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1.
Protein Cell ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919742

RESUMO

Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washing-process. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.

2.
J Phys Chem Lett ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951143

RESUMO

The "water-in-salt" electrolytes open up exciting new avenues for expanding the electrochemical window of aqueous electrolytes. In this work, we investigated the solvation structure and dynamics of highly concentrated lithium bis(trifluoromethane)sulfonimide aqueous electrolyte using experimentally corroborated molecular dynamics simulations. The simulations revealed the heterogeneous structure of the electrolyte comprises percolating networks of ion and water domains/aggregates. Interestingly, the ionic regions are composed of more TFSI- ions than Li+ ions. The Li+ ion transport mechanism was further explored. Li+ ions can hop along the coordinated TFSI- ions in the ionic aggregates. The calculated correlated transference number of the 20 m electrolyte is ~0.32, reasonably high for the high concentration due to a weak negative correlation between the motion of cations and anions within the heterogeneous microscopic domains. These MD results connect the heterogeneous structure of the electrolyte with the correlated dynamics of the Li+ ion and provide a new understanding of the Li+ ion transport mechanism in this novel electrolyte.

3.
Acta Otolaryngol ; : 1-7, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31933416

RESUMO

Background: The traditional transcervical approach is frequently applied but limited in handling the tumors in parapharyngeal space.Objectives: We explore a new transcervical endoscopic approach with more direct visualization, less complications, and better outcomes.Material and methods: Eight cadaver heads (sixteen sides) were prepared for endoscopic dissection. Clinical cases were carefully selected, and thirty patients accepted the transcervical endoscopic surgery.Results: The transcervical approach with an endoscopic video system clearly exposed the detailed structures in the parapharyngeal space. The stylopharyngeus, styloglossus muscles, and styloid process were critical landmarks in this approach. During the thirty cases of clinical surgeries, internal carotid arteries and cranial nerves could be effectively exposed and protected with the endoscopic video system. Accurate hemostasis could be achieved under endoscopic transcervical approach with a mean amount between 30 to 100 ml of hemorrhaging. There was no postoperative hemorrhages and emergency tracheotomies. The follow up led to promising results.Conclusions and significance: The transcervical endoscopic approach provides a wide corridor for surgery in the parapharyngeal space. With accurate hemostasis, this approach can be applied as the first-line strategy for parapharyngeal surgeries in selected patients.

4.
Arch Oral Biol ; 109: 104578, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31589997

RESUMO

OBJECTIVE: The aim of this study was to observe the effect of V. parvula on the physiological activity of S. mutans and elucidate the role of V. parvula on dental caries. DESIGN: We constructed dual-species biofilms formed by V. parvula and S. mutans, and measured the pH dynamics, biofilm growth, Extracellular Polysaccharide (EPS) synthesis, and expression of S. mutans EPS synthesis-associated genes affected by V. parvula. RESULTS: pH dynamics were not altered when V. parvula and S. mutans were co-cultured during a 120 -h test period. However, S. mutans cell number and EPS synthesis in dual-species biofilms were found to be significantly higher than in single-species biofilms. Moreover, expression levels of genes encoding glucosyltransferases (gtfs), gtfB and gtfC specifically, were up-regulated when S. mutans was co-cultured with V. parvula. CONCLUSIONS: Our findings indicate that V. parvula is not, as previously thought, protective and associated with caries health. On the contrary, V. parvula might participate in caries development through interactions with S. mutans. This study suggests that V. parvula may have an impact on the pathogenesis of dental caries.


Assuntos
Biofilmes , Streptococcus mutans/fisiologia , Veillonella/fisiologia , Proteínas de Bactérias/genética , Técnicas de Cocultura , Cárie Dentária/microbiologia , Matriz Extracelular de Substâncias Poliméricas , Regulação Bacteriana da Expressão Gênica , Glucosiltransferases/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-31797004

RESUMO

Transglutaminase (TG) from Streptomyces mobaraensis has been widely used in the food industry. It is secreted naturally as an inactive zymogen, which is then activated by the removal of the N-terminal pro-peptide. In this study, the mtg gene from S. mobaraensis was expressed in a food-grade strain of bacterium, Bacillus subtilis. When its native signal peptide was replaced by signal peptide SacB (SPsacB) and the pro-peptide was replaced by that derived from S. hygroscopicus, an extracellular activity of 16.1 U/mg was observed. A modified Saccharomyces cerevisiae vacuolar ATPase subunit (VMA) intein was introduced into the zymogen to simplify its activation process by controlling temperature. When the cleavage site in the C-terminal of VMA was placed between the pro-peptide and core domain, the activation process was carried out at 18 °C. Promoter replacement further increased the enzymatic activity. Finally, the extracellular enzymatic activity reached 2.6 U/mg under the control of the constitutive promoter PyvyD. This is the first report on the extracellular production of active-form Streptomyces TG in B. subtilis without splicing with the cleavage enzyme.

6.
J Radiat Res ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822893

RESUMO

Silica is an independent risk factor for lung cancer in addition to smoking. Chronic silicosis is one of the most common and serious occupational diseases associated with poor prognosis. However, the role of radiotherapy is unclear in patients with chronic silicosis. We conducted a retrospective study to evaluate efficacy and safety in lung cancer patients with chronic silicosis, especially focusing on the incidence of radiation pneumonitis (RP). Lung cancer patients with chronic silicosis who had been treated with radiotherapy from 2005 to 2018 in our hospital were enrolled in this retrospective study. RP was graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Of the 22 patients, ten (45.5%) developed RP ≥2. Two RP-related deaths (9.1%) occurred within 3 months after radiotherapy. Dosimetric factors V5, V10, V15, V20 and mean lung dose (MLD) were significantly higher in patients who had RP >2 (P < 0.05). The median overall survival times in patients with RP ≤2 and RP>2 were 11.5 months and 7.1 months, respectively. Radiotherapy is associated with excessive and fatal pulmonary toxicity in lung cancer patients with chronic silicosis.

7.
Front Microbiol ; 10: 2693, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824464

RESUMO

Objectives: Our aim of this work was to investigate the regrowth of implant-related biofilms after various antimicrobial treatments in vitro. Methods: Saliva-derived microcosm biofilms were grown on titanium discs in an active attachment model. Treatments including hydrogen peroxide (HP), citric acid (CA), chlorhexidine (CHX), and distilled water (control), at different concentrations, were applied to 2-day biofilms for 1 or 5 min. The viability, lactic acid production, and composition of the biofilms were followed for 3 days. The biofilm composition was analyzed by 16S rDNA amplicon sequencing. Results: The short treatments of CA, CHX, and HP resulted in a 2-3 log reduction in biofilm viability and lactic acid production immediately. However, both parameters returned to the pre-treatment level within 2 days due to biofilm regrowth. The alpha diversity of the regrown biofilms in antimicrobial-treated groups tended to decrease, whereas the diversity of those in water-treated group increased. The composition of the regrown biofilms altered compared to those before treatments. Streptococcus and Enterobacteriaceae were enriched in the regrown biofilms. Conclusions: Although the antimicrobial treatments were efficient, the multi-species biofilms were indeed able to regrow within 2 days. The regrown biofilms display an altered microbial diversity and composition, which in the oral cavity may lead to an aggressive infection.

8.
Radiat Oncol ; 14(1): 229, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842910

RESUMO

OBJECTIVES: To observe the risk factors affecting the occurrence of RP after gemcitabine-based induction chemotherapy. METHODS: Between January 2010 and December 2017, patients with NSCLC received gemcitabine or docetaxel chemotherapy, followed by radiotherapy at Zhejiang cancer hospital were enrolled in this study. Patients were treated with gemcitabine or docetaxel induction chemotherapy, followed by radiotherapy or concurrent chemoradiotherapy. Acute radiation pneumonitis was scored post chemoradiotherapy. RESULTS: One hundred and eighty-four patients with NSCLC were included in the gemcitabine group and 144 in the docetaxel group. The gemcitabine group experienced a higher incidence of grade ≥ 2 RP, compared with docetaxel group (25.5% Vs. 13.2%, P = 0.005). The optimal cutoff values of lung V5, V20, V30 and MLD were set at 44% (AUC [area under the curve] = 0.593), 24% (AUC = 0.607), 14.2% (AUC = 0.622) and 1226 cGy (AUC = 0.626). On multivariate analysis, only lung V30 was identified as a predictor for grade ≥ 2 RP (P = 0.03). The grade ≥ 2 RP rate was only 9.4% for the low-risk group (Lung V5 ≤ 44%, V20 ≤ 24%, V30 ≤ 14.2%, and MLD ≤ 1226 cGy) in patients received gemcitabine induction chemotherapy. CONCLUSIONS: Gemcitabine chemotherapy before thoracic radiotherapy in NSCLC patients was related to a higher incidence of grade ≥ 2 RP, compared with docetaxel chemotherapy. The Lung dose-volume variable V30 was the best predictor of grade ≥ 2 RP.

9.
J Clin Invest ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874109

RESUMO

The incidence of human papillomavirus (HPV)+ head and neck squamous cell carcinoma (HNSCC) has surpassed that of cervical cancer and is projected to increase rapidly until 2060. The co-evolution of HPV with transforming epithelial cells leads to the shutdown of host immune detection. Targeting proximal viral nucleic acid-sensing machinery is an evolutionarily conserved strategy among viruses to enable immune evasion. However, E7 from the dominant HPV subtype-16 in HNSCC shares low homology with HPV18 E7, which was shown to inhibit the STING-DNA-sensing pathway. The mechanisms by which HPV16 suppresses STING remain unknown. Recently, we characterized the role of the STING-type-I interferon (IFN-I) pathway in maintaining immunogenicity of HNSCC in mouse models. Here we extended those findings into clinical domain utilizing tissue microarrays and machine-learning-enhanced profiling of STING signatures with immune subsets. We additionally showed that HPV16 E7 employs distinct mechanisms than HPV18 E7 to antagonize the STING pathway. We identified NLRX1 as a critical intermediary partner to facilitate HPV16 E7-potentiated STING turnover. The depletion of NLRX1 resulted in significantly improved IFN-I-dependent T-cell infiltration profiles and tumor control. Overall, we discovered a unique HPV16 viral strategy to thwart host innate immune detection that can be further exploited to restore cancer immunogenicity.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 117965, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31869683

RESUMO

Exploring the interaction between an azobenzene-based photoswitch and natural protein can help elucidate how the photo-control of an optical molecule participates in the transmission and delivery of proteins, as well as the effects of azo-switch trans and cis states on protein configurations. In this study, fluorescence analysis, circular dichroism spectroscopy, molecular docking, and molecular dynamics simulations were used to study the interaction among different configurations of tetra-ortho-methoxy substituted azobenzene di-maleimide (toM-ABDM), a red light-induced optical azo-switch, and lysozyme (LYZ). Results showed that toM-ABDM caused the static quenching of LYZ. The cis toM-ABDM had stronger binding affinity than trans toM-ABDM. The noncovalent interaction, hydrogen bonds and van der Waals forces, could not regulate the conformation of LYZ in photo-control. A binding model of toM-ABDM and LYZ in different forms induced by red and blue light was further established by computer simulation.

11.
Int J Biol Macromol ; 145: 476-483, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31887384

RESUMO

Fresh Lentinula edodes were dried using two process technologies-freeze drying (FD) and hot-air drying (HD). The physicochemical, antioxidant and immunomodulatory properties of purified polysaccharides from dried L. edodes (LEP) were then comparatively investigated. Two neutral polysaccharides (FLEP-1 and HLEP-1) and two acidic polysaccharides (FLEP-2 and HLEP-2) were obtained by DEAE-52 cellulose column. The HD treated LEP had higher levels of uronic acid than that of the FD treated LEP. The molar ratios of monosaccharides in FLEP-1, FLEP-2, HLEP-1 and HLEP-2 were different. Moreover, HD treated LEP had more galactose and less glucose. The (1 â†’ 3)-α-glucan structure was dominant in the two neutral polysaccharides, whereas the (1 â†’ 6)-ß-glucan was dominant in the two acidic polysaccharides. Hot-air drying could thus promote the α-configuration in neutral polysaccharides while reducing the ß-configuration in acidic polysaccharides. FLEP-1, FLEP-2, HLEP-1 and HLEP-2 had potential scavenging capacity against the ABTS+, whereas freeze-dried polysaccharides exhibited a stronger scavenging ability than that of hot-air dried polysaccharide. LEP could improve immunity by inducing the secretions of NO, TNF-α and IL-6, whereas hot-air drying improved the immunomodulatory activity of LEP. Our results suggested that freeze drying and hot air drying could be appropriately used to obtain functional polysaccharides from L. edodes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31751197

RESUMO

A novel Gram-stain-positive, rod shaped and anaerobic bacterium, designated as W6T, was isolated from Shengli oilfield in China. Strain W6T was observed to grow from 20 to 45 °C with pH 6.5-9.0 (optimally at 40 °C and pH of 7.5) and without addition of NaCl. The major cellular fatty acids were iso-C15 : 0 (29.1%), C14 : 0 (27.0%) and C16 : 0 (12.2%), and the main polar lipids were lipids (L) and aminolipids (AL). The DNA G+C content is 42.9 mol%. Based on 16S rRNA gene sequence analysis, strain W6T showed highest similarities to Tissierella creatinini DSM 9508T (94.9%) and Soehngenia saccharolytica DSM 12858T (94.1%). The morphological, physiological, biochemical, phylogenetic and phylogenomic analyses demonstrated strain W6T (CCAM 534T=DSM 28124T=CGMCC 1.5291T) represents a novel species in a new genus, for which the name Gudongella oleilytica gen. nov. sp. nov. is proposed. The family Tissierellaceae is proposed as a new family containing the genera Anaerosalibacter, Gudongella, Keratinibaculum, Soehngenia, Sporanaerobacter, Tepidimicrobium, Tissierella, Urmitella and species Clostridium ultunense based on the phylogenetic and phylogenomic analyses.

13.
Anesthesiology ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31714269

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Coupling of neuronal oscillations between brain regions is correlated with higher level brain activityPermutation cross mutual information can be used to evaluate information integration in the electroencephalogram during anesthesia. WHAT THIS ARTICLE TELLS US THAT IS NEW: Using electrocorticography in subjects anesthetized with propofol, the genuine permutation cross mutual information demonstrated that, with loss of consciousness, there was a loss of efficient global information transmission and increased local functional segregation in the cortical network BACKGROUND:: The neurophysiologic mechanisms of propofol-induced loss of consciousness have been studied in detail at the macro (scalp electroencephalogram) and micro (spiking or local field potential) scales. However, the changes in information integration and cortical connectivity during propofol anesthesia at the mesoscopic level (the cortical scale) are less clear. METHODS: The authors analyzed electrocorticogram data recorded from surgical patients during propofol-induced unconsciousness (n = 9). A new information measure, genuine permutation cross mutual information, was used to analyze how electrocorticogram cross-electrode coupling changed with electrode-distances in different brain areas (within the frontal, parietal, and temporal regions, as well as between the temporal and parietal regions). The changes in cortical networks during anesthesia-at nodal and global levels-were investigated using clustering coefficient, path length, and nodal efficiency measures. RESULTS: In all cortical regions, and in both wakeful and unconscious states (early and late), the genuine permutation cross mutual information and the percentage of genuine connections decreased with increasing distance, especially up to about 3 cm. The nodal cortical network metrics (the nodal clustering coefficients and nodal efficiency) decreased from wakefulness to unconscious state in the cortical regions we analyzed. In contrast, the global cortical network metrics slightly increased in the early unconscious state (the time span from loss of consciousness to 200 s after loss of consciousness), as compared with wakefulness (normalized average clustering coefficient: 1.05 ± 0.01 vs. 1.06 ± 0.03, P = 0.037; normalized average path length: 1.02 ± 0.01 vs. 1.04 ± 0.01, P = 0.021). CONCLUSIONS: The genuine permutation cross mutual information reflected propofol-induced coupling changes measured at a cortical scale. Loss of consciousness was associated with a redistribution of the pattern of information integration; losing efficient global information transmission capacity but increasing local functional segregation in the cortical network.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31729828

RESUMO

BACKGROUND: Dental implants and abutments are exposed to challenging oral environment. Corrosion of these materials can affect the overall performance of titanium implants. PURPOSE: To investigate the effects of biofilm-induced bio-aging on corrosion behavior of different implant materials surface. MATERIALS AND METHODS: Commercial polished titanium (Polish), sand-blasted, large grit, acid-etched surface treated titanium (SLA), microarc oxidation (MAO), and hydroxyapatite (HA) coated titanium were bio-aged with saliva biofilm for 30 days. Titanium surfaces topography, chemical composition, roughness, and water contact angle changes were evaluated. In addition, human gingival fibroblasts (HGFs) adhesion, Streptococcus sanguinis (S. sanguinis) biofilm formation were determined. RESULTS: Surface topography, roughness, and chemical composition have no significant changes for all groups after bio-aging (P > .05). Water contact angle of bio-aged SLA was greatly increased (P < .05). While other groups showed no sign of change (P > .05). Adhesion and proliferation of HGFs on the bio-aged SLA titanium surfaces were decreased (P < .05), but increased on bio-aged Polish and HA titanium (P < .05). S. sanguinis biofilm viability was promoted with bio-aging in HA group (P < .05). CONCLUSIONS: Biological characteristics of Polish, SLA, and HA titanium surfaces were influenced by bio-aging. While MAO group was relatively resistant to saliva biofilm bio-aging.

15.
Int J Biol Macromol ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31706814

RESUMO

In this study, polysaccharides from Stropharia rugosoannulata were isolated and purified by macroporous adsorption resin and ion exchange chromatography to produce SRP-1 and SRP-2. Preliminary structural characteristics of SRP-1 and SRP-2 were also investigated. Our results showed that SRP-1 was neutral, while SRP-2 was acidic polysaccharides. The molar ratios of monosaccharides in SRP-1 and SRP-2 were different, but glucose was the main monosaccharide. Both α-type and ß-type glycosidic linkages were detected in SRP-1, whereas ß-constitution was dominant in SRP-2. Both SRP-1 and SRP-2 had a (1 → 6)-α-D-glucan backbone. Furthermore, the antioxidant activities of polysaccharides against ABTS+, DPPH and OH- radicals were determined in vitro. The results indicated that SRP-2 had a stronger antioxidant capacity than that of SRP-1. Our results may be valuable with regard to the utilization of polysaccharides from S. rugosoannulata as potential pharmaceuticals.

16.
Environ Sci Technol ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31747260

RESUMO

Although arsenic at a high concentration imposes strong selective pressure on microbes, various microbes have been found to grow in As-rich environments. So far, little is known about how microbes can sense and move toward arsenate in the environment, and the underlying molecular mechanisms have not been revealed. Here, we report the chemotaxis response toward arsenate (As(V)) by Shewanella putrefaciens CN-32, a model dissimilatory metal-reducing bacterium (DMRB), and elucidate the mechanisms. We find that S. putrefaciens CN-32 exhibits a chemotactic behavior toward As(V) and diverse electron acceptors. To sense As(V), S. putrefaciens CN-32 requires functional arsenate respiratory reductase but does not depend on its metal-reducing-like respiratory pathway. We observe that such a sense is governed by an energy taxis mechanism and mediated by several methyl-accepting chemotaxis proteins (MCPs), rather than a specific MCP. Moreover, we reveal that the chemotactic signal transduction pathway is conserved in Shewanella, and histidine kinase and flagella-mediated motility are essential for taxis toward As(V). This work reverses the conventional view about arsenic as a chemotactic inhibitor to microbes by revealing the positive chemotaxis of Shewanella to As(V).

17.
Orthop Surg ; 11(6): 1072-1081, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31679187

RESUMO

OBJECTIVE: To determine whether lumbar anatomy parameters are in dynamic change and related factors. METHODS: This is a retrospective study. Participants who did lumbar computed tomography (CT) scanning in Shandong University Qilu Hospital from October 2017 to March 2019 were selected. The 476 participants were randomly selected as male or female, with the age ranging from 17 to 87 years (mean, 55.19; standard deviation, 14.28 years). All the measurements were taken based on the CT scanning image and the measurement of lumbar morphology was conducted using picture archiving and communication systems (PACS). The angle between the horizontal alignment and pedicle center on median sagittal view, the angle between upper endplate and lower endplate on median sagittal view as well as transverse section angle (TSA) using Magerl point in the axial view was determined by reconstructive CT analysis. RESULTS: In the overall participants, the angle between the horizontal alignment and pedicle center on median sagittal view of lumbar one to three was significantly decreased with aging, from 3.90° ± 2.81° to -4.18° ± 6.86° (P = 0.002), 5.60° ± 2.89° to -4.14° ± 5.90° (P = 0.030), and 4.75° ± 2.95° to -2.87° ± 4.68° (P < 0.001), respectively. Additionally, the angle between the horizontal alignment and pedicle center on median sagittal view in male participants of lumbar two was dramatically decreased, from 4.83° ± 2.79° to -4.45° ± 5.97° (P = 0.30). And that of lumbar three in female participants was significantly decreased, from 4.56° ± 2.52° to -2.88° ± 5.03° (P = 0.029). Furthermore, of the overall participants, the angle between upper endplate and lower endplate on median sagittal view of lumbar one to four was associated with aging (P < 0.001, P < 0.001, P = 0.015, P < 0.001, respectively). The angle of lumbar one, two and four in male participants and lumbar one to four in female participants were all significantly related to aging (all P < 0.05). Moreover, in the participants overall, the TSA of lumbar one to three was significantly associated with aging (P = 0.015, P = 0.006 and P = 0.007, respectively). In addition, this angle in lumbar one to lumbar four in male participants were all negatively associated with aging (P = 0.017, P = 0.001, P = 0.005 and P = 0.036, respectively). CONCLUSION: Lumbar anatomy parameters are in dynamic change in an age and gender dependent manner. During spine surgery in elderly patients, more attention should be paid to these anatomic changes.

18.
Am J Physiol Renal Physiol ; 317(6): F1513-F1525, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31566435

RESUMO

The metabolic sensor AMP-activated protein kinase (AMPK) inhibits the epithelial Na+ channel (ENaC), a key regulator of salt reabsorption by the kidney and thus total body volume and blood pressure. Recent studies have suggested that AMPK promotes the association of p21-activated kinase-interacting exchange factor-ß1 ß1Pix, 14-3-3 proteins, and the ubiquitin ligase neural precursor cell expressed developmentally downregulated protein (Nedd)4-2 into a complex that inhibits ENaC by enhancing Nedd4-2 binding to ENaC and ENaC degradation. Functional ß1Pix is required for ENaC inhibition by AMPK and promotes Nedd4-2 phosphorylation and stability in mouse kidney cortical collecting duct cells. Here, we report that AMPK directly phosphorylates ß1Pix in vitro. Among several AMPK phosphorylation sites on ß1Pix detected by mass spectrometry, Ser71 was validated as functionally significant. Compared with wild-type ß1Pix, overexpression of a phosphorylation-deficient ß1Pix-S71A mutant attenuated ENaC inhibition and the AMPK-activated interaction of both ß1Pix and Nedd4-2 to 14-3-3 proteins in cortical collecting duct cells. Similarly, overexpression of a ß1Pix-Δ602-611 deletion tract mutant unable to bind 14-3-3 proteins decreased the interaction between Nedd4-2 and 14-3-3 proteins, suggesting that 14-3-3 binding to ß1Pix is critical for the formation of a ß1Pix/Nedd4-2/14-3-3 complex. With expression of a general peptide inhibitor of 14-3-3-target protein interactions (R18), binding of both ß1Pix and Nedd4-2 to 14-3-3 proteins was reduced, and AMPK-dependent ENaC inhibition was also attenuated. Altogether, our results demonstrate the importance of AMPK-mediated phosphorylation of ß1Pix at Ser71, which promotes 14-3-3 interactions with ß1Pix and Nedd4-2 to form a tripartite ENaC inhibitory complex, in the mechanism of ENaC regulation by AMPK.

19.
Acta Biomater ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31629895

RESUMO

Infection is a main cause of implant failure. Early implant-related infections often occur in the first 4 weeks post-operation. Inhibiting bacterial adhesion and biofilm formation at the early stage and promoting subsequent implant osseointegration are important for implant success. Our previous studies demonstrated that dimethylaminododecyl methacrylate (DMADDM) provided dental materials with antibacterial effects. In the present study, DMADDM and hydroxyapatite (HA) are loaded on to the titanium (Ti) surface via poly dopamine (PDA) self-polymerization. This local DMADDM-delivery Ti is referred as Ti-PHD. Here we report the two-staged capability of Ti-PHD: (1) in the first stage, releasing DMADDM during the high-infection-risk initial period post-implantation for 4 weeks; (2) then in the second stage, enhancing osteogenesis and promoting osseointegration. Ti-PHD has a porous surface with higher average roughness and greater hydrophilicity than pure Ti. Its biocompatibility is verified in vitro and in vivo. During the first 4 weeks of release, both DMADDM remaining on Ti surface and DMADDM released into the soaking medium greatly reduced the adherence and growth of pathogens. This is further confirmed by the prevention of bone destruction in a rat osteomyelitis model. After releasing DMADDM for 4 weeks, Ti-PHD promotes osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and new bone formation around the implants in vivo. This article represents the first report on the two-staged, time-dependent antibacterial and osteogenesis effects of Ti-PHD, demonstrating its potential for clinical applications to inhibit implant-associated infections. STATEMENT OF SIGNIFICANCE: The present study develops a two-staged time-dependent system for local dimethylaminododecyl methacrylate (DMADDM) delivery via Ti implant (referred to as Ti-PHD). DMADDM and hydroxyapatite (HA) are loaded on to the Ti surface with poly dopamine (PDA). Ti-PHD can release DMADDM during the high-risk period of infection in the first stage, and then promote osseointegration and new bone formation in the second stage. This bioactive and therapeutic Ti is promising to inhibit infections and enhance implant success.

20.
Braz. j. otorhinolaryngol. (Impr.) ; 85(5): 588-596, Sept.-Oct. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1039291

RESUMO

Abstract Introduction: There is still no general method for discriminating between benign and malignant leukoplakia and identifying vocal fold leukoplakia. Objective: To evaluate the reliability of a morphological classification and the correlation between morphological types and pathological grades of vocal fold leukoplakia. Methods: A total of 375 patients with vocal fold leukoplakia between 2009 and 2015 were retrospectively reviewed. Two observers divided the vocal fold leukoplakia into flat and smooth, elevated and smooth, and rough type on the basis of morphological appearance. The inter-observer reliability was evaluated and the results of classification from both observers were compared with final pathological grades. Clinical characteristics between low risk and high risk group were also analyzed. Results: The percentage inter-observer agreement of the morphological classification was 78.7% (κ = 0.615, p < 0.001). In the results from both observers, the morphological types were significantly correlated with the pathological grades (p1 < 0.001, p2 < 0.001, Kruskal-Wallis test; r1 = 0.646, p1 < 0.001, r2 = 0.539, p2 < 0.001, Spearman Correlation Analysis). Multivariate analysis showed patient's age (p = 0.018), the size of lesion (p < 0.001), and morphological type (p < 0.001) were significantly different between low risk group and high risk group. Combined receiver operating characteristic curve analysis of significant parameters revealed an area under the receiver operating characteristic curve of 0.863 (95% CI 0.823-0.903, p < 0.001). Conclusions: The proposed morphological classification of vocal fold leukoplakia was consistent between observers and morphological types correlated with pathological grades. Patient's age, the size of lesion, and morphological type might enable risk stratification and provide treatment guidelines for vocal fold leukoplakia.


Resumo Introdução: Ainda não há um método universal estabelecido para diferenciar entre a leucoplasia benigna e maligna ou identificar as leucoplasias das pregas vocais. Objetivo: Avaliar a confiabilidade de uma classificação morfológica e a correlação entre os tipos morfológicos e os graus histopatológicos das leucoplasias de pregas vocais. Método: Os registros de 375 pacientes com leucoplasia da prega vocal assistidos entre 2009 e 2015 foram revisados retrospectivamente. Dois observadores dividiram a leucoplasia da prega vocal entre tipo plano e liso, elevado e liso, e rugoso, com base na aparência morfológica. A confiabilidade interobservador foi avaliada e os resultados de classificação de ambos os observadores foram comparados com os graus histopatológicos finais. As características clínicas entre os grupos de baixo risco e alto risco também foram analisadas. Resultados: A porcentagem da concordância interobservador da classificação morfológica foi de 78,7% (κ = 0,615, p < 0,001). Nos resultados de ambos os observadores, os tipos morfológicos correlacionaram-se significativamente com os graus histopatológicos (p1 < 0,001, p2 < 0,001, teste de Kruskal-Wallis; r1 = 0,646, p1 < 0,001, r2 = 0,539, p2 < 0,001, análise de correlação de Spearman). A análise multivariada mostrou que a idade do paciente (p = 0,018), o tamanho da lesão (p < 0,001) e o tipo morfológico (p < 0,001) foram significativamente diferentes entre o grupo de baixo risco e o de alto risco. A análise da curva ROC (Receiver Operating Characteristic) combinada de parâmetros significativos revelou uma área sob a curva de 0,863 (IC 95%: 0,823 ± 0,903, p < 0,001). Conclusões: A classificação morfológica proposta para leucoplasia de prega vocal foi consistente entre observadores e os tipos morfológicos correlacionaram-se com os graus histopatológicos. A idade do paciente, o tamanho da lesão e o tipo morfológico podem permitir a estratificação de risco e fornecem diretrizes de tratamento para a leucoplasia da prega vocal.

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