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1.
ACS Chem Biol ; 15(3): 774-779, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32141733

RESUMO

Thioamide substitutions in peptides can be used as fluorescence quenchers in protease sensors and as stabilizing modifications of hormone analogs. To guide these applications in the context of serine proteases, we here examine the cleavage of several model substrates, scanning a thioamide between the P3 and P3' positions, and identify perturbing positions for thioamide substitution. While all serine proteases tested were affected by P1 thioamidation, certain proteases were also significantly affected by other thioamide positions. We demonstrate how these findings can be applied by harnessing the combined P3/P1 effect of a single thioamide on kallikrein proteolysis to protect two key positions in a neuropeptide Y-based imaging probe, increasing its serum half-life to >24 h while maintaining potency for binding to Y1 receptor expressing cells. Such stabilized peptide probes could find application in imaging cell populations in animal models or even in clinical applications such as fluorescence-guided surgery.

2.
Nano Lett ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32207976

RESUMO

The dimensionality of crystal structure plays an important role in electronic structures of materials. Ruddlesden-Popper perovskite oxides offer an attractive platform for studying this role due to their dimensional flexibility. The effects of dimensionality on physical properties in those oxides have been widely reported. However, the study of dimensional dependence on the chemical properties is still lacking. Here, we synthesized a serious of Ruddlesden-Popper perovskite nickelates LanSrNinO3n+1 (n = 1, 2, 3, and ∞) to explore the correlation between the dimensionality and electrocatalytical activities for water oxidation. We found that as the dimensionality increased with n, the nickelates exhibited an enhanced performance towards water oxidation. Electronic structure studies revealed that the increase in dimensionality induced an insulator-to-metal transition due to the weakening of effective electron correlations among Ni 3d electrons, which was associated with a strengthened Ni 3d-O 2p hybridization. Both the enhanced conductivity and metal-oxygen hybridization accelerated the kinetics of oxygen evolution reaction. This work sets up a bridge between the dimensionality and electrocatalysis, which provides guidance for designing oxygen-evolving catalysts with excellent performance.

3.
Int Immunopharmacol ; 83: 106383, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32193099

RESUMO

Kelch-like ECH-associated protein (Keap1)-nuclear factor erythroid-2-related factor 2 (Nrf2) protein-protein interaction has become an important drug target for the treatment of Alzheimer's disease. In this study, we found a novel piperine derivative (HJ22) synthesized by our group with great ability to bind to Keap-1 and activate Keap1-Nrf2-ARE signaling pathway in vitro, driving us to investigate the beneficial effects of HJ22 on ibotenic acid (IBO)-induced neurological disorders in rats and underlying mechanisms. Interestingly, HJ22 significantly ameliorated IBO-induced cognitive impairment in Morris water maze, Y-maze and passive avoidance tests. Moreover, HJ22 significantly attenuated cholinergic dysfunction and neuronal morphological changes via inhibiting apoptotic cell death induced by IBO. Notably, HJ22 inhibited the interaction between Keap1 and Nrf2, and subsequently up-regulated nuclear Nrf2 expression, thereby inhibiting oxidative stress and Thioredoxin-interacting protein (TXNIP)-mediated Nod-like receptor protein 3 (NLRP3) inflammasome activation. These findings demonstrated that HJ22 exhibited potent therapeutic effects against IBO-induced cognitive impairment by alleviating cholinergic damage, oxidative stress, apoptosis and neuroinflammation, which might be partly attributed to its inhibitory activity on Keap1-Nrf2 protein-protein interaction.

4.
J Agric Food Chem ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32208625

RESUMO

Tyrosol is a pharmacologically active phenolic compound widely used in the pharmaceutical and chemical industries. Microbial fermentation has potential value as an environmentally friendly approach to tyrosol production but suffers from low tyrosol yields and the need for expensive media additives. In this study, Escherichia coli MG1655 was modified by integrating an E. coli codon-optimized version of the Saccharomyces cerevisiae phenylpyruvate decarboxylase gene, named ARO10*, into the lacI locus. The resulting strain (YMGA*) produced 0.14 mM tyrosol from 2% glucose without the need for expensive media supplements. Subsequent deletion of E. coli genes designed to eliminate competing metabolic pathways (feaB, pheA, tyrB) or undesirable gene regulation (tyrR) produced a strain (YMGA*R) that produced 3.11 mM tyrosol. Tyrosol production was then increased to 10.92 mM by increasing the ARO10* copy number to five copies (strain YMG5A*R). Finally, tyrosol production was increased to 28 mM (ca. 3.9 g/L) by optimizing fermentation conditions in a 5-L fermenter. Engineering a productive E. coli strain with high tyrosol titer from glucose using a medium that does not require added amino acids, inducer, or antibiotic, which provides a solid basis to produce tyrosol through microbial fermentation.

5.
Biomed Res Int ; 2020: 8241637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104707

RESUMO

Objective: To assess the value of clinically relevant data for predicting the failure of removal of the urinary catheter within 48 hours after TUERP. Materials and Methods. We retrospectively analyzed the medical records of 357 patients who underwent TUERP between January 2015 and July 2018, all of whom stopped bladder irrigation and removed urinary catheter within 48 hours after the operation. According to whether the removal of the catheter was successful, the patients were classified into 2 groups: Group A was successful and group B was a failure. Univariate analysis was performed to determine the association between the failure of removal of the catheter and the patients' preoperative clinical characteristics. Logistic regression analysis and receiver operating characteristic analysis (ROC) were conducted to establish the prediction model. Then the area under the curve (AUC) and the cut-off value were calculated. Results: 357 patients were divided into group A (n = 305, 85.4%) and group B (n = 305, 85.4%) and group B (P=0.006), history of acute urinary retention (AUR) (P=0.006), history of acute urinary retention (AUR) (P=0.006), history of acute urinary retention (AUR) (P=0.006), history of acute urinary retention (AUR) (P=0.006), history of acute urinary retention (AUR) (P=0.006), history of acute urinary retention (AUR) (P=0.006), history of acute urinary retention (AUR) (P=0.006), history of acute urinary retention (AUR) (P=0.006), history of acute urinary retention (AUR) (. Conclusion: This study demonstrated that IPSS, QoL, drug medication, history of AUR, TPV, and IPP are independent factors associated with the failure of removal of the urethral catheter within 48 hours after TUERP.

6.
Nano Lett ; 20(2): 1403-1409, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31967840

RESUMO

Exploring the high-performance non-Pt electrocatalysts for oxygen reduction reaction (ORR), the bottleneck process in fuel cells, is desirable but challenging. Here, we report the Pd@PdFe core-shell icosahedra as an active and durable electrocatalyst toward ORR in alkaline conditions, which feature a three-atomic-layer tensile-strained PdFe overlayer on Pd icosahedra. Our optimized catalyst shows 2.8-fold enhancement in mass activity and 6.9-fold enhancement in specific activity than commercial Pt/C catalyst toward ORR, representing one of the best non-Pt electrocatalysts. Moreover, the boosted ORR catalysis is strongly supported by the assembled fuel cell performance using Pd@PdFe core-shell icosahedra as the cathode electrocatalyst. The density functional theory calculations reveal that the synergistic coupling of tensile strain and alloy effects enables the optimum binding strength for intermediates, thus causing the maximum activity. The present work suggests the coupling between multiple surface modulations endows larger room for the rational design of remarkable catalysts.

7.
Cell Death Dis ; 11(1): 10, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907353

RESUMO

Ubiquitin-conjugating enzyme E2O (UBE2O) is a large E2 ubiquitin-conjugating enzyme that possesses both E2 and E3 ligase activities. Ectopic UBE2O overexpression is associated with a variety of human diseases, especially cancers. However, the expression profile and functional biology of UBE2O in human breast cancer (BC) remain unclear. In this study, we found that UBE2O was significantly overexpressed in human BC tissues and cells. Patients with high UBE2O expression tended to have a high risk of metastasis and poor prognosis. In vitro assays revealed that UBE2O promoted BC cell proliferation and epithelial-mesenchymal transformation (EMT) and endowed BC cells with cancer stemness properties (CSPs). UBE2O knockdown in MDA-MB-231 cells suppressed tumour growth and lung metastasis in MDA-MB-231 xenograft mouse models. Mechanistically, UBE2O functioned as a ubiquitin enzyme of AMPKα2, promoting its ubiquitination and degradation and thus activating the mTORC1 signal pathway and contributing to BC oncogenesis and metastasis. Furthermore, as a downstream factor of the UBE2O/AMPKα2/mTORC1 axis, the oncoprotein MYC transcriptionally promoted UBE2O and formed a positive feedback loop in human BC. Collectively, our study demonstrated that UBE2O/AMPKα2/mTORC1-MYC forms a positive feedback loop in human BC cells that regulates BC cell proliferation and EMT and endows BC cells with CSPs.

8.
Sci Total Environ ; 710: 136329, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31918182

RESUMO

The contamination of the aquatic environments by tetracycline antibiotics (TCs) is an increasingly pressing issue. Here, we used the addition of exogenous surfactants and in situ biosynthesis of biosurfactants to remove tetracycline (TC), oxytetracycline (OTC), chlortetracycline (CTC), and their mixtures using the co-culture of probiotic Bacillus clausii T and Bacillus amyloliquefaciens HM618 producing surfactin. The addition of exogenous biosurfactants to remove TCs was superior to nonionic surfactants. The maximal bio-removal efficiencies for OTC and CTC among mixed antibiotics under the co-culture of B. clausii T and B. amyloliquefaciens HM618 were 76.6% and 88.9%, respectively, which were both better than the efficiency of the pure culture of B. clausii T. TCs were removed mainly through biotransformation rather than absorption and hydrolysis. The removal efficiency was in the order CTC > OTC > TC. The co-culture of B. clausii T and B. amyloliquefaciens HM618 alleviated the cytotoxicity of OTC and CTC. The toxicity of the biotransformation products was lower than that of the parent compounds. Demethylation, hydroxylation, and dehydration are likely the major mechanisms of TC biotransformation. These results illustrate the potential of using surfactants in the bioremediation of tetracycline antibiotics, and provide new avenues for further exploration of the bioremediation of antibiotics pollution.

9.
J Cell Biochem ; 121(2): 1227-1237, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31595563

RESUMO

BACKGROUND: Toll-like receptor-7 (TLR7) is functionally involved in the pathogenesis of Hunner-type interstitial cystitis (HIC). In addition, maternally expressed gene 3 (MEG3) is implicated in many urethral diseases. In this study, we aimed to verify the hypothesis that exosomal MEG3 in urine can be used as a novel diagnostic biomarker for HIC. METHODS: Electron microscopy was utilized to observe the distribution of urinary exosomes between the case group and the control group. Receiver operating characteristic analysis was utilized to compare the diagnostic values of MEG3 and miR-19a-3p. Computational analysis and luciferase assay were conducted to identify the correlation between MEG3 and miR-19a-3p as well as between TLR7 and miR-19a-3p. In addition, real-time polymerase chain reaction and Western blot were performed to establish the signaling pathways implicated in the pathogenesis of HIC. RESULTS: When age and gender distributions are excluded, urinary exosomes were equally distributed between case and control groups. The area under the curve of MEG3 was larger than that of miR-19a-3p, indicating that MEG3 has a better value in the diagnosis of HIC. In addition, patients with HIC showed elevated MEG3 expression and inhibited miR-19a-3p expression, thus establishing a negative correlation between MEG3 and miR-19a-3p. MEG3 and TLR7 were both identified as targets of miR-19a-3p, establishing a MEG3/miR-19a-3p/TLR7 signaling pathway, in which MEG3 enhances the expression of TLR7 via inhibiting the expression of miR-19a-3p. CONCLUSION: MEG3 level was upregulated in patients with HIC. In addition, MEG3 downregulated miR-19a-3p expression while upregulating TLR7 expression. Furthermore, MEG3 contributes to the pathogenesis of HIC. Therefore, exosomal MEG3 in urine can be used as a biomarker for HIC diagnosis.

10.
J Atheroscler Thromb ; 27(3): 245-254, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462617

RESUMO

AIMS: To investigate the association of chronic kidney disease (CKD) and intracranial artery stenosis (ICAS), as well as its effects on ICAS distribution in the middle-aged and elderly population. METHODS: Data from the China Hypertension Survey in Beijing was analyzed. Estimated glomerular filtration rate (eGFR) was used to evaluate CKD, and ICAS was assessed by transcranial doppler. Clinical and biochemical variables were compared between the ICAS group and the non-ICAS group, as well as in different vascular distribution groups. Univariable and multivariable logistic regression analyses were introduced to demonstrate the association between CKD and ICAS. RESULTS: A total of 3678 subjects were included in this study, with a mean age of 62 years old. Of which, 19.2% presented with decreased eGFR (eGFR <60 ml/min/1.73 m2) and 17.4% for ICAS. The percentage of anterior circulation ICAS was 3.5 times than that of posterior circulation (10.9% vs. 3.1%). In multivariable regression analysis, eGFR <45 ml/min/1.73 m2 was independently associated with ICAS after correction for covariates, odds ratio (OR)=1.69, 95% confidence interval (CI) (1.08, 2.65); in particular, this association had a preference for posterior circulation but not anterior circulation ICAS with OR=2.29, 95% CI (1.28, 4.07) and OR=1.44, 95%CI (0.89, 2.33), respectively. CONCLUSION: Severe eGFR decline is associated with ICAS in the middle-aged and elderly population, and this correlation is more related to posterior circulation ICAS.

11.
BMC Plant Biol ; 19(1): 566, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852440

RESUMO

BACKGROUND: Sucrose synthase (SUS) is widely considered a key enzyme participating in sucrose metabolism in higher plants and regarded as a biochemical marker for sink strength in crops. However, despite significant progress in characterizing the physiological functions of the SUS gene family, knowledge of the trajectory of evolutionary processes and significance of the family in higher plants remains incomplete. RESULTS: In this study, we identified over 100 SUS genes in 19 plant species and reconstructed their phylogenies, presenting a potential framework of SUS gene family evolution in higher plants. Three anciently diverged SUS gene subfamilies (SUS I, II and III) were distinguished based on their phylogenetic relationships and unique intron/exon structures in angiosperms, and they were found to have evolved independently in monocots and dicots. Each subfamily of SUS genes exhibited distinct expression patterns in a wide range of plants, implying that their functional differentiation occurred before the divergence of monocots and dicots. Furthermore, SUS III genes evolved under relaxed purifying selection in dicots and displayed narrowed expression profiles. In addition, for all three subfamilies of SUS genes, the GT-B domain was more conserved than the "regulatory" domain. CONCLUSIONS: The present study reveals the evolution of the SUS gene family in higher plants and provides new insights into the evolutionary conservation and functional divergence of angiosperm SUS genes.

12.
Oxid Med Cell Longev ; 2019: 4748312, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885795

RESUMO

Epidemiologic studies revealed a context between lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and metabolic syndrome. However, molecular mechanisms underlying this relationship are largely unknown. Prostate enlargement and increased prostate smooth muscle tone are important factors in the pathophysiology of LUTS suggestive of BPH. In the present study, we studied effects of the metabolic hormone ghrelin on prostate enlargement in rats with experimentally induced BPH, growth of cultured stromal cells from human prostate (WPMY-1), and smooth muscle contraction of human prostate tissues. Ghrelin (20 nmol/kg daily, p.o., 2 weeks) increased prostate size in rats with testosterone-induced BPH. Microarray identified 114 ghrelin-upregulated genes (2-fold or more) in these prostates, with possible roles in growth, smooth muscle contraction, or metabolism. 12 genes were selected for further analyses. In human prostate tissues, mRNA levels of 11 of them correlated positively with ghrelin receptor (GHSR) expression, but only two with the degree of BPH. Accordingly, no correlation was evident between GHSR expression level and BPH in human prostate tissues. In WPMY-1 cells, the GHRS agonist MK0677 upregulated 11 of the selected genes. MK0677 induced proliferation of WPMY-1 cells, shown by EdU assay, colony formation, proliferation markers, flow cytometry, and viability. In myographic measurements, GHSR agonists enhanced contractions of human prostate strips. Together, ghrelin may aggravate prostate enlargement, stromal cell growth, and prostate smooth muscle contraction in BPH. Ghrelin may deteriorate urethral obstruction independently from BPH, qualifying the ghrelin system as an attractive new target to be tested for LUTS treatment in BPH.

13.
Nano Lett ; 19(12): 8774-8779, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31675477

RESUMO

The obstacle for efficient electrochemical water splitting lies in the kinetically sluggish oxygen evolution reaction. Despite the various efforts that have been made to understand and tune the active sites for oxygen evolution reaction, an insight into the configurations of active sites from the electronic perspective is still lacking. Here, we report an atomic doping strategy to break the Oh symmetry of the CoO6 octahedron in LiCoO2. The specific activity of the La-doped LiCoO2 was 3.14 mA cm-2 at the overpotential of 0.35 V, which was 8.3 times higher than that of pristine LiCoO2. The overpotential with a value of 330 mV at 10 mA cm-2 was the lowest among the LiCoO2-based OER electrocatalysts ever reported. Mechanistic studies revealed that the superior activity originated from the asymmetric octahedral coordination of Co, resulting in the enhanced electronic conductivity and Co-O hybridization for the accelerated oxygen evolution kinetics. This work opens a door to enhance the catalytic performance through the manipulation of local symmetry.

14.
Lipids Health Dis ; 18(1): 184, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647035

RESUMO

BACKGROUND: This study aimed to investigate the angiotensin converting enzyme (ACE) co-expression genes and their pathways involved in ST-segment elevation myocardial infarction (STEMI) at different time points. METHODS: The array data set of GSE59867 was examined for the ACE co-expression genes in peripheral blood samples from 111 patients with STEMI at four time points (admission, discharge, and 1 and 6 months after MI). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Gene Ontology (GO) annotation and protein-protein interaction (PPI) of the co-expression genes were determined using online analytical tools. The Cytoscape software was used to create modules and hub genes. RESULTS: The number of biological processes (BP), cellular components (CC) and molecular functions (MF) was 43, 22 and 24 at admission; 18, 19 and 11 at discharge; 30, 37 and 21 at 1 month after MI; and 12, 19 and 14 at 6 months after MI; respectively. There were 6 BP, 8 CC and 4 MF enriched at every time point. The co-expression genes were substantially enriched in 12, 5, 6 and 14 KEGG pathways at the four time points, respectively, but no KEGG pathway was found to be common in all time points. We identified 132 intersectional co-expression genes (90 positive and 42 negative) from the four time points and 17 BP, 13 CC, 11 MF and 7 KEGG pathways were enriched. In addition, the PPI network contained 129 nodes and 570 edges, and only 1 module was identified to be significantly enriched in just 1 BP (chromatin-mediated maintenance of transcription). CONCLUSIONS: The results of the present study showed that the ACE co-expression genes and their pathways involved in STEMI were significantly different at four different time points. These findings may be helpful for further understanding the functions and roles of ACE in different stages of STEMI, and providing reference for the treatment of STEMI.

15.
Eur J Med Chem ; 181: 111564, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376563

RESUMO

The P2Y14 receptor (P2Y14R) plays a key role in the modulation of inflammatory process, but very few classes of antagonists have been reported. A series of 3-amide benzoic acid derivatives were identified as novel and potent P2Y14R antagonists. The most potent antagonist, 16c, showed comparable activity (IC50 = 1.77 nM) to PPTN, the most potent P2Y14R antagonist reported. Compound 16c demonstrated dramatically improved aqueous solubility and excellent metabolic stability in rat and human microsomes. Investigation of the anti-inflammatory effect of 16c was performed in MSU treated THP-1 cells by flow cytometry, Western Blot and immunofluorescence labeling technology, which exhibited that 16c might be a promising candidate for further research.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ácido Benzoico/química , Ácido Benzoico/farmacologia , Antagonistas do Receptor Purinérgico P2/química , Antagonistas do Receptor Purinérgico P2/farmacologia , Amidas/síntese química , Amidas/química , Amidas/farmacologia , Animais , Anti-Inflamatórios/síntese química , Ácido Benzoico/síntese química , Linhagem Celular , Desenho de Drogas , Humanos , Simulação de Acoplamento Molecular , Antagonistas do Receptor Purinérgico P2/síntese química , Ratos , Receptores Purinérgicos P2/metabolismo
16.
J Cancer ; 10(18): 4165-4177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413735

RESUMO

Background: Once prostate cancer developed bone metastasis, the quality of life and prognosis of patients are seriously affected as no effective treatment is currently available. It is necessary to explore the mechanism of bone metastasis and new therapeutic targets. Purpose: To find out the differentially expressed serum proteins in prostate cancer patients with bone metastasis and analyze the expression of key proteins in prostate cancer tissues, serum and prostate cancer cell lines. So as to provide a basis for revealing the mechanism of bone metastasis and designing new therapeutic targets. Methods: iTRAQ-based proteomics method was used to compare serum differential proteins in prostate cancer patients with and without bone metastasis. Three key proteins (CD59, haptoglobin and tetranectin) which had significant fold changes were selected to validate the results of mass spectrometry. Immunohistochemistry and ELISA were applied to tissues and serum samples from prostate cancer patients, respectively, for validation. Finally, western blot, flow cytometry, and immunocytochemistry were used to analyze the expression of the three differentially expressed proteins in the prostate cancer cell lines PC3, LNCap, and Du145. Results: Thirty-two differentially expressed proteins related to bone metastasis of prostate cancer were identified, of which 11 were up-regulated and 21 were down-regulated. CD59 and haptoglobin were up-regulated in prostate cancer with bone metastasis while tetranectin was down-regulated. Tetranectin showed differential expression in epithelial and stromal cells of prostate cancer and hyperplasia tissues.The expression of CD59 was highest in PC3 and lowest in LNCap, while the expression of haptoglobin and tetranectin was the highest in DU145 and lowest in PC3. Conclusion: Mass spectrometry analysis showed that there were more differentially expressed proteins in the serum of patients with bone metastasis than those without metastasis. It has been verified that CD59, haptoglobin and tetranectin are prostate cancer bone metastasis related proteins.

17.
Asia Pac J Clin Nutr ; 28(3): 607-613, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464408

RESUMO

BACKGROUND AND OBJECTIVES: The aim of the present study was to evaluate the relationship between retinol and risk of diabetic retinopathy in Chinese adults. METHODS AND STUDY DESIGN: Eighty-six subjects with type 2 diabetes mellitus (T2DM) and 40 healthy subjects (healthy comparison group, HCG) were recruited in Beijing Luhe Hospital. Of the 86 T2DM subjects, 43 subjects were diagnosed with diabetic retinopathy (DRG), and 43 subjects had no retinopathy (DNRG). RESULTS: Dietary intake of retinol (p<0.001) and retinol equivalent (p<0.05) was significantly higher but serum retinol and (p<0.001) retinol binding protein 4 (RBP4) (p<0.05) were significantly lower in DNRG compared with HCG. Dietary intake of retinol (p<0.05) and retinol equivalent (p<0.05) was significantly lower, and serum retinol and (p<0.01) retinol binding protein 4 (RBP4) (p<0.01) were significantly higher in DRG compared with DNRG. In T2DM subjects, per 100 µg/day higher dietary retinol intake was associated with 17% lower risk of diabetic retinopathy (odds ratio (OR), 0.83; 95% CI, 0.70 to 0.98; p=0.032), and after adjusting for potential confounding factors, the OR was 0.82 (95% CI, 0.69 to 0.99; p=0.036); per 100 µg/day higher in dietary retinol equivalent intake was associated with 12% lower risk of diabetic retinopathy (OR, 0.88; 95% CI, 0.79 to 0.97; p=0.010), and after adjusting for potential confounding factors, the OR was 0.88 (95% CI, 0.79 to 0.98; p=0.025). CONCLUSIONS: Higher dietary intake of retinol or retinol equivalent is associated with lower risk of diabetic retinopathy.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/prevenção & controle , Vitamina A/administração & dosagem , Vitamina A/farmacologia , Idoso , Glicemia , Carotenoides , Estudos de Casos e Controles , Dieta/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Razão de Chances , Fatores de Risco
18.
BMC Cardiovasc Disord ; 19(1): 202, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429711

RESUMO

BACKGROUND: The present study aimed to expound the association between the XK related 6 gene (XKR6) rs7819412 single nucleotide polymorphism (SNP) and serum lipid profiles and the risk of coronary artery disease (CAD) and ischemic stroke. METHODS: The genetic makeup of the XKR6 rs7819412 SNP in 1783 unrelated participants (controls, 643; CAD, 588 and ischemic stroke, 552) of Han Chinese was obtained by the Snapshot technology. RESULTS: The genotypic frequencies of the SNP were disparate between CAD (GG, 81.0%; GA/AA, 19.0%) or ischemic stroke (GG, 81.2%; GA/AA, 18.8%) patients and healthy controls (GG, 85.7%, GA/AA, 14.3%; P < 0.05 vs. CAD or ischemic stroke; respectively). The A allele frequency was also diverse between CAD (10.1%) or ischemic stroke (10.0%) and control groups (7.5%; P < 0.05 vs. CAD or ischemic stroke; respectively). The GA/AA genotypes and A allele were associated with high risk of CAD and ischemic stroke (CAD: P = 0.026 for GA/AA vs. GG, P = 0.024 for A vs. G; Ischemic stroke: P = 0.029 for GA/AA vs. GG, P = 0.036 for A vs. G). The GA/AA genotypes were also associated with increased serum triglyceride (TG) concentration in CAD and total cholesterol (TC) concentration in ischemic stroke patients. CONCLUSIONS: These data revealed that the XKR6 rs7819412 A allele was related to increased serum TG levels in CAD, TC levels in ischemic stroke patients and high risk of CAD and ischemic stroke.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31339079

RESUMO

BACKGROUND: Progranulin (PGRN) mediates cell cycle progression and cell motility as a pleiotropic growth factor and acts as a universal regulator of cell growth, migration and transformation, cell cycle, wound healing, tumorigenesis, and cytotoxic drug resistance as a secreted glycoprotein. PGRN overexpression can induce the secretion of many inflammatory cytokines, such as IL-8, -6,-10,TNF-α. At the same time, this protein can promote tumor proliferation and the occurrence and development of many related diseases such as gastric cancer, breast cancer, cervical cancer, colorectal cancer, renal injury, neurodegeneration, neuroinflammatory, human atherosclerotic plaque, hepatocarcinoma, acute kidney injury, amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. CONCLUSION: In short, PGRN plays a very critical role in injury repair and tumorigenesis, it provides a new direction for succeeding research and serves a target for clinical diagnosis and treatment, thus warranting further investigation. Here, we discuss the potential therapeutic utility and the effect of PGRN on the relationship between inflammation and cancer.

20.
J Clin Invest ; 129(8): 3324-3338, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31305264

RESUMO

Glycosylation of immune receptors and ligands, such as T cell receptor and coinhibitory molecules, regulates immune signaling activation and immune surveillance. However, how oncogenic signaling initiates glycosylation of coinhibitory molecules to induce immunosuppression remains unclear. Here we show that IL-6-activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum-associated N-glycosyltransferase STT3A to catalyze PD-L1 glycosylation and maintain PD-L1 stability. Targeting of IL-6 by IL-6 antibody induced synergistic T cell killing effects when combined with anti-T cell immunoglobulin mucin-3 (anti-Tim-3) therapy in animal models. A positive correlation between IL-6 and PD-L1 expression was also observed in hepatocellular carcinoma patient tumor tissues. These results identify a mechanism regulating PD-L1 glycosylation initiation and suggest the combination of anti-IL-6 and anti-Tim-3 as an effective marker-guided therapeutic strategy.

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