem < 0.1%) results in weak photoluminescence in fluid CH2Cl2, complexes 2 (λem = 585 nm, Φem = 4.9%) and 3 (λem = 589 nm, Φem = 3.2%) with a rigid conformation give a much stronger phosphorescence. The displacement of two σ-bonded phenylacetylide ligands with a diacetylide ligand such as DEBf and DECz to fasten Pt2Au structures facilitates greatly luminescent emission so that the emissive quantum yield in doping film is as high as 89% for 2 and 93% for 3. As revealed by a theoretical study, the severe structural distortion of diacetylide-linked Pt2Au complexes 2 (λem = 585 nm) and 3 (λem = 589 nm) in a triplet excited state gives rise to significant red shifts of phosphorescent emission spectra relative to that of complex 1 (λem = 503 nm). By means of Pt2Au complexes as phosphorescent emitters, solution-processed OLEDs achieved a relatively low external quantum efficiency (EQE < 9.5%) when commercial poly(ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) was used as the hole-injection layer (HIL). In contrast, the peak EQE was increased to 18.3% with a dramatic increase of efficiency by the use of modified HILs composed of PEDOT:PSS and PSS-Na, which provide a higher work function and a better film morphology.

15.
Mol Psychiatry ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31576007

RESUMO

Compelling evidence suggests that synaptic structural plasticity, driven by remodeling of the actin cytoskeleton, underlies addictive drugs-induced long-lasting behavioral plasticity. However, the signaling mechanisms leading to actin cytoskeleton remodeling remain poorly defined. DNA methylation is a critical mechanism used to control activity-dependent gene expression essential for long-lasting synaptic plasticity. Here, we provide evidence that DNA methyltransferase DNMT3a is degraded by the E2 ubiquitin-conjugating enzyme Ube2b-mediated ubiquitination in dorsal hippocampus (DH) of rats that repeatedly self-administrated heroin. DNMT3a degradation leads to demethylation in CaMKK1 gene promotor, thereby facilitating CaMKK1 expression and consequent activation of its downstream target CaMKIα, an essential regulator of spinogenesis. CaMKK1/CaMKIα signaling regulates actin cytoskeleton remodeling in the DH and behavioral plasticity by activation of Rac1 via acting Rac guanine-nucleotide-exchange factor ßPIX. These data suggest that Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on CaMKK1 gene and thus activates CaMKK1/CaMKIα/ßPIX/Rac1 cascade, leading to drug use-induced actin polymerization and behavior plasticity.

16.
J Nutr ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31618431

RESUMO

BACKGROUND: Ectopic fat accumulation in skeletal muscle results in dysfunction and atrophy, but the underlying molecular mechanisms remain unclear. OBJECTIVE: The aim of this study was to investigate the effects of a high-fat diet (HFD) in modulating the structure and energy metabolism of skeletal muscle and the underlying mechanisms in mice. METHODS: Four-week-old male C57BL/6 J mice (n = 30) were allowed 1 wk for acclimatization. After 6 mice with low body weight were removed from the study, the remaining 24 mice were fed with a normal-fat diet (NFD; 10% energy from fat, n = 12) or an HFD (60% energy from fat, n = 12) for 24 wk. At the end of the experiment, serum glucose and lipid concentrations were measured, and skeletal muscle was collected for atrophy analysis, inflammation measurements, and phosphoproteomic analysis. RESULTS: Compared with the NFD, the HFD increased (P < 0.05) body weight (35.8%), serum glucose (64.5%), and lipid (27.3%) concentrations, along with elevated (P < 0.05) expressions of the atrophy-related proteins muscle ring finger 1 (MURF1; 27.6%) and muscle atrophy F-box (MAFBX; 44.5%) in skeletal muscle. Phosphoproteomic analysis illustrated 64 proteins with differential degrees of phosphorylation between the HFD and NFD groups. These proteins were mainly involved in modulating cytoskeleton [adenylyl cyclase-associated protein 2 (CAP2) and actin-α skeletal muscle (ACTA1)], inflammation [NF-κB-activating protein (NKAP) and serine/threonine-protein kinase RIO3 (RIOK3)], glucose metabolism [Cdc42-interacting protein 4 (TRIP10); protein kinase C, and casein kinase II substrate protein 3 (PACSIN3)], and protein degradation [heat shock protein 90 kDa (HSP90AA1)]. The HFD-induced inhibitions of the insulin signaling pathway and activations of inflammation in skeletal muscle were verified by Western blot analysis. CONCLUSIONS: Quantitative phosphoproteomic analysis in C57BL/6 J mice fed an NFD or HFD for 24 wk revealed that the phosphorylation of inflammatory proteins and proteins associated with glucose metabolism at specific serine residues may play critical roles in the regulation of skeletal muscle atrophy induced by an HFD. This work provides information regarding underlying molecular mechanisms for inflammation-induced dysfunction and atrophy in skeletal muscle.

17.
Ann N Y Acad Sci ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31647576

RESUMO

The prevalence of maternal and child overweight/obesity and gestational hyperglycemia has increased greatly in China in recent years. However, studies examining the relationship between maternal hyperglycemia, maternal prepregnancy body mass index (ppBMI), and offspring obesity in China are limited. Here, we conducted a prospective study of 6684 mother-child pairs in Wuhan, China in 2012-2015. Maternal glucose concentrations were measured at approximately 24-28 weeks of gestation; children's weight and length were measured at birth and at 6, 12, and 24 months of age; and BMI-for-age Z-scores (BMIZ) were calculated for different time points. We found that maternal fasting plasma glucose (FPG) concentrations were positively associated with offspring ponderal index and the risk of macrosomia at birth, but not with BMIZ or the risk of overweight/obesity at 6, 12, and 24 months of age. By contrast, maternal ppBMI was positively associated with both an increased risk of macrosomia at birth and overweight/obesity at 6, 12, and 24 months of age. Here, we observed an interaction effect of the association of FPG and ppBMI on offspring macrosomia and a mediating effect of gestational diabetes mellitus on the pathway between ppBMI and macrosomia. Our findings suggest that maternal ppBMI is a more pronounced predictor than gestational FPG concentrations in both the relation to BMIZ and the risk of overweight/obesity in early childhood.

18.
Arch Biochem Biophys ; 676: 108125, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31586554

RESUMO

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder occurred in pregnant women, and the mechanism for such disease is still unclear. The bioinformatics analysis of our previous study has revealed the abnormal expression of endoplasmic reticulum protein 29 (ERp29) in placental tissue of ICP patients. In this study, the function of ERp29 was further explored using in vitro model of ICP. The results showed that up-regulation of ERp29 occurred in TCA (taurocholic acid)-treated human trophoblast HTR-8/SVeno cells, and ERp29 inhibition reversed TCA toxicity via attenuating G2/M arrest and cell apoptosis. Mechanical study revealed ERp29 inhibition suppressed phosphorylation and kinase activity of p38, thus subsequently affecting expression and phosphorylation of p53 (ser18) as well as the transcriptional activity of p53. The conduction of this study might confirm the important role of ERp29 in ICP and which would be helpful for the development of target therapeutic method for ICP.

19.
Biochem Biophys Res Commun ; 520(1): 122-127, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31582217

RESUMO

A wealth of studies illustrate the powerful antioxidant activities and health-promoting functions of dietary phenolic compounds, e.g., anthocyanins, flavonoids, and phenolic compounds. Ferulate is methylated from caffeoyl CoA using S-adenosyl-L-methionine (SAM) as methyl donor catalyzed by caffeoyl CoA methyltransferase (CCoAOMT). Here we show that Arabidopsis CCoAOMT7 contributes to ferulate content in the stem cell wall. CCoAOMT7 was further shown to bind S-adenosyl-L-homocysteine hydrolase (SAHH), a critical step in SAM synthesis to release feedback suppression on CCoAOMT. CCoAOMT7 also bound S-adenosyl-L-methionine synthases (SAMSs) in vivo, which were mediated by SAHH1. Interruptions of endogenous SAHH1 by artificial miRNA or SAMSs by T-DNA insertion significantly reduced ferulate contents in the stem cell wall. This data reveals a novel protein complex of SAM synthesis cycle associated with O-methyltransferase and provides new insights into cellular methylation processes.

20.
J Neurosci ; 39(46): 9130-9144, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31604834

RESUMO

Neuropathic pain is one of the most common and notorious neurological diseases. The changes in cerebral structures after nerve injury and the corresponding contributions to neuropathic pain are not well understood. Here we found that the majority of glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) were inhibited by painful stimulation in male mice. Optogenetic manipulation revealed that these neurons were tonically involved in the inhibitory modulation of multimodal nociception. We further identified the projections to GABAergic neurons in the zona incerta (ZIGABA) mediated the pain inhibitory role. However, MCC Cg2Glu became hypoactive after nerve injury. Although a brief activation of the MCC Cg2Glu to ZIGABA circuit was able to relieve the aversiveness associated with spontaneous ongoing pain, consecutive activation of the circuit was required to alleviate neuropathic allodynia. In contrast, glutamatergic neurons in the area 1 of MCC played opposite roles in pain modulation. They became hyperactive after nerve injury and only consecutive inhibition of their activity relieved allodynia. These results demonstrate that MCC Cg2Glu constitute a component of intrinsic pain inhibitory circuitry and their hypoactivity underlies neuropathic pain. We propose that selective and persistent activation of the MCC Cg2Glu to ZIGABA circuit may serve as a potential therapeutic strategy for this disease.SIGNIFICANCE STATEMENT Glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) are tonically involved in the intrinsic pain inhibition via projecting to GABAergic neurons in the zona incerta. They are hypoactive after nerve injury. Selective activation of the circuit compensates the reduction of its analgesic strength and relieves neuropathic pain. Therefore, MCC Cg2Glu and the related analgesic circuit may serve as therapeutic targets for neuropathic pain. In contrast, MCC Cg1Glu have an opposite role in pain modulation and become hyperactive after nerve injury. The present study provides novel evidence for the concept that neuropathic pain is associated with the dysfunction of endogenous pain modulatory system and new perspective on the treatment of neuropathic pain.

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