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1.
Theor Appl Genet ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797010

RESUMO

KEY MESSAGE: Candidate genes on grain drying rate (GDR) were identified, and drying molecular mechanism of grain was explored by integrating genome-wide association with transcriptomic analysis in maize. Grain drying rate (GDR) is a key determinant of grain moisture at harvest. Here, a genome-wide association study (GWAS) of 309 inbred maize lines was used to identify single-nucleotide polymorphisms (SNPs) associated with drying rates of grain, cob and bract. Out of 217,933 SNPs, seven significant SNPs were repeatedly identified in four environments (P < 10-4). Based on genomic position of significant SNPs, six candidate genes were identified, one of which (Zm00001d047468) was verified by transcriptomic data between inbred lines with high and low GDR, indicating stable and reliable correlation with GDR. To further detect more genes correlated with GDR and explore drying molecular mechanism of grain, expression profile of all GWAS-identified genes (4941) detected from different environments, tissues and developmental stage was evaluated by transcriptomic data of six inbred lines with high or low GDR. Results revealed 162 genes exhibit up-regulated expression and another 123 down-regulated in three higher-GDR inbred lines. Based on GO enrichment, 162 up-regulated genes were significantly enriched into grain primary metabolic process, nitrogen compound metabolic process and macromolecule metabolic process (P < 0.05), which indicated grain filling imposes notable influence on GDR before and after physiological maturity. Our results lay foundation in accelerating development of higher-GDR maize germplasm through marker-assisted selection and clarifying genetic mechanism of GDR in maize.

2.
J Invest Surg ; : 1-10, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31766898

RESUMO

Background: Tranexamic acid (TXA) combined with rivaroxaban (RA) has been widely used in total knee replacement (TKA). This meta-analysis explored the clinical effects of TXA combined with RA on reducing bleeding and preventing venous thrombosis in patients with unilateral TKA.Methods: Five controlled clinical studies that met the inclusion criteria were collected from PubMed, Embase and Cochrane libraries. Fixed effect model and random effect model were used to compare the TXA + RA group with the RA group in 731 patients.Results: Decrease of hemoglobin (Hb), total blood loss, transfusion rate and wound complications of the TXA + RA group is lower than the RA group, the difference was statistically significant (p < 0.05). Deep venous thrombosis (DVT) occurs in the TXA + RA group and the RA group showed no statistically significant difference (p > 0.05). There was no obvious difference of two ways of drug given that intra-articular (IA) and intravenous (IV) effect on Hb decrease, total blood loss, transfusion rate, wound complications, DVT (p > 0.05).Conclusion: The application of TXA combined with RA in the TKA can effectively reduce blood loss without increasing the risk of DVT. However, it should be noted that TXA combined with RA after TKA has a potential increased risk of wound complications.

3.
Bioresour Technol ; 294: 122152, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31557651

RESUMO

A novel wasted sludge-based Biochar modified by Chitosan and Fe/S (BCFe/S) was prepared for tetracycline (TC) removal from water. To investigate the similarities and differences in adsorption behaviors between Biochar and BCFe/S, characterization, kinetics, isotherms and thermodynamics were discussed. The studies on site energy distribution (SED) were also presented. The results showed that the maximum TC adsorption amount was 51.78 mg/g for Biochar, while it was 183.01 mg/g for BCFe/S-4. Meanwhile, electrostatic attraction, π-π stacking, pore filling, silicate bonding and hydrogen bonding were the main adsorption mechanisms for TC removal by Biochar. Besides above mechanisms, chelating and ion exchange were also accounted for adsorption mechanisms for TC uptake by BCFe/S-4. Moreover, SED results revealed that the surface of Biochar was more homogeneous while the surface of BCFe/S-4 was more heterogeneous at higher temperature. Findings of this work could offer valuable information in designing adsorbents and investigating adsorption mechanisms.


Assuntos
Quitosana , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Cinética , Tetraciclina
4.
Med Sci Monit ; 25: 6255-6263, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429423

RESUMO

BACKGROUND Acute lung injury (ALI) is one of major causes of death in newborns, making it urgent to improve therapy. Administration of low dose carbon monoxide (CO) plays a protective role in ALI but the mechanisms are not fully understood. This study was designed to test the therapeutic effect of monoxide-releasing molecule 3 (MORM3) in lipopolysaccharide (LPS) induced neonatal ALI and the possibly associated molecular mechanisms. MATERIAL AND METHODS For this study, 3- to 8-day old Newborn Sprague-Dawley rats were subjected to intraperitoneal injection of 3 mg/kg LPS to induce ALI. Then animals received intraperitoneal injection of carbon monoxide-releasing molecules 3 (CORM3) (8 mg/kg) or inactive CORM3 (iCORM3) for 7 consecutive days. Lung tissues were collected for histological examination and total cell counts and protein content in bronchoalveolar lavage fluid (BALF) were measured. Expression of Cx43 and necroptosis-related markers were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. RESULTS LPS exposure induced significant lung injury indicated by histological damage, increased lung wet/dry weight ratio (W/D) and increased total cell counts and protein concentration in BALF. These changes were significantly ameliorated by administration of CORM3 but not iCORM3. LPS also increased necroptosis-related markers RIP1, RIP3, and MLKL and their elevation was blocked by CORM3. CORM3 administration ameliorated LPS induced elevation of Cx43 expression and adenoviral overexpression of Cx43 abolished lung protective effect of CORM3. CORM3 administration attenuated LPS induced activation of extracellular-signal-regulated kinase (ERK) and its protection against necroptosis was abolished by ERK inhibitor U0126. CONCLUSIONS CORM3 attenuates LPS-Induced ALI in neonatal rats and its lung protective effect might be through downregulation of Cx43 to attenuate ERK signaling and ameliorate necroptosis, suggesting CORM3 as a potential therapeutic drug for ALI in neonates.

5.
Pharmacol Res ; 147: 104355, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386886

RESUMO

Convallatoxin (CNT) is a cardiac glycoside isolated from Adonis amurensis Regel et Radde and has both anti-inflammatory and anti-proliferative properties. In the present study, the anti-inflammatory mechanisms of action of CNT was investigated in vitro and in vivo. Stimulation of mouse macrophages with lipopolysaccharide induced secretion of proinflammatory cytokines via suppression of peroxisome proliferator-activated receptor gamma (PPARγ) and activation of nuclear factor-κB (NF-κB), two transcription factors implicated in many inflammatory diseases. Notably, the effects of lipopolysaccharide were reversed by concomitant treatment of macrophages with CNT. Knockdown of PPARγ by siRNA inhibited the effect of convallatoxin on NF-κB activation. Because these transcription factors play a role in the development of ulcerative colitis in humans, the mice with experimental colitis induced by dextran sodium sulfate (DSS) was employed. Indeed, concomitant treatment with CNT ameliorated DSS-induced colitis symptoms, tissue damage, inflammatory cell infiltration, and proinflammatory cytokine production in the colon, and also reversed the activation of NF-κB and suppression of PPARγ. Collectively, these data indicate that CNT ameliorates colitic inflammation via activation of PPARγ and suppression of NF-κB, and suggest that CNT may be a promising treatment for inflammatory bowel disease (IBD).

6.
Invest New Drugs ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31267380

RESUMO

T cells are important effectors in anti-tumor immunity, and aberrant expression of B7 family members may contribute to tumor evasion. In this study, we analyzed expression of costimulatory molecules on human hematologic tumor cells and explored whether B7-H3, a member of the B7 superfamily, is an effective target for T cell mediated cytotoxicity toward hematologic malignancy. We investigated the bispecific antibody anti-CD3 × anti-B7-H3 (B7-H3Bi-Ab) for its ability to redirect T cells to target B7-H3 positive hematologic tumors, including Thp-1, K562, Daudi cells and a primary culture. The capacity of T cells armed with B7-H3Bi-Ab to kill hematologic tumors was evaluated by lactate dehydrogenase assay, flow cytometry, ELISA, and luciferase quantitative assay at an effector/target ratio of 5:1. Compared with unarmed T cells, B7-H3Bi-Ab-armed T cells exhibited significant cytotoxicity toward hematological tumor cells. Moreover, B7-H3Bi-Ab-armed T cells secreted more IFN-γ, TNF-α, IL-2, and Granzyme B and expressed higher levels of activating marker CD69 compared to unarmed T cells. In conclusion, B7-H3Bi-Ab enhances the ability of T cells to kill hematologic tumor cells, and B7-H3 may serve as a novel target for immunotherapy against hematologic malignancy.

7.
PLoS One ; 14(7): e0219939, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31318951

RESUMO

OBJECTIVES: The main objective of this study was to explore the associations of family relationships and negative life events with depressive symptoms among Chinese adolescents. METHODS: A cross-sectional study of 3081 middle school students was conducted in Ganzhou City, Jiangxi Province, China. Students were asked to complete questionnaires regarding family relationships, negative life events, and depressive symptoms. A mediation analysis was carried out using a multiple regression analysis and the PROCESS macro method. RESULTS: Of all participants, 19.9% reported experiencing depressive symptoms. The prevalence of depressive symptoms was 13.0% and 29.2% in participants with good and poor parental relationships, and the prevalence of depressive symptoms was 11.4% and 30.9% in participants with closed and alienated parental-child relationships, respectively. Parental relationships, parental-child relationships, and negative life events were positively correlated with depressive symptoms. The effect of parental relationships on depressive symptoms was fully mediated by negative life events (Effect = 0.052, 95% CI = [0.023, 0.082]), while the effect of parent-child relationships on adolescent depressive symptoms was partially mediated by negative life events (Effect = 0.075, 95% CI = [0.048, 0.104]). CONCLUSIONS: Our results showed a high prevalence of depressive symptoms in Chinese adolescents. Poor family relationships may have the potential to increase the risk of depressive symptoms, and they could affect depressive symptoms through negative life events.

8.
J Affect Disord ; 257: 108-115, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301610

RESUMO

BACKGROUND: Limited published research has examined the relationships of coping styles and sleep quality with anxiety symptoms in Chinese school adolescents. We aimed to explore the effect of coping styles and sleep quality on anxiety symptoms. Furthermore, we investigated the interactions of coping styles and sleep quality with anxiety symptoms. METHODS: The survey was conducted in Jiangxi Province, China. The Simplified Coping Style Questionnaire, Pittsburgh Sleep Quality Index and Chinese Secondary School Students Anxiety Scale were utilized to assess sleep quality, coping styles and anxiety symptoms, respectively. Multiple logistic regression analysis was applied to explore the relationships of coping styles and sleep quality with anxiety symptoms. RESULTS: A total of 3081 students participated in this study, 50.8% of whom were boys; the number of participants in grades 1, 2 and 3 were 979, 1085 and 1017, respectively. The prevalence of anxiety symptoms was 27.3%. Individuals with poor sleep quality were 3.558 (95% CI = 2.716-4.660) times as likely to have anxiety symptoms than those with good sleep quality. Higher negative coping style scores increased the prevalence of anxiety symptoms (OR = 2.101, 95% CI = 1.894-2.332), whereas higher positive coping style scores were related to reduced odds of anxiety symptoms (OR = 0.892, 95% CI = 0.800-0.995). Interactions of coping styles and sleep quality with anxiety symptoms were not found (all p > 0.05). The association between negative coping style and anxiety symptoms was mediated by sleep quality. LIMITATIONS: This study was cross-sectional and limited to Ganzhou City. CONCLUSIONS: The results of our study showed a higher prevalence of anxiety symptoms compared with the result of a previous study in Chinese school adolescents. Negative coping style and poor sleep quality were associated with an increased prevalence of anxiety symptoms, whereas positive coping style was related to a decreased prevalence of anxiety symptoms. Sleep quality was a mediating factor between negative coping style and anxiety symptoms.

9.
Am J Alzheimers Dis Other Demen ; 34(7-8): 523-529, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266345

RESUMO

OBJECTIVES: This study examined the efficacy of the General Practitioner Assessment of Cognition-Chinese version (GPCOG-C) in screening dementia and mild cognitive impairment (MCI) among older Chinese. METHODS: Survey questionnaires were administered to 293 participants aged 80 or above from a university hospital in mainland China. Alzheimer disease and MCI were diagnosed in light of the National Institute on Aging and the Alzheimer's Association (NIA/AA) criteria. The sensitivity and specificity of GPCOG-C and Mini-Mental State Examination (MMSE) in screening dementia and MCI were compared to the NIA/AA criteria. RESULTS: The GPCOG-C had the sensitivity of 62.3% and specificity of 84.6% in screening MCI, which had comparable efficacy as the NIA/AA criteria. In screening dementia, GPCOG-C had a lower sensitivity (63.7%) than the MMSE and a higher specificity (82.6%) higher than the MMSE. CONCLUSIONS: The GPCOG-C is a useful and efficient tool to identify dementia and MCI in older Chinese in outpatient clinical settings.

10.
Huan Jing Ke Xue ; 40(3): 1375-1381, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087987

RESUMO

A synthetic wastewater was employed to investigate the realization of short-cut nitrification and its phosphorus removal performance in a CAST reactor operated at 22℃, 25℃, and 28℃. The results showed that TN removal of the system was stable and higher than 80% at different temperatures, and NH4+-N removal performed well. When the temperature was at 22℃ and 25℃, nitrite accumulation was not observed in the system and the phosphorus removal rate were 94.3% and 86.9%, respectively. When the temperature was increased to 28℃, nitrite accumulation efficiency in the reactor reached 87.2%, implying the system achieved a stable short-cut nitrification. In addition, in the short-cut nitrification stage at high temperature (28℃), the phosphorus release and uptake capacity of the system decreased. The anaerobic phosphorus release/COD consumption (P/C) ratio was much lower compared those at 22℃ and 25℃. However, the phosphorus removal performance of the reactor did not deteriorate at this stage. The phosphorus removal rate was 68.9%, indicating that a sufficient carbon source in the influent could not only guarantee the removal of TN, but also detoxify NO2- to reduce its inhibitory effect on the phosphate accumulating organisms (PAOs). The batch tests of phosphorus uptake by the sludge under different temperature conditions revealed that O2, NO3-, and NO2- could all be used as electron acceptors for phosphorus uptake. The aerobic phosphorus uptake rate was higher than that with NO3- and NO2- as electron acceptors. The phosphorus uptake rates of O2 and NO3- as electron acceptors were also found to be negatively correlated with temperature.

11.
J Craniofac Surg ; 30(6): 1825-1828, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31058723

RESUMO

The aim of this study was to investigate the clinical outcomes of orbital blowout fracture repair by using the three-dimensional (3D) printing-assisted fabrication of individual titanium mesh. Clinical and radiologic data were analyzed for 12 patients with orbital floor and/or medial wall fractures. Lower eyelid incision was used to expose the fractures. Preoperative computed tomographic data were input into an imaging software to rebuild a 3D orbit and mirror the unaffected side into the affected side to replace the demolished orbit. A resin model of the reshaped orbit was generated and used to develop an individual titanium mesh for repairing the fractured orbital. The surgical results were assessed by value of enophthalmos and a comparison of preoperative and postoperative orbital volume difference. All patients had a successful treatment outcome without any complications. Clinical significant enophthalmos were not observed after treatment, and diplopia were solved within 2 weeks postoperative. No extraocular muscle limitation was observed. Postoperative computed tomography scans demonstrated appropriate positioning of titanium mesh and there was no implant displacement. The postoperative orbital volume and enophthalmos difference between the 2 eyes decreased significantly than preoperative (P < 0.001). Three-dimensional printing-assisted fabrication of individual titanium mesh is appropriate for use in orbital blowout fracture.

12.
Huan Jing Ke Xue ; 40(3): 1426-1430, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087994

RESUMO

A sequencing batch reactor (SBR) was operated in this study to investigate the effect of temperature on the kinetics of Nitrobacter activity among nitrite oxidizing bacteria. At the beginning of the experiment, the NO2--N concentration in the influent was changed to enrich Nitrobacter. Then, the sludge with enriched Nitrobacter was employed to determine the variation of the specific nitrite oxidation rate (SNiOR) during the nitrite oxidation process in batch tests. Metagenomics species annotation and abundance analysis showed that Nitrobacter accounted for 40.3% of the total bacterial population. The variation of SNiOR in the nitrite oxidation process was investigated under different NO2--N concentrations. The effect of temperature on the kinetics of Nitrobacter was investigated using the Monod model. Furthermore, the kinetics model of the effect of temperature on Nitrobacter activity was fitted for statistical analysis. The results showed that SNiOR reached its maximum at 30℃, which was 1.31 g·(g·d)-1. Statistical analysis showed that the Monod equation could describe the effect of substrate concentration on Nitrobacter activity under different temperature conditions. Calculating the temperature coefficient (θ) in different temperature intervals based on the Phelps equation, showed that when the system temperature is lower than 25℃ or higher than 30℃, the reaction rate is more sensitive to temperature changes.


Assuntos
Reatores Biológicos , Nitrobacter/metabolismo , Temperatura Ambiente , Cinética , Nitritos , Oxirredução , Esgotos
13.
Chest ; 155(4): 740-748, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955572

RESUMO

BACKGROUND: Nasal high-frequency oscillatory ventilation (NHFOV) has been described as supplying the combined advantages of nasal CPAP (NCPAP) and HFOV. However, its effect on preterm infants needs to be further elucidated. Our objective was to assess whether NHFOV could reduce intubation and Pco2 levels as compared with NCPAP during the postextubation phase in preterm infants. METHODS: This was a single-center, randomized, controlled trial, and it was registered at clinicaltrials.gov (NCT03140891) and conducted between May 2017 and May 2018. Ventilated infants born at less than 37 weeks' gestational age and ready to be extubated were included and randomized to either the NHFOV or NCPAP group. Primary outcomes were the incidence of reintubation within 1 week and the Pco2 level within 6 h. RESULTS: A total of 206 preterm infants were included. Of them, 127 (61.7%) were diagnosed with respiratory distress syndrome, 53 (25.7%) with ARDS, and 26 (12.6%) with both respiratory distress syndrome and ARDS. Comparing with NCPAP, NHFOV significantly reduced the reintubation rate (16:87 vs 35:68; 95% CI, 0.18-0.70; P = .002), especially in the subgroup with a gestational age of ≤ 32 weeks (12:34 vs 25:20; 95% CI, 0.12-0.68; P = .004). The Pco2 level was also significant lower in the NHFOV group (49.6 ± 8.7 vs 56.9 ± 9.9; 95% CI, -9.95 to -4.80; P = < .001). Moreover, NHFOV significantly reduced the reintubation rate in preterm infants with ARDS (10:33 vs 21:15; 95% CI, 0.08-0.57; P = .002). CONCLUSIONS: NHFOV was shown to be superior to NCPAP in avoiding reintubation, especially in very preterm infants and those infants diagnosed with ARDS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03140891; URL: www.clinicaltrials.gov.

14.
Bioorg Med Chem Lett ; 29(11): 1357-1362, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935793

RESUMO

The binding properties of CD1d/glycolipid/TCR, glycolipid/TCR interactions in particular, have been investigated using docking computation. Accordingly, efficient modification on C-6' of galactose head was recommended in this report to favor the production of Th2 cytokines. The designed glycolipids have been successfully prepared taking advantages of inverse glycosylation procedure, and their abilities to stimulate mouse iNKT cells in vivo have been tested. Compound 9, having p-hydroxyphenylpropionyl amide group on C-6', presented the best result with respect to the selectivity and quantity on Th2-type cytokine IL-4. We found that the increased glycolipid/TCR interaction might be critical in designing new substrate with Th2-biased cytokine production.

15.
Ecotoxicol Environ Saf ; 178: 211-220, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31009927

RESUMO

Due to similar aerodynamic and micro-nano sized properties between airborne particles and synthetic nanoparticles, a large number of studies have been conducted using carbon-based particles, such as carbon black (CB), carbon nanotubes and graphite, in order to achieve deeper understandings of their adverse effects on human health. It has been reported that particulate matters can aggravate morbidity of patients suffering from bone and joint diseases, e.g. arthritis. However, the molecular mechanism is still elusive thus far. Under this context, we employed two cell lines of osteoblasts, MC3T3-E1 and MG-63, upon exposure to 4 different CB samples with differential physicochemical properties in research of mechanistic insights. Our results indicated that the carbon/oxygen ratio differed in these 4 CB materials showing the order: SB4A < Printex U < C1864 < C824455. In stark contrast, their cytotoxicity and capacity to trigger reactive oxygen species (ROS) in MC3T3-E1 and MG-63 cells closely correlated to oxygen content, revealing the reverse order: SB4A < Printex U < C1864 < C824455. It would be reasonable to speculate that ROS production was a predominant cause of CB cytotoxicity, which strongly relied on the oxygen content of CB. Our study further manifested that all CB samples even at low concentrations significantly inhibited osteoblast differentiation, as reflected by remarkably reduced activity of alkaline phosphatase (ALP) and compromised expression of the differentiation-related genes. And the inhibition on osteoblast differentiation also closely correlated to oxygen content of CB samples. Taken together, our combined data recognized oxygen-associated toxicity towards osteoblasts for CBs. More importantly, we uncovered a new adverse effect of CB exposure: suppression on osteoblast differentiation, which has been overlooked in the past.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Nanopartículas/toxicidade , Osteoblastos/efeitos dos fármacos , Material Particulado/toxicidade , Fuligem/toxicidade , Fosfatase Alcalina/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Camundongos , Nanopartículas/química , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Tamanho da Partícula , Material Particulado/química , Espécies Reativas de Oxigênio/metabolismo , Fuligem/química , Propriedades de Superfície
16.
Medicine (Baltimore) ; 98(9): e14640, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30817583

RESUMO

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantaviruses (HVs). Climate factors have a significant impact on the transmission of HFRS. Here, we characterized the dynamic temporal trend of HFRS and identified the roles of climate factors in its transmission in Changchun, China.Surveillance data of HFRS cases and data on related environmental variables from 2013 to 2017 were collected. A principal components regression (PCR) model was used to quantify the relationship between climate factors and transmission of HFRS.During 2013 to 2017, a distinctly declining temporal trend of annual HFRS incidence was identified. Four principal components were extracted, with a cumulative contribution rate of 89.282%. The association between HFRS epidemics and climate factors was better explained by the PCR model (F = 10.050, P <.001, adjusted R = 0.456) than by the general multiple regression model (F = 2.748, P <.005, adjusted R = 0.397).The monthly trends of HFRS were positively correlated with the mean wind velocity but negatively correlated with the mean temperature, relative humidity, sunshine duration, and accumulative precipitation of the different previous months. The study results may be useful for the development of HFRS preventive initiatives that are customized for Changchun regarding specific climate environments.


Assuntos
Clima , Epidemias/estatística & dados numéricos , Vírus Hantaan , Febre Hemorrágica com Síndrome Renal/epidemiologia , Vigilância da População , China/epidemiologia , Febre Hemorrágica com Síndrome Renal/etiologia , Febre Hemorrágica com Síndrome Renal/virologia , Humanos , Umidade , Incidência , Fatores de Risco , Temperatura Ambiente , Vento
17.
Sci Rep ; 9(1): 2536, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30796297

RESUMO

The MoS2-catalyzed transamidation reaction with high yields using N,N-dimethylformamide and other amides as carbonyl sources is developed here. The protocol is simple, does not require any additive such as acid, base, ligand, etc., and encompasses a broad substrate scope for primary, secondary and heterocyclic amines. Moreover, the acetylation and propanylation of amines also can be achieved with good to excellent yield by this strategy.

18.
Bioorg Med Chem Lett ; 29(6): 853-858, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30728113

RESUMO

The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumor angiogenesis, growth, and metastasis and is recognized as an important potential therapeutic target for cancer. Here, we designed and synthesized three novel series of ursolic acid derivatives containing an aminoguanidine moiety and evaluated them as HIF-1α inhibitors and anti-cancer agents using human cancer cell lines. Most of the compounds exhibited significant inhibition of HIF-1α transcriptional activity, as measured using a Hep3B cell-based luciferase reporter assay. Among these compounds, 7b was the most potent inhibitor of HIF-1α expression under hypoxic conditions (IC50 4.0 µM) and did not display significant cytotoxicity against any cell lines tested. The mechanism of action of 7b was investigated, we found that 7b downregulated HIF-1α protein expression, possibly by suppressing its synthesis, reduced production of vascular endothelial growth factor, and inhibited the proliferation of cancer cells.

19.
Invest New Drugs ; 37(5): 1036-1043, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30706335

RESUMO

Inhibition of the B7-H3 immune checkpoint is reported to limit the tumor growth of B7-H3+ tumors. In this study, we demonstrated B7-H3 expression in human melanoma cells, including a primary culture and several cell lines. Furthermore, we investigated whether B7-H3 could serve as a target for T cell-mediated immunotherapy against melanoma. The cytotoxic capacity of activated T cells (ATCs) armed with an anti-CD3 x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) to melanoma cells was measured using a bioluminescent signal through a luciferase reporter on tumor cells. In contrast to unarmed ATCs, B7-H3Bi-Ab-armed ATCs exhibited increased cytotoxicity against melanoma cells at effector/target ratios from 1:1 to 20:1. Moreover, B7-H3Bi-Ab-armed ATCs secreted more interferin-gamma (IFN-γ), accompanied by higher levels of activating marker CD69 and CD25 expression. Infusion of B7-H3Bi-Ab-armed ATCs suppressed melanoma growth in a xenograft mouse model. Taken together, our results indicate that B7-H3Bi-Ab-armed ATCs may be a promising approach to immunotherapy for melanoma patients.

20.
Biomed Environ Sci ; 32(1): 11-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30696535

RESUMO

OBJECTIVE: A strain of Aspergillus niger (A. niger), capable of releasing bound phenolic acids from wheat bran, was isolated. This strain was identified by gene sequence identification. The antioxidant and anti-inflammatory capacity of ferulic acid released from wheat bran by this A. niger strain (FA-WB) were evaluated. METHODS: Molecular identification techniques based on PCR analysis of specific genomic sequences were conducted; antioxidant ability was examined using oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA) assays, and erythrocyte hemolysis assays. RAW264.7 cells were used as a model to detect anti-inflammatory activity. RESULTS: The filamentous fungal isolate was identified to be A. niger. ORAC and CAA assay showed that FA-WB had better antioxidant activity than that of the ferulic acid standard. The erythrocyte hemolysis assay results suggested that FA-WB could attenuate AAPH-induced oxidative stress through inhibition of reactive oxy gen species (ROS) generation. FA-WB could significantly restore the AAPH-induced increase in intracellular antioxidant enzyme activities to normal levels as well as inhibit the intracellular malondialdehyde formation. TNF-a, IL-6, and NO levels indicated that FA-WB can inhibit the inflammation induced by lipopolysaccharide (LPS). CONCLUSION: Ferulic acid released from wheat bran by a new strain of A. niger had good anti-inflammatory activity and better antioxidant ability than standard ferulic acid.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Aspergillus niger/metabolismo , Ácidos Cumáricos/farmacologia , Fibras na Dieta/microbiologia , Animais , Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Aspergillus niger/genética , Aspergillus niger/isolamento & purificação , Ácidos Cumáricos/metabolismo , DNA Fúngico/análise , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Fermentação , Células Hep G2 , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Células RAW 264.7 , Ovinos , Fator de Necrose Tumoral alfa/metabolismo
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