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1.
J Med Virol ; 92(1): 26-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31475732

RESUMO

This study aimed to assess the clinical characteristics and T-helper 1 (Th1)/Th2 profile of human rhinovirus (HRV) infection in children with bronchiolitis and pneumonia, compared with the respiratory syncytial virus (RSV). In September 2013 to August 2014, 335 nasopharyngeal aspirates from children below 14 with bronchiolitis and pneumonia were screened for HRV and 13 other respiratory viruses by PCR or reverse transcription PCR. Interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF)-α were detected by multiplex enzyme-linked immunosorbent assay. HRVs were found in 66 cases (19.7%), including 35 bronchiolitis and 31 pneumonia cases. Compared with the RSV alone group, children with pneumonia had more frequent wheezing episodes in HRV (Pa = .001) and HRV + non-RSV (Pb = .002) groups, and fever in the HRV (Pf = .004) and HRV + RSV (Pg = .005) groups. Among patients with bronchiolitis, cases with HRV alone were more likely to present in winter than those with RSV alone (Pi = .010) and HRV + non-RSV (Pj = .014), and less numerous in summer compared with HRV + non-RSV (Ph = .005). Children with HRV alone were more susceptible to have a history of eczema than RSV alone among bronchiolitis (Pc < .001) and pneumonia (Pe = .033) cases. HRV bronchiolitis cases had increased IL-4/IFN-γ and decreased TNF-α/IL-10 ratios, compared with HRV pneumonia counterparts. HRV is a major non-RSV pathogen causing hospitalization in children with bronchiolitis and pneumonia and induces an imbalanced Th1/Th2 response in bronchiolitis. Compared with RSV infection, HRV bronchiolitis and pneumonia differ significantly regarding wheezing episodes, susceptibility to eczema, fever occurrence, and seasonal prevalence.

2.
J Hazard Mater ; 383: 121124, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31505426

RESUMO

Due to potential adverse effects of excessive fluorine (F), interests regarding considerable accumulation of F in agricultural soils from application of fertilizers are increasing continually. However, less detailed information of hazard and risk of F in fertilizers to human directly by hand-to-mouth pathway can be obtained. Herein, the bioaccessibility of F (Fbio) in fertilizers is determined by Biomimetic Whole Digestion-Plasma in-vitro Method (BWDPM), which is developed to detect the behaviour of bioaccessible F in both the whole digestive system and plasma for the first time. Observations of higher Fbio in small intestinal phases (4.35-56.33%), large intestine (1.01-40.52%) and plasma (8.07-66.70%) yielded them as the major phases which are faced with higher exposure risk of F. Compared with phosphate fertilizer, more bioaccessible F was observed in compound fertilizer. Some studied factors, such as sweat and food, yield insignificant influences on Fbio, whereas can affect the exposure estimations of F considerably. Exposure risks based on Fbio of fertilizers should be highly concerned, especially the occupational exposure to local farmers. In a word, more explicit and realistic information of the potential risk of F on human health could be obtained by the introduction of Fbio.

3.
J Cell Physiol ; 235(2): 1469-1479, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31273789

RESUMO

Aberrant loss of tumor-suppressor genes plays a crucial role in tumorigenesis and development of colorectal cancer (CRC). Extensive studies have reported tha hypermethylation of Ras association domain family member 6 (RASSF6) is common in various solid tumors. Another important mode of epigenetic regulation, microRNA (miRNA) regulation of RASSF6, is far from clear. The aim of the present work was to screen out novel miRNA regulating RASSF6, and to explore its underlying mechanism in CRC. With the use of bioinformatics, clinical sample data, and luciferase binding assay, we determined that microRNA-496 (miR-496) could be a novel oncomiR that directly binds to RASSF6. Next, a series of miR-496 mimics or inhibitor, or RASSF6 small interfering RNA (siRNA) introduced into CRC cells were applied to examine the effect of miR-496 on CRC cell viability, migration, and epithelial-mesenchymal transition (EMT). The results demonstrated that miR-496/RASSF6 could promote cell migration and EMT via Wnt signaling activation, but had no effect on cell viability. Our results confirmed that the miR-496/RASSF6 axis is involved in Wnt pathway-mediated tumor metastasis, highlighting its potential as a therapeutic target for CRC.

4.
Horm Metab Res ; 51(11): 729-734, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31683343

RESUMO

Contrasting data about the association between proliferative diabetic retinopathy (PDR) and vitamin D status remain unknown. First, a hospital-based cross-sectional study consisting of 889 diabetic retinopathy (DR) and non-DR (NDR) patients was admitted. Further the accumulated evidence was performed to explore the association and dose-response relationship. Our study indicated that the odd ratio for PDR in vitamin D deficiency (VDD) individuals was significantly increased (1.60, 95% CI 1.06-2.42), compared with NDR in vitamin D sufficiency individuals, adjusted by age, sex, diabetic duration, and HbA1c. Four studies plus our study with data on vitamin D levels in 4970 patients with PDR and NDR subjects are compared. Association between vitamin D deficiency and risk of PDR exists (OR=1.69, 95% CI 1.40-2.05; I2=0%, p=0.61). Association between a nonlinear trend for vitamin D decrease with risk of DR was significant (chi2=16.53, p=0.0003). No significant heterogeneity in identified studies was found (goodness of fit chi2=2.98, p=0.225). It is concluded that vitamin D deficiency is significantly associated with risk of proliferative diabetic retinopathy.

5.
Childs Nerv Syst ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712902

RESUMO

BACKGROUND: Simulation-based training has been considered as the most promising curriculum for neurosurgical education to finally improve surgical skills with the greatest efficiency and safety. However, most of the simulators including physical models and virtual reality systems are relatively expensive, which limits their promotion. In this study, the authors tried to develop a realistic, low-cost, and reusable simulator for endoscopic third ventriculostomy (ETV) and evaluate its validity. METHODS: A 3D-printed rigid skull with the ventricular system originated from a de-identified patient with obstructive hydrocephalus was constructed. The third ventricular floor was designed as a replaceable module. Thirty-nine neurosurgeons tested the simulator and a rating system was established to assess their performance. All participants filled out questionnaires to evaluate the simulator after training. Five neurosurgical students were recruited to finish the whole training for ten times in order to explore the learning curve of ETV. RESULTS: We found that (1) the more experienced surgeons performed obviously better than the rather inexperienced surgeons which verified that our model could reflect the ability of the trainees; (2) as the training progressed, the scores of the post-graduates increased and the fifth training average score was obviously higher than their first training average score. The feedback questionnaires showed the average scores for value of the simulator as a training tool and global rating were 3.15 and 3.54 (on a 4-point scale). CONCLUSION: Our model was practical for ETV training. The results of our program showed that our model could precisely reflect the operators' ability to perform ETV and could make it more efficient to master basic skills.

6.
Biofouling ; : 1-11, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724449

RESUMO

Metamorphosis is crucial in the life-cycle transition between the larval and juvenile stages of marine invertebrates. Although a number of agonists and antagonists of the adrenergic receptor (AR) are known to regulate larval metamorphosis in Mytilus coruscus (Mc), the molecular basis of the modulation of larval metamorphosis by the AR gene in this species remains elusive. Herein, the role of the AR gene in M. coruscus larval metamorphosis using the RNA interference technique was examined. The Mcα2AR transcript was observed to be present during the entire process of larval development and its level in the post-larvae was significantly increased compared to that in the pediveligers. Mcα2AR-knockdown resulted in a substantial reduction in the abundance of the Mcα2AR transcript and significantly inhibited the metamorphosis of M. coruscus larvae. These findings provide new insights into the molecular basis of modulation of larval metamorphosis in M. coruscus by the AR gene.

7.
Chaos ; 29(10): 103146, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31675801

RESUMO

Multilayer networks are widely used to characterize the dynamic behavior of complex systems. The study of epidemic spreading dynamics on multilayer networks has become a hot topic in network science. Although many models have been proposed to explore epidemic spreading across different networks, there is still a lack of models to study the spreading of diseases in the process of evolution on multilayer homogeneous networks. In the present work, we propose an epidemic spreading dynamic model of homogeneous evolving networks that can be used to analyze and simulate the spreading of epidemics on such networks. We determine the global epidemic threshold. We make the interesting discovery that increasing the epidemic threshold of a single network layer is conducive to mitigating the spreading of an epidemic. We find that the initial average degree of a network and the evolutionary parameters determine the changes in the epidemic threshold and the spreading process. An approach for calculating the falling and rising threshold zones is presented. Our work provides a good strategy to control epidemic spreading. Generally, controlling or changing the threshold in a single network layer is easier than trying to directly change the threshold in all network layers. Numerical simulations of small-world and random networks further support and enrich our conclusions.

8.
IUBMB Life ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675148

RESUMO

microRNAs (miRNAs) can be used as biomarkers for acute myocardial infarction (AMI). However, few reports have focused on the value of exosomal miRNAs in the mechanism of the pathophysiological process from stable coronary artery disease (SCAD) to AMI. Exosomes were isolated via ultracentrifugation after serum samples were collected. The exosomes were then identified by transmission electron microscopy, western blotting, and nanoparticle tracking analysis. The differential expression of miRNAs in exosomes from six AMI and six matching SCAD patients was screened using the Agilent Human miRNA Microarray Kit. Target genes of the candidate miRNAs were predicted via an online miRNA database, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Further validation was conducted through quantitative real-time polymerase chain reaction with 60 exosome samples. The expression of 13 miRNAs was significantly downregulated in the AMI samples compared with the SCAD samples. In addition, we identified various target genes that are mainly involved in the pathways of cardiac rehabilitation and remodelling. Validation of the expression of candidate miRNAs indicated that exosomal miR-1915-3p, miR-4,507, and miR-3,656 were significantly less expressed in AMI samples than in SCAD samples, and area under the receiver-operating-characteristic curve (AUC) analysis showed that the expression of these miRNAs resulted in good predictive accuracy [miR-1915-3p (AUC: 0.772); miR-4,507 (AUC: 0.684); and miR-3,656 (AUC: 0.771)], suggesting that these serum exosomal miRNAs might be predictive for AMI at an early stage. Hence, exosomal miRNAs might play an important role in the pathophysiology of AMI and could serve as diagnostic biomarkers.

9.
Sci Rep ; 9(1): 16391, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704981

RESUMO

Haemolymph microbiome was considered to be unique to healthy invertebrates and beneficial to the host against external pathogens, including disease resistance and maintenance of homeostasis. Here, we investigated the effects of elevated water temperature on infection of haemolymph microbiome of the hard-shelled mussel (Mytilus coruscus). Exposure to Vibrio. cyclitrophicus resulted in high mortality of mussels on day nine at 27 °C. The haemolymph was collected to determine the microbiota by 16 S rRNA gene sequencing. Exposure to waterborne V. cyclitrophicus increased the mortality of mussels that was associated with a reduction in the diversity of their microbial community. Principal coordinate analysis (PCoA) revealed that temperature was an essential factor in shaping microbial communities in mussel haemolymph. Vibrio exposure promoted the proliferation of opportunistic pathogens (e.g., Arcobacter and Francisella) at a lower temperature. A high abundance of Vibrio present in live and dead mussels, at 27 °C might contribute greatly to mortality, as indicated by linear discriminant analysis effect size (LEfSe). These data suggested that the dynamics of microbial community have unique biomarker species in mussel haemolymph that could be used as health indicators. An elevated temperature may reduce the ability of bacterial elimination function against infection in mussel haemolymph.

10.
Insect Sci ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769205

RESUMO

MEAM1 (Middle East-Asia Minor 1, "B" biotype) and MED (Mediterranean, "Q" biotype) are the two most destructive cryptic species of the Bemisia tabaci complex on the planet. Our previous studies have shown that MEAM1 outcompetes MED on cabbage; the underlying mechanism is unknown. In the Brassicaceae family, the glucosinolate-myrosinase defense system plays a crucial role in deterring feeding, inhibiting growth, and causing acute toxicity against a wide range of generalist herbivores. In the present study, we first compared the survival of MEAM1 and MED exposed to sinigrin (a glucosinolate) and myrosinase (an enzyme that degrades glucosinolates); we found that survival of both species was high in response to sinigrin alone but was near zero in response to sinigrin + myrosinase. We then used electropenetrography (electrical penetration graphs, EPG) to assess the feeding behaviors of MEAM1 and MED whiteflies on cabbage. The EPG results revealed that the mean duration of each potential drop (pd, indicating an intracellular puncture) was substantially longer for MED than MEAM1 on cabbage, indicating that the exposure to the toxic hydrolysates of glucosinolate and myrosinase is greater for MED than for MEAM1. We therefore conclude that differences in penetrating behaviors may help explain the different effects of cabbage on MEAM1 and MED whitefly species. This article is protected by copyright. All rights reserved.

11.
Sci Total Environ ; 703: 134805, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31733499

RESUMO

Microplastics (MPs), polymer particles capable of adsorbing heavy metals from ambient environment, have been found in diverse human food resources. Through the consumption of MPs, heavy metals adsorbed on MPs might be transported into human body. This study aims to explore the behavior of heavy metal-contaminated MPs in human digestive system which is not previously researched. Firstly, a chromium (Cr) adsorption/desorption study was conducted with four commonly used nondegradable MPs [polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) and polystyrene (PS)] as well as one degradable MP (polylactic, PLA). Then, the whole digestive system in-vitro method (WDSM), a systematic model including mouth, gastric, small intestine, and large intestine digestive phases, was conducted on the Cr-loaded MPs. Additionally, the bioaccessibilities and hazard quotients (HQs) of Cr(VI) and Cr(III) were evaluated. Among five MPs, although PLA showed the weakest adsorption capacity for Cr, the Cr(VI) bioaccessibilities for PLA reached the highest values of 19.9%, 15.6% and 3.9% in gastric, small intestinal and large intestinal phases, respectively. The bioaccessibilities of Cr(VI) in gastric phase were significantly higher than those in other phases, while no Cr release from MPs was detected in the mouth phase. In gastric phase, the bioaccessibilities of Cr(VI) were significantly higher than those of Cr(III) in the gastric phase, and both of them approached to a similar level in intestinal phases. In the WDSM, the HQs of Cr(VI) and Cr(III) on MPs were lower than the critical level for both adults and children. Based on the measured bioaccessibilities, the maximum daily total Cr intake for different human groups (female children, male children, female adults and male adults) through MP consumption was estimated from 0.50 to 1.18 µg/day. In general, the five tested MPs were potential to serve as Cr vectors in the WDSM.

12.
Peptides ; : 170212, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31770577

RESUMO

In type 2 diabetes, lipotoxicity damages islet microvascular endothelial cells (IMECs), leading to pancreatic islet ß cell dysfunction directly or indirectly. Glucagon-like peptide-1 (GLP-1) and its analogs have beneficial roles in endothelial cells. However, the protective effects of GLP-1 agents on IMECs and their potential mechanism remained obscure. In this study, exposure of MS-1 (a cell line derived from mouse IMECs) to different concentrations of palmitic acid (PA) was used to establish an injury model. The cells exposed to PA (0.25 mmol/L) were treated with a GLP-1 analog liraglutide (3, 10, 30, and 100 nmol/L). Reactive oxygen species (ROS) generation, apoptosis-related protein level, and endothelin-1 production were detected. The protein levels of signaling molecules were analyzed and specific inhibitors or blockers were used to identify involvement of signaling pathways in the effects of liraglutide. Results showed that PA significantly increased ROS generation and the levels of pro-apoptotic protein Bax, and decreased the levels of anti-apoptotic protein Bcl-2 and the mRNA expression and secretion of endothelin-1. Meanwhile, PA downregulated the protein levels of GLP-1 receptor (GLP-1R), phosphorylated protein kinase A (PKA), guanosine 5'-triphosphate cyclohydrolase 1 (GTPCH1), and endothelial nitric oxide synthase (eNOS). Furthermore, liraglutide ameliorated all these effects of PA in a dose-dependent manner. Importantly, GLP-1R antagonist exendin (9-39), PKA inhibitor H89, GTPCH1 inhibitor 2,4-diamino-6-hydroxypyrimidine, or NOS inhibitor N-nitro-L-arginine-methyl ester abolished the liraglutide-mediated amelioration in PA-impaired MS-1 cells. In conclusion, liraglutide ameliorates the PA-induced oxidative stress, apoptosis, and endothelin-1 secretion dysfunction in mouse IMECs through GLP-1R/PKA and GTPCH1/eNOS signaling pathways.

13.
Biomolecules ; 9(12)2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31771142

RESUMO

In this work, a monoclonal antibody-based indirect competitive enzyme-linked immunosorbent assay (icELISA) was established to detect tylosin and tilmicosin in milk and water samples. A sensitive and specific monoclonal antibody was prepared by rational designed hapten, which was achieved by directly oxidizing the aldehyde group on the side chain of tylosin to the carboxyl group. Under the optimized conditions, the linear range of icELISA for tylosin and tilmicosin were 1.3 to 17.7 ng/mL and 2.0 to 47.4 ng/mL, with half-maximal inhibition concentration (IC50) values of 4.7 and 9.6 ng/mL, respectively. The cross-reactivity with other analogues of icELISA was less than 0.1%. The average recoveries of icELISA for tylosin and tilmicosin ranged from 76.4% to 109.5% in milk and water samples. Besides, the detection results of icELISA showed good correlations with HPLC-MS/MS. The proposed icELISA was satisfied for rapid and specific screening of tylosin and tilmicosin residues in milk and water samples.

14.
Int Orthop ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773186

RESUMO

PURPOSE: To define and analyze the learning curve of percutaneous endoscopic transforaminal decompression (PETD) for lumbar spinal stenosis (LSS). METHODS: From July 2015 to September 2016, 78 patients underwent PETD; one of whom was converted to open surgery, two were lost, and 75 were included in this study. Clinical results were assessed by using the Oswestry Disability Index (ODI) and visual analog scale (VAS). The learning curve was assessed by a logarithmic curve-fitting regression analysis. Of these 75 patients, 35 were defined as the "early" group, and 40 were defined as the "late" group for comparison. RESULTS: The mean follow-up was 25.37 ± 4.71 months. The median operative time gradually decreased from 95 (interquartile range, IQR, 85-110) minutes for the early group to 70 (IQR, 60-80) minutes for the late group (P < .000), and an asymptote was reached after approximately 35 cases. After surgery, the VAS for leg pain (LP) and ODI decreased significantly and remained constant during the follow-up. However, the VAS of low back pain (LBP) increased mildly. The total complication rate was 6.6%. ODI, VAS of LP and of LBP, and complication rate did not significantly differ between two groups. Early ambulation and short hospital stay after surgery were achieved. CONCLUSION: The learning curve of PETD for LSS was assessed and good clinical results were achieved. The surgeon's experience with this technique correlated with reduced operation time. Proper patient selection, familiarity with pathological anatomy, and manipulation under endoscopic view may shorten the learning curve and decrease complications.

15.
J Asian Nat Prod Res ; : 1-10, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31773971

RESUMO

Gramine can be intelligently and efficiently supplied with N, N-dimethylamino group and then reacted with the corresponding sulfonyl chlorides to synthesize N, N-dimethylarylsulfonamides. We herein designed and controlled synthesis of N, N-dimethylarylsulfonamide derivatives, and first reported the results of the nematicidal activity of 15 title compounds 3a-o against Meloidogyne incongnita in vitro, respectively. Among all of the title derivatives, compounds 3a, 3c, 3k, and 3o exhibited potent nematicidal activity with median lethal concentration (LC50) values ranging from 0.22 to 0.26 mg/L. Most noteworthy, N, N-dimethyl-4-methoxyphenylsulfonamide (3c) and N, N-dimethyl-8-quinolinesulfonamide (3o) showed the best promising and pronounced nematicidal activity, with LC50 values of 0.2381 and 0.2259 mg/L, respectively.

16.
Inorg Chem ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774665

RESUMO

The design and synthesis of polynuclear metal cluster-based coordination cages is of considerable interest due to their appealing structural characteristics and potential applications. Herein, we report a calix[4]resorcinarene-based [Co12] coordination cage, [Co12(TPC4R-I)2(1,3-BDC)10(µ3-OH)4(H2O)10(DMF)2]·7DMF·23H2O (1), assembled with 2 bowl-shaped calix[4]resorcinarenes (TPC4R-I), 10 angular 1,3-benzenedicarboxylates (1,3-BDC), and 12 Co(II) cations. Remarkably, it is shown to be a highly efficient recyclable heterogeneous catalyst for CO2 conversion due to its exposed Co(II) Lewis acid sites.

17.
Lipids Health Dis ; 18(1): 207, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775868

RESUMO

OBJECTIVE: Endoplasmic reticulum (ER) stress and mitochondrial function affected intramuscular fat accumulation. However, there is no clear evident on the effect of the regulation of ER stress and mitochondrial function by Angiotensin-converting enzyme 2 (ACE2) on the prevention of intramuscular fat metabolism. We investigated the effects of ACE2 on ER stress and mitochondrial function in skeletal muscle lipid metabolism. METHODS: The triglyceride (TG) content in skeletal muscle of ACE2 knockout mice and Ad-ACE2-treated db/db mice were detected by assay kits. Meanwhile, the expression of lipogenic genes (ACCα, SREBP-1c, LXRα, CPT-1α, PGC-1α and PPARα), ER stress and mitochondrial function related genes (GRP78, eIF2α, ATF4, BCL-2, and SDH6) were analyzed by RT-PCR. Lipid metabolism, ER stress and mitochondrial function related genes were analyzed by RT-PCR in ACE2-overexpression C2C12 cell. Moreover, the IKKß/NFκB/IRS-1 pathway was determined using lysate sample from skeletal muscle of ACE2 knockout mice. RESULTS: ACE2 deficiency in vivo is associated with increased lipid accumulation in skeletal muscle. The ACE2 knockout mice displayed an elevated level of ER stress and mitochondrial dysfunctions in skeletal muscle. In contrast, activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced TG content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice. Additionally, ACE2 improved skeletal muscle lipid metabolism and ER stress genes in the C2C12 cells. Mechanistically, endogenous ACE2 improved lipid metabolism through the IKKß/NFκB/IRS-1 pathway in skeletal muscle. CONCLUSIONS: ACE2 was first reported to play a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function. This study may provide a strategy for treating insulin resistance in skeletal muscle.

18.
Biotechnol Lett ; 41(12): 1439-1449, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31659576

RESUMO

OBJECTIVE: To enhance ergot alkaloid production of Claviceps purpurea Cp-1 strain by epigenetic modification approach. RESULTS: The chemical epigenetic modifiers were screened to promote ergot alkaloid production of the Cp-1 strain. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) was found to significantly enhance the alkaloid productivity of the strain. Particularly, the titers of total ergot alkaloids were gradually increased with the increase of SAHA concentration in the fermentation medium, and the highest production of ergot alkaloids could be achieved at the concentration of 500 µM SAHA. Specially, the titers of ergometrine and total ergot alkaloids were as high as 95.4 mg/L and 179.7 mg/L, respectively, which were twice of those of the control. Furthermore, the mRNA expression levels of the most functional genes in the ergot alkaloid synthesis (EAS) gene cluster were up-regulated under SAHA treatment. It was proposed that SAHA might increase histone acetylation in the EAS gene cluster region in the chromosome, which would loosen the chromosome structure, and subsequently up-regulate the mRNA expression levels of genes involved in the biosynthesis of ergot alkaloids, thereby resulting in the markedly increase in the production of ergot alkaloids. CONCLUSIONS: The ergot alkaloid production by the C. purpurea Cp-1 strain can be effectively increased by the application of histone deacetylase inhibitor. Our work provides a reference for using the chemical epigenetic modifiers to improve SM production in other fungi.

19.
J Exp Clin Cancer Res ; 38(1): 427, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31656203

RESUMO

BACKGROUND: A promising strategy to overcome the chemoresistance is the tumor blood vessel normalization, which restores the physiological perfusion and oxygenation of tumor vasculature. Thalidomide (Thal) has been shown to increase the anti-tumor effect of chemotherapy agents in solid tumors. However, it is not yet known whether the synergistic effect of Thal combined with other cytotoxic drugs is attributable to tumor vascular normalization. METHODS: We used two homograft mice models (4 T1 breast tumor model and CT26 colorectal tumor model) to investigate the effect of Thal on tumor growth, microvessel density, vascular physiology, vascular maturity and function, drug delivery and chemosensitivity. Immunofluorescence, immunohistochemistry and scanning electron microscopy were performed to determine the vessel changes. Protein array assay, qPCR and western blotting were used to detect the molecular mechanism by which Thal regulates tumor vascular. RESULTS: Here we report that Thal potently suppressed tumor growth, angiogenesis, hypoxia, and vascular permeability in animal models. Thal also induced a regular monolayer of endothelial cells in tumor vessels, inhibiting vascular instability, and normalized tumor vessels by increasing vascular maturity, pericyte coverage and endothelial junctions. The tumor vessel stabilization effect of Thal resulted in a decrease in tumor vessel tortuosity and leakage, and increased vessel thickness and tumor perfusion. Eventually, the delivery of cisplatin was highly enhanced through the normalized tumor vasculature, thus resulting in profound anti-tumor and anti-metastatic effects. Mechanistically, the effects of Thal on tumor vessels were caused in part by its capability to correct the imbalance between pro-angiogenic factors and anti-angiogenic factors. CONCLUSIONS: Our findings provide direct evidence that Thal remodels the abnormal tumor vessel system into a normalized vasculature. Our results may lay solid foundation for the development of Thal as a novel candidate agent to maximize the therapeutic efficacy of chemotherapeutic drugs for solid tumors.

20.
Nutr Clin Pract ; 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31606911

RESUMO

BACKGROUND: Many health benefits have been proposed for citrulline, but they lack evidence based on human research. This study was to evaluate whether an oral citrulline supplement affects body weight changes and laboratory values in patients with hepatobiliary and pancreatic surgery. METHODS: Patients who underwent hepatobiliary and pancreatic surgery during January to June 2015 were screened for analysis. Patients using citrulline during hospital stay and at discharge were classified as the citrulline group, whereas those without any records of citrulline were designated as the control group. The primary efficacy outcome was the change in body weight at discharge and at first outpatient visit. Other outcomes included change in laboratory values. RESULTS: A total of 138 patients were included in analysis. Citrulline group and control group did not differ with respect to baseline characteristics except for white blood cell count. Percent in change of body weight and body mass index from discharge to first outpatient visit was significantly different between the 2 groups, showing less weight loss in citrulline group than in controls (-0.8 ± 2.7% vs -2.5 ± 3.8%, P < 0.05). Especially in men, citrulline use significantly affected weight loss from the multivariate analysis (P < 0.05); percent change in weight in citrulline group was predicted to increase by 2.1 units. During hospital stay, significant differences between the 2 groups were found in changes of cholesterol and protein levels. CONCLUSION: Citrulline supplement reduced weight loss in surgical patients during recovery.

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