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1.
Photodiagnosis Photodyn Ther ; 36: 102516, 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34469794

RESUMO

BACKGROUND AND AIM: It is generally believed that bacteria can not develop resistance to antimicrobial photodynamic therapy (aPDT). This work employed a polymyxin-resistant Escherichia coli clinical isolate (E15017) to study whether it could become resistant to aPDT mediated by haematoporphyrin monomethyl ether (HMME) via consecutive photodynamic treatments at sub-lethal condition. METHODS: The sub-lethal and lethal photodynamic treatment conditions for E15017 were determined by colony forming units (CFU) assay. Bacterial cells of E15017 were treated with 20 cycles of repeated sub-lethal HMME-mediated aPDT, and subsequently subjected to aPDT at lethal condition. The antibiotic susceptibility, zeta-potential and membrane integrity of sub-lethal aPDT treated E15017 cells were also investigated. RESULTS: After 20 cycles of repeated HMME-mediated aPDT treatments at sub-lethal condition, E15017 cells didn't become more resistant to aPDT. Sub-lethal HMME-mediated aPDT decreased the MIC values of E15017 to ceftazidime and polymyxin E by 4 and 2-fold, respectively, and increased the electronegativity of bacterial surface and affected the bacterial membrane integrity. CONCLUSIONS: The results obtained in this study confirmed that antibiotic-resistant bacteria could not develop resistance to aPDT, and HMME-mediated aPDT is an attractive potential treatment for MDR E. coli caused infections.

2.
J Am Chem Soc ; 143(36): 14573-14580, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34464111

RESUMO

Quantum-size metal clusters with multiple delocalized electrons could support collective plasmon excitation, and thus, theoretically, coupling of plasmons in the few-atom limit might exist between assembled metal clusters, while currently few experimental observations about this phenomenon have been reported. Here we examined the optical absorption of DNA-templated Ag nanoclusters (DNA-AgNCs) assembled through DNA hybridization and found their absorption peaks were sensitive to the assembled distances, which share common characteristics with classical plasmon coupling. Dipolar charge distribution, multiple transition contributed optical absorption, and strongly enhanced electric field simulated by time-dependent density functional theory (TDDFT) indicated the origin of the absorption of individual DNA-AgNCs is a plasmon. The consistency of the peak-shifting trend between experimental and simulation results for assembled DNA-AgNCs suggested the possible presence of plasmon coupling. Our data imply the possibility for quantum-size structures to support plasmon coupling and also show that DNA-AgNCs possess the potential to be promising materials for construction of plasmon-coupling devices with ultrasmall size, site-specific and stoichiometric binding abilities, and biocompatibility.

3.
Clin Transl Gastroenterol ; 12(8): e00398, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397041

RESUMO

INTRODUCTION: Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation. METHODS: We included 3,407 participants aged 50-74 years undergoing colonoscopy from a colorectal cancer screening trial. For the risk-adapted screening strategy, subjects were referred for subsequent colonoscopy or FIT according to their risk scores. Diagnostic performance was evaluated for FIT and the risk-adapted screening method with various positivity thresholds. Furthermore, a modeled screening cohort was established to compare the yield and cost using colonoscopy, FIT, and the risk-adapted screening method in a single round of screening. RESULTS: Risk-adapted screening method had higher sensitivity for advanced neoplasm (AN) (27.6%-76.3% vs 13.8%-17.3%) but lower specificity (46.6%-90.8% vs 97.4%-98.8%) than FIT did. In a modeled screening cohort, FIT-based screening would be slightly affected because the threshold varied with a reduction of 76.0%-80.9% in AN detection and 82.0%-84.4% in cost when compared with colonoscopy. By contrast, adjusting the threshold of Asia-Pacific Colorectal Screening score from 3 to 5 points for risk-adapted screening varied from an increase of 12.6%-14.1% to a decrease of 55.6%-60.1% in AN detection, with the reduction of cost from 4.2%-5.3% rising to 66.4%-68.5%. DISCUSSION: With an appropriate positivity threshold tailored to clinical practice, the risk-adapted screening could save colonoscopy resources and cost compared with the colonoscopy-only and FIT-only strategies.

4.
Chemistry ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383348

RESUMO

Imines are important intermediates in drug synthesis. Photocatalytic aerobic oxidative coupling of amines has been considered as a clean and promising way to produce imines and has attracted great attention. Herein, we designed and synthesized a novel two-dimensional porphyrin-based covalent organic framework (Por-BC-COF) which adopts an AA stacking mode with excellent crystallinity, high Brunauer-Emmett-Teller surface areas (1200 m2 g-1 ), wide light absorption range (200-1300 nm) and good stability in a variety of organic solvents. Por-BC-COF can be used as a metal-free heterogeneous photocatalyst for the photocatalytic oxidation of amines to imines under visible light and red light with a high yield (97 %). This work presents a novel and efficient COF photocatalyst in the application of light-driven organic synthesis.

5.
Clin Transl Gastroenterol ; 12(8): e00389, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34408121

RESUMO

INTRODUCTION: Fecal immunochemical tests (FITs) detect colorectal adenoma inefficiently. The gut microbiota participates in colorectal cancer development. We aimed to explore fecal microbial signatures for advanced adenomas and evaluate their diagnostic value and complementary capacity to FIT. METHODS: Using 16S rRNA sequencing, we studied gut microbiota in feces from 1,546 subjects in a screening setting, including 268 patients with advanced adenomas, 490 patients with nonadvanced adenomas, and 788 healthy subjects. Feature selections were performed using linear discriminant analysis effect size, multivariate association with linear models, and least absolute shrinkage and selection operator. The diagnostic performance of microbial signatures and their auxiliary role to FITs and the added value of the Asia-Pacific Colorectal Screening score were evaluated. We applied 0.632+ bootstrapping to adjust the potential overfitting. RESULTS: We identified 13 microbial signatures to show the joint diagnostic value for advanced adenoma, with genus Tyzzerella 4 demonstrating the highest adjusted area under the curve (AUC) of 0.545 (95% confidence interval [CI], 0.520-0.610). The 13-bacteria increased the adjusted AUC to 0.607 (95% CI, 0.548-0.660). Compared with individual FIT (adjusted AUC = 0.527; 95% CI, 0.519-0.571), 13-bacteria and FITs collectively reached an adjusted AUC of 0.641 (95% CI, 0.579-0.691). At cutoff values yielding specificities of 90% and 80%, the adjusted sensitivities were 28.4% (95% CI, 19.3-36.8) and 41.1% (95% CI, 29.9-49.4), respectively. The Asia-Pacific Colorectal Screening score further boosted the adjusted AUC to 0.706 (95% CI, 0.648-0.750). DISCUSSION: In this study using fecal samples from a screening setting, the identified microbial signatures could complement FITs for detecting advanced adenomas. Gut microbiota can act as a promising tool to optimize the current colorectal cancer screening modalities.

6.
Med Phys ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412155

RESUMO

PURPOSE: Accurate quantification of gastrointestinal stromal tumors' (GISTs) risk stratification on multicenter endoscopic ultrasound (EUS) images plays a pivotal role in aiding the surgical decision-making process. This study focuses on automatically classifying higher-risk and lower-risk GISTs in the presence of a multicenter setting and limited data. METHODS: In this study, we retrospectively enrolled 914 patients with GISTs (1824 EUS images in total) from 18 hospitals in China. We propose a triple normalization-based deep learning framework with ultrasound-specific pretraining and meta attention, namely, TN-USMA model. The triple normalization module consists of the intensity normalization, size normalization, and spatial resolution normalization. First, the image intensity is standardized and same-size regions of interest (ROIs) and same-resolution tumor masks are generated in parallel. Then, the transfer learning strategy is utilized to mitigate the data scarcity problem. The same-size ROIs are fed into a deep architecture with ultrasound-specific pretrained weights, which are obtained from self-supervised learning using a large volume of unlabeled ultrasound images. Meanwhile, tumors' size features are calculated from the same-resolution masks individually. Afterward, the size features together with two demographic features are integrated to the model before the final classification layer using a meta attention mechanism to further enhance feature representations. The diagnostic performance of the proposed method was compared with one radiomics-based method and two state-of-the-art deep learning methods. Four evaluation metrics, namely, the accuracy, the area under the receiver operator curve, the sensitivity, and the specificity were used to evaluate the model performance. RESULTS: The proposed TN-USMA model achieves an overall accuracy of 0.834 (95% confidence interval [CI]: 0.772, 0.885), an area under the receiver operator curve of 0.881 (95% CI: 0.825, 0.924), a sensitivity of 0.844 (95% CI: 0.672, 0.947), and a specificity of 0.832 (95% CI: 0.762, 0.888). The AUC significantly outperforms other two deep learning approaches (p < 0.05, DeLong et al). Moreover, the performance is stable under different variations of multicenter dataset partitions. CONCLUSIONS: The proposed TN-USMA model can successfully differentiate higher-risk GISTs from lower-risk ones. It is accurate, robust, generalizable, and efficient for potential clinical applications.

7.
NeuroRehabilitation ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34334431

RESUMO

BACKGROUND: This is the first large study of onabotulinumtoxinA as treatment for pediatric upper limb spasticity. OBJECTIVE: Evaluate efficacy and safety of a single treatment with onabotulinumtoxinA plus occupational therapy (OT). METHODS: In this registrational phase III, multinational study (NCT01603602), participants were randomized 1:1:1 to onabotulinumtoxinA 3 U/kg/OT, 6 U/kg/OT, or placebo/OT. Primary endpoint was average change from baseline at weeks 4 and 6 in Modified Ashworth Scale-Bohannon (MAS) score. Secondary endpoints included Modified Tardieu Scale (MTS), Clinical Global Impression of Change (CGI) and functional Goal Attainment Scale (GAS). RESULTS: 235 participants were randomized. At weeks 4 and 6, onabotulinumtoxinA groups had greater mean reductions in MAS (both -1.9; p < 0.001) versus placebo (-1.2). OnabotulinumtoxinA doses improved dynamic tone per MTS. Mean CGI at weeks 4 and 6 was unchanged in the overall population, but improved in a post hoc analysis of patients with a single affected upper limb (UL) muscle group (elbow or wrist). GAS score for passive goals was significantly higher for 6 U/kg versus placebo at week 12. Most AEs were mild/moderate in severity; overall incidence was similar between groups. CONCLUSIONS: OnabotulinumtoxinA (3 and 6 U/kg) was safe and effective in reducing upper limb spasticity in pediatric participants.

8.
J Microbiol Biotechnol ; 31(9): 1200-1209, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319262

RESUMO

Sepsis is an acute inflammatory response that leads to life-threatening complications if not quickly and adequately treated. Cytolysin, hemolysin, and pneumolysin are toxins produced by gram-positive bacteria and are responsible for resistance to antimicrobial drugs, cause virulence and lead to sepsis. This work assessed the effects of aloe-emodin (AE) and photodynamic therapy (PDT) on sepsis-associated gram-positive bacterial toxins. Standard and antibiotic-resistant Enterococcus faecalis, Staphylococcus aureus, and Streptococcus pneumonia bacterial strains were cultured in the dark with varying AE concentrations and later irradiated with 72 J/cm-2 light. Colony and biofilm formation was determined. CCK-8, Griess reagent reaction, and ELISA assays were done on bacteria-infected RAW264.7 cells to determine the cell viability, NO, and IL-1ß and IL-6 pro-inflammatory cytokines responses, respectively. Hemolysis and western blot assays were done to determine the effect of treatment on hemolysis activity and sepsis-associated toxins expressions. AE-mediated PDT reduced bacterial survival in a dose-dependent manner with 32 µg/ml of AE almost eliminating their survival. Cell proliferation, NO, IL-1ß, and IL-6 cytokines production were also significantly downregulated. Further, the hemolytic activities and expressions of cytolysin, hemolysin, and pneumolysin were significantly reduced following AE-mediated PDT. In conclusion, combined use of AE and light (435 ± 10 nm) inactivates MRSA, S. aureus (ATCC 29213), S. pneumoniae (ATCC 49619), MDR-S. pneumoniae, E. faecalis (ATCC 29212), and VRE (ATCC 51299) in an AE-dose dependent manner. AE and light are also effective in reducing biofilm formations, suppressing pro-inflammatory cytokines, hemolytic activities, and inhibiting the expressions of toxins that cause sepsis.

9.
BMJ Open ; 11(6): e044322, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193481

RESUMO

OBJECTIVES: To determine the incidence and intensity of household impoverishment induced by cancer treatment in China. DESIGN: Average income and daily consumption per capita of the households and out-of-pocket payments for cancer care were estimated. Household impoverishment was determined by comparing per capita daily consumption against the Chinese poverty line (CPL, US$1.2) and the World Bank poverty line (WBPL, US$1.9) for 2015. Both pre-treatment and post-treatment consumptions were calculated assuming that the households would divert daily consumption money to pay for cancer treatment. PARTICIPANTS: Cancer patients diagnosed initially from 1 January 2015 to 31 December 2016 who had received cancer treatment subsequently. Those with multiple cancer diagnoses were excluded. DATA SOURCES: A household questionnaire survey was conducted on 2534 cancer patients selected from nine hospitals in seven provinces through two-stage cluster/convenience sampling. FINDINGS: 5.89% (CPL) to 12.94% (WBPL) households were impoverished after paying for cancer treatment. The adjusted OR (AOR) of post-treatment impoverishment was higher for older patients (AOR=2.666-4.187 for ≥50 years vs <50 years, p<0.001), those resided in central region (AOR=2.619 vs eastern, p<0.01) and those with lower income (AOR=0.024-0.187 in higher income households vs the lowest 20%, p<0.001). The patients without coverage from social health insurance had higher OR (AOR=1.880, p=0.040) of experiencing post-treatment household impoverishment than those enrolled with the insurance for urban employees. Cancer treatment is associated with an increase of 5.79% (CPL) and 12.45% (WBPL) in incidence of household impoverishment. The median annual consumption gap per capita underneath the poverty line accumulated by the impoverished households reached US$128 (CPL) or US$212 (WBPL). US$31 170 395 (CPL) or US$115 238 459 (WBPL) were needed to avoid household impoverishment induced by cancer treatment in China. CONCLUSIONS: The financial burden of cancer treatment imposes a significant risk of household impoverishment despite wide coverage of social health insurance in China.


Assuntos
Características da Família , Neoplasias , China/epidemiologia , Estudos Transversais , Gastos em Saúde , Humanos , Neoplasias/epidemiologia , Pobreza
10.
Microb Biotechnol ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34165875

RESUMO

Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non-invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe-emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE-mediated aPDT for T. rubrum-caused tinea corporis in vivo and tinea unguium ex vivo. The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE-mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE-mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE-mediated aPDT against dermatophytosis were assessed in T. rubrum-caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE-mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dose-dependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE-mediated aPDT demonstrated effective therapeutic effects for T. rubrum-caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved.

11.
Nat Commun ; 12(1): 3583, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117225

RESUMO

Construction of C-C bonds via reductive coupling of aldehydes and ketones is hindered by the highly negative reduction potential of these carbonyl substrates, particularly ketones, and this renders the formation of ketyl radicals extremely endergonic. Here, we report the efficient activation of carbonyl compounds by the formation of specific host-guest interactions in a hydroxyl-decorated porous photocatalyst. MFM-300(Cr) exhibits a band gap of 1.75 eV and shows excellent catalytic activity and stability towards the photoreductive coupling of 30 different aldehydes and ketones to the corresponding 1,2-diols at room temperature. Synchrotron X-ray diffraction and electron paramagnetic resonance spectroscopy confirm the generation of ketyl radicals via confinement within MFM-300(Cr). This protocol removes simultaneously the need for a precious metal-based photocatalyst or for amine-based sacrificial agents for the photochemical synthesis.

12.
Ultrasound Med Biol ; 47(8): 2404-2415, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34052063

RESUMO

This study aims to investigate the feasibility of quantitative ultrasonic backscatter in evaluating human cortical and trabecular bone densities in vivo based on a head-down-tilt bed rest study, with 36 participants tested through 90 d of bed rest and 180 d of recovery. Backscatter measurements were performed using an ultrasonic backscatter bone diagnostic instrument. Backscatter parameters were calculated with a dynamic signal-of-interest method, which was proposed to ensure the same ultrasonic interrogated volume in cortical and trabecular bones. The backscatter parameters exhibited significant correlations with site-matched bone densities provided by high-resolution peripheral quantitative computed tomography (0.33 < |R| < 0.72, p < 0.05). Some bone densities and backscatter parameters exhibited significant changes after the 90-d bed rest. The proposed method can be used to characterize bone densities, and the portable ultrasonic backscatter bone diagnostic device might be used to non-invasively reveal mean bone loss (across a group of people) after long-term bed rest and microgravity conditions of spaceflight missions.


Assuntos
Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Espalhamento de Radiação , Ondas Ultrassônicas , Adulto , Repouso em Cama , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Masculino
13.
Chin Med J (Engl) ; 134(11): 1335-1344, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34039863

RESUMO

BACKGROUND: Fecal immunochemical tests (FITs) are the most widely used non-invasive tests in colorectal cancer (CRC) screening. However, evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse. METHODS: Based on a CRC screening trial (TARGET-C), we included 3144 pre-colonoscopy fecal samples, including 24 CRCs, 230 advanced adenomas, 622 non-advanced adenomas, and 2268 participants without significant findings at colonoscopy. Three self-administered qualitative FITs (Pupu tube) with positivity thresholds of 8.0, 14.4, or 20.8 µg hemoglobin (Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT (OC-Sensor) with a positivity threshold of 20 µg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory. The diagnostic performance of the FITs for detecting colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds (for the quantitative FIT). RESULTS: At the thresholds preset by the manufacturers, apart from the qualitative FIT-3, significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1 (33.9% [95% CI: 28.7-39.4%]) and qualitative FIT-2 (22.2% [95% CI: 17.7-27.2%]) compared to the quantitative FIT (11.7% [95% CI: 8.4-15.8%]), while at a cost of significantly lower specificities. However, such difference was not observed for detecting CRC. For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly, there were no significant differences in terms of sensitivity, specificity, positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs, which was further evidenced in ROC analysis. CONCLUSIONS: Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the positivity thresholds preset by the manufacturer, such heterogeneity could be overcome by adjusting thresholds to yield comparable specificities or positivity rates. Future CRC screening programs should select appropriate types of FITs and define the thresholds based on the targeted specificities and manageable positivity rates.


Assuntos
Neoplasias Colorretais , Laboratórios , Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Fezes , Hemoglobinas/análise , Humanos , Sangue Oculto , Sensibilidade e Especificidade
14.
PLoS Pathog ; 17(5): e1009598, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34015051

RESUMO

Tyrosine phosphatases are often weaponized by bacteria colonizing mucosal barriers to manipulate host cell signal transduction pathways. Porphyromonas gingivalis is a periodontal pathogen and emerging oncopathogen which interferes with gingival epithelial cell proliferation and migration, and induces a partial epithelial mesenchymal transition. P. gingivalis produces two tyrosine phosphatases, and we show here that the low molecular weight tyrosine phosphatase, Ltp1, is secreted within gingival epithelial cells and translocates to the nucleus. An ltp1 mutant of P. gingivalis showed a diminished ability to induce epithelial cell migration and proliferation. Ltp1 was also required for the transcriptional upregulation of Regulator of Growth and Cell Cycle (RGCC), one of the most differentially expressed genes in epithelial cells resulting from P. gingivalis infection. A phosphoarray and siRNA showed that P. gingivalis controlled RGCC expression through Akt, which was activated by phosphorylation on S473. Akt activation is opposed by PTEN, and P. gingivalis decreased the amount of PTEN in epithelial cells. Ectopically expressed Ltp1 bound to PTEN, and reduced phosphorylation of PTEN at Y336 which controls proteasomal degradation. Ltp-1 induced loss of PTEN stability was prevented by chemical inhibition of the proteasome. Knockdown of RGCC suppressed upregulation of Zeb2 and mesenchymal markers by P. gingivalis. RGCC inhibition was also accompanied by a reduction in production of the proinflammatory cytokine IL-6 in response to P. gingivalis. Elevated IL-6 levels can contribute to periodontal destruction, and the ltp1 mutant of P. gingivalis incited less bone loss compared to the parental strain in a murine model of periodontal disease. These results show that P. gingivalis can deliver Ltp1 within gingival epithelial cells, and establish PTEN as the target for Ltp1 phosphatase activity. Disruption of the Akt1/RGCC signaling axis by Ltp1 facilitates P. gingivalis-induced increases in epithelial cell migration, proliferation, EMT and inflammatory cytokine production.


Assuntos
Infecções por Bacteroidaceae/microbiologia , Doenças da Gengiva/microbiologia , Doenças Periodontais/microbiologia , Porphyromonas gingivalis/enzimologia , Proteínas Tirosina Fosfatases/metabolismo , Transdução de Sinais , Animais , Ciclo Celular , Movimento Celular , Proliferação de Células , Células Epiteliais/microbiologia , Transição Epitelial-Mesenquimal , Gengiva/microbiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação , Porphyromonas gingivalis/genética , Proteínas Tirosina Fosfatases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima
15.
Chemosphere ; 278: 130413, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33823349

RESUMO

The study was based on the removal of nitrate and sulfide, and aimed to nitrite accumulation. The process of autotrophic denitrification driven by sulfide as an electron donor was investigated in a sequencing batch reactor. The research showed that autotrophic denitrification successfully started on day 22, and the removal rates of NO3--N and S2--S were 95.8% and 100%, respectively, when the S/N molar ratio was 1.45. When the S/N ratio was reduced to 0.94, the phenomenon of NO2--N accumulation was observed. NO2--N continuously accumulated, and the maximum accumulation rate was 55.3% when the S/N ratio was 0.8. In the batch test, the study showed that NO2--N accumulation was optimal when the S/N ratio was 0.8, and the NO2--N concentration increased with increasing NO3--N concentration at the same S/N ratio. Microbial communities also changed based on the high-throughput analysis, and Proteobacteria (59.5%-84%) was the main phylum. Arenimonas (11.4%-28.2%) and uncultured_f_ Chromatiaceae (5.7%-27.5%) were the dominant bacteria, which complete denitrification and desulfurization throughout the operating system. Therefore, this study provided a theoretical basis for the simultaneous removal of NO3--N and S2--S, as well as the accumulation of nitrite, and provided material support for anaerobic ammonia oxidation technology.


Assuntos
Nitratos , Nitritos , Processos Autotróficos , Reatores Biológicos , Desnitrificação , Nitrogênio , Sulfetos , Enxofre
16.
Int J Pharm ; 601: 120553, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33794325

RESUMO

Pancreatic cancer (PC) is an aggressive form of cancer with dense stroma and immune-suppressive microenvironment, which are the major barriers for treatment. To address such barriers, this study aimed to develop a sequential receptor-mediated mixed-charge targeted delivery system for PC based on 2-(3-((S)-5-amino-1-carboxypentyl)-ureido) pentanedioate (ACUPA-) and triphenylphosphonium (TPP+) modified nanomicelles containing ingenol-3-mebutate (I3A), which was named ACUPA-/TPP+-I3A or ACUPA/TPP-I3A. ACUPA/TPP-I3A induced immunogenic cell death (ICD), which significantly increased the number of tumor-infiltrating T lymphocytes, activated adaptive immunity, and achieved superior survival time. I3A, a novel anticancer drug, could induce PC cell necrosis to release damage-associated molecular patterns, thereby activating adaptive immunity. With certain ratios of negatively (ACUPA-) and positively (TPP+) charged ligands, ACUPA/TPP-I3A acquired a negative charge in plasma (pH 7.4, to inhibit aggregation and uptake in the circulation) and was neutral in the acidic tumor microenvironment (pH 5.0-6.0, to overcome electrostatic hindrances and facilitate transcytosis). Furthermore, neovascular endothelium-specific ACUPA enabled rapid transcytosis of ACUPA/TPP-I3A across tumor vessel walls, entering into endosome/lysosomes (pH 4.5-5.0, its charge became positive and exhibited lysosome escape). Then, ACUPA/TPP-I3A selectively targeted mitochondria, which correlated with TPP-mediated effect. Finally, I3A was released to induce ICD that activated adaptive immunity and achieved superior survival time. Therefore, reshaping of the tumor microenvironment and potentiating antitumor immunity using ACUPA-/TPP+-I3A constituted a novel strategy to prolong the survival time.


Assuntos
Nanopartículas , Neoplasias Pancreáticas , Linhagem Celular Tumoral , Humanos , Morte Celular Imunogênica , Nanomedicina , Neoplasias Pancreáticas/tratamento farmacológico , Microambiente Tumoral
17.
Artigo em Inglês | MEDLINE | ID: mdl-33844628

RESUMO

There is a significant acoustic impedance contrast between the cortical bone and the surrounding soft tissue, resulting in difficulty for ultrasound penetration into bone tissue with high frequency. It is challenging for the conventional pulse-echo modalities to give accurate cortical bone images using uniform sound velocity model. To overcome these limitations, an ultrasound imaging method called full-matrix Fourier-domain synthetic aperture based on velocity inversion (FM-FDSA-VI) was developed to provide accurate cortical bone images. The dual linear arrays were located on the upper and lower sides of the imaging region. After full-matrix acquisition with two identical linear array probes facing each other, travel-time inversion was used to estimate the velocity distribution in advance. Then, full-matrix Fourier-domain synthetic aperture (FM-FDSA) imaging based on the estimated velocity model was applied twice to image the cortical bone, utilizing the data acquired from top and bottom linear array, respectively. Finally, to further improve the image quality, the two images were merged to give the ultimate result. The performance of the method was verified by two simulated models and two bone phantoms (i.e., regular and irregular hollow bone phantom). The mean relative errors of estimated sound velocity in the region-of-interest (ROI) are all below 12%, and the mean errors of cortical section thickness are all less than 0.3 mm. Compared to the conventional synthetic aperture (SA) imaging, the FM-FDSA-VI method is able to accurately image cortical bone with respect to the structure. Moreover, the result of irregular bone phantom was close to the image scanned by microcomputed tomography ( µ CT) in terms of macro geometry and thickness. It is demonstrated that the proposed FM-FDSA-VI method is an efficient way for cortical bone ultrasonic imaging.

18.
J Immunol Res ; 2021: 5557095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860060

RESUMO

Periodontitis is an oral chronic inflammatory disease that is initiated by periodontal microbial communities and requires disruption of the homeostatic responses. The prevalence of periodontal disease increases with age; more than 70% of adults 65 years and older have periodontal disease. A pathogenic microbial community is required for initiating periodontal disease. Dysbiotic immune-inflammatory response and bone remodeling are characteristics of periodontitis. The transcription factor forkhead box protein O1 (FOXO1) is a key regulator of a number of cellular processes, including cell survival and differentiation, immune status, reactive oxygen species (ROS) scavenging, and apoptosis. Although accumulating evidence indicates that FOXO1 activity can be induced by periodontal pathogens, the roles of FOXO1 in periodontal homeostasis and disease have not been well documented. The present review summarizes how the FOXO1 signaling axis can regulate periodontal bacteria-epithelial interactions, immune-inflammatory response, bone remodeling, and wound healing.

19.
Photodiagnosis Photodyn Ther ; 34: 102311, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33930578

RESUMO

BACKGROUND AND AIM: Antimicrobial photodynamic therapy (aPDT) has shown great potential for treatment of superficial or localized multidrug-resistant (MDR) Acinetobacter baumannii infections. The purpose of this study was to investigate the cytotoxicity and in vivo safety of aloe-emodin (AE), and its photodynamic treatment efficacy against MDR A. baumannii infections. METHODS: The cytotoxicity (dark toxicity) and phototoxicity of AE to human immortalized keratinocytes and mice fibroblasts were detected by CCK-8 kit. Low and high doses of AE were intravenously injected into mice to evaluate the safety of AE in vivo. Bioluminescent MDR A. baumannii strain was employed to establish the infection model on BALB/c mice after skin scald, and infection status and therapeutic effect of AE-mediated aPDT were assessed by animal imaging system. The peripheral blood of mice was analyzed by flow cytometer. RESULTS: AE had low cytotoxicity to human immortalized keratinocytes and mice fibroblasts, and had certain phototoxicity to these cells under light irradiation. The in vivo experiments demonstrated that AE caused no obvious effects on the weight and pathological changes of mice. AE-mediated aPDT was effective in the treatment of MDR A. baumannii caused infections in mice after skin scald. CONCLUSIONS: AE has potential to be used in the photodynamic treatment of MDR A. baumannii caused superficial infections after scald.


Assuntos
Acinetobacter baumannii , Aloe , Anti-Infecciosos , Emodina , Fotoquimioterapia , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana Múltipla , Emodina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
20.
FASEB J ; 35(5): e21530, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33813752

RESUMO

Circadian clock is involved in regulating most renal physiological functions, including water and electrolyte balance and blood pressure homeostasis, however, the role of circadian clock in renal pathophysiology remains largely unknown. Here we aimed to investigate the role of Bmal1, a core clock component, in the development of renal fibrosis, the hallmark of pathological features in many renal diseases. The inducible Bmal1 knockout mice (iKO) whose gene deletion occurred in adulthood were used in the study. Analysis of the urinary water, sodium and potassium excretion showed that the iKO mice exhibit abolished diurnal variations. In the model of renal fibrosis induced by unilateral ureteral obstruction, the iKO mice displayed significantly decreased tubulointerstitial fibrosis reflected by attenuated collagen deposition and mitigated expression of fibrotic markers α-SMA and fibronectin. The hedgehog pathway transcriptional effectors Gli1 and Gli2, which have been reported to be involved in the pathogenesis of renal fibrosis, were significantly decreased in the iKO mice. Mechanistically, ChIP assay and luciferase reporter assay revealed that BMAL1 bound to the promoter of and activate the transcription of Gli2, but not Gli1, suggesting that the involvement of Bmal1 in renal fibrosis was possibly mediated via Gli2-dependent mechanisms. Furthermore, treatment with TGF-ß increased Bmal1 in cultured murine proximal tubular cells. Knockdown of Bmal1 abolished, while overexpression of Bmal1 increased, Gli2 and the expression of fibrosis-related genes. Collectively, these results revealed a prominent role of the core clock gene Bmal1 in tubulointerstitial fibrosis. Moreover, we identified Gli2 as a novel target of Bmal1, which may mediate the adverse effect of Bmal1 in obstructive nephropathy.


Assuntos
Fatores de Transcrição ARNTL/fisiologia , Fibrose/prevenção & controle , Regulação da Expressão Gênica , Nefropatias/prevenção & controle , Proteínas Circadianas Period/fisiologia , Proteína Gli2 com Dedos de Zinco/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo
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