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1.
Carbohydr Polym ; 227: 115362, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590882

RESUMO

A new polysaccharide (pFSP) was first isolated from the originally discarded fibrous roots part of Chinese traditional herb, Bletilla striata. pFSP was composed of D-glucose, D-galactose and D-mannose in a molar ratio of 1: 2.03: 3.45 with molecular weight of 9.1 × 104 Da. It could effectively scavenge DPPH and superoxide radicals with inhibition rate of 64.47% and 72.27% at 5.0 mg/ml, higher than that of polysaccharide from Bletilla striata tuber. Structural investigations of the periodate oxidation studies and Smith-degradation as well as the FT-IR spectroscopy were performed, and combined with 1D and 2D NMR spectroscopy, the repeating unit of pFSP contained (1→4)-linked-α-D-Glcp, (1→4)-linked-ß-D-Manp and (1→3,6)-linked-ß-D-Manp units, together with the branches of (1→6)-linked-ß-D-Galp and terminated with (1→)-linked-ß-D-Manp residue.

2.
J Nanosci Nanotechnol ; 20(2): 1098-1108, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383110

RESUMO

In this study, the 2D porous graphitic carbon nitride (g-C3N4) nanosheets were successfully fabricated via a facile thermal decomposition polymerization method without any help of templates, and then novel porous g-C3N4/CdS complex catalysts of different mass fractions were is situ synthesized by a simple solvothermal process. The results of photocatalytic experiments demonstrate that the coupling g-C3N4/CdS cocatalysts exhibit significant enhanced visible-light-driven photocatalytic activity for the decolorization of methyl orange (MO) compared with individual porous g-C3N4 and CdS. In particular, an optimal porous g-C3N4 content in the hybridized composite has been determined to be 70 wt.%, corresponding to pseudo-first-order rate constant of 0.046 min-1, which is 7 and 11 times faster than that of pure porous g-C3N4 and CdS, respectively. Photoluminescence (PL) spectroscopy measurements clearly confirmed that the recombination of photoproduced electrons and holes in g-C3N4/CdS composites was efficiently inhibited due to the formation of heterojunctions. Furthermore, the possible mechanism of enhanced photocatalytic activity and photostability of prous g-C3N4/CdS are also tentatively proposed.

3.
Mol Plant Pathol ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603283

RESUMO

Verticillium longisporum infects oilseed rape (Brassica napus) and Arabidopsis thaliana. To investigate the early response of oilseed rape to the fungal infection, we determined transcriptomic changes in oilseed rape roots at 6 days post-inoculation (dpi) by RNA-Seq analysis, in which non-infected roots served as a control. Strikingly, a subset of genes involved in abscisic acid (ABA) biosynthesis was found to be down-regulated and the ABA level was accordingly attenuated in 6 dpi oilseed rape as compared with the control. Gene expression analysis revealed that this was mainly attributed to the suppression of BnNCED3-mediated ABA biosynthesis, involving, for example, BnWRKY57. However, this down-regulation of ABA biosynthesis could not be observed in infected Arabidopsis roots. Arabidopsis ABA- defective mutants nced3 and aao3 displayed pronounced tolerance to the fungal infection with delayed and impeded symptom development, even though fungal colonization was not affected in both mutants. These data suggest that ABA appears to be required for full susceptibility of Arabidopsis to the fungal infection. Furthermore, we found that in both 6 dpi oilseed rape and the Arabidopsis nced3 mutant, the salicylic acid (SA) signalling pathway was induced while the jasmonic acid (JA)/ethylene (ET) signalling pathway was concomitantly mitigated. Following these data, we conclude that in oilseed rape the V. longisporum infection triggers a host-specific suppression of the NCED3-mediated ABA biosynthesis, consequently increasing plant tolerance to the fungal infection. We believe that this might be part of the virulence strategy of V. longisporum to initiate/establish a long-lasting compatible interaction with oilseed rape (coexistence), which appears to be different from the infection process in Arabidopsis.

4.
J Agric Food Chem ; 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31588753

RESUMO

A long-term high-fat diet (HFD) can cause a range of health problems. Gut microbiota plays a decisive role in the development of HFD-associated inflammation, involved in function of T cells. This study was designed to probe the regulative effects of dietary stachyose, a functional oligosaccharide, on HFD-induced weight gain, inflammation, gut microbiota dysbiosis and T cell abnormality in C57Bl/6 mice. Mice were divided into three groups which received normal chow, HFD and HFD plus stachyose (400 mg/kg), respectively. Results showed that administration of stachyose diminished the HFD-induced upregulation of serum TNF-α level and elevation of peripheral blood leukocyte populations to alleviate the HFD-caused colonic and hepatic inflammation in mice. Analysis of gut microbiota revealed that stachyose improved the intestinal homeostasis of HFD-fed mice by improving the bacterial diversity with the increases in the relative abundances of Prevotellaceae_NK3B31_group, Parasutterella, Christensenellaceae_R-7_group and Anaerovorax, as well as the fecal level of butanoic acid, while decreasing the ratio of Firmicutes-to-Bacteroidetes and the abundances of Lachnospiraceae_NK4A136_group, Desulfovibrio, Anaerotruncus, Mucispirillum, Roseburia and Odoribacter. Flow cytometric analysis showed that stachyose antagonized the HFD-induced decrease of peripheral CD4+ T cell population in mice. Conclusively, these findings suggest that long-term consumption of stachyose can ameliorate the HFD-associated colonic and hepatic inflammation and its complications by modulating gut microbiota.

5.
Chin Med J (Engl) ; 132(19): 2269-2277, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567477

RESUMO

BACKGROUND: Air pollutants and their pathogenic effects differ among regions and seasons. We aimed to explore the relationship between fine particulate matter (PM2.5), sulfur dioxide (SO2), and ozone-8 hours (O3-8h) concentrations in heating and non-heating seasons and the associated death risk due to cardiovascular diseases (CDs), respiratory diseases (RDs), and malignant tumors. METHODS: Data were collected in Shenyang, China, from April 2013 to March 2016. We analyzed the correlation or lagged effect of atmospheric pollutant concentration, meteorological conditions, and death risk due to disorders of the circulatory system, respiratory system, and malignant tumor in heating and non-heating seasons. We also used multivariate models to analyze the association of air pollutants during holidays with the death risk due to the evaluated diseases while considering the presence or absence of meteorological factors. RESULTS: An increase in the daily average SO2 concentration by 10 µg/m increased the death risk by CDs, which reached a maximum of 2.0% (95% confidence interval [CI]: 1.3%-2.7%) on lagging day 4 during the non-heating season and 0.2% (95% CI: 0.1%-0.4%) on lagging day 3 during the heating season. The risk of death caused by RDs peaked on lagging day 1 by 0.8% (95% CI: 0.4%-1.2%) during the heating season. An increase in O3-8h concentration by 10 µg/m increased the risk of RD-related death on lagging day 2 by 1.0% (95% CI: 0.4%-1.7%) during the non-heating season, which was significantly higher than the 0.1% (95% CI: 0-0.9%) increase during the heating season. Further, an increase in the daily average PM2.5 concentration by 10 µg/m increased the risk of death caused by RDs by 0.3% and 0.8% during heating and non-heating seasons, respectively, which peaked on lagging day 0. However, air pollution was not significantly associated with the risk of death caused by malignant tumors. CONCLUSION: Short-term exposure to PM2.5, SO2, and O3 during the non-heating season resulted in higher risks of CD-related death, followed by RD-related death.

6.
Oxid Med Cell Longev ; 2019: 4848560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565151

RESUMO

Although CD28 is associated with the expression of inflammatory mediators, apoptosis-related protein, immunosuppression, and tumorigenesis, the effects of CD28 deficiency on blast exposure-induced lung injury have not been investigated. In this study, we have explored the effects of CD28 on blast exposure-induced lung injury and studied its potential molecular mechanisms. A mouse model of blast exposure-induced acute lung injury was established. Sixty C57BL/6 wild-type (WT) and CD28 knockout (CD28-/-) mice were randomly divided into control or model groups. Lung tissue samples were collected 24 h and 48 h after blast injury. Histopathological changes and the expressions of inflammatory-related proteins were detected by hematoxylin-eosin, immunohistochemistry, and immunofluorescence staining. Apoptosis and oxidative stress were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and reactive oxygen species (ROS). Inflammation, apoptosis, oxidative stress, and related pathway protein expression were studied by western blotting. In addition, the levels of CD3 and CD28 proteins were measured by flow cytometry. In the current study, we found that CD28 deficiency significantly inhibited blast exposure-induced increases in the lung weight/body weight ratio and wet weight/dry weight ratio; decreased the infiltration of CD44+ leukocytes, CD163+ macrophages, and CD3+ T cells into the lungs; reduced the expressions of proinflammatory cytokines including IL-1ß, TNF-α, and IL-6; and markedly increased IL-10 expression. CD28 deficiency also significantly attenuated blast exposure-induced ROS, MDA5, and IREα expressions; increased SOD-1 expression; lowered the number of apoptotic cells and Bax, Caspase-3, and active Caspase-8 expressions; and increased Bcl-2 expression. Additionally, CD28 deficiency significantly ameliorated blast exposure-induced increases of p-PI3K and p-Akt and ameliorated the decrease in the p-FoxO1 expression. Our results suggest that CD28 deficiency has a protective effect on blast exposure-induced lung injury, which might be associated with the PI3K/Akt/FoxO1 signaling pathway.

7.
Gut ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582403

RESUMO

OBJECTIVE: N6-methyladenosine (m6A) RNA methylation and its associated methyltransferase METTL3 are involved in tumour initiation and progression via the regulation of RNA function. This study explored the biological function and clinical significance of METTL3 in gastric cancer (GC). DESIGN: The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human GC cohort. The biological role and mechanism of METTL3 in GC tumour growth and liver metastasis were determined in vitro and in vivo. RESULTS: The level of m6A RNA was significantly increased in GC, and METTL3 was the main regulator involved in the abundant m6A RNA modification. METTL3 expression was significantly elevated in GC tissues and associated with poor prognosis. Multivariate Cox regression analysis revealed that METTL3 expression was an independent prognostic factor and effective predictor in human patients with GC. Moreover, METTL3 overexpression promoted GC proliferation and liver metastasis in vitro and in vivo. Mechanistically, P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m6A modification of HDGF mRNA, and the m6A reader IGF2BP3 then directly recognised and bound to the m6A site on HDGF mRNA and enhanced HDGF mRNA stability. Secreted HDGF promoted tumour angiogenesis, while nuclear HDGF activated GLUT4 and ENO2 expression, followed by an increase in glycolysis in GC cells, which was correlated with subsequent tumour growth and liver metastasis. CONCLUSIONS: Elevated METTL3 expression promotes tumour angiogenesis and glycolysis in GC, indicating that METTL3 expression is a potential prognostic biomarker and therapeutic target for human GC.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31566940

RESUMO

A simple, low-cost, fluorine-free, and ecofriendly method was applied to prepare a novel superhydrophobic Zn-Fe alloy coating on the surface of carbon steel. First of all, the Zn-Fe coating was obtained in an alkaline glycerol non-cyanide Zn-Fe plating solution. Then tetradecanoic acid was grafted onto the Zn-Fe coating by a coordination reaction, leading to a superhydrophobic surface. The water contact angle was up to 166° and the sliding angle was 4°. The as-prepared superhydrophobic coating exhibited high performances, such as strong adhesion to the substrate, impact resistance, self-cleaning, antifouling, and anticorrosion. Importantly, until now, few reports focus on the use of a non-cyanide alkaline glycerol plating bath for electrodeposition, which is green, composition-stable, and corrosion-free for devices. In addition, the growth mechanism of the Echinopsis multiplex-like hierarchical micro/nanostructure of the superhydrophobic surface was studied in detail.

9.
Anal Chem ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577422

RESUMO

The study of endocytosis, which encompasses diverse mechanisms in biology, requires the utilization of high axial resolution to monitor molecular behavior on both the cell surface and interior of the cell. We have designed a novel axially-resolved fluorescence microscopic technique, termed variable-angle nanoplasmonic fluorescence microscopy. The proof-of-principle of this approach is achieved by selectively following the events in the vicinity of a cell membrane or in a cell. We use a 30 nm Au-coated semi-transparent coverslip as the nanoplasmonic chip to achieve both surface plasmon resonance excitation and critical angle excitation by tuning the incident angles. This approach leads to improved axial resolution compared to total internal reflection fluorescence microscopy, which is a common imaging technique in cell biology. It offers a unique opportunity to semi-quantitatively determine fluorophore axial distributions in the cell. Observing the epidermal growth factor receptor-mediated endocytosis in Caski cells clearly demonstrates the potential application of this new method for cell biology studies.

10.
J Clin Invest ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581151

RESUMO

Potentiating radiotherapy and chemotherapy by inhibiting DNA damage repair is proposed as a therapeutic strategy to improve outcomes for patients with solid tumors. However, this approach risks enhancing normal tissue toxicity as much as tumor toxicity, thereby limiting its translational impact. Using NU5455, a newly-identified highly-selective oral inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity, we found that it was indeed possible to preferentially augment the effect of targeted-radiotherapy on human orthotopic lung tumors without influencing acute DNA-damage or a late radiation-induced toxicity (fibrosis) to normal mouse lung. Furthermore, while NU5455 administration increased both the efficacy and toxicity of a parenterally-administered topoisomerase inhibitor, it enhanced the activity of doxorubicin released locally in liver tumor xenografts without inducing any adverse effect. This strategy is particularly relevant to hepatocellular cancer which is treated clinically with localized drug-eluting beads and for which DNA-PKcs activity is reported to confer resistance to treatment. We conclude that transient pharmacological inhibition of DNA-PKcs activity is effective and tolerable when combined with localized DNA-damaging therapies and thus has promising clinical potential.

11.
Int J Biol Sci ; 15(11): 2320-2329, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595150

RESUMO

Solid tumors consist of various types of stromal cells in addition to cancer cells. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and play an essential role in tumor progression and metastasis in a variety of malignancies, including gastric cancer. However, the effects of CAFs on gastric cancer cells' progression and metastasis are not well studied. Here we show that matrix metalloproteinase 11 (MMP11) in exosomes secreted from CAFs can be delivered into gastric cancer cells. Gastric CAFs promote gastric cancer cell migration partially through exosomal MMP11. Moreover, MMP11 is overexpressed in exosomes purified from plasma of gastric cancer patients and tumor tissues and associated with overall survival of gastric patients. We also find that MMP11 is negatively regulated by exosomal miR-139 in the CAFs of gastric cancer. Exosomal miR-139 inhibits tumor growth and metastasis of gastric cancer cells by decreasing the expression of MMP11 in vitro and in vivo. Thus, we propose that exosomal miR-139 derived from gastric CAFs could inhibit the progression and metastasis of gastric cancer by decreasing MMP11 in tumor microenvironment.

12.
J Agric Food Chem ; 67(38): 10667-10677, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483636

RESUMO

This study investigated the modulatory effects of Decaisnea insignis seed oil (DISO), which was rich in palmitoleic acid (55.25%), palmitic acid (12.25%), and oleic acid (28.74%), on alcohol-induced metabolism disorder in mice. Fifty mice were orally administered with 38% alcohol (0.4 mL/day) and without or with DISO (3, 6, and 12 g/kg) for consecutive 12 weeks. DISO inhibited the alcohol-induced weight loss and liver function abnormality (p < 0.01) and shifted the profiles of cecal microbiome: elevating the abundance of Lactobacillus, Ruminoccoceae_UCG_004 (p < 0.05) and decreasing abundance of Parabacteroides (p < 0.05). This treatment also regulated metabolome response of amino acid and lipid metabolism in cecal content: upregulating 5-hydroxyindole-3-acetic acid (p < 0.05), 6-hydroxynicotinic acid, 5-methoxytryptamine, nicotinamide, and nicotinic acid (p < 0.1) and downregulating androsterone, tryptophan, and indole-3-acetamide (p < 0.05). DISO protected against alcoholic liver injury and gut microbiota dysbiosis by enriching the relative abundance of Lactobacillus, which was positively associated with the improvement of intestinal permeability and tryptophan metabolism.


Assuntos
Álcoois/efeitos adversos , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatias Alcoólicas/prevenção & controle , Magnoliopsida/química , Óleos Vegetais/administração & dosagem , Consumo de Bebidas Alcoólicas/efeitos adversos , Aminoácidos/metabolismo , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Ceco/efeitos dos fármacos , Ceco/microbiologia , Disbiose/metabolismo , Disbiose/microbiologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/microbiologia , Masculino , Metaboloma/efeitos dos fármacos , Camundongos , Microbiota/efeitos dos fármacos , Sementes/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-31529575

RESUMO

A new strategy for the synthesis of a covalent triazine framework (CTF-1) was introduced based on the cyclotrimerization reaction of 1,4-dicyanobenzene using lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) under ionothermal conditions. LiTFSI not only served as a catalyst, but also facilitated the in situ generation and homogeneous distribution of LiF particles across the framework. The hierarchical structure resulting upon integration of CTF-LiF onto an airlaid-paper (AP) offered unique features for lithium metal anodes, such as lithiophilicity from CTF, interface stabilization from LiF, and sufficient lithium storage space from AP. Based on this synergistic effect, the AP-CTF-LiF anode exhibited stable cycling performance even at a current density of 10 mA cm-2 .

14.
J Affect Disord ; 260: 84-90, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31493644

RESUMO

BACKGROUND: Previous studies have investigated the role of cognitive factors in the relationship between stressful life events and depression; however, few studies comprehensively considered cognitive and personality factors. Therefore, this study investigated the multiple mediating roles of fatalism and core self-evaluations in the relationship between stressful life events and depression. METHODS: A cross-sectional survey was conducted with 537 Chinese university students (Mage = 20.20, SD = 1.38) at two universities in Guizhou and Sichuan provinces. The independent variable was stressful life events; mediating variables were fatalism and core self-evaluations; and the dependent variable was extent of depression. Multiple mediation analysis was performed using the PROCESS macro in SPSS. RESULTS: Significant positive correlations were found among stressful life events, fatalism, and depression, while core self-evaluations were significantly negatively correlated with stressful life events, fatalism, and depression. After adjusting for demographic variables, stressful life events directly and positively influenced depression (ß = 0.370, 95% CI = 0.292-0.448). Fatalism and core self-evaluations played multiple mediating roles in the relationship between stressful life events and depression, with stressful life events influencing depression through three mediation pathways (total mediation effect = 0.199, 95% CI = 0.145-0.254), which accounted for 53.85% of the total effect. LIMITATIONS: The data used in this study were self-reported by university students and measureed via cross-sectional designs. CONCLUSIONS: Stressful life events can influence depression either directly or indirectly by simultaneously increasing fatalism and lowering core self-evaluations (parallel mediation) or decreasing core self-evaluations through increasing the level of fatalism (serial mediation).

15.
Waste Manag ; 100: 28-35, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31499449

RESUMO

The waste classification has not been carried out worldwide, especially in developing countries. The high content of water in the kitchen waste will definitely affect the amount of air flowing into waste layer from leachate collection pipe. In this experiment, three lab-scale landfill simulation reactors were established. Reactor A and B are semi-aerobic landfill modes, while reactor C has no vertical gas vent. The void fraction in the waste of reactor B was increased by adding gravel serve as part of the waste. The waste sample used in landfill reactor mainly included kitchen waste (58%). The waste decomposition conditions in the landfill were investigated using temperature sensors embedded in the waste, by determining the velocity and gas flow direction and by measuring the volume and composition of leachate produced. The results showed that the void fraction of waste in reactor A and C was 29.79% and 30.86% respectively, and that of waste in reactor B 34.96%. Compared with reactor A, reactor B had its temperature increase earlier. In addition, the temperature distribution in vertical gas vent of the reactor A and B is higher than in the leachate collection pipe. The gas flux of vertical gas vent increased with the temperature of gas vent. Reactor A and B had significantly lower concentration of chemical oxygen demand (COD) and ammonia nitrogen (NH3+-N) than that of reactor C. It was concluded that landfill decomposition can be accelerated by increasing the void fraction in the waste and keeping a vertical gas vent open.

16.
Environ Int ; 133(Pt A): 105148, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31518941

RESUMO

BACKGROUND: Twin growth discordance is one of the leading causes of perinatal mortality in twin pregnancies. Whether prenatal exposure to fine particle (PM2.5) air pollution is associated with twin growth discordance have not been studied yet. OBJECTIVE: To evaluate the associations of prenatal exposure to PM2.5 and its chemical constituents with twin growth discordance. METHODS: This study included 1917 twin pairs and their mothers drawn from a previous twin birth cohort at the Shanghai First Maternity and Infant hospital in Shanghai, China. Exposure to PM2.5 total mass and 6 key chemical constituents during the whole pregnancy and each trimester of pregnancy was represented by satellite-based models. RESULTS: Maternal exposures to PM2.5 total mass and chemical constituents of sulfate (SO42-) and ammonium (NH4+) during the third trimester were significantly associated with increased within-pair birth weight difference and intertwin birth weight discordance. The within-pair birth weight difference increased by 30.6 g (ß = 30.6, 95% CI, 4.4-56.9), 19.2 g (ß = 19.2, 95% CI, 0.2-38.1) and 33.2 g (ß = 33.2, 95% CI, 7.9-58.6) for an IQR increase in PM2.5 total mass, SO42- and NH4+ exposure, respectively. While the intertwin birth weight discordance increased by 1.3% (ß = 1.3, 95% CI, 0.3-2.2), 0.9% (ß = 0.9, 95% CI, 0.2-1.6) and 1.4% (ß = 1.4, 95% CI, 0.4-2.3) for the same exposure metrics. Moreover, higher SO42- and NH4+ exposure was also associated with increased risk of twin growth discordance in linear dose-response manners. Compared to the lowest quartile of SO42- (OR = 2.51, 95% CI, 1.08-5.82) and NH4+ (OR = 2.97, 95% CI, 1.16-7.58) exposure, the odds of twin growth discordance were doubled in highest quartile of exposure. CONCLUSION: Our results suggest that fine particle air pollution may be a risk factor for twin growth discordance. Late pregnancy seems to be a critical window for the effects of PM2.5 exposure on fetal growth in twins.

17.
Curr Opin Cell Biol ; 61: 117-125, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480011

RESUMO

Autophagy involves the formation of double-membrane autophagosomes and their delivery to lysosomes for degradation. In response to various endogenous and exogenous stimuli, autophagy recycles cellular constituents and removes cytotoxic threats such as protein aggregates and damaged organelles to maintain cellular homeostasis. Dysfunctional autophagy has been linked with multiple human diseases, including neurodegenerative diseases, tumorigenesis, diabetes, and immune diseases. Here we focus on human genetic disorders caused by hypomorphic or regulatory mutations in early acting autophagy genes or by mutations in genes acting at autophagosome maturation. Protein aggregates assembled via liquid-liquid phase separation (LLPS) exhibit distinct biophysical properties that are modulated by disease-related mutations. Abnormal phase transition of protein aggregates affects their removal and is associated with the pathogenesis of various neurodegenerative diseases.

18.
J Exp Clin Cancer Res ; 38(1): 409, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533816

RESUMO

BACKGROUND: ATPase associated with a variety of cellular activities (AAA ATPase) family members are closely linked to tumor formation and progression. However, their roles in hepatocellular carcinoma (HCC) largely remain unclear. METHODS: Bioinformatic analyses of public databases were used to excavate the potential AAA ATPases that may contribute to HCC, and thyroid hormone receptor interactor 13 (TRIP13) was selected to following researches because of its most prominently differential expression. Western blot, qRT-PCR and immunohistochemistry were used to detect the expression of TRIP13 in HCC tissues, and then the relationship between TRIP13 expression and clinicopathological parameters were evaluated. Finally, its functions and potential mechanisms were investigated through a series gain- and loss-of-function strategies both in vitro and in vivo. RESULTS: TRIP13 was significantly overexpressed in HCC tissues and high level of TRIP13 was closely correlated with a worse clinical outcome. Functionally, elevated TRIP13 facilitated cell proliferation, migration, invasion, and promoted cellular epithelial-mesenchymal transition (EMT) in vitro, while promote tumor growth and lung metastasis in vivo. Mechanistically, TRIP13 interacted with ACTN4 and positively regulated its expression, thus activating the AKT/mTOR pathway to drive tumor progression. Moreover, miR-192-5p served as an upstream regulator of TRIP13 by directly binding to TRIP13 mRNA 3' UTR, which may partially explain the high expression of TRIP13 in HCC. CONCLUSION: Our findings identified TRIP13 as a promising candidate oncogene in HCC, and TRIP13 induced cell migration, invasion and metastasis of HCC through the AKT/mTOR signaling via interacting with ACTN4.

19.
Mar Drugs ; 17(10)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547097

RESUMO

Type 2 diabetes mellitus (T2DM) accounts for more than 90% of cases of diabetes mellitus, which is harmful to human health. Herein, neoagaro-oligosaccharides (NAOs) were prepared and their potential as a treatment of T2DM was evaluated in KunMing (KM) mice. Specifically, a T2DM mice model was established by the combination of a high-fat diet (HFD) and alloxan injection. Consequently, the mice were given different doses of NAOs (100, 200, or 400 mg/kg) and the differences among groups of mice were recorded. As a result of the NAOs treatment, the fasting blood glucose (FBG) was lowered and the glucose tolerance was improved as compared with the model group. As indicated by the immunohistochemistry assay, the NAOs treatment was able to ameliorate hepatic macrovesicular steatosis and hepatocyte swelling, while it also recovered the number of pancreatic ß-cells. Additionally, NAOs administration benefited the antioxidative capacity in mice as evidenced by the upregulation of both glutathione peroxidase and superoxide dismutase activity and the significant reduction of the malondialdehyde concentration. Furthermore, NAOs, as presented by Western blotting, increased the expression of p-ERK1/2, p-JNK, NQO1, HO-1, and PPARγ, via the MAPK, Nrf2, and PPARγ signaling pathways, respectively. In conclusion, NAOs can be used to treat some complications caused by T2DM, and are beneficial in controlling the level of blood glucose and ameliorating the damage of the liver and pancreatic islands.

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