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1.
Acta Pharmacol Sin ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424239

RESUMO

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 µg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.

2.
Poult Sci ; 99(5): 2533-2542, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359589

RESUMO

In documents, maternal betaine modulates hypothalamic cholesterol metabolism in chicken posthatchings, but it remains unclear whether this effect can be passed on by generations. In present study, eggs were injected with saline or betaine at 2.5 mg/egg, and the hatchlings (F1) were raised under the same condition until sexual maturation. Both the control group and the betaine group used artificial insemination to collect sperm from their cockerels. Fertilized eggs were incubated, and the hatchlings of the following generation (F2) were raised up to 64 D of age. F2 cockerels in betaine group showed significantly (P < 0.05) lower body weight, which was associated with significantly decreased (P < 0.05) hypothalamic content of total cholesterol and cholesterol ester. Concordantly, hypothalamic expression of cholesterol biosynthetic genes, SREBP2 and HMGCR, were significantly downregulated (P < 0.05), together with cholesterol conversion-related and excretion-related genes, CYP46A1 and ABCA1. These changes coincided with a significant downregulation in mRNA expression of regulatory neuropeptides including brain-derived neurotrophic factor, neuropeptide Y, and corticotropin-releasing hormone. Moreover, genes involved in methyl transfer cycle were also modified. Betaine homocysteine methyltransferase (P < 0.05) was downregulated, yet DNA methyltransferase1 tended to be upregulated (P = 0.06). S-adenosyl methionine/S-adenosylhomocysteine ratio was higher in the hypothalamus of betaine-treated F2 cockerels, which was associated with significantly modified CpG methylation on the promoter of those affected genes. These results suggested that betaine might regulate central cholesterol metabolism and hypothalamic expression of genes related to brain function by altering promoter DNA methylation in F2 cockerels.

4.
Science ; 368(6492)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32409445

RESUMO

Song et al (Reports, 14 February 2020, p. 777) ignore the reported efficient Ni/MgO solid-solution catalysts and overstate the novelty and importance of the Mo-doped Ni/MgO catalysts for the dry reforming of methane. We show that the Ni/MgO solid-solution catalyst that we reported in 1995, which is efficient and stable for the dry reforming, is superior to the Mo-doped Ni/MgO catalyst.

5.
Diabetes ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409491

RESUMO

Maternal stress during pregnancy exposes fetuses to hyper glucocorticoids (GC), which increases the risk of metabolic dysfunctions in offspring. Despite of being a key tissue for maintaining metabolic health, the impacts of maternal excessive GC on fetal brown adipose tissue (BAT) development and its long-term thermogenesis and energy expenditure remain unexamined. To test, pregnant mice were administrated with dexamethasone (DEX), a synthetic GC, in the last trimester of gestation, when BAT development is the most active. DEX offspring had glucose, insulin resistance and adiposity, also displayed cold sensitivity following cold exposure. In BAT of DEX offspring, Ppargc1a expression was suppressed, together with reduced mitochondrial density, and the brown progenitor cells sorted from offspring BAT demonstrated attenuated brown adipogenic capacity. Increased DNA methylation in Ppargc1a promoter had a fetal origin because elevated DNA methylation was also detected in neonatal BAT and brown progenitors. Mechanistically, fetal GC exposure increased GC receptor (GR)/DNMT3b complex in binding to the Ppargc1a promoter, potentially driving its de novo DNA methylation and transcriptional silencing, which impaired fetal BAT development. In summary, maternal GC exposure during pregnancy increases DNA methylation in the Ppargc1a promoter, which epigenetically impairs BAT thermogenesis and energy expenditure, predisposing offspring to metabolic dysfunctions.

6.
J Xray Sci Technol ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32417830

RESUMO

OBJECTIVE: To evaluate skeletal and dental changes in patients with skeletal Class III malocclusion and facial asymmetry after surgical-orthodontic treatment using cone-beam computerized tomography (CBCT). METHODS: This study included forty adult patients diagnosed with skeletal Class III malocclusion and asymmetry who underwent either isolated mandibular surgery or bimaxillary surgery. CBCT scans were taken before treatment (T0), at the completion of presurgical orthodontic treatment (T1) and after treatment (T2). Mimics 17.0 and 3-Matics 7.0 were used to measure skeletal and dental parameters. Skeletal and dental changes within each group from pretreatment to posttreatment were assessed, and Pearson correlation analysis was used to analyze the correlations among skeletal changes. RESULTS: The three-dimensional changes in condylar position were insignificant after surgical-orthodontic treatment in either group (P > 0.05). However, in the one-jaw surgery group, there were significant backward rotations of the condyle and ramus on the nondeviated side (P < 0.05), and the condyle on the deviated side rotated inward and forward significantly in the two-jaw surgery group (P < 0.05) at T2. There were no significant differences in the changes in the total alveolar bone thickness of bilateral first molars during dental decompensation (P > 0.05). The ratio between the buccal and the total bone thickness around the maxillary first molar on the deviated side decreased significantly at T1, as did those around the mandibular first molar on the nondeviated side (P < 0.05). CONCLUSIONS: Condylar angulations were less stable after treatment (7 to 9 months after surgery) in both the one-jaw and the two-jaw surgery groups, while condylar displacements were insignificant. In addition, orthodontists should keep a watchful eye to the relative position of the root in the alveolar bone during tooth decompensation.

7.
J Contemp Dent Pract ; 21(1): 105-112, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32381810

RESUMO

AIM: To test the hypothesis that skeletal and dentoalveolar effects are both important in skeletal class II malocclusion corrected with the Forsus fatigue-resistant device (FRD). MATERIALS AND METHODS: A total of 35 patients (16 females and 19 males; age 12.0 ± 0.6 years) with skeletal class II malocclusion treated with the Forsus FRD were included. Lateral cephalometric radiographies before and after treatment were collected. Cephalometric analysis and superimpositions were applied. Pancherz's analysis was performed to discover the skeletal and dentoalveolar effects on all patients and 60% contribution was set as a milestone to classify. Statistical comparisons were performed by paired t testing (p < 0.05). RESULTS: The mean treatment period of the Forsus FRD was 6.4 ± 0.2 months. All patients (AG) have been corrected to class I molar relationship in three mechanisms: 15 patients in the skeletal group (SG), 10 patients in the dentoalveolar group (DG), and 10 patients in the skeletal and dentoalveolar group (SDG). Four groups showed a significant change in skeletal sagittal relationship improvement (p < 0.05). The AG, SG, and SDG showed a significant improvement in the growth of the mandible (Co-Go, Go-Pog, and Co-Gn, p < 0.05). The DG showed a significant improvement in the growth of the mandibular body (Go-Pog, p < 0.05). CONCLUSION: Three mechanisms were found in skeletal class II malocclusion corrected with the Forsus FRD. Skeletal and dentoalveolar effects are both important in skeletal class II malocclusion corrected with the Forsus FRD. And skeletal and dentoalveolar effects played differential roles in different cases. CLINICAL SIGNIFICANCE: The mechanism of skeletal class II correction with Forsus FRD may divide into mandibular growth, dentoalveolar effects, and both.


Assuntos
Má Oclusão de Angle Classe II , Aparelhos Ortodônticos Funcionais , Cefalometria , Feminino , Humanos , Masculino , Mandíbula , Radiografia
8.
Cancer Immunol Res ; 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299915

RESUMO

Immune checkpoint inhibitors, such as anti-PD-1/PD-L1, have emerged as promising therapies for advanced non-small-cell lung cancer (NSCLC). However, approximately 80% of patients do not respond to immunotherapy given alone because of intrinsic or acquired resistance. Radiotherapy (XRT) can overcome PD-1 resistance and improve treatment outcomes, but its efficacy remains suboptimal. The tyrosine phosphatase SHP-2, expressed in some cancers and in immune cells, has been shown to negatively affect antitumor immunity. Our hypothesis was that SHP-2 inhibition in combination with anti-PD-L1 would enhance immune-mediated responses to XRT and synergistically boost antitumor effects in an anti-PD-1-resistant mouse model. We treated 129Sv/Ev mice with anti-PD-1-resistant 344SQ NSCLC adenocarcinoma with oral SHP099 (a SHP-2 inhibitor) combined with XRT and intraperitoneal anti-PD-L1. Primary tumors were treated with XRT (3 fractions of 12 Gy each), whereas abscopal (out-of-field) tumors were observed but not treated. XRT in combination with SHP099 and anti-PD-L1 promoted local and abscopal responses, reduced lung metastases, and improved mouse survival. XRT also increased SHP-2+ M1 tumor-associated macrophages in abscopal tumors (P=0.019). The addition of SHP099 also associated with a higher M1/M2 ratio, greater numbers of CD8+ T cells, and fewer regulatory T cells. This triple-combination therapy had strong antitumor effects in a mouse model of anti-PD-1-resistant NSCLC and may be a novel therapeutic approach for anti-PD-1-resistant NSCLC in patients.

10.
J Colloid Interface Sci ; 574: 110-121, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32311534

RESUMO

Ag/g-C3N4 plasmonic photocatalysts with porous structure (Ag/PCN) were successfully synthesized via a thermal exfoliation strategy and photo-reduction method. Owing to the combined merits of porous structure and surface plasmon resonance effect of silver nanoparticles, the Ag/PCN catalysts exhibited excellent photocatalytic performance for the degradation of antibiotic agents. With the optimal Ag loading, the Ag/PCN-2 catalyst exhibited the optimal catalytic activity for TC degradation under visible light, which shows about 11.8 times enhancement in the photocatalytic removal efficiency as compared to pure g-C3N4, respectively. This phenomenon can be attributed to the increased specific surface area, broadened visible light absorption and improved charge separation. The radical quenching results confirmed that h+ and O2- radicals were the major active species during removal of TC. The degradation of TC is increased with the increment of Ag/PCN-2 catalysts, and the optimum catalyst was found to be 1.67 g/L. The hindering effect of selected of anions (Cl-, CO3-, H2PO4-) was found to follow the order H2PO4- > CO3- > Cl-. Ag/PCN-2 sample also possessed high stability after six cycles of reuses. Furthermore, the possible degradation pathways of TC and photocatalytic mechanism over Ag/PCN-2 were proposed in detail.

12.
Cell Mol Immunol ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32235916

RESUMO

Toll-like receptor (TLR) signaling pathways need to be tightly controlled to avoid excessive inflammation and unwanted damage to the host. Myeloid differentiation primary response gene 88 (MyD88) is a critical adaptor of TLR signaling. Here, we identified the speckle-type POZ protein (SPOP) as a MyD88-associated protein. SPOP was recruited to MyD88 following TLR4 activation. TLR4 activation also caused the translocation of SPOP from the nucleus to the cytoplasm. SPOP depletion promoted the aggregation of MyD88 and recruitment of the downstream signaling kinases IRAK4, IRAK1 and IRAK2. Consistently, overexpression of SPOP inhibited the TLR4-mediated activation of NF-κB and production of inflammatory cytokines, whereas SPOP depletion had the opposite effects. Furthermore, knockdown of SPOP increased MyD88 aggregation and inflammatory cytokine production upon TLR2, TLR7 and TLR9 activation. Our findings reveal a mechanism by which MyD88 is regulated and highlight a role for SPOP in limiting inflammatory responses.

13.
Phys Chem Chem Phys ; 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32307497

RESUMO

Direct splitting of water over semiconductors under sunlight irradiation would be a promising approach for hydrogen production and solar energy utilization. In this work, BlueP/PN with a 2D van der Waals (vdW) heterostructure is proposed as a novel catalyst for the Z-scheme photocatalytic system. Its electronic structures, optical properties, and combined configuration were systematically evaluated by hybrid density functional theory (DFT) calculations. It was revealed that the 2D vdW heterostructure of BlueP/PN can play an important role in water splitting under visible light irradiation. This predicts a novel design of P-based vdW heterostructures for efficient photocatalysts.

14.
ACS Nano ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32330000

RESUMO

Atomically dispersed metal and nitrogen co-doped carbon (M-N/C) catalysts hold great promise for electrochemical CO2 conversion. However, there is a lack of cost-effective synthesis approaches to meet the goal of economic mass production of single-atom M-N/C with desirable carbon support architecture for efficient CO2 reduction. Herein, we report facile transformation of commercial carbon nanotube (CNT) into isolated Fe-N4 sites anchored on carbon nanotube and graphene nanoribbon (GNR) networks (Fe-N/CNT@GNR). The oxidization-induced partial unzipping of CNT results in the generation of GNR nanolayers attached to the remaining fibrous CNT frameworks, which reticulates a hierarchically mesoporous complex and thus enables a high electrochemical active surface area and smooth mass transport. The Fe residues originating from CNT growth seeds serve as Fe sources to form isolated Fe-N4 moieties located at the CNT and GNR basal plane and edges with high intrinsic capability of activating CO2 and suppressing hydrogen evolution. The Fe-N/CNT@GNR delivers a stable CO Faradaic efficiency of 96% with a partial current density of 22.6 mA cm-2 at a low overpotential of 650 mV, making it one of the most active M-N/C catalysts reported. This work presents an effective strategy to fabricate advanced atomistic catalysts and highlights the key roles of support architecture in single-atom electrocatalysis.

15.
Am J Reprod Immunol ; 83(6): e13239, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215978

RESUMO

PROBLEM: Dendritic cells are the primary antigen-presenting cells that contact trophoblasts at the beginning of pregnancy. Excessive DCs maturity is described in some pregnancy complications, such as pre-eclampsia and fetal growth restriction, which are characterized by impaired trophoblast invasion. However, the mechanism is unclear. The long non-coding RNA long non-coding RNA DC (lnc-DC) is expressed exclusively in conventional human DCs and induces DC differentiation and maturation by promoting signal transducer and activator of transcription 3 (STAT3) phosphorylation. Our previous investigation proved lnc-DC and p-STAT3 are elevated in pre-eclampsia. This research is to study the mechanism of lnc-DC and trophoblast invasion. METHOD OF STUDY: We transfected DCs with lnc-DC shRNA or a lentivirus for lnc-DC overexpression and cocultured these treated DCs with trophoblast under different conditions. Transwell assay and wound healing assay were used to detect the trophoblast invasion ability. We also tested the matured DCs and Th1 cells as well as the p-STAT3. RESULTS: We found that lnc-DC promoted DC maturation and inhibited trophoblast invasion without the involvement of CD4+ T cells. And the p-STAT3 agonist could reverse the lnc-DC function. CONCLUSION: Mature DCs may be involved in altering trophoblast invasion through the overexpression of lnc-DC, which increases p-STAT3 levels and the tissue inhibitor of metalloproteinase-1 (TIMP-1)/matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-2 (TIMP-2)/matrix metalloproteinase-2 (MMP-2) ratios. Thus, lnc-DC is a promising novel target for regulating trophoblast invasion.

16.
Nat Cell Biol ; 22(4): 425-438, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203416

RESUMO

Piwi proteins are normally restricted in germ cells to suppress transposons through associations with Piwi-interacting RNAs (piRNAs), but they are also frequently activated in many types of human cancers. A great puzzle is the lack of significant induction of corresponding piRNAs in cancer cells, as we document here in human pancreatic ductal adenocarcinomas (PDACs), which implies that such germline-specific proteins are somehow hijacked to promote tumorigenesis through a different mode of action. Here, we show that in the absence of piRNAs, human PIWIL1 in PDAC functions as an oncoprotein by activating the anaphase promoting complex/cyclosome (APC/C) E3 complex, which then targets a critical cell adhesion-related protein, Pinin, to enhance PDAC metastasis. This is in contrast to piRNA-dependent PIWIL1 ubiquitination and removal by APC/C during late spermiogenesis. These findings unveil a piRNA-dependent mechanism to switch PIWIL1 from a substrate in spermatids to a co-activator of APC/C in human cancer cells.


Assuntos
Adenocarcinoma/genética , Proteínas Argonauta/genética , Carcinoma Ductal Pancreático/genética , Moléculas de Adesão Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , RNA Interferente Pequeno/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Anáfase , Ciclossomo-Complexo Promotor de Anáfase/genética , Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Animais , Proteínas Argonauta/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Knockout , Camundongos Nus , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Espermatogênese/genética , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Appl Toxicol ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167196

RESUMO

The potential toxicity of cadmium-containing quantum dots (QDs) has received much attention because of increasing biomedical applications. However, little has been known about how cadmium telluride (CdTe) QDs influence the gut microbiota and lipid metabolism. In this study, mice were exposed orally to CdTe QDs (200 µL of 0.2, 2, 20 or 200 µm; twice per week) for 4 weeks. The oral experiments showed CdTe QD exposure led to a decrease of the Firmicutes/Bacteroidetes (F/B) ratio of gut microbiota, which highly negatively correlated with the low-density lipoprotein (LDL), triglyceride (TG) and total cholesterol (TC) levels in serum. In addition, the low-dose (0.2 and 2 µm) CdTe QDs significantly increased the diversity of gut microbiota, and did not elevate the LDL, TG and TC levels in serum. The medium dose (20 µm) of CdTe QDs caused the biggest decrease of the F/B ratio, so it significantly increased the LDL, TG and TC levels compared with the control. Furthermore, high-dose (200 µm) CdTe QDs caused various toxicities in the histopathology of liver and intestine, liver function and intestinal immunity, but did not significantly lead to changes of the LDL, TG and TC levels in serum. This study demonstrates that high-dose oral CdTe QDs mainly lead to tissue damage of the liver and intestine, while the medium and low doses of oral CdTe QDs induce shifts of gut microbiota structure, which are associated with blood lipid levels.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32127793

RESUMO

Brown adipose tissue (BAT) can convert fatty acids and glucose into heat, exhibiting the potential to combat obesity and diabetes. The mass and activity of BAT gradually diminishes with aging. As a newly found regulator of gene expression, long non-coding RNAs (lncRNAs) exhibit a wide range of functions in life processes. However, whether long non-coding RNA (lncRNA) involves in BAT dysfunction with aging is still unclear. Here, using RNA-sequencing technology, we identified 3237 messenger RNAs (mRNAs) and 1312 lncRNAs as differentially expressed in BAT of 10-months-old mice compared with 6- to 8-week-old. The protein-protein interaction network and k-score analysis revealed that the core mRNAs were associated with two important aging-related pathways, including cell cycle and p53 signaling pathway. Gene set enrichment analysis indicated that these mRNAs might participate in lipid metabolism and brown fat dysfunction. Functional enrichment analyses demonstrated that dysregulated lncRNAs were associated with mitochondria, regulation of cellular senescence, cell cycle, metabolic and p53 signaling pathways. Moreover, we revealed that two lncRNAs (NONMMUT024512 and n281160) may involve in the regulation of their adjacent gene peroxisome proliferator-activated receptor alpha (Pparα), a thermogenesis regulator. Collectively, these results lay a foundation for extensive studies on the role of lncRNAs in age-related thermogenic degradation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32219984

RESUMO

Fast, mass, and low-cost production of high-quality graphene, which is alluring, remains a great challenge, even though some approaches have shown potential for mass synthesis of graphene. Very recently a great breakthrough was made by Tour and co-workers (Nature 2020, 577, 647-651): in just a second, easily exfoliated and highly crystalline graphene was produced from abundant carbon-containing species by cost-effective flash Joule heating with a low energy input of 7.2 kJ per gram graphene. Such an ultrafast, economic, and scalable process for high-quality graphene production can be considered as a milestone in the graphene field and is highlighted in this article.

20.
Curr Med Imaging ; 16(3): 214-223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133951

RESUMO

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is a common abnormality among patients in T2DM. AIMS: We aimed to evaluate the feasibility of coronary computed tomography angiography (CCTA) for the assessment of LVDD in type 2 diabetes mellitus (T2DM) patients. METHODS: 80 consecutive T2DM patients who were referred for a clinically dual-source CCTA examination to evaluate suspected coronary artery disease and also underwent 2D echocardiography within 7 days of CCTA inclusion and exclusion criteria, were performed. Correlation between CCTA and echocardiography was tested through linear regression and Bland-Altman analysis. RESULTS: In total, 60 T2DM patients were included for the analysis. Pearson correlation showed good correlation for E (r = 0.28; P = 0.028), E/A (r = 0.69; P < 0.01); E (r = -0.06; P = 0.776), E/A (r = 0.54; P = 0.003) and E (r = 0.64; P < 0.01), E/A (r = 0.83; P < 0.01) in three groups, respectively. Overall, diagnostic accuracy for assessment in CCTA of diastolic dysfunction was 79.76% (95% CI: 68%-91%), 71.43% (95% CI: 58%-85%) and 87.50 (95% CI: 79%-96%) in three groups. CONCLUSION: The presented study proved that CCTA showed good correlations in the estimation of LV filling pressures compared with echocardiography in T2DM patients. Accordingly, retrospectively ECG-gated CCTA may provide valuable information on the evaluation of LVDD in T2DM patients.

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