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1.
Food Chem ; 307: 125546, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639580

RESUMO

Zearalenone (ZEN) is one of the most widely distributed harmful mycotoxins produced by Fusarium species, especially deposited in corn oil. In this study, we systematically tracked the changes of ZEN in the refining of corn oil, and especially during neutralization process. An alkali neutralization process could remove certain amounts of ZEN that was much more than that of others refining steps. In a mimicking condition, ZEN contents decreased continuously and significantly with increasing neutralization temperature. However, when returned to neutral, recoverable ZEN decreased with increasing temperature, which confirmed more degradation of ZEN at high temperature. HPLC-Q/TOF MS and NMR evidence showed that non-reversible hydrolyzate followed decarboxylation was observed in a high-temperature alkali neutralization condition. The results may serve as the scientific basis for the elimination of zearalenone in refined vegetable oils, and provide clues to understanding the oil-safety aspects of elimination of zearalenone.

2.
Genomics ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669700

RESUMO

Temporal lobe epilepsy (TLE) is the most prevalent and often devastating form of epilepsy. The molecular mechanism underlying the development of TLE remains largely unclear, which hinders the discovery of effective antiepileptogenic drugs. Here we adopted a systems-level approach integrating transcriptomic profiles of three epileptogenesis stages to identify key regulators underlying epilepsy progression. Associating stage-specific gene meta-signatures with brain cell-specialized modules revealed positive regulation of glial migration and adhesion, cytokine production, and neuron death, and downregulation of synaptic transmission and ion transport during epileptogenesis. We identified 265 key regulators driving these processes and 72 of them were demonstrated associating with seizure frequency and/or hippocampal sclerosis in human TLE. Importantly, the upregulation of FAM107A, LAMB2, LTBP1 and TGIF1, which are mainly involved in nervous system development, were found contributing to both conditions. Our findings present the evolution landscape of epileptogenesis and provide candidate regulators that may serve as potential antiepileptogenic targets.

3.
J Appl Microbiol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31715079

RESUMO

AIMS: The aim of this work was to transform ginsenoside extract into the pharmacologically active minor ginsenoside 20(S)-Rg3 by three thermostable glycosidases. METHODS AND RESULTS: The GH1 thermostable beta-glucosidase Tpebgl1 from Thermotoga petrophlia was found to have the ability on ginsenoside Rb1 and Rb2 conversion. Its properties concerning ginsenoside conversion was systematically investigated. It had high specific activity for pNPG (162·20 U mg-1 ) and pNPArp (22·14 U mg-1 ). The Km and Vmax of Tpebgl1 for pNPG were 0·28 mmol l-1 and 470·2 U mg-1 and for pNPArp were 17·30 mmol l-1 and 74·28 U mg-1 . Therefore, it could successfully convert ginsenoside Rb1 and Rb2 into ginsenoside Rd, which was proved then. Tpebgl1 also had good tolerance to glucose and some organic solvents. These made Tpebgl1 a good catalyst candidate for industrial application. Finally, it was applied to transform ginsenoside extract into the pharmacologically active minor ginsenoside 20(S)-Rg3, combined with thermostable ginsenoside Rc converting α-1,6-L-arabinofranosidase Tt-Afs and ginsenoside Rd converting ß-glucosidase Tpebgl3. 10 g l-1 of ginsenoside extract was transformed into 3·93 g l-1 of Rg3 in pH 5·0 at 90°C for total 3 h, with a corresponding molar conversion of 98·19%. CONCLUSION: The thermostable enzyme Tpebgl1 was found to be a ginsenoside Rb1 and Rb2 converting enzyme and successfully applied in ginsenoside 20(S)-Rg3 preparation from ginsenoside extract, through a three-step transformation combined with thermostable ginsenoside Rc converting α-1,6-L-arabinofranosidase Tt-Afs and ginsenoside Rb1 converting ß-glucosidase Tpebgl3. SIGNIFICANCE AND IMPACT OF STUDY: Converting all the major ginsenosides in protopanaxadiol type ginsenoside extract would greatly reduce the cost of ginsenoside Rg3 preparation. Enzymes from thermophilic bacteria can meet the requirement of higher reaction temperatures in industrial reactions for substrate solubility promotion and bacterial contamination prevention.

4.
J Ethnopharmacol ; : 112365, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678414

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. (Ginkgoaceae) is a traditional Chinese medicine known to treating stroke and other cardio-cerebrovascular diseases for thousands of years in China. Ginkgo diterpene lactones (GDL) attracted much attention because of their neuroprotective properties. AIM OF THE STUDY: To uncover the effects of GDL, which consist of ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), on ischemic stroke, as well as the underlying molecular mechanisms. MATERIALS AND METHODS: We used middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) models mimicking the process of ischemia/reperfusion in vivo and in vitro, respectively. Anticoagulant effects of GDL were investigated on platelet activating factor (PAF), arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation both in vivo and in vitro. We also evaluated the effects of GDL on lipopolysaccharide (LPS)-induced inflammatory response in primary cultured rats' astrocytes. Infarct size, neurological deficit score, and brain edema were measured at 72 h after MCAO. Immunohistochemistry was utilized to analyze neurons necrosis and astrocytes activation. Expression of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected using enzyme-linked immunosorbent assay (ELISA) and real time PCR. The levels of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) were assessed by real time PCR or Western blot. RESULTS: Compared with MCAO/R rats, GDL significantly reduced infarct size and brain edema, improved neurological deficit score. Meanwhile, GDL suppressed platelet aggregation, astrocytes activation, pro-inflammatory cytokines releasing, TLR4 mRNA expression and transfer of NF-κB from cytoplasm to nucleus. Furthermore, GDL alleviated OGD/R injury and LPS-induced inflammatory response in primary astrocytes, characterized by promoting cell viability, decreasing lactate dehydrogenase (LDH) activity, and inhibiting IL-1ß and TNF-α releasing. CONCLUSIONS: In summary, GDL attenuate cerebral ischemic injury, inhibit platelet aggregation and astrocytes activation. The anti-inflammatory activity might be associated with the downregulation of TLR4/NF-κB signal pathway. Our present findings provide an innovative insight into the novel treatment of GDL in ischemic stroke therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31713705

RESUMO

This study investigated the effects of enzymatic hydrolysate of cottonseed protein (EHCP) supplementation on the growth performance and intestinal health of nursery pigs in Thailand. A total of 180 newly weaned piglets were randomly allocated to 3 groups with 6 replicates in each group and 10 piglets per replicate. Nursery pigs were fed three diets containing 0, 1%, and 1.5% EHCP for 28-63 days of age. The results indicated that 1% EHCP supplementation increased average daily feed intake (ADFI) and average daily gain (ADG) and decreased feed conversion rate (FCR) in the numerical, suggesting that appropriate EHCP supplementation could numerically improve growth performance of nursery pigs in Thailand. Moreover, 1% EHCP supplementation significantly decreased intestinal crypt depth and diarrhea incidence and increased intestinal villus height to crypt depth ratio and fecal consistency, suggesting that optimum EHCP supplementation could improve intestinal morphology and decreased diarrhea incidence of nursery pigs in Thailand. Furthermore, 1% EHCP supplementation significantly improved intestinal glutathione (GSH) level and superoxide dismutase (SOD) activity and indicated that optimal EHCP supplementation could improve intestinal antioxidant capacity of nursery pigs in Thailand. Optimum EHCP supplementation numerically increased growth, significantly decreased diarrhea incidence, significantly improved intestinal morphology and antioxidant capacity of nursery pig in Thailand.

6.
Nat Commun ; 10(1): 5091, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704924

RESUMO

Activated macrophages switch from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect, presenting a potential therapeutic target in inflammatory disease. The endogenous metabolite itaconate has been reported to regulate macrophage function, but its precise mechanism is not clear. Here, we show that 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) directly alkylates cysteine residue 22 on the glycolytic enzyme GAPDH and decreases its enzyme activity. Glycolytic flux analysis by U13C glucose tracing provides evidence that 4-OI blocks glycolytic flux at GAPDH. 4-OI thereby downregulates aerobic glycolysis in activated macrophages, which is required for its anti-inflammatory effects. The anti-inflammatory effects of 4-OI are replicated by heptelidic acid, 2-DG and reversed by increasing wild-type (but not C22A mutant) GAPDH expression. 4-OI protects against lipopolysaccharide-induced lethality in vivo and inhibits cytokine release. These findings show that 4-OI has anti-inflammatory effects by targeting GAPDH to decrease aerobic glycolysis in macrophages.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31725126

RESUMO

STUDY DESIGN: To evaluate the effect of p38 pathway on spinal cord injury (SCI), a rat model of SCI was performed. OBJECTIVE: We determined the effect of p38 on SCI and SCI related inflammation, apoptosis and autophagy. SUMMARY OF BACKGROUND DATA: SCI is a severe clinical problem worldwide. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. p38, a class of mitogen-activated protein kinases (MAPKs), its effect on SCI and SCI related inflammation, apoptosis and autophagy have not been studied very well. METHODS: The rats were randomly divided into the following 4 groups: the sham-operated (sham) group, the SCI group, the SCI + vehicle group, and the SCI + SB203580 (10 mg/kg) group. The p38 inhibitor SB203580 was administered by oral (10 mg/kg/d) gavage once per day for 14 d. Neurological recovery was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotion rating scale. Apoptosis, autophagy and inflammation related proteins were measured by ELISA kits or western blotting. RESULTS: Our results showed that p38 was upregulated after SCI from day 3, which was paralleled with the levels of its proteins ATF-2, suggesting an increase in p38 activity. Our results showed administration of SB203580 attenuated histopathology and promoted locomotion recovery in rats after SCI. SB203580 administration significantly inhibited inflammatory cytokines levels as well as the inflammation signaling pathway. SB203580 administration also modulated the apoptosis and autophagy signaling pathway. CONCLUSION: Our findings suggest that p38 inhibitor SB203580 treatment alleviates secondary SCI by inhibiting inflammation and apoptosis, thereby promoting neurological and locomoter functional recovery, thus suggest the important role of p38 in neuronal protection after SCI. LEVEL OF EVIDENCE: N/A.

8.
BMJ Open ; 9(11): e034592, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690612

RESUMO

INTRODUCTION: Current strategies for the prevention of acute exacerbations in chronic obstructive pulmonary disease (COPD) are primarily based on clinical measurements but fail to target the pathophysiological mechanisms, namely endotypes, of the disease. Studies identifying endotypes underlying exacerbation susceptibility and discovering specific biomarkers may lead to the development of targeted therapeutics but are lacking. This study aims to assess a broad spectrum of biomarkers at multiple biological levels (genetics, airway inflammation and respiratory microbiome) for their ability in predicting acute exacerbations of COPD, thus enables high-resolution disease endotyping and may lead to precision treatment of the disease. METHODS AND ANALYSIS: In this prospective cohort study, participants with stable COPD (n=600) will be recruited and assessed for demographics, symptom scores, spirometry, medication use and comorbidities at baseline. Blood will be obtained for genotyping variants in a panel of nine genes. Induced sputum will be collected for the profile of microbiota using 16S rRNA gene sequencing, quantification of bacterial load, inflammatory mediators assay and sputum cytometry. Participants will be followed up for their exacerbations till 12 months and reassessed for the clinical measurements as baseline. The primary outcomes are total number of exacerbations, severe exacerbations, moderate exacerbations and time to first exacerbation. The secondary outcomes are changes in lung function and symptom scores. The effect of biomarkers representing genetic variants, airway inflammation and respiratory microbiome on predicting the frequent exacerbator phenotype and exacerbation frequency will be analysed with multivariable modelling, and time to first exacerbation with a Cox regression model. ETHICS AND DISSEMINATION: The study has been approved by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University (No. 2018-298). The results of the study will be published on peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR1800019063.

9.
Cell Death Dis ; 10(11): 831, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685803

RESUMO

Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.

10.
Math Biosci Eng ; 16(6): 6209-6230, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31698558

RESUMO

Lagged settlement is a typical accident induced by shield construction in sandy cobble strata. This paper analyzed the process and mechanism of lagged settlement, results show that all phases are in accord with the characteristics of ellipsoid theory of particle flows. Based on this theory, a method for calculating coefficient of lateral earth pressure and loosened earth pressure is proposed in this research. For the coefficient of lateral earth pressure, the boundary of loosened ellipsoid is divided into two parts, the arch zone and the excavation zone, and the lateral pressure coefficients are derived respectively according to the stress state. For loosened earth pressure on tunnel, the Terzaghi earth pressure theory and Protodyakonov earth pressure theory are adapted in different conditions according to the state of loosened cobble soil. Theories developed in this study can be applied on determination of shield excavation parameters, as well as calculation of loosened earth pressure and control of tunnel support.

11.
Fish Physiol Biochem ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701282

RESUMO

An 8-week feeding trial was conducted to investigate the effects of enzyme-treated soy protein (ETSP) supplementation in low protein diets on growth performance as well as flesh sensory quality and healthiness in on-growing grass carp. A total of 540 on-growing grass carp (initial average weight 325.72 ± 0.60 g) were fed six diets, which included a normal protein diet (28% crude protein) and five low protein diets (26% crude protein) supplemented with graded levels of ETSP (0.0, 0.8, 1.2, 1.6, and 2.0%). The results showed that reducing dietary protein by 2% decreased percentage weight gain, feed intake, and flesh flavor (aspartic acid, glutamic acid, histidine, and 5'-inosinic acid contents) and healthiness-related indices (linolenic acid (LA) and docosahexaenoic acid (DHA) contents and polyunsaturated fatty acids to saturated fatty acids ratio). Under the condition of reducing dietary protein by 2%, 0.8-1.2% ETSP supplementation restored above parameters to levels equal or superior to those in 28% crude protein diet group. Although reducing dietary protein by 2% did not deteriorate flesh tenderness and juiciness, 0.8-1.2% ETSP supplementation in low protein diets also improved the two indices compared with 28% crude protein diet. Moreover, ETSP-improved flesh quality was partly related to increased muscle antioxidant enzymes activities and their mRNA levels. In addition, ESTP-enhanced antioxidant enzyme mRNA levels were partly associated with the upregulation of NF-E2-related factor 2 (Nrf2) and target of rapamycin (TOR) signaling. Collectively, 0.8-1.2% ETSP supplementation in low protein diets improved growth performance as well as flesh sensory quality and healthiness in on-growing grass carp.

12.
J Dairy Sci ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704007

RESUMO

Specific DNA mutations underlying several genetic defects associated with embryo loss or reduced calf survivability have been identified in dairy cattle, and a convenient and cost-effective platform is required for their routine screening. We developed Kompetitive allele-specific PCR (KASP) assays for discrimination of the wild-type alleles from the associated defective alleles at each of 8 common genetic defects in Holstein cattle, involving 5 SNP [HH1, HH3, HH4, bovine leukocyte adhesion deficiency (BLAD), and complex vertebral malformation (CVM)] and 3 insertion or deletion mutations [HH5, haplotype for cholesterol deficiency (HCD), and brachyspina (BS)]. A total of 390 cows from a Chinese Holstein herd were genotyped and the carriers identified at 7 of these 8 loci (except HH4), with the highest carrier frequencies found for CVM (10.5%) and HH1 (10.0%), followed by HH3 (2.6%), BS (2.1%), HCD (1.3%), HH5 (0.8%), and BLAD (0.5%). Surprisingly, 102 cows (26.2%) carried at least 1 of the 7 defective alleles. Our results demonstrate that these KASP assays are simple, rapid, and reliable for the detection of multiple genetic defects. The high carrier frequency of these genetic defects indicates an urgent need for routine molecular testing to eliminate the deleterious alleles from Chinese Holstein cattle.

13.
Colloids Surf B Biointerfaces ; 185: 110618, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31706145

RESUMO

Alkaline phosphatase (ALP) is an important biomarker for diagnosis, and the abnormal level of serum ALP is closely related to a variety of diseases. In present work, a ratiometric fluorescence probe based on hybrid nanoparticles CDs@YVO4: Dy3+ nanoparticle is introduced for alkaline phosphatase (ALP) activity determination. The CDs@YVO4: Dy3+ probe is constructed by the carbon dots (CDs) and YVO4: Dy3+ through a simple mixing method, in which the blue emission of CDs at 405 nm acts as the calibrated signal, the green emission of YVO4: Dy3+ at 574 nm decreased with the increasing targets ALP, and used as the output signal. In addition, the Cu2+ and pyrophosphate (PPi) were also employed in this strategy to utilize the excellent fluorescnece quenching efficiency of Cu2+ to the Dy3+ ions emission of CDs@YVO4: Dy3+, as well as the strong affinity of PPi for Cu2+. In the presence of analyts ALP, ALP catalyzes the hydrolysis of PPi, causing the release of Cu2+, resulting in the Dy3+ ions emission quenched, while the CDs emission at 405 nm retained unchanged, based on this, we designed the off-on-off ratiometric fluorescence platform for ALP sensing. The experiment result shows that the ratio of F574/F405 is linear to the concentration of ALP in arange of 0.05∼3000 U/L with a detection limit of 0.04 U/L, which is comparable or better than those reported fluorescence probe, especially the calibrated signal introduction of CDs can eliminate the background interference, improve the accuracy of proposed probe greatly. Furthermore, the discrimination of ALP enzyme inhibitor with the IC50 of 26 µM, and ALP concentration in real human serum sample has also demonstrated the applicability of CDs@YVO4: Dy3+ fluorescence sensor well.

14.
Int J Biol Macromol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759003

RESUMO

A water-soluble heteropolysaccharide was isolated and purified from Enteromorpha prolifera by DEAE-52 and Bio-Gel P-2 column chromatography. Fourier transform infrared spectroscopy (FTIR), high performance liquid chromatography (HPLC), multi-angle laser light scattering (MALLS), and nuclear magnetic resonance (NMR) spectroscopy were used to characterize the structure of E. prolifera polysaccharide degradation (EPP-1). Its anti-oxidative activity was determined in Caenorhabditis elegans via modulation of microRNAs. The average molecular weight of EPP-1 was 4.28 kDa. It contained six types of linkage units as →2)-ß-D-GlcpA-(1→, →3,6)-ß-D-Manp-(1→, →4)-α-D-Glcp-(1→, →6)-ß-D-Galp-(1→, ß-L-Rhap-(1→, and →4)-ß-D-GalpA-(1→. The mean lifespan, ultraviolet-induced oxidative stress, and thermotolerance in C. elegans were improved after treatment of EPP-1. Moreover, EPP-1 significantly increased the total superoxide dismutase levels and decreased the malondialdehyde levels in C. elegans. Intracellular reactive oxygen species accumulation and DNA damage were ameliorated by up-regulation of SKN-1 and DAF-16 expression through miR-48 and miR-51 miR-186 down-regulation. In vivo studies demonstrated that EPP-1 might be applied in functional foods as the antioxidative and anti-ageing ingredient.

15.
BMC Surg ; 19(1): 161, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690303

RESUMO

BACKGROUND: Wound-related complications are an inevitable issue faced by spinal surgeons. Negative pressure drainage remains the most commonly used method to prevent postoperative hematoma and related complications. This prospective, randomized, controlled study was conducted to evaluate the efficacy of compression therapy following posterior lumbar interbody fusion, with emphasis on pain, anemia, and inflammation. METHODS: Sixty consecutive patients who have undergone posterior lumbar interbody fusion in the age range 43-78 years, with an average age of 59 years, were selected and randomly assigned into two groups. Factors, such as drainage volume, visual analog scale (VAS) pain score for back pain, white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels assessed on the 1st, 3rd, and 10th days postoperatively, were compared between the two groups. RESULTS: The average follow-up was 6 months, ranging from 3 to 11 months. Drainage volume, VAS score, and CRP levels on the 10th day after the surgery were found to be significantly lower in the treatment group than in the control group. RBC count and Hb levels on the 3rd and 10th postoperative days were observed to be significantly higher in the treatment group than in the control group (P < 0.05). During discharge, the wounds of the patients of the both groups had healed and neither showed any symptoms of infection, hematoma, or necrosis. CONCLUSION: Compression therapy relieves pain, alleviates anemia, and the inflammatory response following posterior lumbar interbody fusion. TRIAL REGISTRATION: ChiCTR1800015825 on chictr.org.cn, April 23, 2018, the trial registry is Chinese Clinical Trial Registry.

16.
J Am Chem Soc ; 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31707779

RESUMO

Rubriflordilactone B (1) is a schinortriterpenoid isolated by Sun and colleagues, which possesses a tetrasubstituted benzene moiety and eight stereocenters. The previous synthesis of 1 by Li and co-workers uncovered the existence of its naturally occurring stereoisomer "pseudorubriflordilactone B". Here we report a collaborative study by the two groups that elucidates the structure of pseudorubriflordilactone B to be 16,17-bis-epi-rubriflordilactone B (26). Chemical synthesis served as an important tool in the structure determination. Taking advantage of a modular synthetic route, we systematically "mutated" the configurations of C-23, C-22, C-20, and C-16/C-17 located at the right-hand domain of 1, and thus prepared its fifteen stereoisomers for spectrum comparison. The 1H NMR spectra of synthetic 26 in deuterated chloroform and pyridine were identical to those of authentic pseudorubriflordilactone B, respectively. This synthetic sample displayed anti-HIV activity (EC50 = 0.288 µM) in vitro.

17.
Sci China Life Sci ; 62(11): 1420-1458, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31686320

RESUMO

Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31752069

RESUMO

In this study, the acidic lipase from Aspergillus niger (ANL) was homologously expressed in A. niger. The expression of ANL was significantly improved by the expression of the native ANL with the introns, the addition of the kozak sequence and the optimization of the signal sequences. When the cDNA sequence of ANL fused with the glaA signal was expressed under the gpdA promoter in A. niger, no lipase activity could be detected. Then we tried to improve the expression by using the full length ANL gene containing three introns, and the lipase activity in the supernatant reached 75.80 U/mL, which probably contributed by a more stable mRNA structure. The expression was further improved to 100.60 U/mL by introducing a kozak sequence around the start codon due to a higher translation efficiency. Finally, the effects of three signal sequences including the cbhI signal, the ANL signal and the glaA signal on the lipase expression were evaluated. The transformant with the cbhI signal showed the highest lipase activity (314.67 U/mL), which was 1.90 -fold and 3.13 -fold higher than those with ANL signal and glaA signal, respectively. The acidic lipase was characterized. Highest activity was detected at pH 3.0 and a temperature of 45°C. These results provided promising strategies for the production of the acidic lipase from A. niger.

19.
Cancer Lett ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31765737

RESUMO

Most cancers are caused by somatic mutations. Some common mutations in the same cancer type can form a "signature" to specifically predict the prognosis or to distinguish it from other cancers. In this study, 710 somatic cell mutations were identified in 142 cases, including digestive, lung and urogenital cancers, and the digestive cancers were further divided into liver, stomach, intestinal, esophageal and cardia cancer. The above mutations were located in 166 genes. In addition, a group of high-frequency mutation genes with specific characteristics were screened to form predictive signatures for each cancer. Verification using TCGA suggested that the signatures could predict the stages, progression-free survival, and overall survival of digestive, intestinal, and liver cancers (P<0.05). The validation cases further confirmed the predictive role of digestive and liver cancers signatures in diagnosis and prognosis. Overall, this study established predictive signatures for different cancer systems and their subtypes. These findings enable a better understanding in cancer genome, and contribute to the personalized diagnosis and treatment.

20.
J Evol Biol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747079

RESUMO

Fig-pollinating wasps (Agaonidae) only reproduce within fig-tree inflorescences (figs). Agaonid offspring sex ratios are usually female-biased and often concur with local mate competition theory (LMC). LMC predicts less female-bias when several foundresses reproduce in a fig due to reduced relatedness among intra-sexually competing male offspring. Clutch size, the offspring produced by each foundress, is a strong predictor of agaonid sex ratios and correlates negatively with foundress number. However, clutch size variation can result from several processes including egg-load (eggs within a foundress), competition among foundresses and oviposition site limitation, each of which can be used as a sex allocation cue. We introduced into individual Ficus racemosa figs single Ceratosolen fusciceps foundresses and allowed each to oviposit from zero to five hours thus variably reducing their eggs-loads, and then introduced each wasp individually into a second fig. Offspring sex ratio (proportion males) in second figs correlated negatively with clutch size, with males produced even in very small clutches. C. fusciceps lay mainly male eggs first then female eggs. Our results demonstrate that foundresses do not generally lay or attempt to lay a 'fixed' number of males, but do 're-set to zero' their sex allocation strategy on entering a second fig. With decreasing clutch size gall failure increased, probably due to reduced pollen. We conclude that C. fusciceps foundresses can use their own egg-loads as a cue to facultatively adjust their offspring sex ratios, and that foundresses may also produce more 'insurance' males when they can predict increasing rates of offspring mortality.

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