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1.
Food Chem Toxicol ; : 112240, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33932521

RESUMO

Wheat Embryo Globulin (WEG) is a high-quality plant-derived protein with anti-inflammatory, antioxidant, and immunity enhancement effects. WEG was prepared and characterized using free amino acid analysis, circular dichroism (CD), and scanning electron microscope (SEM). The liver protection effect of WEG on mice after acute alcohol stimulation was also investigated. Male KM mice were randomly divided into four groups (n=10). Animals were orally administrated with WEG (60 mg/kg), silymarin (50 mg /kg), and the same volume of saline solution daily for 30 days, before administering an alcohol-intragastric injection. Results displayed that the liver index, the levels of serum total cholesterol (TC), serum triglyceride (TG), liver malondialdehyde (MDA) and the mRNA expression of CYP2E1were significantly decreased in WEG-treated mice compared with the model group. Meanwhile, the levels of serum high-density lipoprotein-cholesterol (HDL-C), hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and the mRNA expression of ADH2 and ALDH2 were remarkably increased. Effect of WEG on histopathology of liver tissue confirmed its protective function. Meanwhile, GSH level of ileal was significantly increased, MDA was remarkably decreased in WEG-treated mice, which also indicated that WEG possessed a positive effect on intestinal micro ecological environment health to some extent. In conclusion, WEG is a promising agent for the prevention of acute alcoholic liver injury.

2.
J Pharm Pharmacol ; 73(4): 545-552, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33793827

RESUMO

OBJECTIVE: This study assessed whether physcion-8-O-beta-D-monoglucoside (PG) sensitises paclitaxel (PTX)-resistant ovarian cancer cells and explored the underlying mechanism. METHODS: Ovarian cancer SK-OV-3 cells were used to establish PTX-resistant SK-OV-3 (SK-OV-3/PTX) cells. The Cell Counting Kit-8 assay and crystal violet staining were used to determine cell viability. P-glycoprotein (P-gp) and nuclear factor (NF)-κB expression and cell distributions were detected using immunofluorescence. Cell apoptosis and protein expression changes were detected using flow cytometry and western blotting, respectively. Effect of PG in vivo was evaluated using a xenograft tumour model. P-gp expression in tumour tissues was detected using immunohistochemical staining. KEY FINDINGS: PG (1-10 µm) did not significantly affect SK-OV-3/PTX cell proliferation but significantly downregulated P-gp expression. PG pretreatment (1-10 µm) enhanced PTX cytotoxicity. PG treatment decreased the quantity of phosphorylated-NF-κB p65 in SK-OV-3/PTX cell total proteins and upregulated IKBα expression. Simultaneously, it decreased NF-κB p65 levels in nuclear proteins. PG (1-10 µm) inhibited NF-κB p65 entry into the nucleus. PTX plus PG significantly inhibited SK-OV-3/PTX xenograft tumour growth. PG (1-10 µm) reduced P-gp expression in transplanted tumour tissue. CONCLUSIONS: PG can enhance the sensitivity of PTX-resistant ovarian cancer cells SK-OV-3/PTX to PTX, and this effect is related to inhibiting NF-κB from entering the nucleus and down-regulating the expression of P-gp protein.

3.
Front Immunol ; 12: 657803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815420

RESUMO

The role of IL-33/ST2 signaling in cardiac allograft vasculopathy (CAV) is not fully addressed. Here, we investigated the role of IL-33/ST2 signaling in allograft or recipient in CAV respectively using MHC-mismatch murine chronic cardiac allograft rejection model. We found that recipients ST2 deficiency significantly exacerbated allograft vascular occlusion and fibrosis, accompanied by increased F4/80+ macrophages and CD3+ T cells infiltration in allografts. In contrast, allografts ST2 deficiency resulted in decreased infiltration of F4/80+ macrophages, CD3+ T cells and CD20+ B cells and thus alleviated vascular occlusion and fibrosis of allografts. These findings indicated that allografts or recipients ST2 deficiency oppositely affected cardiac allograft vasculopathy/fibrosis via differentially altering immune cells infiltration, which suggest that interrupting IL-33/ST2 signaling locally or systematically after heart transplantation leads different outcome.

4.
J Anim Ecol ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844855

RESUMO

Food web stability and resilience are at the heart of understanding the structure and functioning of ecosystems. Previous studies show that models of empirical food webs are substantially more stable than random ones, due to a few strong interactions embedded in a majority of weak interactions. Analyses of trophic interaction loops show that in empirical food webs the patterns in the interaction strengths prevent the occurrence of destabilizing heavy loops and thereby enhances resilience. Yet, it is still unexplored which biological mechanisms cause these patterns that enhance food web resilience. We quantified food web resilience using the real part of the maximum eigenvalue of the Jacobian matrix of the food web from a seagrass bed in the Yellow River Delta (YRD) wetland, that could be parameterized by the empirical data of the food web. We found that the empirically based Jacobian matrix of the YRD food web indicated a much higher resilience than random matrices with the same element values but arranged in random ways. Investigating the trophic interaction loops revealed that the high resilience was due to a negative correlation between the negative and positive interaction strengths (per capita top-down and bottom-up effects, respectively) within positive feedback loops with three species. The negative correlation showed that when the negative interaction strengths were strong the positive was weak, and vice versa. Our invented reformulation of loop weight in terms of biomasses and specific production rates showed that energetic properties of the trophic groups in the loop and mass-balance constraints, e.g. the food uptake has to balance all losses, created the negative correlation between the interaction strengths. This result could be generalized using a dynamic intraguild predation model, which delivered the same pattern for a wide range of model parameters. Our results shed light on how energetic constraints at the trophic group and food web level create a pattern in interaction strengths within trophic interaction loops that enhances food web resilience.

5.
Food Chem Toxicol ; 152: 112235, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33894295

RESUMO

We explored the effect of carboxymethylated wheat bran dietary fibers (DFs) on mice with type 2 diabetes (T2D) (induced by HFD combined with STZ) and their possible hypoglycemic mechanism. After feeding the diabetic mice with modified DFs for four weeks, the DFs had lipid lowering and anti-hyperglycemic effect, via increasing the levels of insulin, GLP-1, PYY, and SCFAs in diabetic mice, and improving the histopathology of liver and pancreas. qRT-PCR results showed that the intake of DFs up-regulated the expression levels of G6Pase and Prkce, and down regulated the expression levels of Glut2 and InsR in the liver of diabetic mice. It is suggested that DFs may play a role by inhibiting 1,2-DAG-PKCε pathway, improving insulin receptor activity and insulin signal transduction. 16 S rDNA high-throughput sequencing results showed that the DFs significantly improved the relative abundance of Akkermansia muciniphila, increased the diversity of gut microbiota and reduced the ratio of Firmicutes to Bacteroidetes, thus promoting the hypoglycemic and hypolipidemic effect on diabetic mice. Our study can foster the further understanding of the gut modulatory biomarkers and related metabolites, and may extend the basis for DFs as a potential dietary intervention to prevent or treat the T2D.

6.
Ecotoxicol Environ Saf ; 217: 112240, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33901783

RESUMO

Quorum sensing (QS) plays an important role in the intensive communication between plants and microbes in the rhizosphere during the phytoremediation. This study explored the influence of the root exudates of hyperaccumulator Sedum alfredii on Pseudomonas aeruginosa based on QS. The effects of the components of root exudates, genes expression and transcription regulation of QS system (especially the las system) in Pseudomonas aeruginosa wild-type strain (WT) and rhl system mutant strain (ΔrhlI) were systematically analyzed and discussed. The WT and ΔrhlI exposed to gradient root exudates (0×, 1×, 2×, 5× and 10×) showed a concentration-corrective inhibition on protease production, with the inhibition rates of 51.4-74.5% and 31.2-50.0%, respectively. Among the components of the root exudates of Sedum alfredii, only thymol had an inhibition effects to the root exudates on the activity of protease and elastase. The inhibition rates of 50 µmol/L thymol on protease and elastase in WT were 44.7% and 24.3%, respectively, which was consistent with the variation in ΔrhlI. The gene expression of lasB declined 36.0% under the 1× root exudate treatment and 73.0% under the 50 µmol/L thymol treatment. Meanwhile, there was no significant impact on N-3-oxo-dodecanoyl-L-homoserine lactone signal production and the gene expression of lasI and lasR. Therefore, thymol from Sedum alfredii root exudates could inhibit the formation of protease and elastase in Pseudomonas aeruginosa by suppressing the expression of lasB, without any significant influence on the main las system as a potential natural QS inhibitor.

7.
Zhen Ci Yan Jiu ; 46(2): 87-94, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33788427

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20), "Shuigou" (GV26), etc. on the expressions of vascular endothelial growth factor (VEGF), collagen fibrillary acidic protein (GFAP), neuronal nucleus antigen(NeuN), ß-catenin and Axin2 protein and mRNA in rats with cerebral ischemia (CI), so as to explore its mechanism underlying improvement of ischemic stroke. METHODS: A total of 108 male SD rats were randomly divided into control, model and EA groups, which were further divided into 7 d, 14 d and 21 d subgroups, with 12 rats in each group. The CI model was established by occlusion of the middle cerebral artery. EA (2 Hz/100 Hz, 2-4 V) was applied to GV20, GV26, bilateral "Sanyinjiao" (SP6) and bilateral "Neiguan" (PC6) for 30 min, once daily (except Sundays) for 21 days at most. The neurological deficit score was evaluated according to Longa's methods. The cerebral infarction state was assessed by using a magnetic resonance T2 imaging system. The expression levels of neurovascular markers as VEGF,GFAP and NeuN, and ß-catenin and Axin2 protein and mRNA in the ischemic brain tissue were detected by using immunohistochemistry and quantitative real-time PCR, respectively. RESULTS: After modeling, the neurological deficit score and cerebral infarction size were significantly increased (P<0.01), and the expression of NeuN and Axin2 proteins and mRNAs were significantly and gradually decreased with time (day 7, 14 and 21) (P<0.01), whereas the expression levels of VEGF, GFAP, ß-catenin proteins and mRNAs were significantly increased on day 7, 14 and 21 in the model group relevant to the control group (P<0.01). Compared with the model group, the neurological deficit score, cerebral infarction size and the expressions of Axin2 protein and mRNA were significantly decreased on day 7, 14 and 21 (P<0.01), whereas the expression levels of VEGF, GFAP and NeuN and ß-catenin proteins and mRNAs were considerably up-regulated in the EA group on day 7, 14 and 21 (P<0.01). CONCLUSION: EA can protect the neurovascular units from injury, reduce the volume of cerebral infarction and improve the symptoms of neurological deficit in cerebral ischemic rats, which may be related to its effects in up-regulating ß-catenin expression and in down-regulating Axin2 expression to further activate classical Wnt/ ß-catenin signal pathway.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/terapia , Infarto Cerebral , Masculino , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/genética , beta Catenina/genética
8.
Emerg Microbes Infect ; 10(1): 461-471, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33660592

RESUMO

Ehrlichia chaffeensis causes human monocytic ehrlichiosis (HME), which is one of the most prevalent, life-threatening emerging infectious zoonoses. The life cycle of E. chaffeensis includes ticks and mammals, in which E. chaffeensis proteins are expressed differentially contributing to bacterial survival and infection. Among the E. chaffeensis P28-OMP outer membrane proteins, OMP-1B and P28 are predominantly expressed in tick cells and mammalian macrophages, respectively. The mechanisms regulating this differential expression have not been comprehensively studied. Here, we demonstrate that the transcriptional regulators EcxR and Tr1 regulate the differential expression of omp-1B and p28 in E. chaffeensis. Recombinant E. chaffeensis Tr1 bound to the promoters of omp-1B and p28, and transactivated omp-1B and p28 promoter-EGFP fusion constructs in Escherichia coli. The consensus sequence of Tr1 binding motifs was AC/TTATA as determined with DNase I footprint assay. Tr1 showed a higher affinity towards the p28 promoter than the omp-1B promoter as determined with surface plasmon resonance. EcxR activated the tr1 expression in response to a temperature decrease. At 37°C low level of Tr1 activated the p28 expression. At 25°C high level of Tr1 activated the omp-1B expression, while repressing the p28 expression by binding to an additional site upstream of the p28 gene. Our data provide insights into a novel mechanism mediated by Tr1 regulating E. chaffeensis differential gene expression, which may aid in the development of new therapeutics for HME.

9.
Waste Manag ; 125: 172-181, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33689991

RESUMO

Anaerobic digestion is promising for waste activated sludge (WAS) degradation. However, conventional processes were generally stuck with limited hydrolysis and poor pathogen destruction. Hyperthermophilic digestion at 70 °C has drawn attention in overcoming those issues at a relatively low energy requirement and operating difficulties. In order to illuminate its operation characteristics, a single-stage hyperthermophilic digester was controlled at 70 °C and operated continuously to degrade WAS. 88.7 mL/g VSadded of methane yield could be achieved in the hyperthermophilic system, fourfold higher than that in the mesophilic system. Kinetic analysis revealed that hyperthermophilic digestion was advantageous in converting the non-degradable fraction. Consequently, hydrolysis under the hyperthermophilic condition was able to be significantly improved. Above 10 d was necessary for the hyperthermophilic system to gain such a high methane production. In the case of stability, the organic loading of higher than 10.2 g VS/L/d resulted in increasing limitation from methanogenesis and accumulation of propionic, butyric and valeric acids. In addition to the dominant acetoclastic genus Methanothrix for methane production in the hyperthermophilic system, two hydrogenotrophic methanogens Methanospirillum and Methanothermobacter reached 18.84% and 8.31%, respectively. The genus Coprothermobacter, affiliated with the phylum Firmicutes, made more contribution to protein hydrolysis in the hyperthermophilic digester.


Assuntos
Microbiota , Esgotos , Anaerobiose , Reatores Biológicos , Cinética , Metano
10.
J Am Soc Mass Spectrom ; 32(4): 913-928, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33710905

RESUMO

The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies to facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography-mass spectrometry application. Successful implementation of MAM as a purity-indicating assay requires new peak detection (NPD) of potential process- and/or product-related impurities. The NPD interlaboratory study described herein was carried out by the MAM Consortium to report on the industry-wide performance of NPD using predigested samples of the NISTmAb Reference Material 8671. Results from 28 participating laboratories show that the NPD parameters being utilized across the industry are representative of high-resolution MS performance capabilities. Certain elements of NPD, including common sources of variability in the number of new peaks detected, that are critical to the performance of the purity function of MAM were identified in this study and are reported here as a means to further refine the methodology and accelerate adoption into manufacturer-specific protein therapeutic product life cycles.

11.
Eye (Lond) ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707765

RESUMO

OBJECTIVE: To explore the association between sleep disorders and subfoveal choroidal thickness (SFCT) in preschool children. METHODS: In this population-based cross-sectional study, children aged 60-72 months were measured for SFCT using spectral-domain optical coherence tomography (SD-OCT) and for sleep disorders using the Chinese version of Children's Sleep Habits Questionnaire (CSHQ). Multiple linear regression analyses were performed to assess the association between sleep disorders and SFCT. RESULTS: A total of 1337 children (mean (SD) age: 66.88 (3.41) months) were included in the analyses. In multivariable linear analysis, a higher total CSHQ score (indicating higher likelihood of sleep disorders) was associated with a thinner subfoveal choroid (beta, -0.070; 95% CI, -0.141 to -0.001; P = 0.046). When each of eight CSHQ subscale scores was analysed by the multivariable model, only the Daytime Sleepiness subscale score was negatively associated with the SFCT (beta, -0.115; 95% CI, -0.183 to -0.046; P = 0.001). The children with clinically significant daytime sleepiness (n = 364, 27.2%) had significantly thinner subfoveal choroid than other children (295.47 vs. 308.52 µm, P = 0.007). CONCLUSIONS: Only daytime sleepiness was significantly associated with SFCT in preschool children in this study. The potential relationship between sleep disorders during childhood and children's ocular development needs further research.

12.
Int J Biol Macromol ; 180: 187-193, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33675831

RESUMO

Cyclodextrinase (CDase) and cyclodextrin glucosyltransferase (CGTase) were synergistically used to provide a novel enzymatic method in lowing in vitro digestibility of waxy maize starch. The molecular structure, malto-oligosaccharide composition, and digestibility properties of the generated products were investigated. The molecular weight was reduced to 0.3 × 105 g/mol and 0.2 × 105 g/mol by simultaneous and sequential treatment with CDase and CGTase, while the highest proportion of chains with degree of polymerization (DP) < 13 was obtained by simultaneous treatment. The resistant starch contents were increased to 27.5% and 36.9% by simultaneous and sequential treatments respectively. Dual-enzyme treatment significantly promoted the content of malto-oligosaccharides (MOSs) by hydrolyzing cyclodextrins from CGTase with CDase. However, the replacement of cyclodextrins by MOSs did not obviously influence the digestibility of the products. The starch digestion kinetics further revealed the hydrolysis pattern of these two enzymes on the starch hydrolysate. It was proved that the starch digestibility could be lowered by modulating the molecular structure and beneficial MOSs content by this dual-enzyme treatment.

13.
Anal Chem ; 93(8): 4059-4065, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33600159

RESUMO

Mitochondrial redox homeostasis plays a vital role in many biological processes. Hydrogen peroxide (H2O2), one of the most important components for the balance between oxidizing species and reducing species, also acts as the messenger of mitochondrial damage. Thus, an accurate in situ quantitative detection of H2O2 in mitochondria is very important for the evaluation of mitochondrial redox homeostasis. Here, we develop robust surface-enhanced Raman spectroscopy (SERS) nanoprobes based on Au nanoparticles as SERS substrate and functionalized carrier, which is further modified with a phenylboronic acid pinacol ester for specific H2O2 response and a location peptides for mitochondrial targeting by creating a robust Au-Se interface. The SERS nanoprobes show good resistance to abundant thiol under biological conditions and superior performance for mitochondria H2O2 monitoring in living cells than the SERS nanoprobes with the traditional Au-S interface, which enables us to achieve in situ quantification of mitochondrial H2O2 and obtain its real-time dynamic change under oxidative stress.

14.
Ann Palliat Med ; 10(2): 2254-2259, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33549030

RESUMO

BACKGROUND: Radiotherapy is the cornerstone in cancer treatment, and its adverse effects have been recognized widely nowadays. In response, effective and nontoxic therapies are in demand for patients affected by radiotherapy-induced adverse effects (RIAE). As a multitude of clinical studies have suggested that acupuncture therapies seem to be potential in treating RIAE, this study aims to make a systematic review and Bayesian network meta-analysis (NMA) to evaluate effectiveness and safety of different acupuncture treatments. METHODS: A full-scale search will be performed in the following databases from inception to June, 2020: PubMed/Medline, Cochrane library, Web of Science, Ebsco, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database and China Biology Medicine disc (CBM). Randomized controlled trials meeting the eligible criteria based on PICOS elements will be included. The primary outcome is the response rate of RIAE or the incidence of RIAE. The secondary outcome is the incidence of adverse events directly related to acupuncture. Cochrane risk-of-bias tool (ROB 2.0) will be employed to evaluate the quality of chosen literatures. Stata, Addis and OpenBUGS will be performed to manage data. DISCUSSION: The results can provide a relatively objective evidence to assess effectiveness and safety of acupuncture therapies for each RIAE, which may be rewarding as a guiding proposal for researchers concerning RIAE. TRIAL REGISTRATION: This study has been registered at INPLASY (https://inplasy.com/) with a registration ID INPLASY202070054.

15.
Food Funct ; 12(5): 2257-2269, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33596303

RESUMO

Due to the scarcity of the data on digestion and metabolism of wheat embryo proteins WEP, a simulated gastrointestinal digestion (SGID) scheme in vitro was utilized to explain the protein hydrolysis and biological activity of WEP during the digestion process. WEP had a certain degree of resistance to gastric digestion, especially the protein with a molecular weight of 50 kDa. In all the samples, no visually intact protein band emerged in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) during the intestinal phase, which was consistent with a gradually increasing content of released free amino acids. Moreover, the resistant digestion peptides (the amino acid sequences were ISQFXX and GTVX) were identified at the end of the gastrointestinal digestion (GID) product by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Although the complete protein in the sample was degraded, the antioxidant activity was not negatively affected, rather it showed an increasing trend and maintained a higher level of activity. The amount of the ß-sheet gradually increased as that of the α-helix declined, the random coil decreased, whereas no obvious change was noticed in ß-turn content. The results provide a better understanding for optimal selection of peptide candidates for designing protein products in the food processing industry as well as for WEP digestion and metabolism in the human body.

16.
Environ Sci Technol ; 55(5): 2859-2868, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33577293

RESUMO

Ultrafine particles (UFPs) dominate the particle number population in the urban atmosphere and revealing their chemical composition is important. The thermal desorption chemical ionization mass spectrometer (TDCIMS) can semicontinuously measure UFP composition at the molecular level. We modified a TDCIMS and deployed it in urban Beijing. Radioactive materials in the TDCIMS for aerosol charging and chemical ionization were replaced by soft X-ray ionizers so that it can be operated in countries with tight regulations on radioactive materials. Protonated N-methyl-2-pyrrolidone ions were used as the positive reagent ion, which selectively detects ammonia and low-molecular weight-aliphatic amines and amides vaporized from the particle phase. With superoxide as the negative reagent ion, a wide range of inorganic and organic compounds were observed, including nitrate, sulfate, aliphatic acids with carbon numbers up to 18, and highly oxygenated CHO, CHON, and CHOS compounds. The latter two can be attributed to parent ions or the decomposition products of organonitrates and organosulfates/organosulfonates, respectively. Components from both primary emissions and secondary formation of UFPs were identified. Compared to the UFPs measured at forest and marine sites, those in urban Beijing contain more nitrogen-containing and sulfur-containing compounds. These observations illustrate unique features of the UFPs in the urban environment and provide insights into their origins.


Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Atmosfera , Pequim , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/análise
17.
PLoS One ; 16(2): e0247248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33600459

RESUMO

The conversion of cellular prion protein (PrPC) to disease-provoking conformer (PrPSc) is crucial in the pathogenesis of prion diseases. Heparin has been shown to enhance mammalian prion protein misfolding. As spontaneous prion disease has not been reported in non-mammalian species, such as chicken, it is interesting to explore the influence of heparin on the conversion of chicken prion protein (ChPrP). Herein, we investigated the influences of heparin on biochemical properties of full-length recombinant ChPrP, with murine prion protein (MoPrP) as control. The results showed that at low heparin concentration (10 µg/mL), a great loss of solubility was observed for both MoPrP and ChPrP using solubility assays. In contrast, when the concentration of heparin was high (30 µg/mL), the solubility of MoPrP and ChPrP both decreased slightly. Using circular dichroism, PK digestion and transmission electron microscopy, significantly increased ß-sheet content, PK resistance and size of aggregates were observed for MoPrP interacted with 30 µg/mL heparin, whereas 30 µg/mL heparin-treated ChPrP showed less PK resistance and slight increase of ß-sheet structure. Therefore, heparin can induce conformational changes in both MoPrP and ChPrP and the biochemical properties of the aggregates induced by heparin could be modified by heparin concentration. These results highlight the importance of concentration of cofactors affecting PrP misfolding.

18.
J Cancer Res Clin Oncol ; 147(5): 1315-1324, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33543328

RESUMO

PURPOSE: The identification of HER2 overexpression in a subset of gastric adenocarcinoma (GA) patients represents a significant step forward in unveiling the molecular complexity of this disease. The predictive and prognostic value of HER2 amplification in advanced HER2 inhibitor-treated GA patients has been investigated. However, its predictive value in resectable patients remains elusive. METHODS: We enrolled 98 treatment-naïve resectable Chinese GA patients with HER2 overexpression assessed using IHC. Capture-based targeted sequencing using a panel consisting of 41 gastrointestinal cancer-related genes was performed on tumor tissues. Furthermore, we also investigated the correlation between HER2 copy number (CN) and survival outcomes. RESULTS: Of the 98 HER2-overexpressed patients, 90 had HER2 CN amplification assessed using next-generation sequencing, achieving 92% concordance. The most commonly seen concurrent mutations were occurring in TP53, EGFR and PIK3CA. We found HER2 CN as a continuous variable was an independent predictor associated with DFS (p = 0.029). Our study revealed HER2 CN-high patients showed a trend of intestinal-type GA predominant (p = 0.075) and older age (p = 0.07). The median HER2 CN was 15.34, which was used to divide the cohort into CN-high and CN-low groups. Patients with high HER2 CN had a significantly shorter DFS than patients with low HER2 CN (p = 0.002). Furthermore, HER2 CN as a categorical variable was also an independent predictor associated with DFS in patients. CONCLUSION: We elucidated the mutation spectrum of HER2-positive resectable Chinese GA patients and the association between HER2 CN and DFS. Our work revealed HER2 CN as an independent risk factor predicted unfavorable prognosis in HER2-positive GA patients and allowed us to further stratify HER2-positive resectable GA patients for disease management.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Variações do Número de Cópias de DNA/genética , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Amplificação de Genes/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico
19.
J Clin Pharm Ther ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393690

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The antibiotic concentration in abdominal drainage fluid is very important for the treatment of patients with severe acute pancreatitis (SAP). Previous studies show that quinolones and carbapenems have high abdominal tissue levels, whereas aminoglycosides fail to penetrate into abdominal tissue in sufficient concentrations. However, there are limited data with respect to vancomycin. This case aims to investigate the penetration of vancomycin to abdominal drainage fluid in a 44-year-old SAP patient. CASE SUMMARY: We report a case of a 44-year-old female with SAP, on treatment of vancomycin. The time courses of vancomycin concentration in plasma and abdominal drainage fluid of the patient were described. Simultaneous measurement of abdominal drainage fluid and serum concentrations demonstrated that vancomycin can rapidly penetrate into abdominal tissue in acceptable amounts. WHAT IS NEW AND CONCLUSION: This case demonstrated that it took about 30 minutes for vancomycin to get from plasma to abdominal drainage fluid and about 76% of vancomycin could move into abdominal drainage fluid for SAP patients.

20.
Nutr Cancer ; : 1-13, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33432844

RESUMO

Although several epidemiological studies have investigated associations between poultry and fish consumption and pancreatic cancer (PC) risk, these findings have been inconsistent. The present study aimed to perform a meta-analysis to comprehensively evaluate these associations. We retrieved Eligible cohort studies and case-control studies published before February 2020 from the Medline, EMBASE, and Cochrane Library and applied a random or fixed effects model to calculate the pooled relative risk (RR) and the corresponding 95% confidence intervals (CI). Publication bias was detected using funnel plots, Begg's test, and Egger's test, and the study quality was evaluated using the Newcastle-Ottawa scale. We included 25 studies in the analyses. The pooled RR of PC for the highest vs. lowest poultry intake category was 1.14 (95% CI: 1.02-1.26) in cohort studies. There was no appreciable link between fish intake and PC risk (RR: 1.00, 95% CI: 0.93-1.07). Our results suggest that large amount of poultry intake may increase PC risk, while fish intake is unlikely to be linked to PC risk. These links require further investigation, particularly between poultry and PC.

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