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1.
Oncogene ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477833

RESUMO

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Currently, the prognosis of the patients with GBM is very poor and new molecular targets and treatment strategies are urgently needed to combat it. MicroRNA-148a (miR-148a) has been shown to be dysregulated in certain tumor types. However, the role of miR-148a in the pathogenesis of GBM is not fully understood. Here we comprehensively analyzed the roles of miR-148a, downstream DLGAP1, and their molecular pathways in GBM. We showed that miR-148a promote the proliferation and growth of GBM cells both in vitro and in vivo, and also induced the migration, invasion, and EMT (epithelial-mesenchymal transition) program of GBM cells by directly targeting DLGAP1. Furthermore, we identified 31 new miR-148a targets and found that miR-148a function was mainly involved in the cell adhesion signaling pathway and was associated with nervous system diseases. Our findings provide a new mechanism for miR-148a-mediated GBM cell invasion and reveal previously unreported targets of miR-148a as well as novel miR-148a-mediated regulatory networks in GBM. These results increase the understanding of the role of miR-148a in GBM and may lead to novel therapeutic strategies for GBM.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31444203

RESUMO

This study reports that a high concentration of the endo-ß-1,3-glucanase ENG (200 µg mL-1) induced heat-inactivated stipe wall extension of C. cinerea, whereas a high concentration of the extracellular ß-glucosidase BGL2 (1000 µg mL-1) did not; however, in combination, low concentrations of ENG (25 µg mL-1) and BGL2 (260 µg mL-1) induced heat-inactivated stipe cell wall extension. In contrast to the previously reported chitinase-reconstituted stipe wall extension, ß-1,3-glucanase-reconstituted heat-inactivated stipe cell wall extension initially exhibited a fast extension rate that quickly decreased to zero after approximately 60 min; the stipe cell wall extension induced by a high concentration of ß-1,3-glucanase did not result in stipe breakage during measurement, and the inner surfaces of glucanase-reconstituted extended cell walls still remained as amorphous matrices that did not appear to have been damaged. These distinctive features of the ß-1,3-glucanase-reconstituted wall extension may be because chitin chains are not only cross-linked to the nonreducing termini of the side chains and the backbones of ß-1,6 branched ß-1,3-glucans but also to other polysaccharides. Remarkably, a low concentration of either the ß-1,3-glucanase ENG or of chitinase ChiE1 did not induce heat-inactivated stipe wall extension, but a combination of these two enzymes, each at a low concentration, showed stipe cell wall extension activity that exhibited a steady and continuous wall extension profile. Therefore, it is concluded that the stipe cell wall extension is the result of the synergistic actions of glucanases and chitinases.IMPORTANCE We previously reported that the chitinase could induce stipe wall extension and involve in stipe elongation growth of mushroom C. cinerea In this study, we explored that ß-1,3-glucanase also induced stipe cell wall extension. Interestingly, the extension profile and extended ultra-architecture of ß-1,3-glucanase-reconstituted stipe wall were different from that of chitinase-reconstituted stipe wall. However, ß-1,3-glucanase cooperated with chitinase to induce stipe cell wall extension. The significance of this synergy between glucanases and chitinases is that it enables a low concentration of active enzymes to induce wall extension and the involvement of ß-1,3-glucanases is necessary for the cell wall remodeling and the addition of new ß-glucans during stipe elongation growth.

3.
Medicine (Baltimore) ; 98(31): e16488, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374010

RESUMO

INTRODUCTION: Intrapancreatic accessory spleen (IPAS) has been rarely noted radiologically because the spatial resolution of conventional images was low. The infrequent presence of the accessory spleen in the pancreatic tissue could lead to inappropriate diagnosis, thereby necessitating a therapeutic approach. The present study reported such cases and summarized the available imaging findings to reduce unnecessary invasive surgeries. PATIENT CONCERNS: The patient's complaint was "a pancreatic mass was found for half a month." DIAGNOSIS: IPAS was eventually diagnosed by pathology. INTERVENTIONS: Laparoscopic spleen-preserving pancreatic resection. OUTCOMES: Postoperative course was uneventful and the patient was discharged from our hospital after 10 days. CONCLUSIONS: When an asymptomatic pancreatic mass is detected, the diagnosis of IPAS should not be excluded, especially if the lesion has the same imaging features as the spleen. As a definite diagnosis of IPAS is difficult by a single examination, multiple techniques might be essential.


Assuntos
Laparoscopia/métodos , Pâncreas/cirurgia , China , Feminino , Humanos , Laparoscopia/normas , Pessoa de Meia-Idade , Baço/lesões , Baço/cirurgia , Tomografia Computadorizada por Raios X/métodos
4.
Int J Biol Macromol ; 140: 858-870, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31446105

RESUMO

One purified fraction from crude Fuzhuan brick tea polysaccharides (FBTPS), FBTPS-3, was obtained through column chromatography of DEAE Sepharose Fast Flow. The chemical properties and probiotic effects of FBTPS-3 were evaluated by fermentation in vitro. Moreover, the effects of FBTPS-3 on the function and metabolic pathway of gut microbiota were investigated by metagenomic sequencing. The results showed that FBTPS-3 was an heteropolysaccharide with molecular weight of 741 kDa, which was mainly composed of Man, Rha, GalA, Gal and Ara in molar ratio of 8.7:15.5:42.2:19.7:13.9. The contents of carbohydrates and uronic acid in FBTPS-3 were 44.78 ±â€¯2.85% and 40.4 ±â€¯2.11%, respectively. After fermentation, the molecular weight of FBTPS-3 and content of carbohydrates were significantly decreased, indicating that FBTPS-3 could be utilized by gut microbiota. Furthermore, the relative abundances of Bacteroides, Megasphaera and Prevotella were significantly increased by FBTPS-3. FBTPS-3 also significantly promoted the production of acetic, propionic and n-butyric acids. Based on the metagenomic sequencing, it was found that FBTPS-3 significantly enriched the metabolic pathway of starch and sucrose. All the results suggest that FBTPS-3 is expected to be developed as functional ingredients or foods to improve the host health through regulating the gut microbiota and physiological metabolic functions.

5.
J Phys Chem Lett ; 10(15): 4297-4302, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31318568

RESUMO

A cyanuric acid and melamine (CA·M) supramolecular network, prepared via the drop-casting method under ambient conditions, can be utilized as a spacer layer to decouple electronic interactions between upper organics and the metal substrate. Typical semiconducting organics 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) and C60 are deposited on the CA·M network under ultrahigh vacuum conditions, forming an organics/CA·M/metal heterosystem. Both geometric and electronic structures of the upper organics are characterized by using scanning tunneling microscopy/spectroscopy (STM/STS). On the CA·M network, PTCDA molecules form a well-ordered herringbone structure in submonolayer patterns, whereas C60 molecules aggregate into multilayered islands. STS spectra reveal that the energy gap between the highest occupied and the lowest unoccupied molecular orbitals (HOMO - LUMO) is 3.6 eV for PTCDA and 3.8 eV for the first layer of C60 on CA·M. The remarkable bandgap broadening compared with the metal-organic contact indicates successful electronic decoupling of the upper molecules from the metal surface due to the CA·M network.

6.
J Med Chem ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31276399

RESUMO

Glycoconjugation is a promising modification strategy for the optimization of peptide drugs. In this study, five different monosaccharide derivatives (7a-e) were covalently linked to the N-terminal of R-lycosin-I, which yielded five glycopeptides (8a-e). They demonstrated increased or reduced cytotoxicity depending on monosaccharide types, which might be explained by the changes of physicochemical properties. Among all synthesized glycopeptides, only 8a exhibited increased cytotoxicity (IC50 = 9.6 ± 0.3 µM) and selectivity (IC50 = 37.4 ± 5.9 µM). The glucose transporter 1 (GLUT1) with high expression in cancer cells was approved to be involved in the cytotoxicity and selectivity enhancement of 8a. Furthermore, 8a but not R-lycosin-I inhibited tumor growth in the nude mice xenograft model without generating side effects intraperitoneally. Taken together, this study reveals the different monosaccharide roles in peptide modification and also provides an optimized anticancer peptide with high activity and selectivity, that is, 8a might be a promising lead for developing anticancer drugs.

7.
J Vet Sci ; 20(3): e23, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161741

RESUMO

The clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is a versatile genome editing tool with high efficiency. A guide sequence of 20 nucleotides (nt) is commonly used in application of CRISPR/Cas9; however, the relationship between the length of the guide sequence and the efficiency of CRISPR/Cas9 in porcine cells is still not clear. To illustrate this issue, guide RNAs of different lengths targeting the EGFP gene were designed. Specifically, guide RNAs of 17 nt or longer were sufficient to direct the Cas9 protein to cleave target DNA sequences, while 15 nt or shorter guide RNAs had loss-of-function. Full-length guide RNAs complemented with mismatches also showed loss-of-function. When the shortened guide RNA and target DNA heteroduplex (gRNA:DNA heteroduplex) was blocked by mismatch, the CRISPR/Cas9 would be interfered with. These results suggested the length of the gRNA:DNA heteroduplex was a key factor for maintaining high efficiency of the CRISPR/Cas9 system rather than weak bonding between shortened guide RNA and Cas9 in porcine cells.

8.
Theriogenology ; 135: 19-24, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31189122

RESUMO

Approximately 40% of mammalian genome is made of transposable elements (TEs), and during specific biological processes, such as gametogenesis, they may be activated by global demethylation, so strict silencing mechanism is indispensable for genomic stability. Here, we performed small RNA-seq on Dicer1 knockdown (KD) oocytes in pig, and observed short interspersed nuclear elements 1B (SINE1B) derived endogenous small interfering RNAs (endo-siRNAs), termed SINE1B-siRNAs, were significantly decreased and their biogenesis was dependent on Dicer1 and transcript of SINE1B. Furthermore, by injection of mimics and inhibitors of the SINE1B-siRNAs into germinal vesicle-stage (GV-stage) oocytes, we found the maturation rate was significantly decreased by SINE1B-siRNAs, indicating the SINE1B-siRNAs are indispensible for in vitro maturation (IVM) of porcine oocyte. To figure out the mechanism, we checked the expression pattern and DNA methylation status of SINE1B during IVM of porcine oocytes, and demonstrated the SINE1B-siRNAs could repress SINE1B expression induced by hypomethylation at a post-transcriptional level. Our results suggest that during gametogenesis when the erasure of DNA methylation occurs, endo-siRNAs act as a chronic response to limit retrotransposon activation.

9.
Biomaterials ; 216: 119252, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31212086

RESUMO

Development of high-performance photoactive agents with tumor-specific capability for effective nanotherapeutics has received much attention in the past decades. Herein, we report a nanotherapeutic based on bis-diketopyrrolopyrrole (BDPP) conjugated polymer nanoparticles (PBDPP NPs) with remarkable near-infrared (NIR) absorption at 808 nm and high photothermal energy conversion efficiency up to 60%. In particular, precise glioblastoma-specific capability and killing ability for glioblastoma cells were effectively achieved in vitro by treating with only PBDPP NPs to induce cell apoptosis or by interaction with PBDPP NPs under NIR laser irradiation to trigger cell necrosis. Impressively, a half-maximal inhibitory concentration as low as of ∼0.15 µg mL-1 was achieved, and the magnitude is 5 to 4.4 × 104-fold lower than those of reported agents. In vivo experiment with mice further shows that the PBDPP NPs show good efficacy of photothermal therapy and complete tumor elimination using a record-low dosage of 0.35 mg mL-1 under 808 nm irradiation of low power (0.5 W cm-2). This study thus demonstrates a promising strategy of low-dose, high-efficacy polymer-based nanoagonist for specific phototherapy of glioblastoma.

10.
J Immunol Res ; 2019: 2431617, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240232

RESUMO

Th17 activity has been implicated in systemic lupus erythematosus (SLE), which is a systemic autoimmune disease with a typical clinical manifestation of lupus nephritis (LN). Retinoic acid receptor-related orphan receptor gamma t (RORγt) has been shown to be important for Th17 differentiation. In this study, we evaluated the inhibition of RORγt activity by 3ß-acetyloxy-oleanolic acid (AOA), a small molecule isolated from the root of Symplocos laurina, a traditional herb belonging to South China. We demonstrated that AOA can inhibit RORγt activity and prevent SLE pathogenesis in a pristane-induced LN model. The results showed that AOA decreased RORγt transcription activity in a reporter assay and prevented Th17 differentiation in vitro. In vivo studies showed that AOA treatment decreased serum anti-dsDNA antibody and alleviated renal pathologic damage as well as antibody complex accumulation in the pristane-induced LN model. These results demonstrated that AOA can improve the clinical manifestation of LN, indicating potential application in SLE therapy.

11.
J Food Sci ; 84(7): 1746-1757, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31206686

RESUMO

'Anji Baicha' (Camellia sinensis) is a low-temperature-sensitive tea variety. During the development of young shoots, the leaves of 'Anji Baicha' exhibit periodic albinism. The quality of 'Anji Baicha' is closely related to the color of the fresh leaves, with whiter leaves affording a higher amino acid content and superior sensory quality after processing. However, the metabolic mechanism of its quality formation is still unclear. In this study, we analyzed the metabolomic changes of young shoots of 'Anji Baicha' and screened for metabolic markers that may be involved in the periodic albinism. Positive- and negative-mode UPLC-QTOF-MS was applied to the metabolomic analysis of young leaves of 'Anji Baicha' during three developmental stages (i.e., the pre-albescent, albescent, and regreening stages). The results revealed significant differences in the metabolic profiles of the young leaves at the three stages. The differential metabolites were mainly related to the pathways of flavonoid, phenylpropanoid, and amino acid biosynthesis. The concentrations of several amino acids (primarily l-theanine, l-glutamate, N2 -acetyl-l-ornithine, l-aspartic acid, d-proline, l-glutamine, l-leucine, and pyroglutamic acid) and 12-OPDA were significantly higher in the albescent stage. In contrast, during the albescent stages, the concentrations of several carbohydrates (d-fructose, ß-d-galactopyranose, 3-O-fucopyranosyl-2-acetamido-2-deoxyglucopyranose, galactose-ß-1, 4-xylose acetyl-maltose, and 2-fucosyllactose) were significantly lower. Moreover, catechins (mainly epigallocatechin and catechin derivatives), dimeric catechins (primarily proanthocyanidins), and flavonol and flavonol/flavone glycosides (mainly kaempferol, myricetin, quercetin, cyanidin, and delphinidin glycosides) were detected at the highest levels in the regreening or pre-albescent stages. The obtained results enhance the current understanding of the metabolic mechanisms of periodic albinism and quality development formation in 'Anji Baicha'. PRACTICAL APPLICATION: The obtained results not only provide information regarding differential metabolites but also advance the understanding of the mechanism of periodic albinism in 'Anji Baicha' at the metabolite level and open up new possibilities for the genetic improvement of tea cultivars.

12.
Diabetes ; 68(9): 1747-1755, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31167879

RESUMO

We examined the causal direction between gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) or its predecessors and cardiometabolic diseases, such as risk of type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), myocardial infarction (MI), stroke, atrial fibrillation (AF), and chronic kidney disease (CKD). We used genetic variants as instruments to test the causal associations. Genetically predicted higher TMAO and carnitine were not associated with higher odds of T2DM, AF, CAD, MI, stroke, and CKD after Bonferroni correction (P ≤ 0.0005). However, we observed that genetically increased choline showed a suggestive association with higher risk of T2DM (odds ratio 1.84 [95% CI 1.00-3.42] per 10 units, P = 0.05). In contrast, genetically predicted higher betaine (0.68 [0.48-0.95] per 10 units, P = 0.023) was suggestively associated with a lower risk of T2DM. We observed a suggestive association of genetically increased choline with a lower level of body fat percentage (ß ± SE -0.28 ± 0.11, P = 0.013) but a higher estimated glomerular filtration rate (0.10 ± 0.05, P = 0.034). We further found that T2DM (0.130 ± 0.036, P < 0.0001) and CKD (0.483 ± 0.168, P = 0.004) were causally associated with higher TMAO levels. Our Mendelian randomization findings support that T2DM and kidney disease increase TMAO levels and that observational evidence for cardiovascular diseases may be due to confounding or reverse causality.

13.
J Agric Food Chem ; 67(23): 6476-6486, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31117504

RESUMO

This work aims to improve the antiarthritic activity of (-)-epigallocatechin gallate (EGCG) and glucosamine (GA) through fabrication and optimization of casein protein nanoparticles (EGC-NPs). Optimized EGC-NPs were obtained with a EGCG/GA/casein ratio of 1:2:8 (w/w/w). The EGC-NPs gave a mean size of 186 ± 3.5 nm and an entrapment efficiency of 86.8 ± 2.7%, and they exhibited a greater inhibitory activity against human fibroblast-like synoviocytes-osteoarthritis cells and human fibroblast-like synoviocytes-rheumatoid arthritis cells compared with that of the EGCG-GA mixture by 33.5% and 20.8%, respectively. Freeze-dried EGC-NPs stored at 25 °C during 12 months showed high dispersion stability. Moreover, the redispersion of the freeze-dried EGC-NPs produced almost no significant changes in their physicochemical properties and bioactivity. Rat experiments demonstrated that the antiarthritis effect of the EGC-NPs was significantly higher than that of EGCG-GA mixture, as assessed through an analysis of anti-inflammatory efficacy, radiographic images and histopathological assessments of paw joints, and immunohistochemical changes in serum cytokines. The enchanced antiarthritic activity in vivo was consistent with that in vitro. The EGC-NPs demonstrate potential as a food supplement for the treatment of arthritis.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Artrite/tratamento farmacológico , Caseínas/química , Catequina/análogos & derivados , Glucosamina/química , Animais , Artrite/sangue , Catequina/administração & dosagem , Catequina/química , Citocinas/sangue , Portadores de Fármacos/química , Composição de Medicamentos , Feminino , Humanos , Nanopartículas/química , Ratos , Ratos Wistar
14.
Nat Microbiol ; 4(8): 1378-1388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31110366

RESUMO

Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-ß-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner. MPT53 induces disulfide bond formation at C210 on TAK1 to facilitate its interaction with TRAFs and TAB1, thus activating TAK1 to induce the expression of pro-inflammatory cytokines. Furthermore, MPT53 and its disulfide oxidoreductase activity is required for Mtb to induce the host inflammatory responses via TAK1. Our findings provide an alternative pathway for host signalling proteins to sense Mtb infection and may favour the improvement of current vaccination strategies.

15.
Appl Environ Microbiol ; 85(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31126941

RESUMO

The elongation growth of the mushroom stipe is a characteristic but not well-understood morphogenetic event of basidiomycetes. We found that extending native stipe cell walls of Coprinopsis cinerea were associated with the release of N-acetylglucosamine and chitinbiose and with chitinase activity. Two chitinases among all detected chitinases from C. cinerea, ChiE1 and ChiIII, reconstituted heat-inactivated stipe wall extension and released N-acetylglucosamine and chitinbiose. Interestingly, both ChiE1 and ChiIII hydrolyze insoluble crystalline chitin powder, while other C. cinerea chitinases do not, suggesting that crystalline chitin components of the stipe cell wall are the target of action for ChiE1 and ChiIII. ChiE1- or ChiIII-reconstituted heat-inactivated stipe walls showed maximal extension activity at pH 4.5, consistent with the optimal pH for native stipe wall extension in vitro; ChiE1- or ChiIII-reconstituted heat-inactivated stipe wall extension activities were associated with stipe elongation growth regions; and the combination of ChiE1 and ChiIII showed a synergism to reconstitute heat-inactivated stipe wall extension at a low action concentration. Field emission scanning electron microscopy (FESEM) images showed that the inner surface of acid-induced extended native stipe cell walls and ChiE1- or ChiIII-reconstituted extended heat-inactivated stipe cell walls exhibited a partially broken parallel microfibril architecture; however, these broken transversely arranged microfibrils were not observed in the unextended stipe cell walls that were induced by neutral pH buffer or heat inactivation. Double knockdown of ChiE1 and ChiIII resulted in the reduction of stipe elongation, mycelium growth, and heat-sensitive cell wall extension of native stipes. These results indicate a chitinase-hydrolyzing mechanism for stipe cell wall extension.IMPORTANCE A remarkable feature in the development of basidiomycete fruiting bodies is stipe elongation growth that results primarily from manifold cell elongation. Some scientists have suggested that stipe elongation is the result of enzymatic hydrolysis of cell wall polysaccharides, while other scientists have proposed the possibility that stipe elongation results from nonhydrolytic disruption of the hydrogen bonds between cell wall polysaccharides. Here, we show direct evidence for a chitinase-hydrolyzing mechanism of stipe cell wall elongation in the model mushroom Coprinopsis cinerea that is different from the expansin nonhydrolysis mechanism of plant cell wall extension. We presumed that in the growing stipe cell walls, parallel chitin microfibrils are tethered by ß-1,6-branched ß-1,3-glucans, and that the breaking of the tether by chitinases leads to separation of these microfibrils to increase their spacing for insertion of new synthesized chitin and ß-1,3-glucans under turgor pressure in vivo.

16.
Immunity ; 51(1): 43-49.e4, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097341

RESUMO

Gasdermin D (GSDMD) is an effector molecule for pyroptosis downstream of canonical and noncanonical inflammasome signaling pathways. Cleavage of GSDMD by inflammatory caspases triggers the oligomerization and lipid binding by its N-terminal domain, which assembles membrane pores, whereas its C-terminal domain binds the N-terminal domain to inhibit pyroptosis. Despite recent progress in our understanding of the structure and function of the murine gasdermin A3 (mGSDMA3), the molecular mechanisms of GSDMD activation and regulation remain poorly characterized. Here, we report the crystal structures of the full-length murine and human GSDMDs, which reveal the architecture of the GSDMD N-terminal domains and demonstrate distinct and common features of autoinhibition among gasdermin family members utilizing their ß1-ß2 loops. Disruption of the intramolecular domain interface enhanced pyroptosis, whereas mutations at the predicted lipid-binding or oligomerization surface reduced cytolysis. Our study provides a framework for understanding the autoinhibition, lipid binding, and oligomerization of GSDMD by using overlapping interfaces.

17.
Appl Microbiol Biotechnol ; 103(13): 5269-5283, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31020379

RESUMO

Gut microbiota play a key role in the regulation of obesity and associated metabolic disorders. To study the relationship between them, antibiotics have been widely used to generate pseudo-germ-free rodents as control models. However, it is not clear whether antibiotics impact an animal's metabolic phenotype. Therefore, the effect of antibiotics-induced gut microbial perturbations on metabolic phenotypes in high-fat diet (HFD) fed mice was investigated. The results showed that antibiotics perturbed gut microbial composition and structure. Community diversity and richness were reduced, and the phyla Firmicutes/Bacteroidetes (F/B) ratio was decreased by antibiotics. Visualization of Unifrac distance data using principal component analysis (PCA) and unweighted pair-group method with arithmetic mean (UPGAM) demonstrated that fecal samples of HFD-fed mice separated from those of chow diet (CD) fed mice. Fecal samples from antibiotics-treated and non-treated mice were clustered into two different microbial populations. Moreover, antibiotics suppressed HFD-induced metabolic features, including body weight gain (BWG), liver weight (LW), epididymal fat weight (EFW), and serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), fasting blood glucose (FBG), and insulin (INS) significantly (P < 0.05). Lachnospiraceae, Ruminiclostridium and Helicobacter, biomarkers of mouse gut microbiota before treatment by antibiotics, were positively correlated with obesity phenotypes significantly (P < 0.05) and were decreased by (92.95 ± 5.09) %, (97.73 ± 2.09) % and (99.48 ± 0.21) % respectively after 30 days of treatment by antibiotics. However, Bacteroidia were enriched in HFD-fed antibiotics-treated mice and were negatively correlated with obesity phenotypes significantly (P < 0.05). We suggested that the antibiotics-induced depletion of Lachnospiraceae, Ruminiclostridium, and Helicobacter, and the decrease in F/B ratio in gut microbiota played a role in the prevention of HFD-induced obesity in mice.

18.
Angew Chem Int Ed Engl ; 58(28): 9581-9585, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31034736

RESUMO

The introduction of optoelectronic functions into viscoelastic polymers can yield highly sophisticated soft materials for biomedical devices and autonomous robotics. However, viscoelasticity and excellent optoelectronic properties are difficult to achieve because the presence of a large number of π-conjugated moieties drastically stiffens a polymer. Here, we report a variation of additive-free viscoelastic conjugated polymers (VE-CPs) at room temperature by using an intact π-conjugated backbone and bulky, yet flexible, alkyl side chains as "internal plasticizers." Some of these polymers exhibit gel- and elastomer-like rheological behaviors without cross-linking or entanglement. Furthermore, binary blends of these VE-CPs exhibit a never-seen-before dynamic miscibility with self-restorable and mechanically induced fluorescence color changes.

19.
Cell Prolif ; 52(3): e12591, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896067

RESUMO

OBJECTIVES: To date, many efforts have been made to establish porcine embryonic stem (pES) cells without success. Extraembryonic endoderm (XEN) cells can self-renew and differentiate into the visceral endoderm and parietal endoderm. XEN cells are derived from the primitive endoderm of the inner cell mass of blastocysts and may be an intermediate state in cell reprogramming. MATERIALS AND METHODS: Porcine XEN cells (pXENCs) were generated from porcine pluripotent stem cells (pPSCs) and were characterized by RNA sequencing and immunofluorescence analyses. The developmental potential of pXENCs was investigated in chimeric mouse embryos. RESULTS: Porcine XEN cells derived from porcine pPSCs were successfully expanded in N2B27 medium supplemented with bFGF for least 30 passages. RNA sequencing and immunofluorescence analyses showed that pXENCs expressed the murine and canine XEN markers Gata6, Gata4, Sox17 and Pdgfra but not the pluripotent markers Oct4, Sox2 and TE marker Cdx2. Moreover, these cells contributed to the XEN when injected into four-cell stage mouse embryos. Supplementation with Chir99021 and SB431542 promoted the pluripotency of the pXENCs. CONCLUSIONS: We successfully derived pXENCs and showed that supplementation with Chir99021 and SB431542 confer them with pluripotency. Our results provide a new resource for investigating the reprogramming mechanism of porcine-induced pluripotent stem cells.


Assuntos
Endoderma/citologia , Endoderma/embriologia , Suínos/embriologia , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Técnicas de Cocultura , Cães , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Endoderma/metabolismo , Expressão Gênica , Camundongos , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Análise de Sequência de RNA , Transdução de Sinais , Suínos/genética , Suínos/metabolismo , Quimeras de Transplante
20.
Food Chem ; 287: 160-166, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30857685

RESUMO

We previously reported that an endo-ß-1,3(4)-d-glucanase, Eng16A, from C. cinerea shows a higher degradation activity toward barley ß-glucan than laminarin. HPAEC-PAD and Q-TOF-MS/MS analyses show that Eng16A-digestion products of barley ß-glucan not only contain some oligosaccharides with (1 → 3)-ß-linkage adjacent to the reducing end, which is consistent with ß-1,3(4)-glucanase-digestion products, but also include some oligosaccharides containing (1 → 4)-ß-linkage adjacent to the reducing end which is consistent with cellulase-digestion products. Thus, Eng16A possesses both cellulase and ß-1,3(4)-glucanase activities. Because Eng16A does not degrade cellulose, we propose that the insertion of a (1 → 3)-ß-linkage among the groups of (1 → 4)-ß-linkages may make these (1 → 4)-ß-linkages prone to cleavage by Eng16A. Furthermore, Eng16A also possesses transglycosylation activity which leads to some products containing one or a few consecutive (1 → 3)-ß-linkages adjacent to the non-reducing end. Therefore, HPAEC-PAD and Q-TOF-MS/MS analyses provide an efficient approach to reveal complicated modes of action of some endo-ß-1,3(4)-d-glucanases on barley ß-glucan.


Assuntos
Celulase/metabolismo , Coprinus/enzimologia , Proteínas Fúngicas/metabolismo , Hordeum/microbiologia , Espectrometria de Massas em Tandem
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