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1.
Cancer Immunol Res ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615816

RESUMO

Current gastric cancer (GC) staging alone cannot predict prognosis and adjuvant chemotherapy benefits in stage II and III GC. Tumor immune microenvironment biomarkers and tumor-cell chemosensitivity might add predictive value to staging. This study aimed to construct a predictive signature integrating tumor immune microenvironment and chemosensitivity-related features to improve the prediction of survival and adjuvant chemotherapy benefits in patients with stage II-III GC. We used immunohistochemistry to assess 26 features related to tumor, stroma, and chemosensitivity in tumors from 223 patients and evaluated association of the features with disease-free survival (DFS) and overall survival (OS). Support vector machine (SVM)-based methods were used to develop the predictive signature, which we call the SVM signature. Validation of the signature was performed in two independent cohorts of 445 patients. The diagnostic signature integrated seven features: CD3+ cells at the invasive margin (CD3 IM), CD8+ cells at the IM (CD8 IM), CD45RO+ cells in the center of tumors (CD45RO CT), CD66b+ cells at the IM (CD66b IM), CD34+ cells, periostin, and cyclooxygenase-2. Patients fell into low- and high-SVM groups with significant differences in 5-year DFS and OS in the training and validation cohorts (all P<0.001). The signature was an independent prognosis indicator in multivariate analysis in each cohort. The signature had better prognostic value than various clinicopathological risk factors and single features. High-SVM patients exhibited a favorable response to adjuvant chemotherapy. Thus, this SVM signature predicted survival and has potential for identifying stage II and III GC patients who could benefit from adjuvant chemotherapy.

2.
Neuroendocrinology ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31655821

RESUMO

BACKGROUND: Neuroendocrine tumor (NET) rarely occurs in the mediastinum and the etiology and pathogenesis are still unclear. OBJECTIVES: This study assessed inherited or de novo mutations in familial mediastinal NETs. METHOD: DNA samples from four persons were subjected to the whole-exome sequencing, and Sanger sequencing was used to identify Deleted in malignant brain tumor 1 (DMBT1) mutations in all 45 family members. RESULTS: All patients showed a germline DMBT1 mutation at 4971C. Sanger sequencing data showed that four NETs and two carriers in the first patient family had this DMBT1 mutation, and two NETs and four carriers in the second patient family had this DMBT1 mutation. The in vitro data showed that ectopic expression of DMBT1 reduced tumor cell viability and migration by arresting the G1/S phase of cell cycle. CONCLUSIONS: The data from current study identified a germline missense mutation in DMBT1D1657E as a susceptibility gene for familial mediastinal NETs.

3.
Mol Med Rep ; 20(4): 3649-3660, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485619

RESUMO

The main purpose of the present study was to recognize the integrative genomics analysis of hub genes and their relationship with prognosis and signaling pathways in esophageal squamous cell carcinoma (ESCC). The mRNA gene expression profile data of GSE38129 were downloaded from the Gene Expression Omnibus database, which included 30 ESCC and 30 normal tissue samples. The differentially expressed genes (DEGs) between ESCC and normal samples were identified using the GEO2R tool. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify the functions and related pathways of the genes. The protein­protein interaction (PPI) network of these DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes and visualized with a molecular complex detection plug­in via Cytoscape. The top five important modules were selected from the PPI network. A total of 928 DEGs, including ephrin­A1 (EFNA1), collagen type IV α1 (COL4A1),  C­X­C chemokine receptor 2 (CXCR2), adrenoreceptor ß2 (ADRB2), P2RY14, BUB1B, cyclin A2 (CCNA2), checkpoint kinase 1 (CHEK1), TTK, pituitary tumor transforming gene 1 (PTTG1) and COL5A1, including 498 upregulated genes, were mainly enriched in the 'cell cycle', 'DNA replication' and 'mitotic nuclear division', whereas 430 downregulated genes were enriched in 'oxidation­reduction process', 'xenobiotic metabolic process' and 'cell­cell adhesion'. The KEGG analysis revealed that 'ECM­receptor interaction', 'cell cycle' and 'p53 signaling pathway' were the most relevant pathways. According to the degree of connectivity and adjusted P­value, eight core genes were selected, among which those with the highest correlation were CHEK1, BUB1B, PTTG1, COL4A1 and CXCR2. Gene Expression Profiling Interactive Analysis in The Cancer Genome Atlas database for overall survival (OS) was applied among these genes and revealed that EFNA1 and COL4A1 were significantly associated with a short OS in 182 patients. Immunohistochemical results revealed that the expression of PTTG1 in esophageal carcinoma tissues was higher than that in normal tissues. Therefore, these genes may serve as crucial predictors for the prognosis of ESCC.

4.
Environ Pollut ; 254(Pt A): 112873, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31369910

RESUMO

Per- and polyfluoroalkyl Substances (PFAS) are ubiquitous in the environmental matrix, and their eco-toxicity on wide life and health risks on humans arising concerns. Due to the information gap, current risk assessments of PFAS ignore the indoor exposure pathway such as indoor dust and the different sources of drinking water. We collected and analyzed 168 indoor dust and 27 drinking water samples (including tap water, filtered water and bottled water). The mean concentrations of six typical PFAS measured in indoor dust and drinking water are in the range of 15.13-491.07 ng g-1 and 0.31-4.14 ng L-1, respectively. For drinking water, PFOA and PFOS were the dominant compounds, while PFHxS was the most abundant in indoor dust. Short-chain PFAS concentrations were higher than long-chain PFAS in both drinking water and indoor dust. Higher concentration of PFAS was observed in tap water and filtered water than bottled water. The total daily intake (TDI) of six PFAS are 20.67-52.97 ng kg-1 d-1 for infants, children, teenagers, and adults. As to children, teenagers, and adults, perfluorooctanoate (PFOA) is the major compound, accounting for 72.9-74.7% of the total daily intake. And PFOA (38.7%) and perfluorooctane sulfonate (PFOS, 42.2%) are the dominant PFAS for infants. The quantitative proportions of exposure sources are firstly revealed in this study, which in the order of foodstuff > indoor dust > drinking water > indoor air. Although the contribution to the PFAS intake of drinking water and indoor dust was not predominant (<9%), the health risks caused by long-term exposure need our attention. The hazard quotient (HQ) values of total PFAS were in the range of 0.154-0.498, which suggesting the relatively lower exposure risk in Chinese population. This study provides important reference to understand PFAS exposure status other than foodstuff.

5.
Molecules ; 24(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454945

RESUMO

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is rich in functional compounds such as rutin, quercetin, d-chiro-inositol, dietary fiber, and essential amino acids. Electric field (EF) treatment before sprout germination results in physiological and chemical changes, and some alterations might lead to positive applications in plant seeds. MTT assay showed that the effect of total flavonoids on human gastric cancer cell line MGC80-3 was significantly changed after EF treatment for different germination days (3-7 days). Among them, the total flavonoids of tartary buckwheat (BWTF) on the third day had the most obvious inhibitory effect on MGC80-3 (p < 0.01). In addition, flow cytometry evidenced that different ratios of quercetin and rutin had effects on the proliferation of MGC80-3. The same content of quercetin and rutin had the best effect, reaching 6.18 ± 0.82%. The anti-cancer mechanism was mainly promoted by promoting the expression of apoptotic proteins. The expression of Bax/Bcl-2 and caspase-8 in MGC80-3 cells was mediated by BWTFs. This study has good research value for improving the biological and economic value of tartary buckwheat.

6.
Lung Cancer ; 135: 188-195, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31446994

RESUMO

OBJECTIVES: Most lung cancer diagnoses occur in elderly patients, who are underrepresented in clinical trials. We present a pooled analysis of safety and efficacy in elderly patients (≥75 years) who received pembrolizumab (a programmed death 1 inhibitor) for advanced non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1)‒positive tumors. METHODS: The pooled analysis included patients aged ≥18 years with advanced NSCLC with PD-L1-positive tumors from the KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) studies. In KEYNOTE-010, patients were randomized to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel, as second- or later-line therapy. In KEYNOTE-024 and KEYNOTE-042, patients were randomized to first-line pembrolizumab 200 mg Q3W or platinum-based chemotherapy. Overall survival (OS) was estimated by the Kaplan-Meier method, and safety data were summarized in elderly patients (≥75 years). RESULTS: The analysis included 264 elderly patients with PD-L1-positive tumors (PD-L1 tumor proportion score [TPS] ≥1%); among these, 132 had PD-L1 TPS ≥ 50%. Pembrolizumab improved OS among elderly patients with PD-L1 TPS ≥ 1% (hazard ratio [HR], 0.76 [95% CI, 0.56-1.02]) and PD-L1 TPS ≥ 50% (HR, 0.40 [95% CI, 0.25-0.64]). Pembrolizumab as first-line therapy also improved OS among elderly patients with PD-L1 TPS ≥ 50% (from KEYNOTE-024 and KEYNOTE-042) compared with chemotherapy (HR, 0.41 [95% CI, 0.23‒0.73]). Pembrolizumab was associated with fewer treatment-related adverse events (AEs) in elderly patients (overall, 68.5% vs 94.3%; grade ≥3, 24.2% vs 61.0%) versus chemotherapy. Immune-mediated AEs and infusion reactions were more common with pembrolizumab versus chemotherapy (overall, 24.8% vs 6.7%; grade 3‒4: 9.4% vs 0%; no grade 5 events). CONCLUSIONS: In this pooled analysis of elderly patients with advanced NSCLC with PD-L1‒positive tumors, pembrolizumab improved OS versus chemotherapy, with a more favorable safety profile. Outcomes with pembrolizumab in patients ≥75 years were comparable to those in the overall populations in the individual studies.

7.
Int J Health Plann Manage ; 34(3): 1013-1024, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31368138

RESUMO

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) in China was 11.6% in 2010. Chronic complications are the main diabetes-related cause of death and disability, accounting for more than 80% of the cost of diabetes treatment. Diabetic nephropathy (DN) is a common microvascular complication and is the second leading cause of end-stage renal failure in China. OBJECTIVE: We aimed to analyse the DN status among community-based T2DM patients and to explore risk factors for T2DM with DN. METHODS: This study was conducted in six communities of Shanghai. We administered a questionnaire, physical examination, and biochemical tests to 5078 patients with T2DM. Logistic regression and the classification tree model were used to analyse risk factors for T2DM with DN. RESULTS: In total, 1937 patients were diagnosed with DN (prevalence 38.4%). The logistic regression model indicated that course of disease more than 15 years, body mass index (BMI) greater than 24 kg/m2 , haemoglobin A1c (HbA1c) greater than 7.5%, fasting blood glucose (FBG) greater than 11.0 mmol/L, total cholesterol (TC), and high-density lipoprotein (HDL)-C control failure, hypertension, and diabetic retinopathy were risk factors for T2DM with DN (P < .05). The classification tree model identified seven risk factors (HbA1c, FBG, hypertension, postprandial blood glucose, BMI, triacylglycerol, and HDL), of which, HbA1c (cut-off point 7.45%), hypertension, and FBG showed the strongest association. CONCLUSION: This suggests that screening for DN based on HbA1c, FBG, and hypertension should be more extensively promoted by the government on a community level, more attention should be focused on patients' health management, and that patients should be educated on self-management.

8.
Int J Health Plann Manage ; 34(3): 998-1012, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31373063

RESUMO

OBJECTIVE: To determine the incidence, progression, and regression rates of diabetic retinopathy (DR), as well as their associated factors, in Chinese type 2 diabetic patients. METHODS: Diabetic patients who participated in a previous survey were recruited for a 1-year follow-up study. Nonmydriatic fundus photographs were acquired to assess the severity of DR as per the International Clinical Diabetic Retinopathy Disease Severity Scale (2002). Factors that potentially influence DR outcomes, including its incidence, progression, and regression, were identified via statistical analyses. RESULTS: We initially recruited 2453 subjects, among whom 2331 were followed and included in the final analysis. The incidences of new and progressed (ie, ≥2 scale steps) DR were 10.6% and 6.1%, respectively. Moreover, 7.3% of patients with established DR at baseline experienced complete regression. Multivariate logistic regression analysis revealed that high glycosylated haemoglobin (HbA1c) (odds ratio [OR] = 1.50, P = .021) and hyperlipidaemia (OR = 1.46, P = .025) were independent predictors of DR development, high HbA1c (OR = 4.16, P = .027) and macroalbuminuria (OR = 5.60, P = .010) predicted DR progression, and low HbA1c (OR = 0.20, P = .001) and low triglyceride levels (OR = 0.34, P = .026) were associated with DR regression. CONCLUSIONS: Albumin and HbA1c levels should be closely monitored as signs of progressive retinal damage in diabetic subjects. Optimized control of glucose and triglyceride levels is vital for reducing the incidence of DR or promoting its regression in afflicted patients.

9.
Parasite ; 26: 54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469072

RESUMO

BACKGROUND: Alveolar echinococcosis (AE) is a rare zoonosis caused by the larval stage of the tapeworm Echinococcus multilocularis. AE lesions affect the liver in more than 98% of cases. AE lesions have various morphological characteristics that are described in the Echinococcus multilocularis Ulm classification for computed tomography (EMUC-CT). One of these characteristics is a cystoid portion. The aim of the study was to compare the density of simple hepatic cysts with cystoid portions of AE lesions classified on the basis of the EMUC-CT. RESULTS: Hounsfield Unit (HU) measurements of the cystoid portions of all EMUC-CT type I-IV AE lesions (n = 155) gave a mean of 21.8 ± 17.6, which was significantly different from that of 2.9 ± 4.5 for the simple hepatic cysts (p < 0.0001). The difference between each of the individual AE types and simple hepatic cysts was also significant. In addition, the HU values of the cystoid portions in types I, II and IIIa/b and simple cysts were each significantly different from type IV (p < 0.0001). The HU measurements in type IV presented by far the highest mean. CONCLUSIONS: The significantly higher density measured in the cystoid portions of hepatic AE lesions offers a good means of differentiation from simple hepatic cysts.

10.
Int J Biol Macromol ; 139: 818-826, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31401276

RESUMO

In this study, the physicochemical properties of an ammonium oxalate extraction pectin (AOP) from Premna microphylla turcz was investigated. Moreover, its cold gelation with undenatured whey protein concentrate (WPC) was studied at room temperature and different pHs. Characterizations of AOP demonstrated that AOP was a linear low-methoxyl pectin rich in homogalacturonan with low branching degree of RG-I, leading to its good gelling properties. Gelation between AOP and WPC was mainly investigated by turbidity measurement, FTIR, CLSM and ITC. The results showed that an optimal complex ratio for gelation was observed at 1:5 at pH 6.0. Moreover, AOP was the backbone of the composite gel and WPC might act as crosslinking agents through electrostatic or hydrophobic interaction at different pHs. When pH was around the pHΦ of the complex, composite gel was mainly constructed by electrostatic interaction. With the increase of pH, the electrostatic interaction between AOP and WPC gradually weakened, while the hydrophobic interaction constantly increased. When pH was higher than the pHc of the complex, composite gel was mainly formed by hydrophobic interaction. The results of this study are conducive to further utilization of Premna microphylla turcz pectin to develop related food products.

11.
Technol Cancer Res Treat ; 18: 1533033819857767, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390948

RESUMO

PURPOSE: To develop a fusion imaging system that combines ultrasound and computed tomography for real-time tumor tracking and to validate the accuracy of performing registration via this approach during a specific breathing phase. MATERIALS AND METHODS: The initial part of the experimental study was performed using iodized oil injection in pig livers and was focused on determining the accuracy of registration. Eight points (A1-4 and B1-4) at different positions and with different target sizes were selected as target points. During respiratory motion, we used our self-designed system to perform the procedure either with (experimental group, E) or without (control group, C) the respiratory monitoring module. The registration errors were then compared between the 2 groups and within group E. The second part of this study was designed as a preliminary clinical study and was performed in 18 patients. Screening was performed to determine the combination of points on the body surface that provided the highest sensitivity to respiratory motion. Registration was performed either with (group E) or without (group C) the respiratory monitoring module. Registration errors were compared between the 2 groups. RESULTS: In part 1 of this study, there were fewer registration errors at each point in group E than at the corresponding points in group C (P < .01). In group E, there were more registration errors at points A1 and B1 than at the other points (P < .05). There was no significant difference in registration errors among the remaining points. During part 2 of the study, there was a significant difference in the registration errors between the 2 groups (P < .01). CONCLUSIONS: Real-time fusion registration is feasible and can be accurately performed during respiratory motions when using this system.

12.
MAbs ; 11(7): 1300-1318, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31318308

RESUMO

Solution stability is an important factor in the optimization of engineered biotherapeutic candidates such as monoclonal antibodies because of its possible effects on manufacturability, pharmacology, efficacy and safety. A detailed atomic understanding of the mechanisms governing self-association of natively folded protein monomers is required to devise predictive tools to guide screening and re-engineering along the drug development pipeline. We investigated pairs of affinity-matured full-size antibodies and observed drastically different propensities to aggregate from variants differing by a single amino-acid. Biophysical testing showed that antigen-binding fragments (Fabs) from the aggregating antibodies also reversibly associated with equilibrium dissociation constants in the low-micromolar range. Crystal structures (PDB accession codes 6MXR, 6MXS, 6MY4, 6MY5) and bottom-up hydrogen-exchange mass spectrometry revealed that Fab self-association occurs in a symmetric mode that involves the antigen complementarity-determining regions. Subtle local conformational changes incurred upon point mutation of monomeric variants foster formation of complementary polar interactions and hydrophobic contacts to generate a dimeric Fab interface. Testing of popular in silico tools generally indicated low reliabilities for predicting the aggregation propensities observed. A structure-aggregation data set is provided here in order to stimulate further improvements of in silico tools for prediction of native aggregation. Incorporation of intermolecular docking, conformational flexibility, and short-range packing interactions may all be necessary features of the ideal algorithm.

13.
Thyroid ; 29(9): 1269-1278, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328653

RESUMO

Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.

14.
Chin J Integr Med ; 25(7): 497-501, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31278627

RESUMO

OBJECTIVE: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS). METHODS: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. RESULTS: After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ± 0.48 × 109/L to 1.08 ± 0.62 × 109/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 µ g/L (P<0.05), 3 months with 33.56 ± 15.28 µ g/L (P<0.05), and 6 months with 36.78 ± 11.92 µ g/L (P<0.05), respectively, as compared with those before treatment (4.08 ± 2.11 µ g/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, µ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, µ g/L, P<0.05). CONCLUSION: QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.

15.
J Infect Dis ; 220(8): 1302-1306, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31199457

RESUMO

We report a case of cytomegalovirus encephalitis in a hematopoietic stem cell transplant recipient. A previously uncharacterized V787E mutation in UL54 was identified in cerebrospinal fluid but not plasma specimens. For the V787E recombinant virus, the half maximal effective concentrations for ganciclovir, foscarnet, and cidofovir were 8.6-, 3.4- and 2.9-fold higher than for wild-type virus, and the replicative capacity was lower. The introduction of a bulkier and negatively charged glutamate residue at position 787 could destabilize the finger domain of UL54 DNA polymerase. Viral genotyping of cerebrospinal fluid is warranted in subjects with cytomegalovirus encephalitis, owing to the low penetration of antivirals in this compartment.

16.
Infection ; 47(5): 703-727, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31147846

RESUMO

PURPOSE: Human alveolar echinococcosis (AE) is a potentially lethal zoonosis caused by the cestode Echinococcus multilocularis. The aim of this systematic review is to establish a comprehensive global AE literature overview taking into account the epidemiologically relevant AE research of the twenty-first century. METHODS: We systematically searched the global literature published from 2001 through 2018 via MEDLINE, EMBASE, the Russian databases eLIBRARY.RU, CyberLeninka, the Chinese databases CNKI, VIP, Journals. RESEARCH: ac.ir (Farsi language-based), Jordan E-Library (Arab language-based) and supplementary Google Scholar, in accordance with the PRISMA guidelines. QGIS software was used for the mapping of the affected countries. RESULTS: We have listed 154 relevant publications in the final literature synopsis in consideration of our quality assessment. Including non-autochthonous cases, human AE was reported in 36 countries within the northern hemisphere from 2001 to 2018. The first publication of AE in Tajikistan, Pakistan, South Korea, Belgium, the Netherlands, Slovakia, Hungary, Lithuania, Latvia, Slovenia and Morocco occurred in this century; further first cases in Taiwan, Thailand, and Denmark were considered to be non-autochthonous by the authors. The highest total case numbers (n ≥ 100 in a single article) were reported in France, Germany, Switzerland, Poland, and Lithuania, including China and Kyrgyzstan with by far the highest prevalence figures. CONCLUSIONS: Our paper emphasises the increasing spread of reported cases and the rise in its numbers in the literature of the twenty-first century, especially in western, northern and eastern Europe, as well as in central Asia. Epidemiological studies on human infections are lacking in many parts of the world.

17.
J Integr Plant Biol ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31207036

RESUMO

Grain size is a major determinant of cereal grain yields; however, the relevant regulatory mechanisms controlling this trait have not been fully elucidated. The rice (Oryza sativa) mutant short grain6 (sg6) was identified based on its reduced grain length and weight. Here, we functionally characterized the role of SG6 in determining grain size through the regulation of spikelet hull cell division. SG6 encodes a previously uncharacterized plant AT-rich sequence and zinc-binding (PLATZ) protein that is ubiquitously localized throughout the cell and is preferentially expressed in the early developing panicles but not in the endosperm. The overexpression of SG6 resulted in significantly larger and heavier grains, as well as increased plant heights, which is consistent with its elevated spikelet hull cell division rate. Yeast two-hybrid analyses revealed that SG6 interacts with the core cell cycle machinery DP protein and several other putative cell division regulators, consistent with our transcriptomic analysis, which showed that SG6 activates the expression of many DNA replication and cell-cycle-related genes. These results confirm the crucial role of SG6 in determining grain size by regulating spikelet hull cell division and provide clues for understanding the functions of PLATZ family proteins and the network regulating cereal grain size.

18.
Chemosphere ; 234: 815-821, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31247491

RESUMO

BACKGROUND: Pyrethroid insecticides have been extensively used in China and worldwide, while their effects on thyroid functions are rarely explored, especially in susceptible pregnant women. OBJECTIVE: To assess the association between 3-phenoxybenzoic acid (3PBA), a major urinary metabolite of pyrethroids, and thyroid hormone levels in pregnant women in China. METHODS: Three hundred and seventy-four pregnant women were recruited during the admission for delivery (third trimester of pregnancy) in a local hospital in Shandong, China during December 2011 to December 2013. Pyrethoids exposure was assessed by examining urinary metabolite of 3PBA levels. Thyroid hormones were detected by measuring serum concentrations of thyroid stimulating hormones (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4) and free thyroxine (FT4). Multiple linear regression models were used to investigate the associations between 3PBA concentrations and thyroid hormones levels. RESULTS: The detection frequency of 3PBA was 90.4%, with a median concentration of 1.14 µg/g creatinine. After adjusted for potential confounders, we found a significant negative relationship between 3PBA and serum FT3 (ß = -0.06, 95% CI = -0.11 to -0.01) as well as an inverse dose dependent association (p for trend = 0.023). No significant association was found between 3PBA concentrations and other thyroid hormones. CONCLUSIONS: Our findings indicated that pyrethroid exposure was widespread and negatively associated with serum FT3 concentrations in pregnant women in northern China. Given to the widespread of pyrethroid exposure and critical role thyroid homeostasis plays during pregnancy, more studies are warranted to explore their relationships as well as underlying mechanisms.

19.
Environ Int ; 129: 573-582, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31174145

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are widely used in China, but little is known about the association between prenatal PFASs exposure and fetal reproductive development as well as its potential mechanism. OBJECTIVE: We investigated the effects of cord blood PFASs on fetal reproductive hormones and its potential mechanism in relation to steroidogenic enzymes. METHODS: Ten selected PFASs (n = 351) including PFOS, PFOA, PFBS, PFDA, PFDoA, PFHpA, PFHxS, PFNA, PFOSA, and PFUA, and two reproductive hormones estradiol (E2) (n = 351) and testosterone (T) (n = 349) were measured in 351 cord blood serum samples from a Chinese birth cohort between 2010 and 2013. Three steroidogenic enzymes including P450arom (n = 125), 3ß-HSD1 (n = 123), and 17ß-HSD1 (n = 116) were measured in 125 placental tissue samples. Linear regression tested the associations between cord blood PFASs and reproductive hormones in cord blood. Mediation analysis assessed the role of placental steroidogenic enzymes between cord blood PFASs and reproductive hormones. RESULTS: The positive associations between PFOA, PFHxS and E2 levels, PFOS, PFUA, PFNA and T levels, and PFOS, PFUA and T/E2 ratio were significant. PFUA, PFNA, PFDA, PFHxS, and ∑PFASs were associated with higher P450arom levels. PFHxS was also associated with increased 3ß-HSD1 and 17ß-HSD1 levels. These associations were more pronounced in females than males when stratified by gender. Furthermore, 17ß-HSD1 demonstrated mediating effects in the positive association between cord blood PFHxS and E2 levels in females. CONCLUSION: Our findings suggested the potential impacts of cord blood PFASs on fetal reproductive hormones, in which steroidogenic enzymes may play important roles. These associations were more pronounced in females than males.

20.
Plant Physiol Biochem ; 141: 431-445, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31238253

RESUMO

S-adenosylmethionine synthetase (SAMS) catalyzes methionine and ATP to generate S-adenosyl-L-methionine (SAM). In plants, accumulating SAMS genes have been characterized and the majority of them are reported to participate in development and stress response. In this study, two putative SAMS genes (CsSAMS1 and CsSAMS2) were identified in cucumber (Cucumis Sativus L.). They displayed 95% similarity and had a high identity with their homologous of Arabidopsis thaliana and Nicotiana tabacum. The qRT-PCR test showed that CsSAMS1 was predominantly expressed in stem, male flower, and young fruit, whereas CsSAMS2 was preferentially accumulated in stem and female flower. And they displayed differential expression profiles under stimuli, including NaCl, ABA, SA, MeJA, drought and low temperature. To elucidate the function of cucumber SAMS, the full-length CDS of CsSAMS1 was cloned, and prokaryotic expression system and transgenic materials were constructed. Expressing CsSAMS1 in Escherichia coli BL21 (DE3) improved the growth of the engineered strain under salt stress. Overexpression of CsSAMS1 significantly increased MDA content, H2O2 content, and POD activity in transgenic lines under non-stress condition. Under salt stress, however, the MDA content of transgenic lines was lower than that of the wild type, the H2O2 content remained high, the polyamine and ACC synthesis in transgenic lines exhibited a CsSAMS1-expressed dependent way. Taken together, our results suggested that both CsSAMS1 and CsSAMS2 were involved in plant development and stress response, and a proper increase of expression level of CsSAMS1 in plants is benificial to improving salt tolerance.


Assuntos
Cucumis sativus/enzimologia , Cucumis sativus/fisiologia , Metionina Adenosiltransferase/metabolismo , Tolerância ao Sal , Antioxidantes/metabolismo , Arabidopsis/metabolismo , Secas , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/química , Metionina Adenosiltransferase/genética , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Poliaminas/química , Sais , Estresse Mecânico , Estresse Fisiológico/genética , Tabaco/metabolismo
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