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1.
Endocrine ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026251

RESUMO

PURPOSE: To investigate the value of ultrasound (US) and clinicopathological features of papillary thyroid cancer (PTC) in predicting Telomerase Reverse Transcriptase (TERT) promoter mutations. METHODS: Preoperative US images of 351 surgically confirmed PTCs were evaluated in terms of PTCs size and US features. The basic clinicopathological features were also retrieved. Univariate and multivariate analyses were performed to identify the risk factors for TERT promoter mutations. A scoring system was developed based on the cumulative number of risk factors. The area under the receiver operating characteristic curve (AUC) and cut-off value were calculated to evaluate the diagnostic performance of the scoring system for predicting TERT promoter mutations. RESULTS: TERT promoter mutations were found in 4.84% (17/351) of patients with PTCs. Patient age >50 years (OR: 6.244, P = 0.006), multifocality (OR: 21.071, P = 0.022), taller-than-wide shape (OR: 4.934, P = 0.029), microlobulated margin (OR: 4786, P = 0.032), and capsule contact or involvement (OR: 4.668, P = 0.030) were independent risk factors for TERT promoter mutations. TERT promoter mutations were relevant to more suspicious US and clinicopathological features than TERT promoter wild-type PTC (median, 4 vs. 1, P < 0.001). The cut-off value was 2.5 and the associated AUC was 0.908 (P < 0.001). CONCLUSIONS: The probability of TERT promoter mutations increases along with the suspicious US features and clinicopathological characteristics, which may help to recognize patients who deserve a different approach, in terms of management and follow-up, in view of the worst outcome associated to this mutation.

3.
Biomed Pharmacother ; 125: 109946, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32004976

RESUMO

OBJECTIVES: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS. METHODS: A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested. RESULTS: Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10. CONCLUSIONS: Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.

4.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(1): 69-74, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32037769

RESUMO

OBJECTIVE: To assess the efficacy of bone anchorage and maxillary facemask protraction devices in treating skeletal class Ⅲ malocclusion in adolescents. METHODS: Articles relating to the use of bone anchorage and maxillary facemask protraction devices for treating skeletal class Ⅲ malocclusion in adolescents were searched from the databases of Cochrane Library, PubMed, EmBase, CNKI, and Wanfang database. Several inclusion and exclusion criteria were developed for the article screening. The clinical data were extracted, and the quality of the selected articles was evaluated. A Meta-analysis of SNA, SNB, ANB, ANS-Me, Wits, and U1-PP change was performed by using RevMan 5.3. RESULTS: Seven studies (264 patients) were included in the Meta-analysis. Among these studies, three were randomized controlled trials, and four were non-randomized controlled trials. Compared with the maxillary facemask protraction device group, the bone ancho-rage device group had higher SNA changes and lower ANS-Me, Wits, and U1-PP changes (P<0.05). No significant differences were observed in the SNB and ANB changes between these two groups. CONCLUSIONS: Compared with the maxillary facemask protraction device, the bone anchorage device can increase the extent of protraction of the maxilla and has better controls for the labial inclination of the maxillary anterior teeth in treating skeletal class Ⅲ malocclusion among adolescents. However, additional high-quality randomized controlled trials must be performed to verify the results.


Assuntos
Má Oclusão de Angle Classe III , Maxila , Adolescente , Cefalometria , Aparelhos de Tração Extrabucal , Humanos , Técnica de Expansão Palatina , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Arthritis Res Ther ; 22(1): 33, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085759

RESUMO

BACKGROUND: Despite expansion in the 2006 Sydney antiphospholipid syndrome (APS) classification criteria to include IgG/IgM anti-ß2-glycoprotein (aß2GPI) antibodies in addition to IgG/IgM anti-cardiolipin antibodies (aCL) and lupus anticoagulant (LAC), some individuals with clinical features of APS remain seronegative (seronegative APS or SNAPS) and are at risk of recurrent thrombosis and pregnancy morbidities. Our aim was to assess the value of "non-criteria" aPL antibodies to detect these SNAPS patients. METHODS: One hundred ninety-two APS patients, 90 SNAPS patients, 193 autoimmune disease controls, and 120 healthy controls were evaluated. Ten antiphospholipid antibodies (aPLs) were tested using commercial kits, including 5 non-criteria aPLs: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, aCL IgA, aß2GPI IgA, and anti-ß2GPI Domain 1 (aß2GPI-D1) IgG. RESULTS: Up to 60.9% of the SNAPS and 93.5% of APS patients were detected by at least one non-criteria aPL. aPS/PT IgG had the highest Youden index in classifying APS and SNAPS from controls. aPS/PT IgG and aß2GPI Domain 1 IgG seem to be the most significant risk factors for thrombotic events and pregnancy morbidity, respectively. aPS/PT IgG/IgM and aß2GPI-D1 IgG were detected in some SNAPS patients, while IgA isotypes of aCL/aß2GPI tended to appear together with other biomarkers. The combined analysis showed enhanced diagnostic performance with the inclusion of non-criteria aPLs. CONCLUSIONS: Recognition of SNAPS patients is critical for clinical management and prevention of potential thrombotic and obstetric adverse events. The non-criteria antiphospholipid antibodies help to identify a considerable portion (60.9%) of these patients who otherwise may remain untreated and at clinical risk.

6.
J Biochem Mol Toxicol ; : e22467, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040235

RESUMO

Oxidative stress induced by long-term cyclosporine A (CsA) administration is a major cause of chronic nephrotoxicity, which is characterized by tubular atrophy, tubular cell apoptosis, and interstitial fibrosis in the progression of organ transplantation. Although hydrogen-rich water (HRW) has been used to prevent various oxidative stress-related diseases, its underlying mechanisms remain unclear. This study investigated the effects of HRW on CsA-induced nephrotoxicity and its potential mechanisms. After administration of CsA (25 mg/kg/day), rats were treated with or without HRW (12 mL/kg) for 4 weeks. Renal function and vascular activity were investigated. Histological changes in kidney tissues were analyzed using Masson's trichrome and terminal deoxynucleotidyl transferase dUTP nick-end labeling stains. Oxidative stress markers and the activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were also measured. We found that CsA increased the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), but it reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Such alterations induced vascular dysfunction, tubular atrophy, interstitial fibrosis, and tubular apoptosis. This was evident secondary to an increase in urinary protein, serum creatinine, and blood urea nitrogen, ultimately leading to renal dysfunction. Conversely, HRW decreased levels of ROS and MDA while increasing the activity of GSH and SOD. This was accompanied by an improvement in vascular and renal function. Moreover, HRW significantly decreased the level of Keap1 and increased the expression of Nrf2, NADPH dehydrogenase quinone 1, and heme oxygenase 1. In conclusion, HRW restored the balance of redox status, suppressed oxidative stress damage, and improved kidney function induced by CsA via activation of the Keap1/Nrf2 signaling pathway.

7.
Mol Cell ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32017896

RESUMO

U6 snRNA, as an essential component of the catalytic core of the pre-mRNA processing spliceosome, is heavily modified post-transcriptionally, with 2'-O-methylation being most common. The role of these modifications in pre-mRNA splicing as well as their physiological function in mammals have remained largely unclear. Here we report that the La-related protein LARP7 functions as a critical cofactor for 2'-O-methylation of U6 in mouse male germ cells. Mechanistically, LARP7 promotes U6 loading onto box C/D snoRNP, facilitating U6 2'-O-methylation by box C/D snoRNP. Importantly, ablation of LARP7 in the male germline causes defective U6 2'-O-methylation, massive alterations in pre-mRNA splicing, and spermatogenic failure in mice, which can be rescued by ectopic expression of wild-type LARP7 but not an U6-loading-deficient mutant LARP7. Our data uncover a novel role of LARP7 in regulating U6 2'-O-methylation and demonstrate the functional requirement of such modification for splicing fidelity and spermatogenesis in mice.

8.
J Agric Food Chem ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32050067

RESUMO

In the Gram-negative bacterium Aeromonas hydrophila, N-acyl homoserine lactone (AHL)-mediated quorum sensing (QS) influences pathogenicity, protein secretion, and motility. However, the catalytic mechanism of AHL biosynthesis and the structural basis and substrate specificity for AhyI members remain unclear. In this study, we cloned the ahyI gene from the isolate A. hydrophila HX-3, and the overexpressed AhyI protein was confirmed to produce six types of AHLs by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, contrasting with previous reports that AhyI only produces N-butanoyl-l-homoserine lactone (C4-HSL) and N-hexanoyl-l-homoserine lactone (C6-HSL). The results of an in vitro biosynthetic assay showed that purified AhyI can catalyze the formation of C4-HSL using S-adenosyl-l-methionine (SAM) and butyryl-acyl carrier protein (ACP) as substrates and indicated that the fatty acyl substrate used in AhyI-mediated AHL synthesis is derived from acyl-ACP rather than acyl-CoA. The kinetic data of AhyI using butyryl-ACP as an acyl substrate indicated that the catalytic efficiency of the A. hydrophila HX-3 AhyI enzyme is within an order of magnitude compared to other LuxI homologues. In this study, for the first time, the tertiary structural modeling results of AhyI and those of molecular docking and structural and functional analyses showed the importance of several crucial residues, as well as the secondary structure with respect to acylation. A Phe125-Phe152 clamp grasps the terminal methyl group to assist in stabilizing the long acyl chains in a putative binding pocket. The stacking interactions within a strong hydrophobic environment, a hydrogen-bonding network, and a ß bulge presumably stabilize the ACP acyl chain for the attack of the SAM α-amine toward the thioester carbon, offering a relatively reasonable explanation for how AhyI can synthesize AHLs with diverse acyl-chain lengths. Moreover, Trp34 participates in forming the binding pocket for C4-ACP and becomes ordered upon SAM binding, providing a good basis for catalysis. The novel finding that AhyI can produce both short- and long-chain AHLs enhances current knowledge regarding the variety of AHLs produced by this enzyme. These structural data are expected to serve as a molecular rationale for AHL synthesis by AhyI.

9.
Mol Med Rep ; 21(2): 903-908, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974618

RESUMO

The KlcAHS gene was previously identified as coexisting with the blaKPC­2 gene in the backbone region of a series of blaKPC­2­harboring plasmids. The purpose of the present study was to determine the association between the KlcAHS and blaKPC­2 genes. KlcAHS deletion and complementation experiments were used to evaluate the association between KlcAHS and carbapenem minimal inhibition concentrations (MICs). Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis was used to detect changes in the expression levels of blaKPC­2 upon knocking out the KlcAHS gene in a blaKPC­2­harboring plasmid. The imipenem MIC of the transformants harboring ΔKlcAHSpHS10842 was lower (16 µg/ml) than that of the transformants harboring wild­type pHS10842 (32 µg/ml), whereas the kanamycin MIC of the transformants harboring pET24a was lower (1,024 µg/ml) than that of the transformants harboring pET24a­KlcAHS (2,048 µg/ml). The imipenem MICs of the two NM1049 Escherichia coli strains carrying plasmids pHS092839 or ΔKlcAHSpHS092839 exceeded 16 µg/ml, whereas the ertapenem MIC of the host strains harboring ΔKlcAHSpHS092839 was 4 µg/ml compared with ≥8 µg/ml observed in the host strains carrying pHS092839. The RT­qPCR results demonstrated that the messenger RNA expression levels of blaKPC­2 in the transformants carrying ΔKlcAHSpHS092839 were significantly downregulated (P=0.007) compared with those in the transformants carrying pHS092839. These findings revealed that KlcAHS elevated the MIC values of various antibiotics by upregulating the expression levels of blaKPC­2. Therefore, KlcAHS can confer increased resistance to carbapenems in host strains. The survival probability of clinical pathogens may be enhanced by the presence of the KlcAHS gene in antibiotics used on a large scale.

10.
Int J Lab Hematol ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958215

RESUMO

INTRODUCTION: To assess the clinical performance and correlations of automated chemiluminescence assay (CIA) and enzyme-linked immunosorbent assay (ELISA) for detecting antiphospholipid (aPL) antibodies in the diagnosis of antiphospholipid syndrome (APS). METHODS: The study recruited 505 subjects, including 192 with APS, 193 with connective tissue diseases other than APS, and 120 healthy donors. We measured anticardiolipin (aCL) and anti-ß2-glycoprotein I (anti-ß2GPI) antibodies IgG, IgM, and IgA in all the samples using both CIA and ELISA. RESULTS: Total agreement between the two methods ranged from 83.50% for anti-ß2GPI IgG antibodies to 92.76% for anti-ß2GPI IgM antibodies in all the groups. Anti-ß2GPI and aCL IgG assays showed the highest Spearman's rho coefficients (anti-ß2GPI IgG = 0.742, aCL IgG = 0.715). Anti-ß2GPI IgG CIA showed the highest sensitivity for diagnosis of APS at 80.21%, which was significantly higher than the sensitivity of anti-ß2GPI IgG ELISA (52.08%). For diagnosis of APS, anti-ß2GPI IgG CIA had the best discrimination power with the area under the curves (AUC) of 0.922, followed by aCL IgG CIA (AUC of 0.905). While the CIA AUC was slightly higher in all cases, the difference was not statistically significant. CONCLUSION: CIA measurements had a good agreement and correlation with comparative ELISA assays. The CIA anti-ß2GPI IgG however was significantly more sensitive for APS diagnosis. The two assay methodologies showed comparable predictive powers and support the value of the CIA method for improved diagnosis and management of patients with APS.

11.
BMC Geriatr ; 20(1): 20, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964344

RESUMO

BACKGROUND: Dementia is a serious and growing health problem, and since most people with dementia live at home, caring responsibilities generally fall on family members. Caregivers are often inadequately supported by formal health services and have poorer psychological and physical health. Our study aimed to compare the contributions of publications from different countries, institutions and authors and present a bibliometric analysis to determine the hotspots and trends in research concerning the health of and interventions for family dementia caregivers. METHODS: Studies published during 1988-2018 were extracted from the Science Citation Index Expanded of the Web of Science. Each abstract of publications was evaluated to obtain the basic information. A bibliometric analysis was used to evaluate the number or cooperation networks of publications, countries, institutions, journals, citations, authors, references, and keywords. The resulting articles were analyzed descriptively, and the publication keywords were visualized using VOSviewer. RESULTS: Five hundred forty-two articles were identified. The annual number of relevant publications has steadily increased since approximately 2006. The USA has the highest number of publications (36.2%), followed by the UK (12.9%). China entered the field late, but research conducted in China has rapidly developed. The most productive institution, journal, and author in this field are University College London, the Journal of the American Geriatrics Society, and Orrell M from the UK, respectively. A co-occurrence analysis of the keywords reveals a mainstream research focus on burden, depression, quality of life, and corresponding interventions for people with dementia caregivers. The keywords "psychosocial intervention", "long-term", "e-learning/online", "communication", and "qualitative research" reflect the latest hotspots, appearing in approximately 2017-2018. CONCLUSION: Our study details the performance statistics, main topics and trends research on the health of and interventions for dementia caregivers from 1988 to 2018 and provides a comprehensive analysis.

12.
Langmuir ; 36(4): 991-1002, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31985231

RESUMO

Aqueous foams are used extensively in many fields and anionic surfactants are commonly used foaming agents. However, potential trouble may arise when they are utilized in hard water areas and/or at low temperatures. Anionic surfactants, like sodium dodecyl sulfate (SDS), may precipitate in the form of crystals when the concentration of divalent counterions such as Mg2+ exceeds a certain limit. In an attempt to prepare ultrastable foams containing precipitated crystals, the behavior of SDS in water was systematically investigated as a function of surfactant concentration at different concentrations of Mg(NO3)2 prior to a study of their foam properties. We quantitatively study the conversion of surfactant micelles to crystals and the redissolution of crystals into micelles. It was found that the presence of surfactant crystals reduced the initial foam volume and foam half-life but greatly improved the long-term stability of foams. Foam studies were also conducted for the supernatant and sediment isolated from crystal dispersions so that the importance of surfactant crystals to foam stability could be established. Despite the foamability of a sediment being low, an order of magnitude increase in foam half-life was related to the coverage of bubble surfaces by surfactant crystals. Both rapid cooling and ultrasonication were shown to influence the surfactant crystal shape and size with an impact on foam properties.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31925430

RESUMO

BACKGROUND: Early identification of patients at risk of severe dengue disease (DD) is critical to guide its management. We evaluated whether the atypical lymphocyte count (ALC), generated from the Sysmex automated full blood count analyzer, is predictive of severe thrombocytopenia secondary to Dengue infection. METHODS: We prospectively collected data on patients admitted with DD between December 2017 and October 2018. ALC data were extracted from the Sysmex XS500i analyzer from day 1 to day 7 of admission. Clinical data were obtained from patients' medical records. RESULTS: We enrolled 256 patients with DD. A negative correlation between ALC on admission and platelet count on day 5 to day 7 (Spearmen's correlation; day 5:-0.485, day 6:-0.428 and day 7:-0.344) (p=0.001) was observed. Based on receiver operator characteristic curve analysis, we found that an ALC of >0.5x103/L had 90% sensitivity and 70% specificity for severe thrombocytopenia (platelet count <50x109/L) on day 5. The positive and negative predictive values were 74.4 and 91.2%, respectively (power 84.7). CONCLUSIONS: We propose that ALC on admission may be a novel negative predictive factor for severe thrombocytopenia on day 5 to day 7 of DD. Further studies are required to validate our findings and evaluate whether ALC is predictive of other complications of DD.

15.
J Hazard Mater ; 387: 121676, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31759761

RESUMO

Organo-functionalized SiO2 nanoparticles are regarded as promising adsorbents for capture of heavy metals. However, actual adsorptivity of a specific functional group onto SiO2 surface is unclear, thus extending a debate on which type of organic group possesses a better affinity toward heavy metals. Herein, surface functionalization of SiO2 with different groups (i.e., -EDTA (ethylenediamine triacetic acid), -COOH, -SO3H, -SH and -NH2) were achieved by a facile silylating reaction. Batch experiments indicated that adsorption capacity of SiO2 was remarkably improved by surface functionalization. Quantitative analysis manifested that one mole of EDTA grafted onto SiO2 surface can adsorb 1.51 mol of Pb(II) ions, which was 7.7, 17.1, 28.4 and 50.2-fold larger than those of COOH-, SO3H-, SH- and NH2-functionalized SiO2, respectively. This is first time to evaluate adsorptivity of functionalized SiO2 on the basis of per effective functional group, which may repair deficiency of conventional assessment method that calculated on the basis of per unit mass. Further, adsorption mechanism of these functionalized SiO2 were identified and uncovered by experimental and theoretical studies. This work not only develops an efficient adsorbent for heavy metal remediation but also provides a valuable insight for evaluation and design of novel SiO2-based materials.

16.
Thromb Res ; 185: 142-149, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31816554

RESUMO

INTRODUCTION: Anti-ß2GPI-Domain 1 (ß2GPI-D1) antibodies are considered to be a pathogenic subset of anti-ß2GPI antibodies and have been strongly associated with thrombosis and pregnancy morbidity in patients with antiphospholipid syndrome (APS). We evaluated the clinical utility of anti-ß2GPI-D1 IgG antibodies for stratifying the risk of thrombosis and/or pregnancy morbidity (PM) in a cohort of Chinese patients with APS and also assessed its correlation with the Global Anti-Phospholipid Syndrome Score (GAPSS). MATERIALS AND METHODS: Sera and plasma from 192 consecutive APS patients, 17 aPL carriers, 193 patients with other systemic autoimmune diseases, and 120 healthy controls were collected and the presence of aCL IgG/IgM, anti-ß2GPI IgG/IgM and anti-ß2GPI-D1 IgG antibodies were assessed by chemiluminescence assays (CIA). Detection of LAC was performed according to international guidelines with the use of screening, mixing and confirmation tests. Anti-phosphatidylserine-prothrombin (aPS/PT) IgG and IgM antibodies were detected by commercial ELISA kits. RESULTS: Anti-ß2GPI-D1 IgG antibodies showed high specificity (97.12%) and moderate sensitivity (64.32%) for the diagnosis of APS. Anti-ß2GPI-D1 antibodies levels were significantly higher in patients with triple aPL positivity than in those with double (P < 0.001) and single positive aPL (P < 0.001) and correlated well with the GAPSS (rho = 0.60, P < 0.001). Anti-ß2GPI-D1 antibodies presented with a higher prevalence and higher titers in patients with late pregnancy morbidity (≥10 weeks) and thrombotic APS compared to those with early pregnancy (<10 weeks) morbidity. Higher anti-ß2GP1-D1 antibodies titers effectively distinguished APS from other autoimmune diseases. CONCLUSION: This study suggests a predictive role of anti-ß2GPI-D1 IgG antibodies as a strong risk factor for both thrombotic and obstetric APS (OAPS), especially for stratification comparing early PM with late PM and thrombosis.

17.
Plant Physiol ; 182(1): 658-668, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31659126

RESUMO

Gibberellin (GA) is known to play an important role in low red/far-red (R:FR) light ratio-mediated hypocotyl and petiole elongation in Arabidopsis (Arabidopsis thaliana). However, the regulatory relationship between low R:FR and GAs remains unclear, especially in gymnosperms. To increase our understanding of the molecular basis of low R:FR-mediated shoot elongation in pines and to determine whether there is an association between low R:FR and GAs action, we explored the morphological and transcriptomic changes triggered by low R:FR, GAs, and paclobutrazol (PAC), a GAs biosynthesis inhibitor, in Pinus tabuliformis seedlings. Transcriptome profiles revealed that low R:FR conditions and GAs have a common set of transcriptional targets in P. tabuliformis We provide evidence that the effect of low R:FR on shoot elongation in P. tabuliformis is at least partially modulated by GAs accumulation, which can be largely attenuated by PAC. GAs are also involved in the cross talk between different phytohormones in the low R:FR response. A GA biosynthesis gene, encoding ent-kaurenoic acid oxidase (KAO), was strongly stimulated by low R:FR without being affected by GAs feedback regulation or the photoperiod. We show that GA signaling is required for low R:FR-induced shoot elongation in P tabuliformis seedlings, and that there are different regulatory targets for low R:FR-mediated GA biosynthesis between conifers and angiosperms.

18.
Soc Psychiatry Psychiatr Epidemiol ; 55(1): 33-43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31456029

RESUMO

BACKGROUND AND AIM: Migraine is a highly prevalent and disabling neurological disorder associated with a wide range of psychiatric comorbidities. Studies have revealed that those with migraine headache and coexisting psychiatric disorders have poorer treatment outcomes and increased disability. The study aims to establish the prevalence, correlates, and comorbidities of migraine headache among the multi-ethnic Asian population in Singapore. METHOD: Data were extracted from the Singapore Mental Health Study 2016 (SMHS 2016), a cross-sectional epidemiological survey of a nationally representative sample. Face-to-face interviews were completed with 6126 participants between 2016 and 2017. The data relating to chronic medical conditions, psychiatric conditions, and 30-day functioning and disability were captured using the World Mental Health Composite International Diagnostic Interview (CIDI) version 3.0. RESULTS: The lifetime prevalence for migraine headache in the Singapore general population was 8.2%. Malay ethnicity (versus Chinese), female gender (versus male), and diploma holders (versus university) were significantly more likely to experience migraine headache. Participants belonging to the older age group (65 years and above versus 18-34 years of age), and those who were economically inactive (versus employed) were less likely to experience migraine headache. The mean age of onset for migraine was 26.4 years (SD = 11.1). Poisson regression analyses showed that migraine headache was also significantly associated with psychiatric conditions such as major depressive disorder (MDD) (prevalence ratio (PR), 1.80; 95% CI, 1.25-2.58), bipolar disorder (BD) (PR, 3.55; 95% CI, 2.29-5.51), generalized anxiety disorder (GAD) (PR, 2.04; 95% CI, 1.12-3.69), obsessive compulsive disorder (OCD) (PR, 2.20; 95% CI, 1.49-3.26), and alcohol use disorder (AUD) (PR, 1.93; 95% CI, 1.20-3.08). Those with migraine headache were significantly associated with poor functioning and disability compared to those without migraine headache. CONCLUSIONS AND DISCUSSION: Our study showed significant associations between migraine headache and psychiatric disorders, as well as with role functioning and disability. The findings of our study emphasise the need for screening for psychiatric comorbidity among those with migraine and the development of appropriate interventions for this group.

19.
Int J Pharm ; 575: 118943, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31830575

RESUMO

Self-assembly of drug-polysacrrides conjugates forming nanostructures provides a simple and promising strategy for the extension of precorneal retention and enhancement of corneal permeability. In the present study, a series of dexamethasone-glycol chitosan (Dex-GCS) conjugates were synthesized and thoroughly characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and ultraviolet-visible (UV-Vis) spectroscopy. The resulting Dex-GCS conjugates were able to self-assemble into nanoparticles spontaneously with particle sizes in the range of 277-289 nm and a positive charge of approximately +15 mV. Roughly spherical nanoparticles were observed by transmission electron microscopy (TEM). The in vitro mucoadhesive properties of Dex-GCS nanoparticles were evaluated by recording the variations in the zeta potential after incubation with different concentrations of mucin. In vitro release studies performed in phosphate-buffered saline (PBS, pH = 7.4) indicated progressive Dex release up to 8 h, followed by a plateau up to 48 h. Dex-GCS nanoparticles caused slight cytotoxicity against L929, HCEC and RAW 264.7 cells after 24 h of incubation and displayed a nearly identical anti-inflammatory efficacy to dexamethasone sodium phosphate (Dexp) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. More importantly, the proposed Dex-GCS nanoparticles showed good ocular tolerance and provided a relatively longer precorneal duration compared with that of the aqueous solution formulation, which suggested that the self-assembled Dex-GCS nanoparticle might be a promising candidate for ophthalmic drug delivery.

20.
Nutr Cancer ; 72(2): 260-272, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31295033

RESUMO

Arca subcrenata Lischke, widely scattering offshore at neritic regions, is very popular on dining table due to its edible and medical functional meatball. This study aims to investigate the suppression of a polypeptide fraction from A. subcrenata (PAS) on human colorectal cancer HT-29 cells, and its underlying mechanism. The results showed that PAS inhibited the growth of HT-29 cells with an IC50 value of 117 µg/ml after 48 h treatment, and significantly suppressed the tumor growth in nude mice bearing-xenografted HT-29 cells at the dosage of 63 mg/kg, with little influence on normal colon cells and normal colonic mucosa. PAS was then inspiringly found to induce apoptosis and G2/M phase arrest in HT-29 cells. The effect mechanism was involved in the inhibition of IGF-1/IGF-1R signaling activation, which was responsible for inactivating downstream Akt/mTOR pathway. Immunofluorescence assay also showed that PAS could reduce phosphorylation of IGF-1R (Tyr1165/1166). IGF-1, an IGF-1R activator, could reverse the suppression of PAS on IGF-1R phosphorylation. Furthermore, PAS significantly inhibited ATP production of HT-29 cells both in vitro and in vivo. Our results provide positive evidence that A. subcrenata has the potential to be a candidate for the treatment of colorectal cancer.

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