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1.
J Int Med Res ; 49(1): 300060520985363, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33472479

RESUMO

OBJECTIVES: Chlorogenic acid (CGA) is an antioxidant dietary factor. We investigated the effects of CGA on endothelial cell dysfunction in diabetic mice and the mechanistic role of nuclear factor erythroid-related factor 2 (Nrf2) in the antioxidant effect of CGA. METHODS: Diabetic (db/db) mice were fed normal chow or chow containing 0.02% CGA for 12 weeks. Human umbilical vein endothelial cells (HUVECs) and mouse aortas were treated with normal or high glucose. RESULTS: CGA treatment induced upregulation of Nrf2 in HUVECs in a dose-dependent manner. CGA pretreatment prevented reactive oxygen species generation and preserved nitric oxide bioavailability in HUVECs and aortas from wild-type but not Nrf2-/- mice. CGA improved endothelium-dependent relaxation in high glucose-treated aortas from wild-type and db/db mice, but not Nrf2-/- mice. Dietary CGA improved endothelium-dependent relaxation in db/db mice. CONCLUSIONS: CGA ameliorates endothelial dysfunction in diabetic mice through activation of the Nrf2 anti-oxidative pathway.

2.
J Colloid Interface Sci ; 582(Pt A): 405-411, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32866807

RESUMO

Fluorescent carbon polymer nanomaterials driven by their important various applications are promising, however, their scalable usages are still hindered by the lack of facile and effective synthesis approaches. Herein, a rapid and facile approach is demonstrated for the preparation of fluorescent carbon polymer hollow spheres (CPHSs), which were synthesized by directly mixing concentrated sulfuric acid (H2SO4) and diethylenetriamine (DETA) at room temperature. Notably, both the solid powders and aqueous dispersion of CPHSs possess the fluorescence properties, similar with the reported carbon polymer dots. The formation of CPHSs could be attributed to the polymerization of DETA in the presence of H2SO4. The present strategy is universal and fluorescent nanomaterials could also be obtained by using hexamethylenetetramine or polyethylenepolayamine as precursors with the aid of concentrated H2SO4. Most importantly, the CPHSs possess peroxidase-like activity and can catalyze oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to its one-electron oxidation product, providing a new method for colorimetric detection of H2O2.

3.
BMJ Open ; 10(12): e035805, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33293303

RESUMO

OBJECTIVE: To explore the association between age-related macular degeneration (AMD) and arthritis in a representative sample of the US population. DESIGN: Population-based, cross-sectional study. SETTING: The National Health and Nutrition Examination Survey (NHANES) 2005-2008. PARTICIPANTS: A total of 4813 participants aged 40 years and older with available information on AMD and arthritis in the 2005-2008 NHANES. METHODS: The status and types of arthritis were obtained from questionnaires. Non-mydriatic fundus photographs were collected. The types of AMD were assessed using the modified Wisconsin Age-Related Maculopathy Grading Classification Scheme. The association between arthritis and AMD was evaluated using logistic regression models. RESULTS: After adjusting for covariates, participants with any or early AMD had significantly lower odds of having any type of arthritis (any AMD: OR=0.56, 95% CI: 0.36-0.86; early AMD: OR=0.55, 95% CI: 0.34-0.88) or osteoarthritis (OA) (any AMD: OR=0.43, 95% CI: 0.26-0.71; early AMD: OR=0.44, 95% CI: 0.25-0.76) compared with those without AMD. When considering AMD as the outcome, significant negative associations were also found between any arthritis or OA and any (any arthritis: OR=0.64, 95% CI: 0.43-0.94; OA: OR=0.52, 95% CI: 0.33-0.82) or early AMD (any arthritis: OR=0.61, 95% CI: 0.40-0.93; OA: OR=0.51, 95% CI: 0.31-0.86) in the multivariable logistic models. There was no significant association between different types of arthritis and late AMD. CONCLUSIONS: People with arthritis, especially those with OA, were less likely to have AMD compared with those without arthritis and vice versa. Further studies are needed to confirm this potential protective effect of arthritis and/or arthritis treatment on AMD and to explore the underlying mechanisms.

4.
Acta Ophthalmol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33191663

RESUMO

PURPOSE: The influence of myopia and ocular biometry parameters on diabetic retinopathy (DR) needs further clarification. We aimed to investigate the association between ocular biometrical parameters and DR in Chinese people with diabetes mellitus (DM) without any ocular intervention. METHODS: This cross-sectional study recruited type 2 DM patients with no history of ocular treatment in Guangzhou, China. The ocular biometrical parameters were obtained by Lenstar (LS900, Haag-Streit AG, Koeniz, Switzerland), including corneal diameter, central corneal thickness (CCT), corneal curvature (CC), anterior chamber depth (ACD), lens thickness (LT) and axial length (AL). The lens power and axial length-to-cornea radius ratio (AL/CR ratio) were calculated. Spherical equivalent (SE) was determined by auto-refraction after pupil dilation. Multivariate logistic regression analyses were performed to explore the associations of ocular biometry with any DR and vision threatening DR (VTDR). RESULTS: A total of 1838 patients were included in the final analysis, involving 1455 (79.2%) patients without DR and 383(20.8%) patients with DR. After adjusting confounding factors, any DR was independently associated with AL (odds ratio (OR) 0.84 per 1 mm increase, 95% confidence interval (CI): 0.74, 0.94) and AL/CR ratio (OR 0.26 per 1 increase, 95%CI: 0.10, 0.70). Similarly, the presence of VTDR was independently related to AL (OR 0.67 per 1 mm increase, 95%CI: 0.54, 0.85) and AL/CR ratio (OR 0.04 per 1 increase, 95%CI: 0.01, 0.25). The lens power may not be significantly correlated with presence of any DR or VTDR. The CC, corneal diameter and refractive status were not significantly correlated with presence of DR or VTDR. CONCLUSION: Longer AL and higher AL/CR ratio may be protective factors against the occurrence and progression of DR. Further longitudinal studies are warranted to verify if refractive status and AL-associated parameters contribute to the occurrence and progression of DR in type 2 DM.

5.
Math Biosci Eng ; 17(5): 4825-4851, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-33120530

RESUMO

Targeted at emergency plans for rainstorm and waterlogging disasters in subway station projects, this work proposes a group decision-making method that uses linguistic intuitionistic fuzzy sets, structural entropy weights, and TOPSIS. An evaluation index system of emergency plans was constructed based on four aspects, namely a scientific basis, completeness, operability, and flexibility. A linguistic interval intuitionistic fuzzy set approach was then used to qualitatively present the decision-makers' understanding of, attitudes about, and preferences for emergency plans. The uncertainty was comprehensively and intuitively represented by the dimensions of the degrees of membership and non-membership. The structural entropy weight method was applied and improved to fully reflect the influences of experts with different characteristics on the index weights. Finally, the TOPSIS method, with a background context of linguistic interval intuitionistic fuzzy sets, was applied. The calculation results of benchmark and verification case highlight the rationality and scientificity of the method proposed in this paper. The emergency decisions regarding waterlogging in 2018 for the Huilong Road West Station Project of Chengdu Metro Line 11 in China were selected as a case study. The case study demonstrates that operability is the most critical of the four primary indicators, and that flexible response to changes in the emergency response level is the most important of the secondary indicators. The uncertainty analysis of data revealed that with the increase of uncertainty, the difference between each scheme and the ideal solution decreased. Compared with the classical TOPSIS method, the new model proposed in this paper is robust and effective, and can be used for similar projects in the future.

6.
Chemosphere ; 264(Pt 2): 128534, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33045508

RESUMO

Biological phosphorus removal (BPR) from wastewater can be generally realized through alternative non-aeration and aeration operation to create anaerobic and aerobic conditions respectively for P release and uptake/accumulation by polyphosphate accumulating organisms (PAOs), with P removal finally achieved by controlled discharge of P-rich sludge. In this study, the response of algal-bacterial aerobic granular sludge (AB-AGS) during BPR to main ions including Ac- (acetate), Cl-, SO42-, NH4+, K+, Mg2+, Ca2+ and Na+ in wastewater was investigated with conventional bacterial AGS (B-AGS) as control and acetate as the sole carbon source. Results show that BPR process mainly involved the changes of Ac-, K+, Mg2+, and Ca2+ rather than Cl-, SO42-, NH4+ and Na+. The mole ratio of ΔP/ΔAc kept almost unchanged during the non-aeration (P release) phase in both B-AGS and AB-AGS systems (ΔPB-AGS/ΔAcB-AGS > ΔPAB-AGS/ΔAcAB-AGS), and it was negatively influenced by the light in AB-AGS systems, in which 62% of acetate was not utilized for P release at the high illuminance of 81 k lux. During the entire non-aeration/aeration period, both ΔK/ΔP and ΔMg/ΔP remained constant, while ΔKAB-AGS/ΔPAB-AGS > ΔKB-AGS/ΔPB-AGS and ΔMgAB-AGS/ΔPAB-AGS ≈ ΔMgB-AGS/ΔPB-AGS. The presence of algae seemed not beneficial for PAOs to remove P, while more K+ and P uptake by algae in AB-AGS suggest its great potential for manufacturing biofertilizer.

7.
Comput Struct Biotechnol J ; 18: 2200-2208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32868983

RESUMO

In less than eight months, the COVID-19 (coronavirus disease 2019) caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus has resulted in over 20,000,000 confirmed cases and over 700,000 deaths around the world. With the increasing worldwide spreading of this disease, the lack of effective drugs against SARS-CoV-2 infection makes the situation even more dangerous and unpredictable. Although many forces are speeding up to develop prevention and treatment therapeutics, it is unlikely that any de novo drugs will be available in months. Drug repurposing holds the promise to significantly save the time for drug development, since it could use existing clinic drugs to treat new diseases. Based on the "steric-clashes alleviating receptor (SCAR)" strategy developed in our lab recently, we screened the library of clinic and investigational drugs, and identified nine drugs that might be repurposed as covalent inhibitors of the priming proteases (cathepsin B, cathepsin L, and TMPRSS2) of the spike protein of SARS-CoV-2. Among these hits, five are known covalent inhibitors, and one is an anti-virus drug. Therefore, we hope our work would provide rational and timely help for developing anti-SARS-CoV-2 drugs.

8.
Curr Microbiol ; 77(12): 3909-3918, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32989486

RESUMO

Wastewater (WW) irrigation to agricultural soils is one of the most economical and effective water-saving strategies. The effects of WW irrigation on soil microbial communities have gained increasing focus as these effects are not well understood. In this study, the effects of WW and groundwater (GW) irrigation on microbial diversity and structure were compared using the high-throughput sequencing analysis of 16S rDNA amplicons. Soil samples irrigated by WW for several decades and maize soil (loamy) samples irrigated by GW were collected from Luancheng Town, Shijiazhuang City, China. Compared to the GW groups, WW groups exhibited non-significant soil bacterial community abundance at the 0-20 and 20-40 cm depths. WW irrigation significantly altered the bacterial community composition and structures compared to GW irrigation. The relative abundance of Proteobacteria and Firmicutes increased in WW irrigated soil, while Actinobacteria decreased. Moreover, 14 significantly abundant biomarkers from Proteobacteria and Firmicutes that corresponded with WW irrigation were identified. Additionally, WW irrigation enriched some KEGG pathways that corresponded with metabolism and human diseases. The physical and chemical properties of WW irrigated soil may shape the compositions and structures of soil bacterial communities. The findings of this study illuminated the effects of wastewater irrigation on microbial characteristics, which is important for estimating the effects of long-term wastewater irrigation on soil environmental health.

9.
Curr Eye Res ; : 1-7, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32865040

RESUMO

PURPOSE: To summarize the research status on the function and mechanism of circRNAs in regulating the occurrence of diabetic retinopathy (DR). Methods: We systematically searched PubMed, Embase.com, and ARVO Abstracts website and reviewed relevant studies. Results: Thousands of circRNAs were found to be aberrantly expressed in DR patients, animal models, or cell models. A few circRNAs, such as cPWWP2A, circDNMT3B, circHIPK3, circ_0005015, et al were demonstrated to play an important role in DR by regulating the angiogenesis, proliferation, apoptosis, and inflammatory response of various cells in the retina. Conclusion: CircRNAs are involved in the development of DR. CircRNAs can not only serve as DR biomarkers, but also become therapeutic targets for DR. The role of plenty of circRNAs in DR is yet to be discovered.

10.
FASEB J ; 34(9): 10907-12921, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32767470

RESUMO

Metabolic reprograming is a hallmark of cancer, and the polyamine metabolic network is dysregulated in many cancers. Ornithine decarboxylase (ODC) is a rate-limiting enzyme for polyamine synthesis in the polyamine metabolic network. In many cancer cells, ODC is over-expressed, so this enzyme has been an attracting anti-cancer drug target. In the catalysis axis (pathway), ODC converts ornithine to putrescine. Meanwhile, ODC's activity is regulated by protein-protein interactions (PPIs), including the ODC-OAZ1-AZIN1 PPI axis and its monomer-dimer equilibrium. Previous studies showed that when ODC's activity is inhibited, the PPIs might counteract the inhibition efficiency. Therefore, we proposed that multipurpose inhibitors that can simultaneously inhibit ODC's activity and perturb the PPIs would be very valuable as drug candidates and molecular tools. To discover multipurpose ODC inhibitors, we established a computational pipeline by combining positive screening and negative screening. We used this pipeline for the forward screening of multipurpose ligands that might inhibit ODC's activity, block ODC-OAZ1 interaction and enhance ODC non-functional dimerization. With a combination of different experimental assays, we identified three multipurpose ODC inhibitors. At last, we showed that one of these inhibitors is a promising drug candidate. This work demonstrated that our computational pipeline is useful for discovering multipurpose ODC inhibitors, and multipurpose inhibitors would be very valuable. Similar with ODC, there are a lot of proteins in human proteome that act as both enzymes and PPI components. Therefore, this work is not only presenting new molecular tools for polyamine study, but also providing potential insights and protocols for discovering multipurpose inhibitors to target more important protein targets.

11.
J Alzheimers Dis ; 77(1): 313-322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804135

RESUMO

BACKGROUND: Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer's disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear. OBJECTIVE: To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI. METHODS: Levels of neurogranin (NGRN) and ß-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-ß 1-40 (Aß40), Aß42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment. RESULTS: Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores. CONCLUSION: GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations.

12.
Transl Vis Sci Technol ; 9(5): 17, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32821489

RESUMO

Purpose: To investigate the relationship between renal function and choroidal thickness (CT) in ocular treatment-naïve patients with diabetes mellitus using swept-source optical coherence tomography (SS-OCT). Methods: This cross-sectional study recruited type 2 diabetes mellitus (T2DM) patients with no history of ocular treatment from communities in Guangzhou, China. The estimated glomerular filtration rates (eGFR) were calculated by using the Xiangya formula. The impaired renal function was defined as eGFR < 60 mL/(min 1.73 m2). The choroid was imaged by using an SS-OCT, and the macular CT was quantified automatically in Early Treatment Diabetic Retinopathy Study maps, and only data from one eye was used. Univariate and multivariate linear regression analyses were performed to explore the influence of eGFR on CT. Results: A total of 1395 patients with T2DM were included in the final analysis. The CT of all macular regions were significantly thinner in patients with renal impairment (all P < 0.001). A significantly positive correlation was observed between the average CT and eGFR (ß = 0.4; 95% confidence interval, 0.041-0.8; P = 0.029) independent of age, sex, and other potential confounding factors. After adjusting for other factors, a higher eGFR was also associated with higher CT values in the central field (P = 0.019) and in the outer superior (P = 0.047), inner superior (P = 0.018), inner inferior (P = 0.025), and inner temporal (P = 0.038) regions. Conclusions: CT decreased in parallel with renal impairment in ocular treatment naïve diabetic patients, providing an accessible window for monitoring renal status. Translational Relevance: Knowledge of association between retinal microvasculature and renal microcirculation would allow applying in both clinical and research settings.

13.
Appl Bionics Biomech ; 2020: 8792143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670404

RESUMO

Angiosperm leaf venation is based on two major patterns, typically dicotyledonous branching and monocotyledonous parallel veins. The influence of these patterns on deformation and fracture properties is poorly understood. In this paper, three species of dicotyledons with netted venation and three species of monocots with parallel venation were selected, and the effect of vein distribution of leaves on their mechanical properties and deformation behavior was investigated. Whole images of leaves were captured using a digital camera, and their vein traits were measured using the image processing software Digimizer. A self-developed mechanical testing apparatus with high precision and low load was used to measure the tensile properties of leaves. The deformation behavior of the leaf was captured using a digital microscope during the tensile test. Results showed that the vein architecture of monocots and dicots is different, which had a remarkable effect on their mechanical properties, deformation behavior, and crack propagation behavior. The greater the diameter and the more the number of veins parallel to the tensile direction, the higher the tensile force, tensile strength, and elastic modulus of the leaves. The netted venation leaves evinced the elastic-plastic fracture type, and the hierarchy venation provided resistance to fracture propagation of cracks in the leaves by lengthening the crack path. The leaves with parallel venation behaved in a predominantly brittle manner or elastic fracture type, and the parallel venation inhibited the initiation of cracks in the leaves by increasing the load at complete fracture of the leaves. The investigation provides reference for a stiffened plate/shell structure and bionic anticrack design.

14.
Graefes Arch Clin Exp Ophthalmol ; 258(12): 2671-2679, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32661699

RESUMO

PURPOSE: Previous studies on the association between macular vessel density (VD) and diabetic retinopathy had conflicting conclusions. This study assessed the alterations of macular VD, as well as other factors, in diabetic patients using swept-source optical coherence tomography angiography (SS-OCTA) in a large-scale sample from Chinese communities. METHODS: Patients with type 2 diabetes without history of ocular treatment were recruited from 2017 to 2018. The average and quadrant parafoveal vessel density (PVD) were obtained with a commercial SS-OCTA device (Triton, Topcon, Japan). The univariate and multivariate linear regression was used to analyse the correlation of PVD with diabetic retinopathy (DR), diabetic macular edema (DME), HbA1c, and other factors. RESULTS: A total of 919 patients were included in the final statistical analysis. After adjusting for other confounding factors, the DR patients had significantly lower average PVD (ß = - 1.062, 95% CI = - 1.424 to - 0.699, P < 0.001) in comparison with those without DR. In addition, the patients with mild DR or vision-threatening diabetic retinopathy (VTDR) also had significantly lower PVD (P < 0.001 for mild DR, and P = 0.008 for VTDR) compared with those without DR. Age and HbA1c were also significantly related to PVD measurements, as shown by multivariable linear regression. Participants with DME had a significantly lower average PVD and temporal PVD than those without DME (P < 0.05). CONCLUSIONS: Reduced PVD was independently associated with more severe DR, older age, higher HbA1c level, and the presence of DME. These findings suggested that macular vessel alterations in DR warrant further evaluation in the longitudinal studies.

15.
Bioresour Technol ; 315: 123797, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32683288

RESUMO

Fenton modification, involving iron-promoted pyrolysis followed by H2O2 oxidation, was first employed to improve the adsorptive and magnetic capabilities of biochar. Modified biochars were prepared from rubber tree bark and coconut shell through iron-promoted pyrolysis and subsequent H2O2 oxidation, and their adsorption behaviors toward Cr (VI) and MB were evaluated in aqueous solution. The modified biochars pyrolyzed at 300 and 400 ˚C displayed much higher adsorption capabilities than corresponding pristine biochars for Cr (VI) and MB, respectively, ascribing to introduction of COOH, CO and C-O groups by Fenton oxidation. More importantly, saturation magnetization could be enhanced by transforming nonmagnetic iron oxides into γ-Fe2O3 through H2O2 oxidation. The removal of Cr (VI) and MB could be primarily contributed to the adsorption of biochar matrix by reduction/hydrogen bonding/cation exchange/electrostatic interaction and hydrogen bonding/cation exchange/electrostatic interaction, respectively. This would provide a novel and efficient strategy for making highly adsorptive magnetic biochar.


Assuntos
Peróxido de Hidrogênio , Poluentes Químicos da Água/análise , Adsorção , Carvão Vegetal , Cromo , Fenômenos Magnéticos
16.
Bioact Mater ; 5(3): 611-623, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405576

RESUMO

Magnesium alloy is considered as one of the ideal cardiovascular stent materials owing to its good mechanical properties and biodegradability. However, the in vivo rapid degradation rate and the insufficient biocompatibility restrict its clinical applications. In this study, the magnesium alloy (AZ31B) was modified by combining the surface chemical treatment and in-situ self-assembly of 16-phosphonyl-hexadecanoic acid, followed by the immobilization of chitosan-functionalized graphene oxide (GOCS). Heparin (Hep) and GOCS were alternatively immobilized on the GOCS-modified surface through layer by layer (LBL) to construct the GOCS/Hep bioactive multilayer coating, and the corrosion resistance and biocompatibility were extensively explored. The results showed that the GOCS/Hep bioactive multilayer coating can endow magnesium alloys with an excellent in vitro corrosion resistance. The GOCS/Hep multilayer coating can significantly reduce the hemolysis rate and the platelet adhesion and activation, resulting in an excellent blood compatibility. In addition, the multilayer coating can not only enhance the adhesion and proliferation of the endothelial cells, but also promote the vascular endothelial growth factor (VEGF) and nitric oxide (NO) expression of the attached endothelial cells on the surfaces. Therefore, the method of the present study can be used to simultaneously control the corrosion resistance and improve the biocompatibility of the magnesium alloys, which is expected to promote the application of magnesium alloys in biomaterials or medical devices, especially cardiovascular stent.

17.
Prostate ; 80(10): 764-776, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32356608

RESUMO

BACKGROUND: Aging is the most important risk factor for prostate cancer (PCa), but how age contributes to PCa is poorly understood. Aging is characterized by low-grade systemic inflammation (i.e., inflammaging) that is often attributed to the progressive activation of immune cells over time, which may play an important role in prostate carcinogenesis. Th17 response is elevated in aging humans and mice, but it remains unknown whether it is increased in prostate tissue or contributes to prostate carcinogenesis during aging. In this study, we aimed to determine the role of age-related Th17 response in PCa cell growth, migration, and invasion. METHODS: C57BL/6J (B6) mouse was used as an aging animal model and the prostate histopathology during aging was analyzed. Splenic CD4+ T cells were isolated from young (16-20 weeks old) and aged (96-104 weeks old) mice, and cultured in the presence of plate-bound anti-CD3/anti-CD28, with or without Th17 differentiation conditions. The cells were collected and used for subsequent flow cytometry or quantitative reverse transcription polymerase chain reaction. The supernatant was collected and used to treat PCa cell lines. The treated PCa cells were analyzed for cell viability, migration, invasion, and nuclear factor kappa B (NF-κB) signaling. RESULTS: Aged mice had enlarged prostate glands and increased morphological alterations, with not only increased inflammatory cell infiltration but also increased Th17 cytokines in prostate tissue, compared to young mice. Naïve CD4+ T cells from aged mice differentiated increased interleukin (IL)-17-expressing cells. CD4+ T cells from aged mice spleen had increased Th17 cells, Th17 cytokines and Th17/Treg ratio compared to young mice. Factors secreted from aged CD4+ T cells, especially from ex vivo differentiated Th17 cells, not only promoted PCa cell viability, migration, and invasion but also activated the NF-κB signaling in PCa cells compared to young mice. CONCLUSIONS: These results indicate that age-related CD4+ T cells, especially Th17 cells-secreted factors have the potential to contribute to prostate carcinogenesis. Our work could prompt further research using autochthonous PCa mouse models at different ages to elucidate the functional role of Th17 response in prostate carcinogenesis during aging.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Neoplasias da Próstata/imunologia , Células Th17/imunologia , Envelhecimento/imunologia , Animais , Linfócitos T CD4-Positivos/patologia , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Movimento Celular/imunologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , NF-kappa B/imunologia , Invasividade Neoplásica , Células PC-3 , Neoplasias da Próstata/patologia , Células Th17/patologia
18.
J Med Genet ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381727

RESUMO

BACKGROUND: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening. METHODS: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited. RESULTS: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis. CONCLUSION: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

19.
Curr Eye Res ; 45(12): 1526-1533, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32255371

RESUMO

Purpose: To investigate the associations of the estimated glomerular filtration rate (eGFR) with peripapillary choroidal thickness (pCT) and retinal nerve fiber layer (pRNFL) thickness in diabetic patients by using swept-source optical coherence tomography (SS-OCT). Methods: Ocular treatment-naïve patients with type 2 diabetes mellitus registered in the community health system in Guangzhou, China, were recruited to participate in this prospective cross-sectional study. The eGFR was determined using the Xiangya formula, and the renal function was categorized into non-chronic kidney disease (non-CKD), mild CKD, and moderate to severe CKD (MS-CKD) according to the guidelines. The pCT and pRNFL thicknesses at 12 o'clock were obtained using an SS-OCT by a circular scan with a diameter of 3.4 mm centering on the optic nerve head, and the data from only one eye in each patient were used. Results: This study included 1,408 diabetic patients, with a mean age of 64.4 ± 7.8 years. The average pCT decreased with renal function deterioration, with 126.0 ± 58.0 µm for non-CKD, 112.0 ± 51.2 µm for mild CKD and 71.0 ± 22.9 µm for MS-CKD, respectively (P < .001). The pCT was found to be significantly thinner in CKD patients in all quadrantes (P < .05 in all regions) with the exception of the inferior quadrant, and the average pCT was positively correlated with eGFR (ß = 0.3, 95%CI = 0.0 to 0.6, P = .021) after adjusting for other factors. The pRNFL thickness in the nasal quadrant was significantly reduced in patients with CKD, and pRNFL thickness was positively correlated with eGFR (ß = 0.1, 95%CI = 0.0-0.2, P = .009) after adjusting for other factors. Conclusion: Impaired renal function was associated with a reduction of pCT and pRNFL thickness in patients with type 2 diabetes. The measurement of pCT and pRNFL may provide additional information for predicting renal impairment.

20.
Am J Hypertens ; 33(7): 610-619, 2020 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-32242611

RESUMO

BACKGROUND: Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS: Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS: CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-ß1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS: A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.

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