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1.
Artigo em Inglês | MEDLINE | ID: mdl-32212906

RESUMO

Intrinsic disorder is a common structural characteristic of proteins and a central player in the biochemical processes of species. However, the role of intrinsic disorder in the evolution of plant-pathogen interactions is rarely investigated. Here we explored the role of intrinsic disorder in the development of the pathogenicity in the RXLR AVR2 effector of Phytophthora infestans. We found AVR2 exhibited high nucleotide diversity generated by point mutation, early-termination, altered start codon, deletion/insertion and intragenic recombination and is predicted to be an intrinsically disordered protein. AVR2 amino acid sequences conferring a virulent phenotype had a higher disorder tendency in both the N-terminal and C-terminal regions compared to sequences conferring an avirulent phenotype. In addition, we also found virulent AVR2 mutants gained 1-2 short linear interaction motifs (SLiMs), the critical components of disordered proteins required for protein-protein interactions. Furthermore, virulent AVR2 mutants were predicted to be unstable and have a short protein half-life. Taken together, these results support the notion that intrinsic disorder is important for the effector function of pathogens and demonstrate that SLiM mediated protein-protein interaction in C-terminal effector domain might contribute greatly to the evasion of R protein detection in P. infestans.

2.
J Biomed Mater Res A ; 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32223058

RESUMO

A proper biological microenvironment conducive to tissue repair and regeneration, while the bio-implant interface directly affects the local microenvironment. In this study, to improve the biological microenvironment, a nano-sized tantalum boride (Ta-B) was coated on a titanium alloy substrate (Ti6Al4V, TC4) using magnetron co-sputtering. The sample surface was characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). To investigate the effects of tantalum boride coating on the microenvironment, rabbit bone marrow stromal cells (BMSCs) and RAW 264.7 cells were respectively seeded on the sample surface and relevant experiments were conducted in vitro. The pure tantalum coating (Ta) and naked TC4 were prepared as controls. Our results showed that the Ta-B coating enhanced cell proliferation and adhesion and inhibited the inflammatory response. Findings of alkaline phosphatase (ALP) staining, alizarin red staining and real-time PCR for osteoblastic gene expression indicated that Ta-B and Ta coating improve the osteogenesis, in which Ta-B coating showed higher osteogenesis than Ta coating. Thus, this study suggests that Ta-B coating with excellent biocompatibility could have new applications for wound healing in bone tissue engineering.

3.
mBio ; 11(2)2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209696

RESUMO

The appressoria that are generated by the rice blast fungus Magnaporthe oryzae in response to surface cues are important for successful colonization. Previous work showed that regulators of G-protein signaling (RGS) and RGS-like proteins play critical roles in appressorium formation. However, the mechanisms by which these proteins orchestrate surface recognition for appressorium induction remain unclear. Here, we performed comparative transcriptomic studies of ΔMorgs mutant and wild-type strains and found that M. oryzae Aa91 (MoAa91), a homolog of the auxiliary activity family 9 protein (Aa9), was required for surface recognition of M. oryzae We found that MoAA91 was regulated by the MoMsn2 transcription factor and that its disruption resulted in defects in both appressorium formation on the artificial inductive surface and full virulence of the pathogen. We further showed that MoAa91 was secreted into the apoplast space and was capable of competing with the immune receptor chitin elicitor-binding protein precursor (CEBiP) for chitin binding, thereby suppressing chitin-induced plant immune responses. In summary, we have found that MoAa91 is a novel signaling molecule regulated by RGS and RGS-like proteins and that MoAa91 not only governs appressorium development and virulence but also functions as an effector to suppress host immunity.IMPORTANCE The rice blast fungus Magnaporthe oryzae generates infection structure appressoria in response to surface cues largely due to functions of signaling molecules, including G-proteins, regulators of G-protein signaling (RGS), mitogen-activated protein (MAP) kinase pathways, cAMP signaling, and TOR signaling pathways. M. oryzae encodes eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), and MoRgs1, MoRgs3, MoRgs4, and MoRgs7 were found to be particularly important in appressorium development. To explore the mechanisms by which these proteins regulate appressorium development, we have performed a comparative in planta transcriptomic study and identified an auxiliary activity family 9 protein (Aa9) homolog that we named MoAa91. We showed that MoAa91 was secreted from appressoria and that the recombinant MoAa91 could compete with a chitin elicitor-binding protein precursor (CEBiP) for chitin binding, thereby suppressing chitin-induced plant immunity. By identifying MoAa91 as a novel signaling molecule functioning in appressorium development and an effector in suppressing host immunity, our studies revealed a novel mechanism by which RGS and RGS-like proteins regulate pathogen-host interactions.

4.
J Phys Chem Lett ; : 1614-1621, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32048850

RESUMO

Lubrication plays a pivotal role in reducing energy consumption and machinery wear, profoundly impacting technological and economic development and the environment. A recent study ( Erdemir , A. , et al. Nature 2016 , 536 , 67 ) reported the effective extraction of carbon-based tribofilms from lubricating oil by catalytic activation of the coating material, opening new possibilities for innovative lubrication material research and development. Here, we showcase a solute-atom-strengthened and catalytically functionalized coating design and demonstrate its implementation in a TiN-Ag solid solution film that exhibits concurrent ultralow friction and ultralow wear. Indentation tests and Raman and X-ray photoelectron spectroscopy combined with quantum mechanical simulations uncover the rare superhard nature of the TiN-Ag film along with a solute-Ag-atom-induced self-oxidation mechanism for its outstanding catalytic capacity. These findings identify an outstanding type of mechanically strong and catalytically active coating material with simultaneous superior protective and lubricating functionality, holding great promise for applications ranging from microdevices to large-scale industrial equipment.

5.
Int J Biol Macromol ; 148: 41-48, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917981

RESUMO

We obtained a new acidic soy hull polysaccharide (SHP-1) with a molecular weight (Mw) of 4.81 × 105 g/mol through ammonium oxalate and microwave assisted extraction. SHP-1 was mainly composed of galacturonic acid, galactose, rhamnose and arabinose (molar ratio = 46.59%:17.95%:14.77%:13.97%) with small amounts of fucose, glucose, mannose and xylose. The chemical structure was presumed to be of pectin-I type, consisting of 2/3 HGA and 1/3 RG-I. Furthermore, the rheological information and the chain morphology of SHP-1 were different in five solvents. Surfactant, salt and alkali solutions enhanced the solubility and flexibility of the polysaccharide, but the polysaccharide showed decreased fluidity under acidic conditions. The addition of ions and alkali increased the consistency coefficient of the solution, but the effect was far less than that of the cross-linking morphology. The structural and morphological information of purified SHP should aid in further study of its structure-function relationships and applications.

6.
Food Chem ; 313: 126095, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31923873

RESUMO

Core-shell hydrogel beads were successfully produced from soybean hull polysaccharides (SHP). Using electron microscopy, the beads were found to be spherical with smooth surfaces and have tight gel network internal structures. Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction were used to investigate the interaction between soy isoflavone and SHP in the gel beads mesh-like structure. Furthermore, the encapsulation efficiency and loading capacity of gel beads for soy isoflavone are 66.90% and 4.67%, respectively, and have the ability of pH-responsive release in vitro. Through the mathematical model of kinetics, we found that the release of soy isoflavone from gel beads showed Fickian diffusion in release media (pH 2.0 and 7.4), but showed non-Fickian diffusion at pH 4.0 and 6.8. This polymer can be extended to prepare more versatile delivery and controlled release system, appealing for food, pharmaceutical, biomedicine and cosmetics applications.


Assuntos
Hidrogéis/química , Isoflavonas/química , Polissacarídeos/química , Soja/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Isoflavonas/metabolismo , Cinética
7.
Nutrients ; 12(2)2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31991934

RESUMO

This study aimed to investigate the effect of sesamol (SEM) on the protein kinase A (PKA) pathway in obesity-related hepatic steatosis treatment by using high-fat diet (HFD)-induced obese mice and a palmitic acid (PA)-treated HepG2 cell line. SEM reduced the body weight gain of obese mice and alleviated related metabolic disorders such as insulin resistance, hyperlipidemia, and systemic inflammation. Furthermore, lipid accumulation in the liver and HepG2 cells was reduced by SEM. SEM downregulated the gene and protein levels of lipogenic regulator factors, and upregulated the gene and protein levels of the regulator factors responsible for lipolysis and fatty acid ß-oxidation. Meanwhile, SEM activated AMP-activated protein kinase (AMPK), which might explain the regulatory effect of SEM on fatty acid ß-oxidation and lipogenesis. Additionally, the PKA-C and phospho-PKA substrate levels were higher after SEM treatment. Further research found that after pretreatment with the PKA inhibitor, H89, lipid accumulation was increased even with SEM administration in HepG2 cells, and the effect of SEM on lipid metabolism-related regulator factors was abolished by H89. In conclusion, SEM has a positive therapeutic effect on obesity and obesity-related hepatic steatosis by regulating the hepatic lipid metabolism mediated by the PKA pathway.

8.
Medicine (Baltimore) ; 99(4): e18876, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977891

RESUMO

The relationship between monocyte count and mortality seemed to be varied in different diseases, and it remains unclear in type 2 diabetes (T2D). We conducted a prospective study to investigate whether monocyte count predict all-cause mortality in patients with T2D.In this prospective study, a total of 1073 patients with T2D were enrolled at baseline and 880 patients completed the follow up. The median follow-up time was 47 months. At baseline, clinical characteristics including height, weight, waist circumference, blood pressure were recorded. Biochemical parameters including counts of white blood cells (WBCC), neutrophil (NC) and monocyte (MC), lipid profiles, glycated hemoglobin (HbA1c), serum creatinine were measured. Charlson comorbidity index (CCI) was calculated based on age and comorbidities. Participants were stratified into low, median, and high tertiles according to the baseline MC. Regression models were used to analyze the associations of peripheral MC and the all-cause mortality.Compared to the survived subjects, the baseline MC was significantly higher in patients who deceased during the follow-up (0.45 ±â€Š0.16 vs 0.37 ±â€Š0.15 × 10/L, P = .003). In the multivariate Cox hazard models, subjects in higher MC tertile showed higher risks of all-cause mortality (low tertile as the reference, hazard ratio [HR] 95%CI 2.65 [0.84,8.31] and 3.73 [1.14,12.24] for middle and high MC tertile, respectively) after adjusted for gender, body mass index, CCI, duration of T2D, history of hypertension and metabolic syndrome, drugs, levels of high-sensitivity C-reactive protein, systolic blood pressure, HbA1c, WBCC, and NC. In T2D patients with macro-vascular complications at baseline, 1-SD increment of MC resulted in 1.92-fold higher risk of all-cause mortality. However, the relationship disappeared in subjects without macro-vascular complications at baseline (1.13 [0.72, 1.78], P = .591).Peripheral monocyte count is an independent predictor of all-cause mortality in T2D, especially for subjects with macro-vascular complications.


Assuntos
Diabetes Mellitus Tipo 2/mortalidade , Angiopatias Diabéticas/mortalidade , Monócitos/metabolismo , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/metabolismo , Humanos , Pessoa de Meia-Idade , Monócitos/patologia , Modelos de Riscos Proporcionais , Estudos Prospectivos
9.
Biochem Biophys Res Commun ; 522(2): 471-478, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31780258

RESUMO

The inhibition of high glucose on the proliferation and differentiation of osteoblast in alveolar bone are well documented. However, a comprehensive study focused on the molecular mechanisms is still unknown. Recent studies have revealed that caspase-1 participates in the pathological processes of hepatic injury, cancers and diabetes related complications. However, the relationship between pyroptosis and proliferation and differentiation of osteoblasts has not been investigated. This study aimed to explore the possible pyroptosis participating in the inhibition of high glucose on the proliferation and differentiation of osteoblast in alveolar bone. The diabetes model was constructed both in vitro and in vivo to detect the expression of pyroptosis related factors. These results show that high glucose inhibits proliferation and differentiation of osteoblast in alveolar bone through pyroptosis pathway. Furthermore, caspase-1 inhibitor was co-administered with high glucose in ME3T3-E1 cells, which shows that caspase-1 inhibitor could repress effect of high glucose on the proliferation and differentiation of osteoblast. In conclusion, High glucose could activate the pyroptosis through the caspase-1/GSDMD/IL-1ß pathway to inhibit the proliferation and differentiation of osteoblast in alveolar bone, which provides a theoretical basis for clinical treatment of alveolar bone disease in diabetic patients.

10.
Colloids Surf B Biointerfaces ; 186: 110707, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31830706

RESUMO

The interaction between soyasaponin and soy ß-conglycinin (7S) or glycinin (11S), adsorption of their mixtures at air-water interface, and foaming properties of the mixed system were investigated in this study. Fluorescence spectroscopy results showed that there was a weak binding of soyasaponin with 7S or 11S in bulk solutions, leading to the conformational changes of protein by nonspecific hydrophobic interactions. Dynamic surface properties of soyasaponin-7S/11S mixtures indicated that the composite layers formed via their weak interactions due to the synergy of reducing surface tension and the plateau of elasticity at the interface. Most mixtures represented high foam forming ability and stability except 0.2 % soyasaponin mixture, which could be a consequence that the surface behavior was dominated by soyasaponin under this concentration, and low surface elasticity lead to a less stable interfacial film. Overall, foamability of soyasaponin-7S mixtures were better than 11S ones. All data of this work was helpful to understand air-water behaviors of soyasaponin-7S/11S mixtures. This mixed system has shown good potential for further foam related industrial applications.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31795269

RESUMO

Left-behind children (LBC) are a newly emerged social group in China. Poor nutritional status is particularly prominent in this population. However, their food insecurity tends to attract very little attention. This study aims to investigate the relationship between food insecurity and undernutrition (stunting and anaemia) in 3 to 5-year-old LBC in rural China. Face-to-face interviews were administered to 553 LBC caregivers in 40 rural villages of Hunan Province, China. The Household Food Insecurity Access Scale (HFIAS) was used to assess household food insecurity (HFI). Dietary diversity score (DDS) and food group consumption frequency were measured by 24 h-recall and food frequency questionnaires (FFQ). Hemoglobin tests and anthropometric measurements including height and weight were measured by trained health professionals. Logistic regression was constructed to assess the association between household food insecurity and dietary diversity, stunting, and anaemia. A high prevalence of household food insecurity was determined (67.6%). The weighted prevalence of stunting and anaemia were 16.6% and 26.5%, respectively. Food insecurity was positively associate with LBC stunting (severe HFI: OR = 6.50, 95% CI: 2.81, 15.00; moderate HFI: OR = 3.47, 95% CI: 1.60, 7.54), and anaemia (severe HFI: OR = 1.91, 95% CI: 1.02, 3.57). LBC with food insecurity had significantly lower dietary diversity than those who were food-secure (p < 0.001). The prevalence of household food insecurity among LBC in poor rural China is high and is associated with low DDS, stunting, and anaemia. Nutritional intervention programs and policies are urgently needed to reduce household food insecurity and undernutrition for this vulnerable population.

12.
Cell Rep ; 29(11): 3693-3707.e5, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31825845

RESUMO

When the core body temperature is higher than 40°C, life is threatened due to heatstroke. Tumor repressor p53 is required for heat-induced apoptosis at hyperthermia conditions (>41°C). However, its role in sub-heatstroke conditions (≤40°C) remains unclear. Here, we reveal that both zebrafish and human p53 promote survival at 40°C, the heatstroke threshold temperature, by preventing a hyperreactive heat shock response (HSR). At 40°C, both Hsf1 and Hsp90 are activated. Hsf1 upregulates the expression of Hsc70 to trigger Hsc70-mediated protein degradation, whereas Hsp90 stabilizes p53 to repress the expression of Hsf1 and Hsc70, which prevents excessive HSR to maintain cell homeostasis. Under hyperthermia conditions, ATM is activated to phosphorylate p53 at S37, which increases BAX expression to induce apoptosis. Furthermore, growth of p53-deficient tumor xenografts, but not that of their p53+/+ counterparts, was inhibited by 40°C treatment. Our findings may provide a strategy for individualized therapy for p53-deficient cancers.

13.
Food Nutr Res ; 632019.
Artigo em Inglês | MEDLINE | ID: mdl-31692782

RESUMO

Background: Obesity has currently become a serious social problem to be solved. Sesamol, a natural bioactive substance extracted from sesame oil, has shown multiple physiological functions, and it might have an effect on the treatment of obesity. Objective: This study was conducted to investigate the therapeutic effect and potential mechanisms of sesamol on the treatment of obesity and metabolic disorders in high-fat diet (HFD)-induced obese mice. Methods: C57BL/6J male mice were fed HFD for 8 weeks to induce obesity, followed by supplementation with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage) for another 4 weeks. Hematoxylin and eosin staining was used to observe lipid accumulation in adipose tissues and liver. Chemistry reagent kits were used to measure serum lipids, hepatic lipids, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. ELISA kits were used to determine the serum insulin and free fatty acid (FFA) levels. Western blotting was used to detect the protein levels involved in lipid metabolism in the liver. Results: Sesamol significantly reduced the body weight gain of obese mice and suppressed lipid accumulation in adipose tissue and liver. Sesamol also improved serum and hepatic lipid profiles, and increased insulin sensitivity. In the sesamol-treated group, the levels of serum ALT and AST decreased significantly. Furthermore, after sesamol treatment, the hepatic sterol regulatory element binding protein-1 (SREBP-1c) decreased, while the phosphorylated hormone sensitive lipase (p-HSL), the carnitine palmitoyltransferase 1α (CPT1α), and the peroxisome proliferator-activated receptor coactivator-1α (PGC1α) increased, which were responsible for the fatty acid synthesis, lipolysis, and fatty acid ß-oxidation, respectively. Conclusions: Sesamol had a positive effect on anti-obesity and ameliorated the metabolic disorders of obese mice. The possible mechanism of sesamol might be the regulation of lipid metabolism in the liver.

14.
Med Sci Monit ; 25: 8230-8241, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677259

RESUMO

BACKGROUND With the progress in surgical techniques and management of complications, pancreatic resection can be safely performed in experienced hospitals. Pancreatic resection enables surgeons to assess the effect of surgery for metastatic cases, even when there is limited information. In the present study we evaluated the role of primary tumor resection for metastatic pancreatic cancer (mPC) by using the Surveillance, Epidemiology and End Results (SEER) database. MATERIAL AND METHODS Metastatic pancreatic cancer patients treated at our hospital from 2004 to 2015 were identified. The effect of surgery on cancer-specific survival was assessed by restricted mean survival time (RMST) and stabilized inverse probability of treatment weight-adjusted analysis after propensity score matching (PSM). RESULTS A total of 2694 mPC patients were included. Of this population, 365 adults underwent primary tumor resection. After propensity matching, postsurgical patients had longer RMST than non-surgery patients (1: 1 PSM 11.60 months vs. 8.98 months; 1: 2 PSM 11.61 months vs. 9.10 months; p<0.01). Stabilized inverse probability of treatment weight-adjusted analysis yielded similar results (p<0.01). CONCLUSIONS Our study supports the hypothesis that patients with mPC can benefit from primary tumor surgery. However, the surgical inclusion criteria and the appropriate role of surgery, such as its effect on symptom control, quality of life, and the extent to which it prolongs survival for metastatic pancreatic cancer, remain to be completely assessed by well-designed, prospective, randomized clinical trials.

15.
Gastroenterol Res Pract ; 2019: 3903451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687013

RESUMO

Background: Permissive hypercapnia has been recommended during the treatment of chronic diseases; however, there are insufficient clinical data to investigate the feasibility of permissive hypercapnia in relatively long-term surgeries such as laparoscopic surgery for rectal carcinoma. This prospective study is aimed at investigating the efficacy and safety of permissive hypercapnia under different CO2 pneumoperitoneum pressures during the laparoscopic surgery for rectal carcinoma. Methods: A total of 90 patients undergoing laparoscopic surgery for rectal carcinoma were recruited from July 2016 to March 2017. They were randomly assigned to high hypercapnia group (n = 30), low hypercapnia group (n = 30), or control group (n = 30), whose PaCO2 levels were maintained at 56-65 mmHg, 46-55 mmHg, or 35-45 mmHg, respectively. The primary endpoint was peak pressure. Plateau pressure, dynamic compliance, arterial blood analysis, and hemodynamic measures were collected as secondary outcomes. Adverse events were monitored. Results: High hypercapnia group were reported to be associated with significantly lower peak pressure and plateau pressure, but higher dynamic compliance compared to low hypercapnia and control group (all P < 0.01). Moreover, patients in the high hypercapnia group had higher postoperation oxygenation index values compared to those in the low hypercapnia and control group (all P < 0.01). There is no significant difference in the pH, Spo2, MAP, heart rate, and adverse events among the three groups. Conclusion: Permissive hypercapnia with a PaCO2 level of 56-65 mmHg was able to improve respiratory function after laparoscopic surgery in rectal cancer patients.

16.
J Med Food ; 22(12): 1271-1279, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31718395

RESUMO

Hepatic injury is significant in the pathogenesis and development of many types of liver diseases. Punicalagin (PU) is a bioactive antioxidant polyphenol found in pomegranates. To explore its protective effect against carbon tetrachloride (CCl4)-induced liver injury and the mechanism, Institute of Cancer Research (ICR) mice and L02 cells were used to observe the changes of serum biochemical indicators, histopathological liver structure, cell viability, antioxidative indices, and autophagy-related proteins were assessed. In ICR mice, PU ameliorated the CCl4-induced increase of the serum aspartate aminotransferase, alanine aminotransferase, the activity of liver lactate dehydrogenase, and the damage of histopathological structure, and exhibited a hepatoprotective effect against CCl4. PU attenuated oxidative stress by decreasing the liver malondialdehyde level and increasing the activities of liver superoxide dismutase, glutathione peroxidase, and the expression of the liver nuclear factor E2-related factor (Nrf2) protein. Furthermore, according to the vivo and vitro experiments, PU might activate autophagy through the mediation of the Akt/FOXO3a and P62/Nrf2 signaling pathway. Taken together, these results suggest that PU may protect against CCl4-induced liver injury through the upregulation of antioxidative activities and autophagy.

17.
Nutrients ; 11(11)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731808

RESUMO

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

18.
J Agric Food Chem ; 67(50): 13948-13959, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31698901

RESUMO

The aim of this study was to investigate the protective effect of punicalagin (PU), which is a main component of pomegranate polyphenols, against liver injury induced by Type 2 diabetes mellitus (T2DM) and to explore the molecular mechanism based on autophagy in vivo and in vitro. In T2DM mice, we found that PU significantly improved liver histology, reversed serum biochemical abnormalities, and increased the autophagosome number in the liver. In HepG2 cells cultured in a high-glucose environment, PU upregulated the glucose uptake level. Both in vivo and in vitro, PU upregulated the expression of autophagy-related proteins, such as LC3b and p62, and reduced the phosphorylated Akt/total Akt and phosphorylated FoxO3a/total FoxO3a protein ratios, and these effects were enhanced by LY294002 (a PI3K/Akt inhibitor). In summary, our current findings suggest that PU protects against liver injury induced by T2DM by restoring autophagy through the Akt/FoxO3a signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Proteína Forkhead Box O3/metabolismo , Taninos Hidrolisáveis/administração & dosagem , Hepatopatias/prevenção & controle , Fígado/lesões , Substâncias Protetoras/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Proteína Forkhead Box O3/genética , Humanos , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
19.
mBio ; 10(5)2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615964

RESUMO

ADP ribosylation factor (Arf) small GTPase family members are involved in vesicle trafficking and organelle maintenance in organisms ranging from Saccharomyces cerevisiae to humans. A previous study identified Magnaporthe oryzae Arf6 (MoArf6) as one of the Arf proteins that regulates growth and conidiation in the rice blast fungus M. oryzae, but the remaining family proteins remain unknown. Here, we identified six additional Arf proteins, including MoArf1, MoArl1, MoArl3, MoArl8, MoCin4, and MoSar1, as well as their sole adaptor protein, MoGga1, and determined their shared and specific functions. We showed that the majority of these proteins exhibit positive regulatory functions, most notably, in growth. Importantly, MoArl1, MoCin4, and MoGga1 are involved in pathogenicity through the regulation of host penetration and invasive hyphal growth. MoArl1 and MoCin4 also regulate normal vesicle trafficking, and MoCin4 further controls the formation of the biotrophic interfacial complex (BIC). Moreover, we showed that Golgi-cytoplasm cycling of MoArl1 is required for its function. Finally, we demonstrated that interactions between MoArf1 and MoArl1 with MoGga1 are important for Golgi localization and pathogenicity. Collectively, our findings revealed the shared and specific functions of Arf family members in M. oryzae and shed light on how these proteins function through conserved mechanisms to govern growth, transport, and virulence of the blast fungus.IMPORTANCE Magnaporthe oryzae is the causal agent of rice blast, representing the most devastating diseases of rice worldwide, which results in losses of amounts of rice that could feed more than 60 million people each year. Arf (ADP ribosylation factor) small GTPase family proteins are involved in vesicle trafficking and organelle maintenance in eukaryotic cells. To investigate the function of Arf family proteins in M. oryzae, we systematically characterized all seven Arf proteins and found that they have shared and specific functions in governing the growth, development, and pathogenicity of the blast fungus. We have also identified the pathogenicity-related protein MoGga1 as the common adaptor of MoArf1 and MoArl1. Our findings are important because they provide the first comprehensive characterization of the Arf GTPase family proteins and their adaptor protein MoGga1 functioning in a plant-pathogenic fungus, which could help to reveal new fungicide targets to control this devastating disease.

20.
Oncogenesis ; 8(10): 59, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597912

RESUMO

Chemoresistance has been the biggest obstacle in ovarian cancer treatment, and STAT3 may play an important role in chemoresistance of multiple cancers, but the underlying mechanism of STAT3 in ovarian cancer chemoresistance has long been truly illusive, particularly in association with p53 and RAS signaling. In this study, by using wild type, constitutive active, and dominant negative STAT3 constructs, wild-type p53, and RAS-mutant V12, we performed a series of in vitro and in vivo experiments by gene overexpression, drug treatment, and animal assays. We found that phosphorylation of STAT3 Y705 but not S727 promoted cancer cell EMT and metastasis through the Slug-mediated regulation of E-cadherin and Vimentin. The phosphorylation of STAT3 at Y705 also activated the MAPK and PI3K/AKT signaling to inhibit the ERS-mediated autophagy through down-regulation of pPERK, pelf2α, ATF6α, and IRE1α, which led to increased cisplatin resistance. Induction of wild type p53 in STAT3-DN-transfected cells further diminished the chemoresistance and tumor growth through the upregulation of the MAPK- and PI3K/AKT-mediated ERS and autophagy. Introduction of STAT3-DN deprived the RASV12-induced ERS, autophagy, oncogenicity, and cisplatin resistance, whereas introduction of p53 in STAT3-DN/RASV12 expressing cells induced additional tumor retardation and cisplatin sensitivity. Thus, our data provide strong evidence that the crosstalk between STAT3 and p53/RAS signaling controls ovarian cancer cell metastasis and cisplatin resistance via the Slug/MAPK/PI3K/AKT-mediated regulation of EMT and autophagy.

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