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1.
Cell ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31474362

RESUMO

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.

2.
J Am Heart Assoc ; 8(17): e012504, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31475602

RESUMO

Background Identification of occult diastolic dysfunction often requires invasive right heart catheterization with provocative maneuvers such as fluid challenge. Non-invasive predictors of occult diastolic dysfunction have not been identified. We hypothesized that echocardiographic measures of diastolic function are associated with occult diastolic dysfunction identified at catheterization. Methods and Results We retrospectively examined hemodynamic and echocardiographic data from consecutive patients referred for right heart catheterization with fluid challenge from 2009 to 2017. A replication cohort of 52 patients who prospectively underwent simultaneous echocardiography and right heart catheterization before and after fluid challenge at Monaldi Hospital, Naples, Italy. In the retrospective cohort of 126 patients (83% female, 56+14 years), 27/126 (21%) had occult diastolic dysfunction. After adjusting for tricuspid regurgitant velocity and left atrial volume index, E velocity (odds ratio 1.8, 95% CI 1.1-2.9, P=0.01) and E/e' (odds ratio 1.9, 95% CI 1.1-3, P=0.005) were associated with occult diastolic dysfunction with an optimal threshold of E/e' >8.6 for occult diastolic dysfunction (sensitivity 70%, specificity 64%). In the prospective cohort, 5/52 (10%) patients had diastolic dysfunction after fluid challenge. Resting E/e' (odds ratio 8.75, 95% CI 2.3-33, P=0.001) and E velocity (odds ratio 7.7, 95% CI 2-29, P=0.003) remained associated with occult diastolic dysfunction with optimal threshold of E/e' >8 (sensitivity 73%, specificity 90%). Conclusions Among patients referred for right heart catheterization with fluid challenge, E velocity and E/e' are associated with occult diastolic dysfunction after fluid challenge. These findings suggest that routine echocardiographic measurements may help identify patients like to have occult diastolic dysfunction non-invasively.

3.
Lymphat Res Biol ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31381473

RESUMO

Background: Lymphatic malformations (LMs) are congenital low-flow vascular anomalies resulting from abnormal embryogenesis. Clinical researches have shown that rapamycin, a specific inhibitor of mTOR, is effective in treating LMs. It suggests the abnormality of mTOR signal pathway in LMs. Methods and Results: From January 2009 to December 2018, 10 patients who accepted the resection of LMs were enrolled into the study. Samples of each subtype of LMs (macrocystic, microcystic, and mixed subtypes) were further investigated. Expression of molecules in mTOR signal pathway-mTORC1, p70 S6, p-p70 S6, elF4EBP1, and p-elF4EBP1-in LMs were investigated by immunohistochemical staining. Location of mTORC1, p70 S6, and elF4EBP1 in LMs were shown by immunofluorescence co-staining. Phosphorylation level of mTOR signal pathway in LMs was examined by Western blotting. Immunohistochemical staining showed the expression of mTORC1, p70 S6, p-p70 S6, eIF4EBP1, and p-eIF4EBP1 in LMs. Immunofluorescence staining further verified the co-expression of mTORC1, p70 S6, and eIF4EBP1 in the lymphatic endothelium of LMs. Western blotting analysis revealed obviously higher phosphorylation level of mTOR signal pathway in LMs than that in normal skins (P < 0.05). Conclusions: The results showed that the mTOR signal pathway was overactivated in LMs. The study provides compelling evidence for treating LMs or syndromes with lymphatic anomalies by inhibiting mTOR signaling.

4.
Cancer Res ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383647

RESUMO

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has limited treatment options. Snail family transcriptional repressor 1 (SNAI1) is a master regulator of epithelial-mesenchymal transition (EMT) and has been implicated in HCC initiation and progression. However, the precise role of SNAI1 and the way it contributes to hepatocarcinogenesis have not been investigated in depth, especially in vivo. Here, we analyzed the functional relevance of SNAI1 in promoting hepatocarcinogenesis in the context of the AKT/c-Met driven mouse liver tumor model (AKT/c-Met/SNAI1). Overexpression of SNAI1 did not accelerate AKT/c-Met-induced HCC development or induce metastasis in mice. Elevated SNAI1 expression rather led to the formation of cholangiocellular (CCA) lesions in the mouse liver, a phenotype that was paralleled by increased activation of Yap and Notch. Ablation of Yap strongly inhibited AKT/c-Met/SNAI-induced HCC and CCA development, whereas inhibition of the Notch pathway specifically blocked the CCA-like phenotype in mice. Intriguingly, overexpression of SNAI1 failed to induce EMT, indicated by strong E-cadherin expression and lack of vimentin expression by AKT/c-Met/SNAI tumor cells. SNAI1 mRNA levels strongly correlated with the expression of CCA markers including SOX9, CK19 and EPCAM, but not with EMT markers such as E-cadherin and ZO-1, in human HCC samples. Overall, our findings suggest SNAI1 regulates the CCA-like phenotype in hepatocarcinogenesis via regulation of Yap and Notch.

5.
J Exp Bot ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31384929

RESUMO

The 70-kD heat shock proteins function as molecular chaperones and are involved in diverse cellular processes. However, the functions of the plant mitochondrial HSP70s (mtHSC70s) remain unclear. Severe growth defects were observed in the Arabidopsis thalianamtHSC70-1 knockout lines, mthsc70-1a and mthsc70-1b. Conversely, the introduction of the mtHSC70-1 gene into the mthsc70-1a background fully reversed the phenotypes, indicating that mtHSC70-1 is essential for plant growth. The loss of mtHSC70-1 functions resulted in abnormal mitochondria and alterations to respiration because of an inhibition of the cytochrome c oxidase (COX) pathway and the activation of the alternative respiratory pathway. Reducation in the COX abundance was observed in the mtHSC70-1 knockout lines leading to decreased COX activity. The mtHSC70-1 knockout plants have increased levels of reactive oxygen species (ROS). The introduction of the Mn-superoxide dismutase 1 (MSD1) or the catalase 1 (CAT1) gene into the mthsc70-1a plants decreased ROS levels, inhibited the activation of the alternative respiratory pathway and partially rescued growth, Taken together, the data presented here suggest that mtHSC70-1 plays important roles in the establishment of COX-dependent respiration.

6.
Biosensors (Basel) ; 9(3)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466277

RESUMO

Conductive polymers, owing to their tunable mechanical and electrochemical properties, are viable candidates to replace metallic components for the development of biosensors and bioelectronics. However, conducting fibers/wires fabricated from these intrinsically conductive and mechanically flexible polymers are typically produced without protective coatings for physiological environments. Providing sheathed conductive fibers/wires can open numerous opportunities for fully organic biodevices. In this work, we report on a facile method to fabricate core-sheath poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) PEDOT:PSS-silk fibroin conductive wires. The conductive wires are formed through a wet-spinning process, and then coated with an optically transparent, photocrosslinkable silk fibroin sheath for insulation and protection in a facile and scalable process. The sheathed fibers were evaluated for their mechanical and electrical characteristics and overall stability. These wires can serve as flexible connectors to an organic electrode biosensor. The entire, fully organic, biodegradable, and free-standing flexible biosensor demonstrated a high sensitivity and rapid response for the detection of ascorbic acid as a model analyte. The entire system can be proteolytically biodegraded in a few weeks. Such organic systems can therefore provide promising solutions to address challenges in transient devices and environmental sustainability.

7.
J Therm Biol ; 84: 111-120, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31466743

RESUMO

Temperature influences many physiological processes including antioxidant defense and immunity. The hypothesis that air temperatures has no effects on antioxidant defense and innate immunity in Mongolian gerbils (Meriones unguiculatus) was tested. Thirty-three male gerbils were randomly divided into the 4 °C (n = 11), 23 °C (n = 11) and 32 °C groups (n = 11), in which the treatment course lasted for 27 days. We found that air temperatures had no effects on body mass. At lower temperature, gross energy intake and the masses of most organs were higher, whereas fat free dry carcass and body fat were lower. H2O2 titres increased in liver but decreased in small intestine, and remained unchanged in heart, kidney and testis upon cold exposure. At lower temperature, malonaldehyde (MDA) content was higher in the liver, lower in kidneys and testis, and did not differ in the heart and small intestine. The activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC) in liver were higher in 4 °C group than 23 °C group, while liver catalase (CAT) activity was lower in the 4 °C group than in the 23 °C group. No significant difference was observed in the activities of SOD, CAT and T-AOC in the heart, kidney, testis and small intestine among the 4 °C, 23 °C and 32 °C groups. As expected, bacteria killing capacity indicating innate immunity, white blood cells and thymus mass were all not affected by air temperatures. Similarly, air temperatures had no effect on the levels of testosterone and corticosterone, both of which were not correlated with innate immunity, H2O2 and MDA levels, the activity of SOD, CAT, and T-AOC in all the detected tissues. In conclusion, air temperature affected antioxidant capacity, but not immune responses or serum concentrations of corticosterone and testosterone. Overall, up-regulation or maintenance of antioxidant defenses and immunity might be an important mechanism for gerbils to survive highly variable temperature.

8.
Nanoscale ; 11(34): 16026-16035, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31432057

RESUMO

Controllable integration of gold building blocks into mesoscopic architecture produces improved optical signals with preferable stability for biological sensing. Here, we developed novel optical labels with homogeneous and high-density implanted hydrophobic gold nanoparticles (AuNPs) throughout three-dimensional silica scaffolds. The dendritic silica supports with an extra-large pore size and highly accessible central-radial channels were employed as metal-affinity templates, for anchoring with AuNPs directly from the organic phase. The nano-assemblies exhibited a high unit loading capacity while maintaining the intrinsic optical characteristics of AuNPs. After phase transfer by the alkylsilane intermediate layer and exterior silica shell encapsulation, the nanocomposites revealed an amplified plasmonic absorption signal, excellent colloidal/optical stability and convenient surface functionalization. By integrating the silica labels into the lateral flow immunoassay strip for signal enhancement, the sensitive point-of-care detection of methamphetamine in urine was established. The limit of detection achieved 0.026 ng mL-1, with a detection range from 0.023 to 375 ng mL-1 in a 10 min assay, allows both visual and on-site quantitative analysis. Encouragingly, the potential interfering drugs in the sample matrix showed a negligible influence on the results, validating the superior specificity of the current immunoassay. The newly developed gold-implanted optical labels show prospects for point-of-care testing in a complex biological matrix with the desirable stability and signal amplification.

9.
Lipids ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463983

RESUMO

Vitamin D deficiency has been frequently reported in chronic liver disease. However, its influence on hepatic lipid accumulation in alcoholic liver disease remains unclear. The present study investigated the effects of vitamin D deficiency on acute alcohol-induced hepatic lipid metabolism in mice. Mice were fed with vitamin D deficient diet, in which vitamin D was depleted for 12 weeks to establish an animal model of vitamin D deficiency. Some mice were administered a single gavage of alcohol (4 g/kg bodyweight) before they were euthanized. Results show that feeding mice with vitamin D deficient diet did not induce hepatic lipid accumulation. In contrast, vitamin D deficiency markedly reduced alcohol-induced triacylglycerol (TAG) content and prevented hepatic lipid accumulation. Moreover, vitamin D deficiency significantly attenuated alcohol-induced sterol-regulated element-binding protein (SREBP)-1c activation, which regulates genes for hepatic fatty acid (FA) and TAG synthesis, and the expression of its target genes fatty acid synthase (Fasn) and acetyl-coenzyme- A carboxylase (Acc). In addition, vitamin D deficiency alleviated alcohol-induced downregulation of hepatic nuclear peroxisome proliferator-activated receptor (PPAR)α, which governs FA transport and ß-oxidation, and the expression of Carnitine palmitoyltransferase (Cpt)-1α, cytochrome P450, family 4, subfamily a, polypeptide (Cyp4a)10, and Cyp4a14, which are key enzymes for hepatic fatty acids ß-oxidation and ω-oxidation. Taken together, these results suggest that vitamin D deficiency is not a direct risk factor for hepatic lipid accumulation. Vitamin D deficiency alleviates acute alcohol-induced hepatic lipid accumulation through inhibiting hepatic de novo fatty acid syntheses and promoting fatty acid ß-oxidation and ω-oxidation.

10.
ACS Chem Neurosci ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31378059

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Neuroinflammation is a prevalent pathogenic stress leading to neuronal death in AD. Targeting neuroinflammation to keep neurons alive is an attractive strategy for AD therapy. 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) is a potent inhibitor of soluble epoxide hydrolase (sEH) and can enter into the brain. It has good efficacy on a wide range of chronic inflammatory diseases in preclinical animal models. However, the anti-neuroinflammatory effects and molecular mechanisms of TPPU for potential AD interventions remain elusive. With an aim to develop multitarget therapeutics for neurodegenerative diseases, we screened TPPU against sEH from different mammalian species and a broad panel of human kinases in vitro for potential new targets relevant to neuroinflammation in AD. TPPU inhibits both human sEH and p38ß kinase, two key regulators of inflammation, with nanomolar potencies and distinct selectivity. To further elucidate the molecular mechanisms, differentiated SH-SY5Y human neuroblastoma cells were used as an AD cell model, and we investigated the neuroprotection of TPPU against amyloid oligomers. We found that TPPU effectively prevents neuronal death by mitigating amyloid neurotoxicity, tau hyperphosphorylation, and mitochondrial dysfunction, promoting neurite outgrowth and suppressing activation and nuclear translocation of NF-κB for inflammatory responses in human nerve cells. The results indicate that TPPU is a potent and selective dual inhibitor of sEH and p38ß kinase, showing a synergistic action in multiple AD signaling pathways. Our study sheds light upon TPPU and other sEH/p38ß dual inhibitors for potential pharmacological interventions in AD.

11.
Bioanalysis ; 11(14): 1337-1345, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31392890

RESUMO

Aim: A urine drug concentration method was developed for the evaluation of oral ibandronte absorption based on the fact that ibandronate is excreted unchanged by the kidneys. Methodology: Ibandronate was isolated from the urine matrix by coprecipitated with 2.5 M CaCl2 and 1 M K2HPO4 in basic conditions. After a liquid-liquid extraction, the analytes were derivatized with trimethylsilydiazomethane prior to detection. Results: The calibration curves exhibited excellent linearity (r > 0.99) between 1 and 250 ng/ml in human urine. Ibandronate was recovered >86.5% with the inter- and intraday relative standard deviations less than 15%. Conclusion: The method is selective, accurate, practical and was successfully applied to study the influence of vitamin D3 on the absorption of ibandronate.

12.
ACS Appl Mater Interfaces ; 11(35): 32449-32459, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31405273

RESUMO

A series of Cr-doped In2-xCrxO3 (ICO) semiconductor thin films were epitaxially grown on (111)-oriented 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 (PMN-0.29PT) single-crystal substrates by the pulsed laser deposition. Upon the application of an electric field to the PMN-0.29PT substrate along the thickness direction, we realized in situ, reversible, and nonvolatile control of the electronic properties and Fermi level of the films, which are manifested by abundant physical phenomena such as the n-type to p-type transformation, metal-semiconductor transition, metal-insulator transition, crossover of the magnetoresistance (MR) from negative to positive, and a large nonvolatile on-and-off ratio of 5.5 × 104% at room temperature. We also strictly disclose that both the sign and the magnitude of MR are determined by the electron carrier density of ICO films, which could modify the s-d exchange interaction and weak localization effect. Our results demonstrate that the ferroelectric gating approach using PMN-PT can be utilized to gain deeper insight into the carrier-density-related electronic properties of In2O3-based semiconductors and provide a simple and energy efficient way to construct multifunctional devices which can utilize the unique properties of composite materials.

13.
Pancreas ; 48(8): 1003-1014, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31404031

RESUMO

OBJECTIVE: Identify the molecular mechanism of inflammatory stimuli induced pancreatic cancer progression. METHODS: RNA-seq, microarray assay and bioinformatics analyses were used to identify differentially expressed genes. Immunohistochemical staining was performed to evaluate CD68, CD163, ß-catenin, CD103, CCL3 markers. Quantitative real-time polymerase chain reaction (qRT-PCR), luciferase reporter assay, apoptosis assay, wound healing assay and immunofluorescence were performed to study the relationship of inflammatory stimuli and WNT/ß-catenin pathway. RESULTS: Differentially expressed genes of macrophage-conditioned medium-treated pancreatic cancer cells were related with WNT/ß-catenin pathway. Inflammatory stimuli could activate WNT/ß-catenin signaling pathway. In 106 pancreatic cancer patients, nuclear ß-catenin expression of CD68-high group was much higher than CD68-low group (P < 0.05), as same as CD163 (P < 0.05). Inflammatory stimuli downregulated the expression of CCL3 via WNT/ß-catenin pathway and inhibited the chemotaxis of CD103 dendritic cells. Six pancreatic cancer prognosis associating genes were upregulated by inflammatory stimuli via WNT/ß-catenin pathway. Transforming growth factor-ß promoted malignant biological behavior of pancreatic cancer cells through WNT/ß-catenin pathway-dependent mechanism. CONCLUSIONS: Our present study provided a novel mechanism involved in the inflammation-driven cancer progression through tumor immune escape and downstream gene regulation of WNT/ß-catenin pathway-dependent manner.

14.
BMC Plant Biol ; 19(1): 370, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438851

RESUMO

BACKGROUND: Accumulating evidences show that SPLs are crucial regulators of plant abiotic stress tolerance and the highly conserved module miR156/SPL appears to balance plant growth and stress responses. The halophyte Tamarix chinensis is highly resistant to salt tress. SPLs of T. chinensis (TcSPLs) and theirs roles in salt stress responses remain elusive. RESULTS: In this study, we conducted a systematic analysis of the TcSPLs gene family including 12 members belonging to 7 groups. The physicochemical properties and conserved motifs showed divergence among groups and similarity in each group. The microRNA response elements (MREs) are conserved in location and sequence, with the exception of first MRE within TcSPL5. The miR156-targeted SPLs are identified by dual-luciferase reporter assay of MRE-miR156 interaction. The digital expression gene profiles cluster suggested potential different functions of miR156-targeted SPLs vs non-targeted SPLs in response to salt stress. The expression patterns analysis of miR156-targeted SPLs with a reverse expression trend to TcmiR156 suggested 1 h (salt stress time) could be a critical time point of post-transcription regulation in salt stress responses. CONCLUSIONS: Our work demonstrated the post-transcription regulation of miR156-targeted TcSPLs and transcription regulation of non-targeted TcSPLs in salt stress responses, and would be helpful to expound the miR156/SPL-mediated molecular mechanisms underlying T. chinensis salt stress tolerance.


Assuntos
MicroRNAs/fisiologia , Proteínas de Plantas/fisiologia , RNA de Plantas/fisiologia , Estresse Salino/genética , Tamaricaceae/genética , Fatores de Transcrição/fisiologia , Motivos de Aminoácidos , Sequência Conservada , Genes de Plantas , Família Multigênica , Filogenia , Transcriptoma
15.
Appl Clin Inform ; 10(3): 479-486, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31269530

RESUMO

BACKGROUND: Medical students may observe and subsequently perpetuate redundancy in clinical documentation, but the degree of redundancy in student notes and whether there is an association with scholastic performance are unknown. OBJECTIVES: This study sought to quantify redundancy, defined generally as the proportion of similar text between two strings, in medical student notes and evaluate the relationship between note redundancy and objective indicators of student performance. METHODS: Notes generated by medical students rotating through their medicine clerkship during a single academic year at our institution were analyzed. A student-patient interaction (SPI) was defined as a history and physical and at least two contiguous progress notes authored by the same student during a single patient's hospitalization. For some students, SPI pairs were available from early and late in the clerkship. Redundancy between analogous sections of consecutive notes was calculated on a 0 to 100% scale and was derived from edit distance, the number of changes needed to transform one text string into another. Indicators of student performance included United States Medical Licensing Exam (USMLE) scores. RESULTS: Ninety-four single SPIs and 58 SPI pairs were analyzed. Redundancy in the assessment/plan section was high (40%) and increased within individual SPIs (to 60%; p < 0.001) and between SPI pairs over the course of the clerkship (by 30-40%; p < 0.001). Students in the lowest tertile of USMLE step II clinical knowledge scores had higher redundancy in the assessment/plan section than their classmates (67 ± 24% vs. 38 ± 22%; p = 0.002). CONCLUSION: During the medicine clerkship, the assessment/plan section of medical student notes became more redundant over a patient's hospital course and as students gained clinical experience. These trends may be indicative of deficiencies in clinical knowledge or reasoning, as evidenced by performance on some standardized evaluations.

16.
Infect Dis Ther ; 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31256335

RESUMO

INTRODUCTION: Agreement between available procalcitonin (PCT) assays is unclear. We sought to compare concordance between Roche and bioMérieux PCT assays using pediatric samples. METHODS: We evaluated 213 plasma samples from 208 children. We tested each sample on both the Roche and bioMérieux PCT platforms. RESULTS: At ranges < 2 µg/L, the Roche platform had a mean negative bias of 0.13 µg/L versus the bioMérieux platform. This bias resulted in PCT levels that crossed accepted cut points in 12.7% of patients. CONCLUSIONS: PCT levels measured on either platform are similar, especially at PCT ranges used for antibiotic decision-making algorithms. FUNDING: This work was supported by an investigator-initiated research agreement through bioMérieux and by the National Institute of Allergy and Infectious Diseases Childhood Infection Research Program (ChIRP), National Institute of Health and the National Center for Advancing Translational Sciences of the National Institute of Health.

17.
Curr Med Sci ; 39(4): 622-630, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347000

RESUMO

High-risk human papillomavirus (hrHPV) infection plays an important role in the development of cervical intraepithelial neoplasia and cervical cancer. A total of 11 549 women were enrolled from the Maternal and Child Health Hospital of Hubei Province. Each participant accepted hrHPV testing and completed a self-administered questionnaire about basic information and potential risk factors. The univariable and multivariable logistic regression model was used to explore the associations between variants and hrHPV infection. Our results showed that hrHPV prevalence was 16.09% in Hubei Province, among which, hrHPV was more likely to be positive in women aged 51 years or above (OR=1.65, 95% CI: 1.28-2.14), and in women who had symptoms of bleeding after intercourse (OR=1.32, 95% CI:1.17-1.50), had first sexual intercourse at the age of 18 years or below (OR=1.33, 95% CI:1.07-1.64), had at least three male sexual partners (OR=2.50, 95% CI:2.07-3.03), and who had been diagnosed with sexually transmitted infections (OR=1.50, 95% CI:1.12-2.03). Married women (OR=0.66, 95% CI: 0.55-0.78) and women who frequently used condoms (OR=0.75, 95% CI:0.67-0.84) had a relatively lower hrHPV prevalence. This study confirms that hrHPV infection was associated with age, marital status, symptoms of intercourse bleeding, history of sexually transmitted infections, and sex-related behaviors. Above all, this study provides a baseline database prior to obtaining vaccinations for dynamic tracking of the changes in hrHPV prevalence.

18.
Biosci Rep ; 39(7)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31262973

RESUMO

Oxymatrine (OMT) is an important quinoxaline alkaloid that has a wide range of pharmacological effects and has been shown to alleviate ulcerative colitis due to its profound anti-inflammatory effects. The RhoA/ROCK (Rho kinase) signaling pathway has been shown to be related to the pathogenesis of several autoimmune diseases; however, the specific mechanisms of RhoA/ROCK signaling in inflammatory bowel disease (IBD) remain elusive. Therefore, we sought to determine whether OMT could ameliorate acute intestinal inflammation by targeting the RhoA/ROCK signaling pathway. The potential therapeutic effect of OMT on acute intestinal inflammation and its impact on the RhoA/ROCK signaling pathway were assessed in six groups of mice treated with low, medium and high doses of OMT (25, 50 and 100 mg/kg, respectively), and an inhibitor of ROCK, Y-27632, as a positive control, after initiating dextran sodium sulfate (DSS)-induced acute intestinal inflammation. The model group and normal group were injected intraperitoneally with equal doses of PBS. Our results showed that OMT treatment could protect the integrity of the epithelial barrier, relieve oxidative stress, inhibit the expression of inflammatory mediators and pro-inflammatory cytokines, restrain the differentiation of Th17 cells and promote the differentiation of Treg cells via inhibition of the RhoA/ROCK pathway, thus providing therapeutic benefits for ulcerative colitis (UC). Therefore, inhibiting the RhoA/ROCK pathway might be a new approach that can be used in UC therapy, which deserves to be investigated further.

19.
Biomed Res Int ; 2019: 3924581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355259

RESUMO

This study investigated the effects of proanthocyanidins (PC) on arsenic methylation metabolism and efflux in human hepatocytes (L-02), as well as the relationships between PC and GSH, MRP1 and other molecules. Cells were randomly divided into blank control group, arsenic trioxide exposure group (ATO, As2O3, 25µmol/L), and PC-treated arsenic exposure group (10, 25, 50mg/L). After 24/48h, the contents of different forms of arsenic were determined, and the methylation indexes were calculated. Intracellular S-adenosyl methionine (SAM), arsenic (+3 oxidation state) methyltransferase (AS3MT), multidrug resistance-associated protein 1 (MRP1), and reduced glutathione (GSH) were ascertained. Changing trends were observed and the correlation between arsenic metabolism and efflux related factors and arsenic metabolites was analyzed. We observed that cells showed increased levels of content/constituent ratio of methyl arsenic, primary/secondary methylation index, methylation growth efficiency/rate, and the difference of methyl arsenic content in cells and culture medium (P<0.05, resp.). Compared with ATO exposure group, the intracellular SAM content in PC-treated group decreased, and the contents of GSH, AS3MT, and MRP1 increased (P<0.05, resp.). There was a positive correlation between the content of intracellular GSH/AS3MT and methyl arsenic. The content of MRP1 was positively correlated with the difference of methyl arsenic content in cell and culture medium; conversely, the SAM content was negatively correlated with intracellular methyl arsenic content (P<0.05, resp.). Taken together, these results prove that PC can promote arsenic methylation metabolism and efflux in L-02 cells, which may be related to the upregulation of GSH, MRP1, and AS3MT levels by PC.

20.
J Environ Sci Health B ; : 1-11, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31343381

RESUMO

The insecticide thiamethoxam (TMX) is one of the most important neonicotinoid pesticides. The chromatographic methods currently employed to detect TMX require multiple operational steps. This study proposes a simple method that detects TMX via surface-enhanced Raman scattering (SERS) spectroscopy with Ag nanoparticles (NPs) as the SERS active substrate. Density functional theory (DFT) was used to calculate the structures and vibrational modes of the Ag- and Ag3-TMX complexes at the B3LYP/6-311++G(d,p)(C,H,N)/LanL2DZ(Ag) level of theory. The results reveal that the atoms in the thiazole ring all lie in the same plane, while the six-membered ring is perpendicular to the thiazole ring. Data from both Ultraviolet-visible and Raman spectroscopy indicated that TMX bonds to Ag through its nitro group, vertically. A weak intramolecular (N22-O23…H26) hydrogen bonding and Ag-O bands shift N-O symmetrical vibration to down to lower wavenumber. This was supported by the appearance of a strong 866 cm-1 band in the SERS spectrum assigned to the N-O symmetrical vibration coupled with the N-N stretching vibrational mode of different excitation wavelength. Notably, a good linear relationship was observed in the TMX concentration range 1.0 × 10-6-1.0 × 10-4 mol·L-1 (R2 = 0.9667). SERS is an extremely simple and rapid technique that requires little sample for analysis.

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