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In this study, the accumulation characteristics and health risks of heavy metals Cd, As, Pb and Cr in soil-vegetable system of Hongta District (HT), Tonghai County (TH) and Yuanjiang County (YJ) in Yuxi city were analyzed. In addition, some vegetables with high concentrations of heavy metal were screened and their cytotoxicity was investigated by in vitro gastrointestinal simulation method (SBRC) and intestinal cell Caco-2 model. The results showed that TH and HT soils were contaminated by As, Cd and/or Pb. The content of Cd in TH and HT brassica vegetables exceeded the limit value of GB 2762-2017 by 13.6 folds and 2.2 folds. The bioaccessibility of TH Brassica oleracea L. var. botrytis L. and Brassica pekinensis (Lour.) Rupr. in gastric stage was 36.40% and 9.84%, and decreased to 0.91% and 0% in intestinal stage, respectively. The bioaccessibility of YJ Houttuynia cordata Thunb. in gastric stage and intestinal stage were 25.23% and 6.69%, respectively. The health risk assessment based on the total content of heavy metals showed TH brassica vegetable may had potential health risks, while bioaccessibility date showed that there was no health risk for the three vegetables. To validate the above-mentioned results, Caco-2 cells were exposed to all bioacces-sible extracts of vegetables, and cell viability was not significantly decreased at 4 h and 8 h in all groups. Collectively, based on the total of heavy metals in vegetables may overestimate their health risk, while the new assessment method based on bioaccessibility data and cytotoxicity maybe a more accurate approach for health risk assessment. [ABSTRACT FROM AUTHOR]

Seaweeds consumption is one of main internal exposure sources of arsenic for human. However, the absence of representative bio-availabilities of arsenic species makes the accurate assessment of arsenic health risk originating from seaweeds consumption impossible. Herein, the arsenic species in various seaweeds collected from Fujian of China were investigated, and the bio-accessibilities/bio-availabilities of arsenic species existing in seaweeds were evaluated in vitro and in vivo. Results revealed that in vitro bio-availabilities of arsenic species presenting in seaweeds, which obtained with Caco-2 cells, were lower than those of pure arsenic standards, and varied with order of inorganic arsenic (iAs) > dimethylarsinic acid (DMA) ≈ arsenobetaine (AsB) > arsenosugars. During gastrointestinal digestion of mice, As 5+ was partly methylated into monomethylarsonic acid (MMA) and DMA, which makes the in vivo bioavailability of iAs (⁓31.8 %) obtained with mouse metabolic experiment is much higher than its in vitro bio-availability (⁓10.3 %). The in vivo bio-availabilities of DMA and total arsenic (tAs) are similar to their in vitro bio-availabilities. As the dominant arsenic species in most seaweeds, arsenosugars have an ⁓0.0 % of in vivo bioavailability and only a ⁓3.7 % of in vitro bioavailability. The simulated calculation of target hazard quotient (THQ) and target cancer risk (TR) revealed that the arsenic risk originating from seaweeds was greatly degraded by taking into consideration of arsenic species and bio-availabilities, and all seaweeds collected from Fujian are safety for consumption. The simulated calculation also revealed that arsenic risk of seaweeds can be also more accurately assessed based on tAs together with bioavailability, which provides a simple but accurate and protective method for the risk assessment of arsenic originating from seaweeds. Our work provides the possible representative bio-availabilities of arsenic species presenting in seaweeds for accurately assessing arsenic risk of seaweeds, and novel insights into the bio-availabilities of arsenic in animal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The contamination of paddy fields by cadmium and lead is a major issue in China. The consumption of rice grown in heavy metals contaminated areas poses severe health risks to humans, where bioavailability and bioaccessibility remains the critical factor for risk determination. Selenium nanoparticles (Se-NPs) can mitigate the toxicity of heavy metals in plants. However, there exists limited information regarding the role of Se-NPs in dictating cadmium (Cd) toxicity in rice for human consumption. Moreover, the impact of Se-NPs under simultaneous field and laboratory controlled conditions is rarely documented. To address this knowledge gap, a field experiment was conducted followed by laboratory scale bioavailability assays. Foliar application of Se-NPs and selenite (at 5, 10 mg L -1 ) was performed to assess their efficiency in lowering Cd accumulation, promoting Se biofortification in rice grains, and evaluating Cd exposure risk from contaminated rice. Obtained results indicate that foliar treatments significantly reduced the heavy metal accumulation in rice grains. Specifically, Se-NP 10 mg L -1 demonstrated higher efficiency, reducing Cd and Pb by 56 and 32 % respectively. However, inconsistent trends for bioavailable Cd (0.03 mg kg -1 ) and bioaccessible (0.04 mg kg -1 ) were observed while simulated human rice intake. Furthermore, the foliage application of Se-NPs and selenite improved rice quality by elevating Se, Zn, Fe, and protein levels, while lowering phytic acid content in rice grains. In summary, this study suggests the promising potential of foliage spraying of Se-NPs in lowering the health risks associated with consuming Cd-contaminated rice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

It is common to combine two or more drugs in clinics in China. Triptolide (TP) has been used primarily for the treatment of inflammatory and autoimmune diseases. Astragaloside IV (AS-IV) has been applied with many other drugs, due to its various pharmacological effects. AS-IV and TP can be used together for the treatment of diseases in clinics in China. This study investigates the effects of astragaloside IV (AS-IV) on the pharmacokinetics of TP in rats and its potential mechanism. The pharmacokinetics of orally administered triptolide (2 mg/kg) with or without AS-IV pre-treatment (100 mg/kg/day for 7 d) were investigated. Additionally, the effects of AS-IV on the transport of triptolide were investigated using the Caco-2 cell transwell model. The results indicated that when the rats were pre-treated with AS-IV, the Cmax of triptolide decreased from 418.78 ± 29.36 to 351.31 ± 38.88 ng/mL, and the AUC0-t decreased from 358.83 ± 19.56 to 252.23 ± 15.75 μg/h/L. The Caco-2 cell transwell experiments indicated that AS-IV could increase the efflux ratio of TP from 2.37 to 2.91 through inducing the activity of P-gp. In conclusion, AS-IV could decrease the system exposure of triptolide when they are co-administered, and it might work through decreasing the absorption of triptolide by inducing the activity of P-gp. [ABSTRACT FROM AUTHOR]

Salmonella can cause severe foodborne diseases. This study investigated the prevalence of Salmonella spp. in fresh foods in Hangzhou market and their harborage of antibiotic resistance and virulence genes, antibiotic susceptibility, and pathogenicity. A total of 500 samples (pork, n = 140; chicken, n = 128; vegetable, n = 232) were collected over a one-year period. Salmonella was found in 4.2% (21) of samples with the detection rate in pork, chicken and vegetables as 4.3% (6), 6.3% (8), and 3% (7), respectively. One Salmonella strain was recovered from each positive sample. The isolates were identified as six serotypes, of which S. Enteritidis (n = 7) and S. Typhimurium (n = 6) were the most predominant serotypes. The majority of isolates showed resistance to tetracycline (85.7%) and/or ciprofloxacin (71.4%). Tetracycline resistance genes showed the highest prevalence (90.5%). The occurrence of resistance genes for β-lactams (blaTEM-1, 66.7%; and blaSHV, 9.5%) and aminoglycosides (aadA1, 47.6%; Aac(3)-Ia, 19%) was higher than sulfonamides (sul1, 42.9%) and quinolones (parC, 38.1%). The virulence gene fimA was detected in 57.1% of isolates. Gene co-occurrence analysis implied that resistance genes were associated with virulence genes. Furthermore, selected S. Typhimurium isolates (n = 4) carrying different resistance and virulence genes up-regulated the secretions of cytokines IL-6 and IL-8 by Caco-2 cells in different degrees, suggesting that virulence genes may play a role in inflammatory transcription. In in vivo virulence test, microbiological counts in mouse feces and tissues showed that all included S. Typhimurium were able to infect mice, with one strain showing significantly higher virulence than others. In conclusion, this study indicates Salmonella contamination in fresh foods in Hangzhou market poses a risk to public health and it should be closely monitored to prevent and control foodborne diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Qian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vibrio parahaemolyticus outbreaks frequently occur, causing gastrointestinal sickness owing to the consumption of aquatic foods by various virulence factors; however, the mechanism of pathogenesis is still unknown. In this study, a non-typical strain of V. parahaemolyticus , named VP353, was isolated from shrimp in China. Its comparative genome and transcriptome after infection with Caco-2 cells were examined to illustrate the mechanisms of its pathogenesis. VP353 was a tdh-trh - strain but uncommonly manifested robust cytotoxicity towards Caco-2 cells. Compared with the standard strain RIMD2210633, VP353 harbored alpha-hemolysins (hlyA , hlyB , hlyC , and hlyD) was first reported in V. parahaemolyticus and showed high diversity in the T3SS2 gene cluster. Moreover, the expression of flagella, T2SS, quorum sensing-related genes, hlyA , hlyC were up-regulated, and hlyB , hlyD were down-regulated. In summary, our results demonstrate that some novel virulence factors contribute to the pathogenesis of V. parahaemolyticus infection. • Vibrio parahaemolyticus is considered a widely spread foodborne pathogen in seafood. • V. parahaemolyticus 353 was tdh/trh negative strain and show high cytotoxicity, enterotoxicity, and high diversity in T3SS2 gene cluster. • This is the first report that V. parahaemolyticus 353 harbors hlyA, hlyB, hlyC, and hlyD. • The expression of flagella, type IV pilus, EPS T2SS, quorum sensing related genes were overexpressed after infection towards Caco-2 cells. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare iron bioavailability (Fe BV) from ten selected kinds of Chinese wheat flours in order to provide scientific basis for further human trials and enable plant breeding programs to screen biofortified wheat cultivars. Methods: An in vitro digestion/Caco-2 cell model was used to assess Fe BV of ten flour samples from six leading Chinese wheat cultivars and the stability of Fe BV in one cultivar was studied across three growing environments. Results: Significant differences were observed in both Fe BV and Fe bioavailability per gram of food (Fe BVPG) among cultivars (P<0.01) grown at the same location with the same flour extraction rate. Zhongyou 9507 and Jingdong 8 had Fe BV 37%–54% and Fe BVPG 103%–154% higher than the reference control. In the Anyang environment, Zhongyou 9507 had a higher wheat flour-Fe level and Fe BVPG. Differences in Fe BV were detected in cultivars with different flour extraction rates. Conclusion: Zhongyou 9507 and Jingdong 8 were identified as the most promising cultivars for further evaluation of efficacy by using human subjects. The growing environments had no effect on Fe BV, but did have a significant effect on Fe BVPG. Fe bioavailabilities in low-extraction (40%) flours were higher than those in high-extraction (78%) flours. [Copyright &y& Elsevier]

Rice is a recognized source of cadmium (Cd) exposure. In this study, a total of 102 rice samples were obtained from main producing rice regions of China, and the bioavailability of Cd in rice were assessed by using an in vitro digestion method combined with a Caco-2 cell monolayer model. The results revealed that the average (range of) concentration of Cd in the rice samples was 0.2840 (0.0123-2.4710) mg/kg, and the average (range of) bioavailability of Cd in the rice samples was 23.94% (7.47-39.73%). We analyzed the recent rice consumption data and calculated the target hazard quotients (THQs) to evaluate the noncarcinogenic health risk of Cd in rice consumption for adults and children, respectively. We suggested that the most of investigated regions showed low risks of Cd in rice for general population, and the regions of Cd in rice near the limit deserves might be attracted more attention after taking bioavailability into account. PRACTICAL APPLICATION: The cadmium content of rice itself will affect its corresponding bioavailability to a certain extent. By studying the in vitro bioavailability of cadmium rice with different pollution levels, it is helpful for the dose selection of animal experiments or toxicity tests, and finally, we may provide some references for the establishment of appropriate treatment scheme of rice Cd poisoning., (© 2022 Institute of Food Technologists®.)

E-wastes release toxic metals including Cd, Cu, Ni, Pb and Zn into nearby soils during dismantling process. However, their adverse effects and the associated mechanisms on human intestinal epithelium are poorly understood. In this study, their toxic effects on human colonic epithelial cells Caco-2 and the underlying mechanisms were assessed basing on three soils from Wenling e-waste dismantling site. Since soil-extractable metals are more available for gastrointestinal absorption, we used phosphate buffer saline solution to extract metals at solid to liquid ratio of 1:2. Among metals, total Cd and Ni exceeded the risk screening values in three soils, being 3.8-8.8 and 42.4-155 mg/kg. Furthermore, high extractable-metals at 5.9, 1.9, and 0.87 mg/kg Cd (20-67%) and 4.6, 6.4, and 12.4 mg/kg Ni (3.6-29%) were observed for Soil-1, -2 and -3, respectively. All three extracts triggered cytotoxicity, with Soil-2 showing the strongest inhibition of cell viability. Higher production of reactive oxygen species and stronger inhibition of antioxidant enzymes SOD1 and CAT were observed in Soil-2 and -3. Upregulation of proinflammatory mediators (IL-1β, IL-8 and TNF-α) and apoptosis-regulatory genes (GADD45α, Caspase-3, and Caspase-8) were observed. Our data suggest that soil extracts induced cytotoxicity, oxidative damage, inflammatory response, and cell apoptosis in Caco-2 cells, indicating soil ingestion from e-waste dismantling site may adversely impact human health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Developing safe and efficient iron supplements is significant for the alleviation of iron-deficient anemia (IDA). Myoglobin (Mb) is a heme-protein rich in bioavailable iron. Pneumatophorus japonicus (P. japonicus), one important economic fish in China, contain a high Mb level in its dark meat normally discarded during processing. The present study aimed to determine the structure, physicochemical properties, and iron bioavailability of Mb extracted from P. japonicus. Meanwhile, the effects of glycosylation, a commonly applied chemical modification of proteins, on these parameters were evaluated. Using Box-Behnken design, the optimal conditions for Mb-chitosan glycosylation were obtained: 45.07 °C, pH 6.10 and Mb/chitosan mass ratio of 6.29. The structure and functional properties of the glycosylated Mb (Mb-gly) were investigated. Compared with the original Mb, Mb-gly obtained a more ordered secondary structure. The surface hydrophobicity of Mb-gly was found to be decreased together with the observations of elevated water solubility. Moreover, glycosylation enhanced the Mb antioxidant capacity, and improved its stability in enzymatic digestion system. Regarding to the iron bioavailability, the cellular uptake of Mb‑iron was significantly higher than FeSO 4 , and further elevated by glycosylation. These results provided a basis for the development of Mb-based iron supplements, promoting the utilization of fish-processing industries wastes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In the present experimental series, we have developed a novel nanocomposite to target activated macrophages in the colon with real time imaging and therapeutic capabilities. This binary nanocomposite was formed by the covalent conjugation of mannosylated NPs (Man-NPs) with carbon dots (CDs). Man-NPs were prepared using a self-assembly method based on mannosylated decamethylenediamine-grafted carboxymethyl inulin amphiphilic acid. While, the CDs were synthesized using a simple bottom-up process using citric acid monohydrate and diethylenetriamine, which were tightly bonded to the Man-NPs surface by carbodimide coupling. The resulting nanocomposite had a uniform size of 241.3 nm with a negative charge and a high drug casing density of 25.54 wt% and blue self-fluorescence were emitted. Whereas, in vitro observation of cellular uptake indicated the greater nanocomposite uptake in inflamed macrophage as compared to the untreated macrophage and mannose receptor-negative cell lines, 4T1 respectively. However, in vivo bio distribution exhibited a large number (60%) of CDs/Man-NPs nanocomposite accumulated in the inflamed colon of colitis mice. It should be noted that the novel nanocomposite, as macrophage-targeted drug delivery, could have promise for the treatment of inflammatory bowel disease (IBD)., (Copyright © 2020. Published by Elsevier B.V.)

The aim of this study was to evaluate the probiotic characteristics and safety of seven Enterococcus faecalis isolates from fecal samples of healthy Chinese infants. We evaluated the isolates' tolerance to low pH, survival in bile salts and NaCl, adhesion ability, biofilm formation, antimicrobial activity, toxin gene distribution, hemolysis, gelatinase activity, antibiotic resistance, and virulence to Galleria mellonella. All strains survived at pH 5.0, in 7.0% NaCl, and in 3% bile salt. Adhesion to Caco-2 cells was above 10%. Strain A3-1 had higher adhesion ability toward mucin, collagen, and BSA in vitro, better antibacterial activity, and the strongest biofilm production. We detected seven virulence genes with a distribution of asa1 (100%), cylA (71.4%), esp (85.7%), hyl (14.3%), gelE (85.7%), ace (42.9%), and agg (71.4%). Although all strains were γ-hemolytic, none showed gelatinase activity based on physiological activity detection. All isolates were susceptible to benzylpenicillin, ampicillin, ciprofloxacin, levofloxacin, moxifloxacin, tigecycline, nitrofurantoin, linezolid, and vancomycin; they were not susceptible to erythromycin, quinupristin/dalofopine, and clindamycin. The virulence test of G. mellonella showed that, except for strains 106-1 and 113-1, the other strains had toxicity lower than 10%. Strain A3-1 may have the greatest potential to be developed as a probiotic.

Objectives: To investigate the effect of tumor necrosis factor ligand-related molecule 1A (TL1A) on the intestinal mucosal barrier in mice with chronic colitis., Methods: Male TL1A-overexpressing transgenic mice and male C57BL/6 wild-type mice were used to establish a dextran sodium sulfate (DSS)-induced colitis model. The expression of occludin and claudin-1 was observed. Bacterial distribution in the intestinal mucosa and Th9/interleukin (IL)-9 expression were detected. In vitro co-culture systems of naive CD4 + T cells and Caco-2 cells were established and TL1A was added. Changes in transepithelial electrical resistance and IL-9 expression were measured. CD4+IL-9 cells were detected by flow cytometry., Results: DSS mice showed a significant down-regulation of occludin and claudin-1 compared with controls. Expression levels of occludin, zonulin-1, and claudin-1 in the Caco-2+TGF-β+IL-4+TL1A group were significantly lower than in the Caco-2+TGF-β+IL-4 group. Bacterial distribution was clearly disordered in the DSS group. Transmembrane resistance of the Caco-2+TGF-β+IL-4+TL1A group was significantly lower and IL-9 expression significantly higher than in the Caco-2+TGF-β+IL-4 group., Conclusions: TL1A overexpression promotes destruction of the intestinal mucosal barrier in mice with chronic colitis. The underlying mechanism may be associated with the promoting role of TL1A in Th9/IL-9 expression, which further destroys the mucosal barrier.

This study investigated formation and genotoxicities of disinfection by-products (DBPs) during chlorination of hydrophobic organic compounds (HOCs) extracted from six drinking water reservoirs around the Pearl River Delta region, China. Chemical analyses firstly showed that after chlorination aromatic HOCs (including polycyclic aromatic hydrocarbons, PAHs) decreased but DBPs (including chlorinated PAHs) increased, while genotoxicity assays revealed that the chlorination increased DNA damage in human Caco-2 cells. Although the link between DBPs and the genotoxicity was weak (insignificant correlations, p ≥ 0.05), we observed that chlorination of HOCs from more contaminated reservoirs in general resulted in higher genotoxicity. Secondly, remedial effects of catalase and dietary antioxidants (i.e. vitamin C and epigallocatechin gallate) in protecting cells against DBPs genotoxicity were detected. After 1 h treatment by the antioxidants, the DNA damage in Caco-2 cells (due to previous exposure to DBPs) significantly decreased (p < 0.05) in 7 out of a total of 18 treatments (38.9%). This is the first study demonstrating that catalase, vitamin C and epigallocatechin gallate protected human cells in vitro against DNA damage upon exposure to chlorinated genotoxic DBPs. Image 1 • HOCs extracted from drinking water reservoirs were subjected to chlorination. • Chlorination reduced PAHs and UV 254 in HOCs, but increased genotoxicity of HOCs. • Genotoxicity in chlorinated solutions increased along the contamination gradient. • UV 254 was not a good predictor for DBPs genotoxicity, but ƩPAHs was. • CAT, VC and EGCG protected human cells against DNA damage from chlorinated HOCs. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota is increasingly recognized as the key participant in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) by translocation of its products, such as lipopolysaccharide (LPS), via the dysfunctional intestinal barrier. Qushi Huayu decoction (QHD), a traditional Chinese medicine, is developed specially for NAFLD and used in clinic in China for more than a decade and previously found to ameliorate non-alcoholic steatohepatitis (NASH) induced by high-fat diet (HFD) in mice accompanied with inhibited metabolic endotoxemia and hepatic LPS signalling., Purpose: To investigate the mechanism of LPS gut-leakage inhibition by QHD in NASH., Methods: Effects of QHD on gut microbioa and intestinal barrier were evaluated in NASH induced by HFD in mice. 16S rRNA sequencing is employed to analyse the gut microbiota composition. To identify the potential signalling pathway responsible for tight junction regulation, the colonic phosphoprotein profile is screened via the Phospho Explorer Antibody Array and verified in NASH, intestinal barrier dysfunctional mouse and Caco-2 cells., Results: QHD ameliorates NASH accompanied with regulating the gut microbiota composition, protecting intestinal tight junctions and inhibiting LPS gut-leakage without decreasing the abundance of identified Gram-negative bacteria. The validated data of phosphorylated proteins suggested that mitogen-activated protein kinase (MAPK) pathway is predominantly responsible for the colonic tight junction regulation by QHD., Conclusion: QHD inhibits LPS gut-leakage in NASH, which is associated with downregulation of intestinal MAPK pathway., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background/aims: Kinesin family member 20A (KIF20A) is upregulated in multiple cancers and plays important roles in promoting malignant behavior, whereas its exact role in CRC remains unknown., Results: Both genomic and protein expression levels showed that KIF20A was upregulated in CRC. Further functional analyses revealed that KIF20A had a crucial role in improving cell proliferation and resistance to chemotherapy in CRC. Finally, we provided distinct mechanistic evidence that KIF20A achieved all of its pathological functions in CRC by activating the JAK/STAT3 pathway., Conclusion: Our results suggested that KIF20A regulated a set of malignant characteristics in CRC by activating the JAK/STAT3 pathway. Our findings indicate a new direction for the development of more effective therapeutic treatments for CRC., Methods: Three Gene Expression Omnibus datasets and The Cancer Genome Atlas datasets were used to investigate the expression level of KIF20A in CRC. Further experiments included immunohistochemical staining, western blot analysis, qRT-PCR, gene silencing, and a cell-injected xenograft mouse model to investigate the interaction between KIF20A and the JAK/STAT3 signaling pathway in both patient-derived specimens and CRC cell lines.

Probiotics can be screened according to their abilities to inhibit pathogen adhesion and inhibit the production of pro-inflammatory cytokines. Eleven Lactobacillus strains isolated from traditional fermented dairy foods in Xinjiang, China, were studied for their potential to inhibit adhesion of Escherichia coli to intestinal epithelial cells and to inhibit E. coli-induced production of interleukin (IL)-8 by intestinal epithelial cells. The results showed that the 11 strains could inhibit adhesion of E. coli to Caco-2 cell monolayers and inhibit the induction of IL-8 production by E. coli in HT-29 cells. The inhibiting activities of the Lactobacillus strains against E. coli adhesion and IL-8 induction were strain-specific and not positively correlated, whereas the excluding activity of the strains against E. coli adhesion and their coaggregation with E. coli were positively correlated. The effector molecules of the strains with probiotic potential should be identified to explain the mechanism behind these observations., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Water-soluble polysaccharides from Umbilicaria tornata (UTP) were purified and preliminarily characterized. The antioxidant and antitumor activities of crude UTP and two purified fractions (UTP-1 and UTP-2) were evaluated using in vitro experiments. The results showed that the molecular weights of UTP-1 and UTP-2 were 84.86 and 28.66 kDa, respectively. Both UTP-1 and UTP-2 were composed of glucose and xylose, with their molar ratios being 1.3:0.9 and 0.9:4.6, respectively. In addition, crude UTP, UTP-1 and UTP-2 showed dose-dependent DPPH and hydroxyl radical scavenging and reducing activities. However, crude UTP exhibited stronger antioxidant activity than UTP-1 and UTP-2, particularly in terms of DPPH radicals. Crude UTP and the two purified fractions inhibited the growth of HeLa, HepG2, A375, MCF-7, SGC7901 and Caco2 cancer cells in vitro. Compared with UTP-1 and UTP-2, crude UTP presented significantly higher antitumor activity in vitro against HeLa and HepG2 cells (p < 0.05). These findings provide a scientific basis for the deeper exploration and resource development of U. tornata.

Purpose: Extended-spectrum β-lactamase (ESBL)-producing extraintestinal pathogenic Escherichia coli (ExPEC) sequence type ST131 is pandemic, and it is the major contributor to antibiotic resistance in E. coli. Despite its epidemiological superiority, the physiological reasons that decipher its success remain elusive. We aimed to compare the adhesion, invasion and motility potential of ST131 versus other E. coli lineages., Methodology: In this in vitro comparative study, 14 ESBL-producing ExPEC community-onset bacteremia isolates were chosen from a reported clinical collection (Karfunkel D, Carmeli Y, Chmelnitsky I, Kotlovsky T, Navon-Venezia S. Eur J Clin Microbiol Infect Dis 2013;32:513-521). Isolates were divided into two groups, ST131 (n=7) and 'non-ST131', sporadic sequence types (STs) (n=7). Virulence and adhesion genes were screened by PCR in all isolates. Virotyping and serotyping were performed for ST131 isolates. Adhesion and invasion to Caco-2 epithelial cells, and motility on semi-solid agar were quantified and compared between the two groups. Fluorescence microscopy using anti-LPS E. coli antibodies was used for visualization and confirmation of adhesion and invasion., Results: ST131 isolates belonged to the O25b:H4-B2 subclone. Two ST131 virotypes were found, A (two blaCTX-M-15 H30-Rx) and C (two blaCTX-M-15 H30-Rx and three blaCTX-M-14 H30 isolates). The average number of adhesion and virulence genes carried by ExPEC ST131 isolates and non-ST131 isolates was 5.3 and 3.7, respectively (P<0.05). Group analysis showed that ST131 surpassed non-ST131 lineages in all three physiological properties: adherence (17.1 vs 13.1 %, P<0.001), invasion (0.4 vs 0.17 %, P<0.01), and swarming motility on all media tested (P<0.05)., Conclusion: This study demonstrates ST131 superiority that may explain its improved gut-colonization and dissemination capabilities within the host. These insights are an important step in our understanding of ST131 epidemiological success.

CREPT (cell cycle-related and expression elevated protein in tumor) is highly expressed in many kinds of cancer, and has been shown to be prognostic in certain cancers. However, the clinical significance of CREPT in colorectal cancer (CRC) has not been sufficiently investigated. In this study, we examined the CREPT expression in 225 clinical CRC tissues and paired adjacent normal tissues, and analyzed the correlation between CREPT expression and other clinicopathological features. We also evaluated the biological function of CREPT both in vitro and in vivo using knockdown or overexpressing CRC cells. Our results showed that CREPT expressed in 175 of 225 (77.8%) CRC patients and the CREPT expression was significantly associated with tumor differentiation (P = 0.000), Dukes' stages (P = 0.013) and metastasis (P = 0.038). Patients with high CREPT expression tended to have shorter survival time. Multivariate analysis showed that positive CREPT expression can be used as an independent predictor for CRC prognosis. CREPT knockdown cells showed inhibited cell proliferation and arrested cell cycle, while CREPT overexpressing cells showed increased proliferation and promoted cell cycle. In addition, CREPT overexpression significantly promoted tumor growth in vivo. Mechanism study showed that CREPT may regulate cell proliferation and cell cycle through the regulation on cyclin D3, CDK4 and CDK6., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Lactobacillus plantarum strains isolated and identified from naturally-fermented Chinese sauerkraut were examined in vitro for potential probiotic properties and in vivo for cholesterol-lowering effect in mice. Among 7 isolated L. plantarum strains, strains S2-5 and S4-1 were found to possess desirable probiotic properties including ability to survive at pH 2.0 for 60 min, tolerate pancreatin and bile salts, adhere to Caco-2 cells, produce high β-galactosidase activity and antimicrobial activity against Escherichia coli O157 and Shigella flexneri CMCC(B). In addition, strains S2-5 and S4-1 were susceptible to several antibiotics, and capable of reducing cholesterol level in MRS medium by assimilation of cholesterol at 20.39 and 22.28 μg ml(-1), respectively. The in vivo study with L. plantarum S4-1 showed that feeding with fermented milk containing this strain was able to effectively reduce serum cholesterol level in mice, demonstrating its potential as an excellent probiotic candidate for applications in functional products.

Two new 9,11-secosteroidal glycosides, namely, sinularosides A and B (1, 2), together with the known pregnene glycoside 3β-(β-xylopyranosyloxy)-5α-pregna-20-ene (3), were isolated from the South China Sea soft coral Sinularia humilis Ofwegen. The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. This is the first report of 9,11-secosteroidal glycosides from a soft coral and from nature. In in vitro bioassays, the new compounds exhibited potent antimicrobial activities and showed no growth inhibition activity against the tumor cells HepG2 and Caco-2.

Objectives: The aim of this study was to investigate the effect of continuous blood purification (CBP) on early gut mucosal dysfunction in patients with severe acute pancreatitis (SAP)., Methods: Patients with SAP were randomized to receive 24 hours of continuous veno-venous hemofiltration (CVVH; n = 33) or no CVVH (n = 30). Blood samples were taken from the patients at 0, 6, 12, and 24 hours during CVVH therapy. Serum diamine oxidase (DAO) and endotoxin, epithelial permeability, transepithelial electrical resistance (TER) and F-actin rearrangement of the epithelial monolayer were used as the markers for the assessment of gut barrier function and the effect of CBP therapy in patients with SAP., Results: Patients with SAP had increased levels of serum DAO, endotoxin, and epithelial permeability when compared with normal controls, and the increase was more pronounced in patients with organ dysfunction (p<0.01). F-actin rearrangement, loose cell-cell junction, and iNOS mRNA upregulation were found in all patients. After CBP treatment, Acute Physiology and Chronic Health Evaluation II score and SOFA score improved significantly; levels of serum DAO, endotoxin, and epithelial permeability decreased(p<0.05). CBP also significantly attenuated reorganization of actin and downregulated iNOS mRNA expression and NO production (p<0.05)., Conclusions: CBP can not only improve the general conditions but also effectively improve gut barrier dysfunction. The beneficial effect of CBP on gut barrier dysfunction is associated with the improvement of cytoskeletal instability, by downregulating iNOS through the removal of excess proinflammatory factors.

Ethnopharmacological Relevance: Cibotium barometz (L.) J. Sm. (Dicksoniaceae) has been traditionally used as anti-inflammatory and anodyne., Aim of the Study: To investigate the constituents in the rhizomes of Cibotium barometz, and evaluate their permeability in the human Caco-2 model., Materials and Methods: The rhizomes extracts of Cibotium barometz were isolated by chromatographic techniques. Structures of isolated compounds were identified by spectroscopic methods. The permeability of the main constituents was evaluated using human Caco-2 cell monolayer as a model system., Results: Three unusual sesquiterpenes having 1-indanone nucleus (1, 3 and 4) and an unusual orthoester spiropyranosyl derivative of protocatechuic acid (2) were isolated from the rhizomes of Cibotium barometz. Among these, the bilateral permeation of 1, 3 and 4 in Caco-2 model was examined. The apparent permeability coefficients (P(app)) of 1 was identical with those of propranolol, which is often used as reference standard of high permeability. The P(app) values of 3 and 4 were in agreement with those of atenolol, which is often used as reference standard of poor permeability. The permeation rates of 1, 3 and 4 increased linearly as a function of time up to 180 min and with the concentration within the test range of 25-200 microM., Conclusions: This is the first report on the presence of compounds 2 and 3 in this plant and 4 was a new compound. Compound 1 is assigned for a well-absorbed, and 2 and 3 are assigned for the poorly absorbed compounds in human intestine. A passive diffusion mechanism for transport of 1, 3 and 4 in Caco-2 model was proposed. The results provided some useful information for predicting the oral bioavailability of 1, 3 and 4.

A total of 216 Vibrio parahaemolyticus isolates from seafood and clinical samples in eastern China were investigated for their hemolytic and urea-producing phenotypes, presence of putative virulence genes tdh and trh. Twenty-one clinical isolates (84%, 21/25) and 3 seafood isolates (1.57%, 3/191) were tdh-positive while only 3 clinical isolates (12%) and 7 seafood isolates (3.66%) were positive for trh gene. We further examined the pathogenicity of selected V. parahaemolyticus isolates in in vitro and in vivo systems. The clinical isolates were apparently more enteropathogenic (74.26 per thousand vs 62.07 per thousand expressed as intestine/body weight ratio, P<0.01) and more virulent than their seafood counterparts to mice (log LD(50) 6.86 vs 7.40 via orogastric route, P<0.05). They were also more adherent to in vitro cultured cells and of higher cytotoxicity as measured by LDH release of the HeLa cells although there were no statistical differences. The tdh-positive V. parahaemolyticus isolates were of higher enteropathogenicity (P<0.05, 74.24 per thousand vs 60.55 per thousand) and more virulent (log LD(50) 6.55 vs 7.21 via intraperitoneal route, P<0.05) than tdh-negative isolates. The tdh-positive isolates were generally more cytotoxic and adhesive to the cultured cell lines as well. From the in vitro and in vivo pathogenicity profiles, trh-positive isolates seemed to line between tdh-positive isolates and those without tdh and trh. There were two isolates H8 and H10 from clinical cases having moderate enteropathogenicity and virulence to mice, but were tdh-negative yet trh-positive. These results seem to suggest that hemolysins TDH and/or TRH may not be necessarily the only virulence factors of pathogenic V. parahaemolyticus isolates.

Purpose: The aim of this study was to investigate the mechanism of permeation and cytotoxicity of vanadium compounds, [VO(acac)2], [VO(ma)2], and vanadate., Methods: Absorptive transport were carried out in Caco-2 monolayers grown on transwell inserts. Vanadium was quantified using inductively coupled plasma atomic emission spectrometry (ICP-AES). The change of Caco-2 cells in the microvilli morphology and F-actin structure was visualized by transmission electron microscopy and confocal laser scanning microscopy., Results: The three vanadium compounds were taken up by Caco-2 cells via simple passive diffusion. [VO(acac)2] were mainly transcellularly transported and exhibited the highest apparent permeabilty coefficients (8.2 x 10(-6) cm(-1)). The cell accumulation of [VO(acac)2] was found to be greater than that of [VO(ma)2], and vanadate caused much less accumulation than the other two compounds. Vanadium compounds induced intracellular reactive oxygen species, reduced the transepithelial electric resistance, caused morphological change in microvilli, and led to different perturbation of F-actin structure., Conclusions: The three compounds exhibited different permeability due to different diffusion process and cellular uptake. The toxicity of vanadium complexes on Caco-2 monolayer involved F-actin-related change of tight junction and impairment of microvilli. The toxicity was also related to elevated intracellular reactive oxygen species (ROS) and their cellular accumulation.