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1.
Mol Carcinog ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793679

RESUMO

The high incidence and mortality of esophageal squamous cell cancer (ESCC) is a major health problem worldwide. Precancerous lesions of ESCC may either progress to cancer or revert to normal epithelium with appropriate interventions; the bidirectional instability of the precancerous lesions of ESCC provides opportunities for intervention. Reports suggest that the upregulation of ornithine decarboxylase (ODC) is closely related to carcinogenesis. In this study, we investigated whether ODC may act as a target for chemoprevention in ESCC. Immunohistochemistry (IHC) assays indicate that ODC expression is higher in esophageal precancerous lesions compared with normal tissue controls. Its overexpression promotes cell proliferation and transformation of normal esophageal epithelial cells, and its activity is increased after N-nitrosomethylbenzylamine (NMBA) induction in Shantou human embryonic esophageal cell line (SHEE) and human immortalized cells (Het1A) cells. In addition, p38 α, extracellular regulated kinase (ERK1/2) in the mitogen-activated protein kinase pathway and protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K) pathways are activated in response to NMBA treatment. Difluoromethylornithine (DFMO) is an ODC inhibitor, which inhibits NMBA-induced activation of p38 α, ERK1/2 and AKT/mTOR/p70S6K pathways; this has been verified by Western blotting. DFMO was also found to suppress the development of esophageal precancerous lesions in an NMBA-induced rat model; IHC demonstrated p38 α, ERK1/2, and AKT/mTOR/p70S6K pathways to be downregulated in these rats. These findings indicate the mechanisms by which ODC inhibition suppresses the development of esophageal precancerous lesions by downregulating p38 α, ERK1/2, and AKT/mTOR/p70S6k signaling pathways, ODC may be a potential target for chemoprevention in ESCC.

2.
Mol Med Rep ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31789419

RESUMO

Several microRNAs (miRNAs) are known as regulatory molecules involved in gastric tumor metastasis. The expression of miR­337­3p was revealed to be downregulated in metastatic gastric tumor cells. Overexpression of miR­337­3p in gastric cancer cells resulted in the reduction of their invasive abilities. To characterize the functions of miR­337­3p, miR­337­3p was expressed in a metastatic lymph node­derived gastric tumor cell line, SGC­7901. Overexpression of miR­337­3p reduced the viability of cells but had no effects on the cell cycle. Wound healing and Transwell migration assays revealed that miR­337­3p inhibited the migration capacity of cells. miR­337­3p was capable of binding to the 3'­untranslated region of a cytoskeleton­associated molecule, ARHGAP10. Overexpression of miR­337­3p reduced the mRNA and protein levels of ARHGAP10 and the co­expression of ARHGAP10 and miR­337­3p resulted in the recovery of cell migration capacity. Furthermore, the injection of miR­337­3p­overexpressing SGC­7901 cells into an immunodeficient mouse model resulted in a decrease in tumor metastasis in the liver and lungs. The present results indicated that miR­337­3p regulates gastric tumor metastasis by targeting the cytoskeleton­associated protein ARHGAP10.

3.
BMC Public Health ; 19(1): 1603, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791295

RESUMO

BACKGROUND: An exclusive breastfeeding rate in the first 6 months of life of at least 50% is one of the six World Health Organization global nutrition targets for 2025. However, the exclusive breastfeeding rate in China is quite low and decreasing which makes it urgent to explore effective ways to reverse the current downward trend. As mobile technologies have rapidly developed, mobile communication apps such as WeChat (one of the largest social networking platforms in China) are well accepted and have the potential to improve health behaviors in a convenient way. The current paper describes the study protocol of a WeChat intervention that aims to promote breastfeeding in rural areas in China. METHODS: The study is designed as a randomized controlled trial in rural Qinghai Province, China. Women who are 14-36 weeks pregnant will be randomized to routine antenatal and postnatal care, or routine care plus the WeChat breastfeeding education. pregnant women with a severe disease and complications of pregnancy or HIV-1 will be excluded. Breastfeeding knowledge and promotion information will be delivered to the intervention group through a WeChat official account from 3 months pregnancy to 6 months postpartum. The outcome assessments are conducted at baseline through face-to-face interviews, and at one week, 1 month, 3 months and 6 months postpartum by telephone interviews. The primary outcome is difference in the exclusive breastfeeding rate at 1 month, 3 months, and 6 months postpartum between the intervention group and the control group. Secondary outcomes include the overall duration of any and exclusive breastfeeding across the first 6 months postpartum; mothers' knowledge of breastfeeding; the proportion of early initiation of breastfeeding; and the timing of the introduction of solid food to infants. Intention-to-treat-analysis will be used. Survival analysis will be used to compare the overall duration of any and exclusive breastfeeding between groups. DISCUSSION: This study is the first effort to promote exclusive breastfeeding through WeChat in China. Our results will provide scientific evidence for the effect of health education through WeChat on breastfeeding. Thereby this may offer a comprehensive intervention to promote exclusive breastfeeding in China and other settings. TRIAL REGISTRATION: Chinese Clinical Trial Registry -ChiCTR1800017364. Registered 26 July 2018. http://www.chictr.org.cn/showproj.aspx?proj=29325.

4.
J Nanobiotechnology ; 17(1): 118, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791353

RESUMO

BACKGROUND: Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca2+ concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca2+ concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy. RESULTS: The as-made NaCl-DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca2+ concentration. Changes of Ca2+ broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl-DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect. CONCLUSIONS: This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.

5.
AJR Am J Roentgenol ; 213(6): W293, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31755765
6.
Artigo em Inglês | MEDLINE | ID: mdl-31683465

RESUMO

PURPOSE: The aim of this study was to evaluate the diagnostic value of conventional sonography and ultrasound elastography for thyroid nodules of each Bethesda category and to analyze their potential role in the corresponding management decision. METHODS: This retrospective study included 557 thyroid nodules diagnosed by conventional ultrasound (US) and real-time ultrasound elastography (RTE) before fine-needle aspiration (FNA) from 458 patients. The US, RTE, and cytological results were collected and analyzed according to different Bethesda categories. Differences in the distribution of sonographic features between groups were evaluated by the Chi-square test or Fisher exact test. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of conventional US and RTE for the diagnosis of malignant nodules in each category were then calculated and analyzed. RESULTS: The diagnostic accuracy of the comprehensive US diagnosis in all categories stayed at a relatively high level from 78.4% to 88.6%, and good specificities ranging from 77.3% to 100% were revealed in all Bethesda categories. As to RTE, the diagnostic accuracies in categories I-IV stayed at a relatively low level ranging from 44.6% to 65.6% except for better performance in categories V and VI (85.2%, 89.1%). Besides, the accuracies of comprehensive US (85.2%, 88.6%) and RTE (85.2%, 89.1%) is relatively low compared to the corresponding cytological diagnoses in categories V and VI. CONCLUSIONS: Conventional US is complementary to FNA for providing additional hints especially in categories I-IV for further clinical managements, while RTE failed to provide useful diagnostic information in general.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31668372

RESUMO

Circular RNAs (circRNAs) are a new class of noncoding RNAs, play a crucial role in tumor initiation and development. Hsa_circ_0001546 is a novel circular RNA that was downregulated in gastric cancer (GC) tissues, however its function and mechanism in GC has not been studied. Our study verified that circ_0001546 was decreased in GC and correlated with the poor prognosis. Next, Pull-down assay and dual-luciferase reporter assay verified that miR-421 was a target of circ_0001546 while ATM (Ataxia telangiectasia mutated) was target by miR-421. Overexpression of circ_0001546 inhibited the proliferation and chemoresistance of HGC-27 cells, and increased the expression of ATM. In addition, circ_0001546 overexpression reversed the effect of miR-421 overexpression. What is more, circ_0001546 inhibits the chemoresistance of HGC-27 cells to L-OPH (Oxaliplatin) may through the activation of the ATM/checkpoint kinase 2 (Chk2)/p53-dependent signaling pathway. In summary, our study proved that circ_0001546 sponges miR-421 to upregulate the expression level of ATM and inhibit the proliferation and chemoresistance through the activation of the ATM/Chk2/p53-dependent pathway.

8.
J Fam Psychol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670561

RESUMO

The socialization of emotion in preschool-aged children is an important developmental task, which is associated with a number of socioemotional outcomes. This study examined the contribution of both fathers' and mothers' emotion coaching to their 3- to 4-year-old children's emotion socialization. Two time points of data were collected for 69 families. We employed a time sampling observational method to capture the emotion socialization process in the naturalistic home environment. Fathers' and mothers' emotion coaching and expression, as well as children's emotion expression, were assessed at home using an audio recording device. Children's emotion expressions were also captured during an emotion eliciting task in a lab setting 1 year later. Regression analyses revealed that children of more positively expressive fathers also showed more positive emotion expression concurrently. Paternal emotion coaching, but not maternal emotion coaching, was predictive of children's increased positive expression in the lab 1 year later. This study provides evidence for unique contributions of fathers, above and beyond mothers, to the emotion socialization outcomes of their children. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

9.
Biomacromolecules ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31742385

RESUMO

The α-chitin nanofibril is an alternative to nanocellulose as a building-block for strong films and other nanomaterials. The hypothesis of high film strength for films based on mildly treated insect cuticles was tested. Fibrils from the cuticle of Ruspolia differens (a long-horned bush cricket grasshopper locally known as senene) are disintegrated by a mild process, subsequently characterized by transmission electron microscopy, NMR, Fourier transform infrared spectroscopy, and XRD, and used to prepare strong and transparent films. A mild process (with 20% NaOH treatment for 2 weeks and at room temperature) was used to largely remove the strongly bound protein associated with chitin. The purpose was to reduce chitin degradation. The native structure of chitin was indeed well preserved and close to the native state, as is supported by data for degree of acetylation, molar mass, crystallinity, and crystallite dimensions. The diameter of the smallest chitin fibrils was as small as 3-7 nm (average 6 nm) with lengths larger than or around 1 µm. A stable and well-dispersed colloidal chitin fibril suspension in water was achieved. A nanostructured chitin film prepared by filtration showed high optical transmittance (∼90%) and very high tensile strength (220 MPa). The high tensile strength was attributed to the well-preserved chitin structure, high intrinsic fibril strength, and high colloidal stability of the fibril suspension. Strong, transparent insect chitin films offer interesting alternatives to nanocellulose films because of different resource origins, surface chemistries, and potential antimicrobial properties.

10.
Environ Toxicol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769605

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) are authorized food additives, and children have the highest exposure. Therefore, children are likely more susceptible to the adverse effects of TiO2 NPs than adults. Previous study showed that oral administration of 50 mg/kg body weight (bw) TiO2 NPs increase plasma glucose in mice. However, few studies have directly compared the adverse effects of exposure to TiO2 NPs on plasma glucose metabolism of different age groups. In this study, the developing (age 3 weeks) and adult mice (age 10 weeks) were orally administered with 50 mg/kg bw TiO2 NPs per day. The TiO2 NPs induced hyperglycemia earlier in the developing mice than in the adult mice. Then mechanisms were analyzed after mice were oral administration of TiO2 NPs for 8 weeks and 26 weeks, respectively. Results showed that the treatment with TiO2 NPs activated xenobiotic biodegradation in livers of both developing and adult mice at the early stage. However, only in the developing mice, TiO2 NPs induced endoplasmic reticulum (ER) stress in livers and increased reactive oxygen species in livers and sera in the early stage. The ER stress and ROS activated an inflammation response and mitogen-activated protein kinase pathways, thereby inducing insulin resistance in the livers of developing mice at the early stage. The response of the adult mice was delayed, and these changes were observed in the late stage of the study. The results of this study all suggest that children are more susceptible than adults to the toxicity of orally administered TiO2 NPs.

11.
Life Sci ; 239: 117010, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672578

RESUMO

AIMS: Amlexanox, an inhibitor of nuclear factor κB kinase epsilon (IKKε) and TANK-binding kinase 1(TBK1), was demonstrated to be effective in diabetes and obesity. The aim of this study was to explore the molecular mechanisms of its role in non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: NAFLD mouse models were established by using eight-week-old male C57BL/6 mice fed with high-fat diet (HFD) or (and) lipopolysaccharide (LPS) for 18 weeks. From the beginning of HFD, HFD-induced mice were subjected to amlexanox or vehicle for 18 weeks. HFD + LPS-induced mice were treated with amlexanox or vehicle for the last 6 weeks. Blood biochemistry parameters were determined using automatic biochemistry analyzer. Histological changes of liver tissue were observed by hematoxylin-eosin (H&E) staining and Oil Red O staining. The expressions of IKKε and smooth muscle actin-α (α-SMA) were evaluated through immunohistochemistry. Serum inflammatory mediator was determined by enzyme linked immunosorbent assay (ELISA). Gene expressions involved in glucose and lipid metabolism, insulin signaling pathway were examined using quantitative RT-PCR or Western blotting. KEY FINDINGS: This study demonstrated that amlexanox reversed glucose and lipid metabolic disturbance and hepatic steatosis in NAFLD mice model. IKKε was specific expressed in hepatic stellate cells (HSCs) instead of hepatocytes. This study also found that amlexanox improved insulin signaling (Insulin-IRS-1-Akt) in hepatocytes through inhibiting inflammation (IKKε-NF-κB-TNF-α/IL-1α) in HSCs. SIGNIFICANCE: The present study confirmed that IKKε was specific expressed in HSCs. Inhibition of activated HSCs was responsible for effects of amlexanox on NAFLD, with improving insulin signal pathway in hepatocytes.

12.
J Ethnopharmacol ; : 112433, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31783135

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a frequently occurring disease of the elderly, and "deficiency" is the root of AD. Most famous experts of traditional Chinese medicine believe that the disease is based on deficiency, and the deficiency of kidney essence is the basis. Notopterygium incisum (Qiang huo) is specialized in bladder and liver and kidney. Treatment of liver and kidney deficiency, language difficulty, mental coma. Qiang huo yu feng tang has been used to treat liver and kidney deficiency, unclear language and mental paralysis in many traditional Chinese medicine books and records. In modern times, it has been used to treat AD and exhibited favourable efficacy. AIM OF THE STUDY: This study attempts to investigate the effects of furocoumarins from Notopterygium incisum (NRE) on the Aß cascade, tau pathology and inflammatory pathology of AD. MATERIALS AND METHODS: In this study, we reported a detailed protocol for stabilizing HEK APPswe293T cells with lentivirus for the first time. This cell line can secrete high concentration of Aß. In addition, we treated N2a cells with AKT/PKC specific inhibitors (wortmannin/GF-109203X) and established a tau pathological cell model (AKT/PKC N2a) by activating GSK3ß and triggering hyperphosphorylation of tau. The Aß levels and the expression of phosphorylated tau were detected by ELISA and Western blot. The cognitive ability of NRE on APP/PS1 mice was detected using a Morris water maze (MWM) assay and Aß contents were also evaluated. RESULTS: In HEK APPswe293T cells, NRE (10, 20, 40 µg/mL) significantly inhibited the secretion and production of Aß in dose dependent manner. In addition, NRE also suppressed the expression of phosphorylated tau in wortmannin/GF-109203X treated N2a cells. Furthermore, NRE ameliorated the cognitive impairment of APP/PS1 mice, and the contents of Aß, IL-1ß and TNF-α were significantly depressed in hippocampus and cortex. CONCLUSION: In conclusion, our results demonstrated that NRE has a potential anti-AD effect via the inhibition of the Aß cascade, tau pathology and neuroinflammation in vitro and in vivo.

13.
Anal Chem ; 91(23): 14860-14864, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31668058

RESUMO

Protein persulfidation is one of the most important oxidative translational modifications and plays vital roles in various important biological processes. However, the proteome-wide identification of persulfidation sites is a great challenge because of the difficulties in accurately differentiating persulfide groups with disulfide and thiol groups in proteins as well as the extremely low abundance of persulfidated peptides. By current approaches, the persulfidated peptides were often identified by the cleavage of their persulfide groups by reductants prior to MS analysis; therefore, it would bring about a false positive identification and was unable to identify persulfidation sites accurately for a single peptide with multiple cysteine residues. In this study, a novel strategy for the site-specific quantification of persulfidome (SSQPer) was developed. By this strategy, the persulfidated proteins were first labeled with cleavable isotope-coded affinity tag (c-ICAT) reagents. After digestion, the labeled persulfidated peptides were selectively enriched with streptavidin beads and fractionated by strong cation exchange chromatography, followed by LC-MS/MS identification. To evaluate the performance of SSQPer, the persulfidated BSA digests with 20 persulfidation sites identified were used to spike HeLa cell digests with mass ratios of 1:100 and 1:1000, and 16 and 13 persulfidated sites were respectively identified. We applied SSQPer to the site-specific quantification of persulfidome in the epithelial-mesenchymal transition (EMT) process, and 226 endogenous persulfidation sites were identified, of which 74.3% were newly discovered. All of these results demonstrated that the SSQPer strategy would provide a promising tool to profile the site-specific persulfidome and pave the way for future investigation to expand our knowledge of persulfidation.

14.
Cell Death Differ ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700144

RESUMO

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play important roles in human diseases, including cancer; however, only a few of them have been experimentally validated and functionally annotated. Here, we identify a novel lncRNA that we term HITT (HIF-1α inhibitor at translation level). HITT is commonly decreased in multiple human cancers. Decreased HITT is associated with advanced stages of colon cancer. Restoration of the expression of HITT in cancer cells inhibits angiogenesis and tumor growth in vivo in an HIF-1α-dependent manner. Further study reveals that HITT inhibits HIF-1α expression, mainly by interfering with its translation. Mechanically, HITT titrates away YB-1 from the 5'-UTR of HIF-1α mRNA via a high-stringency YB-1-binding motif. The reverse correlation between HITT and HIF-1α expression is further validated in human colon cancer tissues. Moreover, HITT is one of the most altered lncRNAs upon the hypoxic switch and HITT downregulation is required for hypoxia-induced HIF-1α expression. We further demonstrate that HITT and HIF-1α form an autoregulatory feedback loop where HIF-1α destabilizes HITT by inducing MiR-205, which directly targets HITT for degradation. Together, these results expand our understanding of the cancer-associated functions of lncRNAs, highlighting the HITT-HIF-1α axis as constituting an additional layer of regulation of angiogenesis and tumor growth, with potential implications for therapeutic targeting.

15.
Trends Biotechnol ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31727372

RESUMO

Polyhydroxyalkanoates (PHAs) are a diverse family of biopolyesters synthesized by many natural or engineered bacteria. Synthetic biology and DNA-editing approaches have been adopted to engineer cells for more efficient PHA production. Recent advances in synthetic biology applied to improve PHA biosynthesis include ribosome-binding site (RBS) optimization, promoter engineering, chromosomal integration, cell morphology engineering, cell growth behavior reprograming, and downstream processing. More importantly, the genome-editing tool clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has been applied to optimize the PHA synthetic pathway, regulate PHA synthesis-related metabolic flux, and control cell shapes in model organisms, such as Escherichia coli, and non-model organisms, such as Halomonas. These synthetic biology methods and genome-editing tools contribute to controllable PHA molecular weights and compositions, enhanced PHA accumulation, and easy downstream processing.

16.
Zootaxa ; 4604(3): zootaxa.4604.3.13, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31717187

RESUMO

The genera Bitomoides van Achterberg, 2004, Neopius Gahan, 1917 and Sternaulopius Fischer, 1965 of the subfamily Opiinae are newly discovered in China and one new species of each genus are described and illustrated, viz. Bitomoides platyaulicis Sheng Chen sp. n., Neopius citrinus Sheng Chen, sp. n. and Sternaulopius macrophthalmos Sheng Chen sp. n. The status of the genus Neopius Gahan is discussed.


Assuntos
Himenópteros , Animais , China
17.
Cutis ; 104(3): 173;187-188, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31675399
18.
Artigo em Inglês | MEDLINE | ID: mdl-31679099

RESUMO

Children of depressed mothers are at risk for maladaptive emotion regulation. This study examined a model of maternal rumination that links maternal depressive symptoms to child emotion regulation. A sample of 126 mother-child dyads (65 girls) participated in the current study, at three assessment points when children were age three, four, and five. At all assessment points, mothers reported their depressive symptoms and ruminative response style. Child emotion regulation was assessed observationally from two laboratory tasks, which were designed to elicit anger and sadness. Elevated maternal depressive symptoms were associated with higher concurrent rumination. Maternal rumination at child age four predicted that more child focus on distress during sadness-eliciting tasks and less child active distraction during anger-eliciting tasks 1 year later. Additionally, maternal rumination at child age three and four predicted less child passive behaviors in anger-eliciting tasks prospectively. Findings suggest that maternal rumination is predictive of using maladaptive regulatory strategies among children of depressed mothers. This study has significant implications for intervention programs targeting depressed mothers and their children.

19.
Part Fibre Toxicol ; 16(1): 41, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699096

RESUMO

BACKGROUND: Silicon dioxide nanoparticles (SiO2 NPs) are one of the most widely utilized NPs in various food sectors. However, the potential endocrine toxicity of SiO2 NPs has not been characterized. RESULTS: In the present study, mice were orally administered a series of doses of SiO2 NPs. All doses of SiO2 NPs were absorbed into the blood, liver, and pancreas of the mice. Administration of 100 mg/kg bw (body weight) of SiO2 NPs significantly increased blood glucose levels in mice. However, the same dose of SiO2 fine-particles (FPs) did not result in altered blood glucose. Whole-genome analysis showed that SiO2 NPs affected the expression of genes associated with reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress. In addition, we showed that SiO2 NPs activated xenobiotic metabolism, resulting in ER stress. Endoplasmic reticulum stress resulted in increased ROS production, which activated the NF-κB pathway leading to expression of inflammatory cytokines. Increased inflammatory cytokine expression resulted in serine phosphorylation of IRS1, which induced insulin resistance (IR). Furthermore these inflammatory cytokines activated the MAPK pathway, which further promoted the serine phosphorylation of IRS1. Insulin resistance resulted in elevated blood glucose. The ER stress inhibitor 4-phenylbutyric acid (4-PBA) inhibited SiO2 NP-induced ROS production. The ROS scavenger N-acetylcysteine (NAC) did not affect SiO2 NP-induced ER stress, but inhibited SiO2 NP-induced activation of the NF-κB and MAPK pathways, expression of inflammatory cytokines, SiO2 NP-induced serine phosphorylation of IRS1, and SiO2 NP-induced elevations of blood glucose. CONCLUSION: Silicon dioxide NPs induced IR through ER stress and generation of ROS, but SiO2 FPs did not. Therefore, lifelong exposure of humans to SiO2 NPs may result in detrimental effects on blood glucose. The results of this study strongly suggested that non-nanoformed SiO2 should be used as food additives.

20.
J Mol Model ; 25(11): 340, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713742

RESUMO

In this study, 16 new energetic metal complexes [M(DNABT)(ATDO), M=Cu, Ni] were designed using the mixed complex construct strategy, which was based on two complementary oxygen-rich high-energy ligands of 1,1'-dinitramino-5,5'-bistetrazole (DNABT) and 4-amino-4H-1,2,4-triazole-3,5-diol (ATDO), then combined with metals Cu and Ni, and further adjusted by the introduction of NO2 and NH2. The molecular and electronic structures, heat of formation (HOF), density, detonation velocity, detonation pressure, and sensitivity were investigated by the density functional theory method. The results showed that in metals, the position and amount of NO2/NH2 have great effects on the structure and property of metal complexes, and these effects coupled with each other. N-NO2 bond is the relatively weak bond, and its max length is related with the sensitivity closely. The designed metal complexes all have high HOF (673~868 kJ mol-1), high density (2.06~2.14 g cm-3), and ideal oxygen balance (- 19.2~- 6.7%), which further make them have higher detonation velocity (8.76~9.84 km s-1) and detonation pressure (37.4~46.6 GPa) than three famous high-energy compounds 1,3,5-trinitro-1,3,5-triazine (RDX); 1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX); or even 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). At the same time, they are less sensitive than RDX, HMX, and CL-20, making them potential candidates for high-energy density compounds.

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