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1.
Stat Med ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398899

RESUMO

Statistical methods for analysis of survey data have been developed to facilitate research. More recently, Lumley and Scott (2013) developed an approach to extend the Mann-Whitney-Wilcoxon (MWW) rank sum test to survey data. Their approach focuses on the null of equal distribution. In many studies, the MWW test is called for when two-sample t-tests (with or without equal variance assumed) fail to provide meaningful results, as they are highly sensitive to outliers. In such situations, the null of equal distribution is too restrictive, as interest lies in comparing centers of groups. In this article, we develop an approach to extend the MWW test to survey data to test the null of equal mean rank. Although not as popular as the mean and median, the mean rank is also a meaningful measure of the center of a distribution and is the same as the median for a symmetric distribution. We illustrate the proposed approach and show major differences with Lumley and Scott's alternative using both real and simulated data.

2.
BMC Cancer ; 21(1): 22, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402129

RESUMO

BACKGROUND: An accurate intraoperative prediction of lymph node metastatic risk can help surgeons in choosing precise surgical procedures. We aimed to develop and validate nomograms to intraoperatively predict patterns of regional lymph node (LN) metastasis in patients with esophageal cancer. METHODS: The prediction model was developed in a training cohort consisting of 487 patients diagnosed with esophageal cancer who underwent esophagectomy with complete LN dissection from January 2016 to December 2016. Univariate and multivariable logistic regression were used to identify independent risk factors that were incorporated into a prediction model and used to construct a nomogram. Contrast-enhanced computed tomography reported LN status and was an important comparative factor of clinical usefulness in a validation cohort. Nomogram performance was assessed in terms of calibration, discrimination, and clinical usefulness. An independent validation cohort comprised 206 consecutive patients from January 2017 to December 2017. RESULTS: Univariate analysis and multivariable logistic regression revealed three independent predictors of metastatic regional LNs, three independent predictors of continuous regional LNs, and two independent predictors of skipping regional LNs. Independent predictors were used to build three individualized prediction nomograms. The models showed good calibration and discrimination, with area under the curve (AUC) values of 0.737, 0.738, and 0.707. Application of the nomogram in the validation cohort yielded good calibration and discrimination, with AUC values of 0.728, 0.668, and 0.657. Decision curve analysis demonstrated that the three nomograms were clinically useful in the validation cohort. CONCLUSION: This study presents three nomograms that incorporate clinicopathologic factors, which can be used to facilitate the intraoperative prediction of metastatic regional LN patterns in patients with esophageal cancer.

3.
J Mol Histol ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33394292

RESUMO

Cav3.1, a subfamily of T-type calcium channel, is overexpressed in various human cancers and exerts important functions in tumor progression. This study is to identify the expression pattern and clinical significance of Cav3.1 in oral squamous cell carcinoma (OSCC). Firstly, the expression levels of Cav3.1 in oral mucosa (OM), dysplasia and oral squamous cell carcinoma (OSCC) were determined and compared by real-time quantitative PCR and Western blot analysis. After that, human tissue microarrays, containing 29 OM, 23 dysplasia and 122 primary OSCC samples, were applied to investigate the expression levels of Cav3.1, proliferation markers [Ki-67, proliferating cell nuclear antigen (PCNA)] and cellular anti-apoptosis markers [B cell lymphoma 2 (Bcl-2)] by immunohistochemistry and digital pathology analysis. In addition, we determined the function of Cav3.1 using knockdown assays of Cav3.1 in vitro. The results demonstrated that the mRNA and protein expression of Cav3.1 were significantly higher in OSCC specimens, and Cav3.1 expression in primary OSCCs was correlated with tumor size and pathological grade. Statistical analysis of immunohistochemical staining showed that Cav3.1 was closely correlated with Ki-67, PCNA and Bcl-2. Functional studies showed that the knockdown of Cav3.1 in OSCC cell lines using RNA interference influenced cell proliferation and apoptosis in vitro. Taken together, these findings suggested that Cav3.1 is overexpressed in OSCC tissues, also associated with proliferative and anti-apoptotic activity in oral squamous cell carcinoma.

4.
J Psychiatr Res ; 132: 174-181, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33126011

RESUMO

OBJECTIVE: Wisdom has gained increasing interest among researchers as a personality trait relevant to well-being and mental health. We previously reported development of a new 24-item San Diego Wisdom Scale (SD-WISE), with good to excellent psychometric properties, comprised of six subscales: pro-social behaviors, emotional regulation, self-reflection (insight), tolerance for divergent values (acceptance of uncertainty), decisiveness, and social advising. There is controversy about whether spirituality is a marker of wisdom. The present cross-sectional study sought to address that question by developing a new SD-WISE subscale of spirituality and examining its associations with various relevant measures. METHODS: Data were collected from a national-level sample of 1,786 community-dwelling adults age 20-82 years, as part of an Amazon M-Turk cohort. Participants completed the 24-item SD-WISE along with several subscales of a commonly used Brief Multidimensional Measure of Religiousness/Spirituality, along with validated scales for well-being, resilience, happiness, depression, anxiety, loneliness, and social network. RESULTS: Using latent variable models, we developed a Spirituality subscale, which demonstrated acceptable psychometric properties including a unidimensional factor structure and good reliability. Spirituality correlated positively with age and was higher in women than in men. The expanded 28-item, 7-subscale SD-WISE total score (called the Jeste-Thomas Wisdom Index or JTWI) demonstrated acceptable psychometric properties. The Spirituality subscale was positively correlated with good mental health and well-being, and negatively correlated with poor mental health. However, compared to other components of wisdom, the Spirituality factor showed weaker (i.e., small-to-medium vs. medium-to-large) association with the SD-WISE higher-order Wisdom factor (JTWI). CONCLUSION: Similar to other components as well as overall wisdom, spirituality is significantly associated with better mental health and well-being, and may add to the predictive utility of the total wisdom score. Spirituality is, however, a weaker contributor to overall wisdom than components like pro-social behaviors and emotional regulation. Longitudinal studies of larger and more diverse samples are needed to explore mediation effects of these constructs on well-being and health.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33315564

RESUMO

Image fusion plays a critical role in a variety of vision and learning applications. Current fusion approaches are designed to characterize source images, focusing on a certain type of fusion task while limited in a wide scenario. Moreover, other fusion strategies (i.e., weighted averaging, choose-max) cannot undertake the challenging fusion tasks, which furthermore leads to undesirable artifacts facilely emerged in their fused results. In this paper, we propose a generic image fusion method with a bilevel optimization paradigm, targeting on multi-modality image fusion tasks. Corresponding alternation optimization is conducted on certain components decoupled from source images. Via adaptive integration weight maps, we are able to get the flexible fusion strategy across multi-modality images. We successfully applied it to three types of image fusion tasks, including infrared and visible, computed tomography and magnetic resonance imaging, and magnetic resonance imaging and single-photon emission computed tomography image fusion. Results highlight the performance and versatility of our approach from both quantitative and qualitative aspects.

6.
J Acoust Soc Am ; 148(4): EL353, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33138513

RESUMO

With the increased availability of highly maneuverable unmanned surface/underwater vehicles, abundant ocean data can now be collected. This study uses tomographic techniques to extend the survey area covered by moving vehicles. An acoustic reciprocal transmission experiment was conducted using three tomographic sensors installed on an autonomous underwater vehicle, a fishing ship, and a buoy. The distributed sensing method is applied for currents estimation. The estimated currents near the ship show consistent results with the direct measurements. In particular, an anticyclonic circulation was revealed. Further, a general least-squares method is employed to improve the estimate of this vortical structure.

7.
Opt Express ; 28(20): 29829-29842, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33114873

RESUMO

For a nonisothermal blackbody cavity, different reference temperatures have influence on the calculation of effective emissivity. Previous studies proposed a weighted average method which can be indicated by a priori to calculate the reference temperature. However, these studies did not mention how to define the weight function but used some arbitrary temperature or the temperature of a fixed position like the central bottom of the cavity as the reference temperature. In this study, a quantitative analysis and calculation method, which is implemented in the Monte Carlo method based optical simulation software Tracepro, is proposed to define the weight coefficients and optimize the reference temperature. To do so, in the Tracepro software, a surface source is placed in front of the cavity opening and emits radiation to the blackbody cavity. The radiation from this surface source can be absorbed or reflected many times in the cavity, and finally the incident radiation distribution in the cavity can be obtained. According to the principle of light path reversibility, the normalized incident radiation can be considered as the contribution of its position to the effective emissivity. In the experiment, the actual temperatures of two different-shaped blackbody cavities are measured with the non-contact method in 873 K temperature. By dividing the inner surface of each blackbody cavity into several regions based on the positions of the actually measured temperature points, the incident radiation from the surface source to each segmented region is calculated and normalized to the total incident radiation across all regions as its weight coefficient; the reference temperature is the sum of the weighted temperature (by multiplying each weight coefficient with its measured temperature) in each region. Different from previous studies, this study optimizes the reference temperature by considering the contribution of the whole cavity to the effective emissivity, which should be more consistent with the actual situation. Moreover, the influences of different shapes of the blackbody cavities, different radiation characteristics of the inner surface materials and different viewing conditions of the effective emissivity on the reference temperature are discussed and compared. The results suggest that the optimization of reference temperature has close link with above factors and thus should be calculated individually.

8.
Aging Ment Health ; : 1-11, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000647

RESUMO

OBJECTIVES: There has been growing research interest in loneliness and wisdom in recent decades, but no cross-cultural comparisons of these constructs using standardized rating measures in older adults, especially the oldest-old. This was a cross-sectional study of loneliness and wisdom comparing middle-aged and oldest-old adults in Cilento, Italy and San Diego, United States. METHOD: We examined loneliness and wisdom, using the UCLA Loneliness Scale Version 3 (UCLA-3) and San Diego Wisdom Scale (SD-WISE), respectively, in four subject groups: adults aged 50-65 and those ≥90 years from Cilento, Italy (N = 212 and 47, respectively) and San Diego, California, USA (N = 138 and 85, respectively). RESULTS: After controlling for education, there were no significant group differences in levels of loneliness, while on SD-WISE the Cilento ≥90 group had lower scores compared to the other three groups. There was a strong inverse correlation between loneliness and wisdom in each of the four subject groups. Loneliness was negatively associated while wisdom was positively associated with general health, sleep quality, and happiness in most groups, with varying levels of significance. CONCLUSION: These results largely support cross-cultural validity of the constructs of loneliness and wisdom, and extend previous findings of strong inverse correlations between these two entities. Loneliness has become a growing public health problem, and the results of our study suggest that wisdom could be a protective factor against loneliness, although alternative explanations are also possible. Research on interventions to reduce loneliness by enhancing wisdom in older adults is needed.

9.
Nanomaterials (Basel) ; 10(9)2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32932650

RESUMO

Scanning Kelvin probe microscopy (SKPM), electrostatic force microscopy (EFM) are used to study the microscopic processes of the photo-induced charge separation at the interface of Ag and conductive polymers, i.e., poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) and poly(3-hexylthiophene-2,5-diyl) (P3HT). They are also widely used in order to directly observe the charge distribution and dynamic changes at the interfaces in nanostructures, owing to their high sensitivity. Using SKPM, it is proved that the charge of the photo-induced polymer PCPDTBT is transferred to Ag nanoparticles (NPs). The surface charge of the Ag-induced NPs is quantified while using EFM, and it is determined that the charge is injected into the polymer P3HT from the Ag NPs. We expect that this technology will provide guidance to facilitate the separation and transfer of the interfacial charges in the composite material systems and it will be applicable to various photovoltaic material systems.

10.
Phytother Res ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32757226

RESUMO

Puerarin is a major isofiavone compound isolated from the root of Pueraria lobata. It was reported that puerarin had antioxidant, antiinflammatory, antitumor, cholesterol lowering, liver protective, and neuroprotective properties. However, few studies have explored the antiviral effect of puerarin and its target mechanism related to influenza virus. Here, the antiinfluenza activity of puerarin in vitro and in vivo and its mode of action on the potential inhibition of neuraminidase (NA) were investigated. Puerarin displayed an inhibitory effect on A/FM/1/1947(H1N1) (EC50 = 52.06 µM). An indirect immunofluorescence assay indicated that puerarin blocked the nuclear export of viral NP. The inhibition of NA activity confirmed that puerarin can block the release of newly formed virus particles from infected cells. Puerarin (100 and 200 mg/kg/d) exhibited effective antiviral activity in mice, conferring 50% and 70% protection from death against H1N1, reducing virus titers, and effectively alleviating inflammation in the lungs. The molecular docking results showed that puerarin had a strong binding affinity with NA from H1N1. The results of the molecular dynamics simulation revealed that puerarin had higher stable binding at the 150-loop region of the NA protein. These results demonstrated that puerarin acts as a NA blocker to inhibit influenza A virus both in cellular and animal models. Thus, puerarin has potential utility for the treatment of the influenza virus infection.

11.
Appl Opt ; 59(23): 6977-6983, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788789

RESUMO

The emissivity of the blackbody is a very important parameter in spectral radiance measurement systems. In the conventional method, the emissivity is calculated based on the isothermal model. However, the actual temperature distribution in the blackbody cavity is always nonisothermal; the emissivity calculated based on the isothermal model may not accurately present the radiation characteristic of the blackbody. In this study, the actual temperature distributions of two blackbodies (one has an extended cone shape, and the other a 65-mm diameter cylindrical shape) are measured, and the emissivities are calculated accordingly based on the nonisothermal model at a certain temperature (873 K). The results show there are different tendencies of temperature distributions in the two blackbodies. When compared with the isothermal model, the emissivities in the 873 K temperature and 2.0-20.0 µm wavelength condition are about 1.75% and 0.18% lower at the nonisothermal model for the extended cone shape and cylindrical blackbodies, respectively. To improve the emissivity, different types of apertures are customized for the two blackbodies. For the extended cone-shaped blackbody, the emissivity in the 873 K temperature and 2.0-20.0 µm wavelength condition increases by 1.12% when using a ring-shaped graphite aperture in the cavity, whereas for the cylindrical-shaped blackbody, the emissivity in the same condition increases by 0.09% when using a high-reflective aperture in front of the cavity opening. Different from previous studies, this study provides new insight in calculating and improving the effective emissivity of blackbodies by using the measured temperature in the cavity based on the nonisothermal model.

12.
Ann Transl Med ; 8(11): 680, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32617300

RESUMO

Background: To validate the prognostic impacts of the left gastric artery lymph node (No. 7 LN) metastasis and investigate whether the No. 7 LN metastasis should be considered as the predictive LN for extra-gastric LN metastases. Methods: Between January 2003 and December 2011, a total of 1,586 patients who underwent R0 gastrectomy were retrospected. Patients with LN metastases were divided into three groups: (I) patients with only peri-gastric LN metastases (peri-gastric group); (II) patients with peri-gastric and only No. 7 LN metastases (No. 7 group); and (III) patients with other extra-gastric LN metastases (extra-gastric group). Propensity score matching (PSM) was adopted to accurately evaluate prognoses of all patients after surgery. Results: Of 1,586 patients, 235 (14.82%) were pathologically identified to present with the No. 7 LN metastases. Patients with the No. 7 LN metastases presented the significantly lower survival rate both before and after adjustment by pTNM stage, compared to those without the No. 7 LN metastases. Patients in the No. 7 group were identified to present the significant lower survival rate than those in the peri-gastric group, and to present the similar median overall survival (OS) to those in the extra-gastric group. In addition, patients with extra-gastric LN except No. 7 LN metastases failed to show any superiority of survival outcomes, compared with those with extra-gastric LN metastases including the No. 7 LN metastasis. Conclusions: The No. 7 LN metastases had the crucial survival implications. Nevertheless, the No. 7 LN failed to be considered as the predictive LN for the extra-gastric LN metastases in gastric cancer (GC).

13.
Hepatol Commun ; 4(5): 681-695, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32363319

RESUMO

Overconsumption of carbohydrates and lipids are well known to cause nonalcoholic fatty liver disease (NAFLD), while the role of nutritional protein intake is less clear. In Western diet, meat and other animal products are the main protein source, with varying concentrations of specific amino acids. Whether the amount or composition of protein intake is associated with a higher risk for disease severity has not yet been examined. In this study, we investigated associations of dietary components with histological disease activity by analyzing detailed 14-day food records in a cohort of 61 patients with biopsy-proven NAFLD. Furthermore, we used 16S ribosomal RNA gene sequencing to detect associations with different abundances of the gut microbiota with dietary patterns. Patients with definite nonalcoholic steatohepatitis (NAFLD activity score of 5-8 on liver biopsy) had a significantly higher daily relative intake of protein compared with patients with a NAFLD activity score of 0-4 (18.0% vs. 15.8% of daily protein-based calories, P = 0.018). After adjustment for several potentially confounding factors, a higher protein intake (≥17.3% of daily protein-based calories) remained associated with definite nonalcoholic steatohepatitis, with an odds ratio of 5.09 (95% confidence interval 1.22-21.25, P = 0.026). This association was driven primarily by serine, glycine, arginine, proline, phenylalanine, and methionine. A higher protein intake correlated with a lower Bacteroides abundance and an altered abundance of several other bacterial taxa. Conclusion: A high protein intake was independently associated with more active and severe histological disease activity in patients with NAFLD. Further studies are needed to investigate the potential harmful role of dietary amino acids on NAFLD, with special attention to meat as their major source.

14.
JAMA Psychiatry ; 77(9): 925-935, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401284

RESUMO

Importance: Wisdom is a neurobiological personality trait made up of specific components, including prosocial behaviors, emotional regulation, and spirituality. It is associated with greater well-being and happiness. Objective: To evaluate the effectiveness of interventions to enhance individual components of wisdom. Data Sources: MEDLINE and PsycINFO databases were searched for articles published through December 31, 2018. Study Eligibility Criteria: Randomized clinical trials that sought to enhance a component of wisdom, used published measures to assess that component, were published in English, had a minimum sample size of 40 participants, and presented data that enabled computation of effect sizes were included in this meta-analysis. Data Extraction and Synthesis: Random-effect models were used to calculate pooled standardized mean differences (SMDs) for each wisdom component and random-effects meta-regression to assess heterogeneity of studies. Main Outcomes and Measures: Improvement in wisdom component using published measures. Results: Fifty-seven studies (N = 7096 participants) met review criteria: 29 for prosocial behaviors, 13 for emotional regulation, and 15 for spirituality. Study samples included people with psychiatric or physical illnesses and from the community. Of the studies, 27 (47%) reported significant improvement with medium to large effect sizes. Meta-analysis revealed significant pooled SMDs for prosocial behaviors (23 studies; pooled SMD, 0.43 [95% CI, 0.22-0.3]; P = .02), emotional regulation (12 studies; pooled SMD, 0.67 [95% CI, 0.21-1.12]; P = .004), and spirituality (12 studies; pooled SMD, 1.00 [95% CI, 0.41-1.60]; P = .001). Heterogeneity of studies was considerable for all wisdom components. Publication bias was present for prosocial behavior and emotional regulation studies; after adjusting for it, the pooled SMD for prosocial behavior remained significant (SMD, 0.4 [95% CI, 0.16-0.78]; P = .003). Meta-regression analysis found that effect sizes did not vary by wisdom component, although for trials on prosocial behaviors, large effect sizes were associated with older mean participant age (ß, 0.08 [SE, 0.04]), and the reverse was true for spirituality trials (ß, -0.13 [SE, 0.04]). For spirituality interventions, higher-quality trials had larger effect sizes (ß, 4.17 [SE, 1.07]), although the reverse was true for prosocial behavior trials (ß, -0.91 [SE 0.44]). Conclusions and Relevance: Interventions to enhance spirituality, emotional regulation, and prosocial behaviors are effective in a proportion of people with mental or physical illnesses and from the community. The modern behavioral epidemics of loneliness, suicide, and opioid abuse point to a growing need for wisdom-enhancing interventions to promote individual and societal well-being.

15.
Cureus ; 12(3): e7173, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32257714

RESUMO

Objective The purpose of this study was to analyze the incidence of infections in patients following placement of External Ventricular Drain (EVD) in either the Emergency Room (ER) or the Intensive Care Unit (ICU)/ Operating Room (OR) at a single Comprehensive Stroke Center. Methods Retrospective analysis of post-procedure infection rates in 710 patients with EVDs placed on site between 2010 and 2018 was performed. We analyzed cases between sex, age, stroke and non-stroke related and further requirement of conversion of the EVD to a ventriculoperitoneal (VP) shunt. Results Significant decrease in EVD related infection (ERIs) rates following the shift in EVD placement from ER to ICU/OR (from 13% to 7.7%, p=.03) among all ages, sex and type of brain injury was observed. Furthermore, our data also shows that the rate of conversion of EVDs to VP shunts is independent of the setting where EVD was placed, but increases in patients who develop ERIs. 23.1% of stroke patients that developed an ERI required a conversion to VP shunt while 67.3% of non-stroke patients that developed an ERI required further VP shunt (p<.001) showing that non-stroke EVD patients with infections are more likely to require VP shunt. Conclusion This is one of the larger retrospective studies conducted on EVD related infections. ERIs were significantly higher when EVDs were placed in the ER. Moreover, our results highlight the relation between ERIs and further requirement of conversion EVD to VP shunt. These figures highlight the importance of focusing on infection rates, and the implications CSF infection has on the long-term care of patients.

16.
Chin J Cancer Res ; 32(1): 51-61, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32194305

RESUMO

Objective: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior (No. 8p, No. 12b/p, No. 13, and No. 14v), and para-aortic (No. 16a2, and No. 16b1) lymph nodes (LNs) in subtotal gastrectomy for advanced gastric antral carcinoma. Methods: A total of 203 patients with advanced gastric cancer (GC) located in the antrum, who underwent R0 gastrectomy with D2 or D2-plus lymphadenectomy between January 2003 and December 2011 were enrolled. Propensity score matching was used to reduce the strength of the confounding factors to accurately evaluate prognoses. The therapeutic value index (TVI) was calculate to evaluate the survival benefit of dissecting each LN station. Results: Of 102 patients with D2-plus lymphadenectomy, 21 (20.59%) were pathologically identified as having LN metastases beyond the extent of D2 lymphadenectomy. After matching, the overall survival (OS) was significantly better in the D2-plus than the D2 group (P=0.030). In the multivariate survival analysis, D2-plus lymphadenectomy (hazard ratio, 0.516; P=0.006) was confirmed to significantly improve the survival rate. In the logistic regression analysis, pN stage [odds ratio (OR), 2.533; 95% confidence interval (95% CI), 1.368-4.691; P=0.003] and extent of LNs metastasis (OR, 5.965; 95% CI, 1.335-26.650; P=0.019) were identified as independent risk factors for LN metastases beyond the extent of D2 lymphadenectomy. The TVI of patient with metastasis to LNs station was 7.1 (No. 8p), 5.7 (No. 12p), 5.1 (No. 13), and 7.1 (both No. 16a2 and No. 16b1), respectively. Conclusions: D2-plus lymphadenectomy may improve the prognoses of some patients with advanced GC located in the antrum, especially for No. 8p, No. 12b, No. 13, and No. 16.

17.
Eur Phys J E Soft Matter ; 43(2): 7, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32006191

RESUMO

Zwitterions are a class of unique molecules that can be modified onto nanomaterials to render them with antifouling properties. Here we report a thorough NMR investigation of dendrimers modified with zwitterions in terms of their structure, hydrodynamic size, and diffusion time in aqueous solution. In this present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were partially decorated with carboxybetaine acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively with different modification degrees. The formed zwitterion-modified G5 dendrimers were characterized using NMR techniques. We show that the zwitterion modification leads to increased G5 dendrimer size in aqueous solution, suggesting that the modified zwitterions can form a hydration layer on the surface of G5 dendrimers. In addition, the hydrodynamic sizes of G5 dendrimers modified with different zwitterions but with the same degree of surface modification are discrepant depending on the type of zwitterions. The present study provides a new physical insight into the structure of zwitterion-modified G5 dendrimers by NMR techniques, which is beneficial for further design of different biomedical applications.

18.
Inflammopharmacology ; 28(1): 299-310, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31446589

RESUMO

BACKGROUND: Influenza is an acute viral respiratory illness that causes high morbidity and mortality globally. Therapeutic actions are limited to vaccines and a few anti-viral drugs. Polygala (P.) japonica herba is rich in Polygalasaponin F (PSF, C53H86O23), used for acute bronchitis, pharyngitis, pneumonia, amygdalitis, and respiratory tract infections treatment in China. Hypercytokinemia is often correlated with severe pneumonia caused by several influenza viruses. PSF was reported to have anti-inflammatory effects and its mechanism is associated with the nuclear factor (NF)-κB signaling pathway. The action of PSF to alleviate pulmonary inflammation caused by influenza A virus (IAV) infection requires careful assessment. In the present study, we evaluated the effect and mechanism of PSF on mice with pneumonia caused by influenza H1N1 (A/FM/1/47). METHODS: Mice were infected intranasally with fifteen 50% mouse lethal challenge doses (MLD50) of influenza virus. BALB/c mice were treated with PSF or oseltamivir (oral administration) for 2 h post-infection and received concomitant treatment for 5 days after infection. On day 6 post-infection, 10 mice per group were killed to collect related samples, measure body weight and lung wet weight, and detect the viral load, cytokine, prostaglandins, pathological changes, and cell pathway protein expression in the lungs. In addition, the survival experiments were carried out to investigate the survival of mice. The expression profile of cell pathway proteins was detected and analyzed using a broad pathway antibody array and confirmed the findings from the array by western blotting. RESULTS: Polygalasaponin F and oseltamivir can protect against influenza viral infection in mice. PSF and oseltamivir significantly relieved the signs and symptoms, reduced body weight loss, and improved the survival rate of H1N1-infected mice. Moreover, PSF efficiently decreased the level of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-4, interferon (IFN)-γ, thromboxane A2 (TXA2), and prostaglandin E2 (PGE2) in lung tissues of mice infected with influenza virus (p < 0.05-0.01). Oseltamivir had a similar effect to lung cytokine of PSF, but did not decrease the levels of TXA2 and PGE2. There was a twofold or greater increase in four cell pathway protein, namely NF-κB p65 (2.68-fold), I-kappa-B-alpha (IκBα) (2.56-fold), and MAPK/ERK kinase 1 (MEK1) (7.15-fold) assessed in the array induced by influenza virus. Western blotting showed that the expression of these proteins was significantly decreased in lung after influenza virus challenge in PSF and oseltamivir-treated mice (p < 0.05-0.01). CONCLUSION: Polygalasaponin F appears to be able to augment protection against IAV infection in mice via attenuation of pulmonary inflammatory responses. Its effect on IAV-induced pulmonary inflammation was associated with suppression of Raf/MEK/ERK and NF-κB expressions.


Assuntos
Vírus da Influenza A Subtipo H1N1/patogenicidade , Infecções por Orthomyxoviridae/complicações , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Citocinas/metabolismo , Feminino , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/metabolismo , Pneumonia/metabolismo , Pneumonia/virologia , Transdução de Sinais/efeitos dos fármacos
19.
Hepatology ; 71(2): 522-538, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31228214

RESUMO

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.


Assuntos
Disbiose/etiologia , Disbiose/imunologia , Hepatite Alcoólica/complicações , Hepatite Alcoólica/imunologia , Intestinos/microbiologia , Micobioma , Adulto , Idoso , Anticorpos Antifúngicos/sangue , Candida/imunologia , Estudos de Coortes , Disbiose/sangue , Feminino , Hepatite Alcoólica/sangue , Humanos , Fenômenos do Sistema Imunológico , Masculino , Pessoa de Meia-Idade , Saccharomyces cerevisiae/imunologia
20.
J Hepatol ; 72(3): 391-400, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31606552

RESUMO

BACKGROUND & AIMS: Alcohol-associated liver disease is a leading indication for liver transplantation and a leading cause of mortality. Alterations to the gut microbiota contribute to the pathogenesis of alcohol-associated liver disease. Patients with alcohol-associated liver disease have increased proportions of Candida spp. in the fecal mycobiome, yet little is known about the effect of intestinal Candida on the disease. Herein, we evaluated the contributions of Candida albicans and its exotoxin candidalysin in alcohol-associated liver disease. METHODS: C. albicans and the extent of cell elongation 1 (ECE1) were analyzed in fecal samples from controls, patients with alcohol use disorder and those with alcoholic hepatitis. Mice colonized with different and genetically manipulated C. albicans strains were subjected to the chronic-plus-binge ethanol diet model. Primary hepatocytes were isolated and incubated with candidalysin. RESULTS: The percentages of individuals carrying ECE1 were 0%, 4.76% and 30.77% in non-alcoholic controls, patients with alcohol use disorder and patients with alcoholic hepatitis, respectively. Candidalysin exacerbates ethanol-induced liver disease and is associated with increased mortality in mice. Candidalysin enhances ethanol-induced liver disease independently of the ß-glucan receptor C-type lectin domain family 7 member A (CLEC7A) on bone marrow-derived cells, and candidalysin does not alter gut barrier function. Candidalysin can damage primary hepatocytes in a dose-dependent manner in vitro and is associated with liver disease severity and mortality in patients with alcoholic hepatitis. CONCLUSIONS: Candidalysin is associated with the progression of ethanol-induced liver disease in preclinical models and worse clinical outcomes in patients with alcoholic hepatitis. LAY SUMMARY: Candidalysin is a peptide toxin secreted by the commensal gut fungus Candida albicans. Candidalysin enhances alcohol-associated liver disease independently of the ß-glucan receptor CLEC7A on bone marrow-derived cells in mice without affecting intestinal permeability. Candidalysin is cytotoxic to primary hepatocytes, indicating a direct role of candidalysin on ethanol-induced liver disease. Candidalysin might be an effective target for therapy in patients with alcohol-associated liver disease.

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