Publications by authors named "Guangwen Zhang"

41 Publications

Oxymatrine hydrazone (OMTH) synthesis and its protective effect for rheumatoid arthritis through downregulation of MEK/NF-κB pathway.

Environ Toxicol 2021 Aug 29. Epub 2021 Aug 29.

Department of Arthroplasty Surgery, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, China.

Rheumatoid arthritis (RA) is one of the inflammatory diseases detected in more than 1% of the world population. In the present study, oxymatrine hydrazone (OMTH) was synthesized and investigated for treatment of RA in vitro in TNF-α induced fibroblast-like synoviocyte cell model. Cell viability and apoptosis were detected using MTT and flow cytometry assays, respectively. ELISA was used for determination of inflammatory cytokines and western blotting for evaluation of protein expression. Pretreatment of HFLS-RA cells with 0.5, 1.0, 1.5, 2.0, and 2.5 μM doses of OMTH suppressed TNF-α induced promotion of proliferative potential in dose-based manner. The OMTH pretreatment of TNF-α exposed HFLS-RA cells significantly increased apoptotic cell proportion. In TNF-α exposed HFLS-RA cells OMTH pretreatment elevated Bax and suppressed Bcl-2 expression. Treatment of HFLS-RA cells with OMTH prevented TNF-α mediated elevation of IL-1β, IL-6 and IL-8. Moreover, OMTH treatment of HFLS-RA cells effectively suppressed TNF-α mediated elevated levels of MMP-1 and MMP-13. Pretreatment of HFLS-RA cells with OMTH reversed TNF-α mediated promotion of iNOS and COX-2 levels. The MEK/1/2 and p65 phosphorylation in TNF-α exposed HFLS-RA cells was reduced by OMTH pre-treatment in dose-based manner. Thus, OMTH successfully inhibited TNF-α-mediated increased viability of RA synovial cells and activated apoptosis. Pretreatment of TNF-α exposed synovial cells with OMTH targeted phosphorylation of MEK/NF-κB. Therefore, OMTH may act as potential therapeutic agent for RA treatment.
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http://dx.doi.org/10.1002/tox.23357DOI Listing
August 2021

Poria cocos polysaccharides attenuate chronic nonbacterial prostatitis by targeting the gut microbiota: Comparative study of Poria cocos polysaccharides and finasteride in treating chronic prostatitis.

Int J Biol Macromol 2021 Aug 21;189:346-355. Epub 2021 Aug 21.

Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong 510632, PR China. Electronic address:

Finasteride is an antiandrogenic drug used for the clinical treatment of chronic nonbacterial prostatitis (CNP). Recently, we reported the anti-CNP activity of Poria cocos polysaccharides (PPs) in a rat model. In this study, we compared the differences between PPs and finasteride in treating CNP, especially their effects on the gut microbiota. Results showed that both PPs and finasteride significantly reduced the prostate weight and prostate index of CNP rats, and improved the histological damages in the inflamed prostate. Moreover, PPs and finasteride inhibited the production of pro-inflammatory cytokines (TNF-α, IL-2 and IL-8) and androgens (dihydrotestosterone and testosterone). By 16S rDNA sequencing, PPs and finasteride were found to reprogram the gut microbiota into distinct profiles. Further analysis presented that PPs but not finasteride recovered CNP-induced changes in the gut microbiota, including Ruminococcaceae NK4A214 group, uncultured bacterium f Ruminococcaceae, Ruminiclostridium 9, Phascolarctobacterium, Coriobacteriaceae UCG-002 and Oribacterium. LDA effect size (LEfSe) analysis revealed that PPs recovered the gut microbiota by targeting Ruminococcaceae NK4A214 group. Our results suggested that PPs alleviated CNP via different mechanisms from finasteride, especially by regulating the gut microbiota, which offers therapeutic target for the treatment of CNP.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.139DOI Listing
August 2021

Comparable Performance of Deep Learning-Based to Manual-Based Tumor Segmentation in KRAS/NRAS/BRAF Mutation Prediction With MR-Based Radiomics in Rectal Cancer.

Front Oncol 2021 29;11:696706. Epub 2021 Jul 29.

Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Radiomic features extracted from segmented tumor regions have shown great power in gene mutation prediction, while deep learning-based (DL-based) segmentation helps to address the inherent limitations of manual segmentation. We therefore investigated whether deep learning-based segmentation is feasible in predicting KRAS/NRAS/BRAF mutations of rectal cancer using MR-based radiomics. In this study, we proposed DL-based segmentation models with 3D V-net architecture. One hundred and eight patients' images (T2WI and DWI) were collected for training, and another 94 patients' images were collected for validation. We evaluated the DL-based segmentation manner and compared it with the manual-based segmentation manner through comparing the gene prediction performance of six radiomics-based models on the test set. The performance of the DL-based segmentation was evaluated by Dice coefficients, which are 0.878 ± 0.214 and 0.955 ± 0.055 for T2WI and DWI, respectively. The performance of the radiomics-based model in gene prediction based on DL-segmented VOI was evaluated by AUCs (0.714 for T2WI, 0.816 for DWI, and 0.887 for T2WI+DWI), which were comparable to that of corresponding manual-based VOI (0.637 for T2WI, =0.188; 0.872 for DWI, =0.181; and 0.906 for T2WI+DWI, =0.676). The results showed that 3D V-Net architecture could conduct reliable rectal cancer segmentation on T2WI and DWI images. All-relevant radiomics-based models presented similar performances in KRAS/NRAS/BRAF prediction between the two segmentation manners.
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http://dx.doi.org/10.3389/fonc.2021.696706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358773PMC
July 2021

Reprogrammed intestinal functions in Astragalus polysaccharide-alleviated osteoporosis: combined analysis of transcriptomics and DNA methylomics demonstrates the significance of the gut-bone axis in treating osteoporosis.

Food Funct 2021 May 21;12(10):4458-4470. Epub 2021 Apr 21.

Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong 510632, P. R. China.

Researchers have noted that organ-organ communication between bone and intestine has significant effects on bone health and its related diseases. In this study, we collected colonic epithelial tissue from dexamethasone-induced osteoporotic rats and Astragalus polysaccharide (APS)-alleviated osteoporotic rats and employed transcriptome sequencing to investigate the functional changes that occurred in the intestine. Principal component analysis showed that both dexamethasone (inducer of osteoporosis) and APS reprogrammed the gene expression profile of the intestine. Further analysis identified 496 and 291 differentially expressed genes (DEGs) in osteoporotic and APS-treated osteoporotic rats, respectively. KEGG enrichment analysis of these DEGs demonstrated osteoporosis-induced intestinal dysfunctions that were further modified by APS treatment. Further analysis demonstrated that APS could restore intestinal functions by reversing the expression of 53 DEGs in osteoporotic rats. Recovery of osteoclast differentiation and the calcium signalling pathway might contribute to the improvement of osteoporosis. Moreover, utilizing methylC-capture sequencing (MCC-Seq), we studied the changes in DNA methylation and performed epigenetic analysis of dexamethasone- and APS-induced gene expression changes. In this study, osteoporosis was observed to cause intestinal dysfunction, which is a complication of this disease. More importantly, APS was determined to reprogram intestinal functions to alleviate osteoporosis via the gut-bone axis. Our results support the existence of a gut-bone axis and suggest new therapeutic opportunities for the treatment of osteoporosis via the gut-bone axis.
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http://dx.doi.org/10.1039/d1fo00113bDOI Listing
May 2021

Chemical, microbial, and metabolic analysis of Taisui cultured in honey solution.

Food Sci Nutr 2021 Apr 18;9(4):2158-2168. Epub 2021 Feb 18.

Department of Food Science and Engineering Jinan University Guangzhou 510632 China.

Taisui, a special substance occasionally found in China, can now be artificially cultured. In order to evaluate the safety of an artificially cultured Taisui (acTS) and develop it into fermented, functional food or oral liquid, the macronutrients, trace elements, microbial community, and extracellular metabolites of Taisui have been investigated in this study. Results showed that the concentrations of total carbohydrates, protein, fat, total ash, and moisture of wet acTS were 2.13 g/100 g, 0.13 g/100 g, 0.07 g/100 g, 0.04 g/100 g, and 88.3%, respectively. The concentrations of top three trace elements of K, Ca, and P, are 1,424.92 mg/kg, 159.96 mg/kg, and 67.89 mg/kg, respectively. , and were the dominant phyla of bacteria, archaea, and fungi, respectively. , and were the three most abundant genera of bacteria; , and , the most abundant genera of archaea; , and the most abundant genera of fungi. There were 311 metabolites increased in acTS. Most of the metabolites are beneficial to human. These metabolites can be contributed to microbes in acTS. In conclusion, acTS is not a good source of macronutrients and of trace elements, while the safeness of some microorganisms in acTS is also unknown. Nevertheless, it still provides some probiotics and beneficial metabolites for human. It is thus possible to develop acTS into foods when the safety of each microorganism is proved.
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http://dx.doi.org/10.1002/fsn3.2185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020961PMC
April 2021

Reprogrammed Epigenetic Landscape-Prophesied Functions of Bioactive Polysaccharides in Alleviating Diseases: A Pilot Study of DNA Methylome Remodeling in Polysaccharide (APS)-Improved Osteoporosis in a Rat Model.

J Agric Food Chem 2020 Dec 15;68(52):15449-15459. Epub 2020 Dec 15.

Department of Food Science and Engineering, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, Guangdong 510632, P. R. China.

DNA methylation is an epigenetic event that plays critical roles in the pathogenesis, progression, and treatment of human diseases. In this study, we investigated the epigenetic mechanisms for polysaccharide (APS)-improved osteoporosis in a rat model. The results showed that APS significantly changed the DNA methylome in colonic epithelia with great efficiency. Gene set enrichment analysis (GSEA) based on differentially methylated sites (DMSs) revealed that APS caused promoter DNA methylation changes of genes associated with calcium homeostasis, osteoclast/osteoblast balance, Wnt signaling, and hormone-related processes. Further analysis showed high consistency of APS-induced gene methylomic changes in colonic epithelia and its effects on diabetes, virus infection, and wound healing, which had been reported already. Moreover, we suggested new functions and the involved mechanisms of APS in heart disease, neurological disorder, reproductive problem, and olfactory dysfunction. In this study, we offered epigenetic mechanisms for APS-improved osteoporosis. More importantly, we proposed and proved a reliable method to explore the beneficial effects of bioactive polysaccharides by studying DNA methylation changes at nonfocal sites. We firmly believed the promising prospects of this method for its great efficiency, rapidness, and economy in exploring possible beneficial or therapeutic effects of functional macromolecules with one single experiment.
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http://dx.doi.org/10.1021/acs.jafc.0c06483DOI Listing
December 2020

The gut microbiota alteration and the key bacteria in Astragalus polysaccharides (APS)-improved osteoporosis.

Food Res Int 2020 12 21;138(Pt B):109811. Epub 2020 Oct 21.

Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong 510632, PR China. Electronic address:

Osteoporosis is a worldwide epidemic, and certain functional foods can alleviate osteoporosis with great efficiency. Here, in a dexamethasone-induced osteoporosis rat model, it was proved that APS could restore the bone mineral density (BMD) and repair the impairment of bone microarchitecture, two major features of osteoporosis. In APS-treated rats, acid phosphatase 5 (ACP5) and pro-inflammatory cytokines (TNF-α and IL-2) were significantly decreased. This suggested that APS might improve osteoporosis by inhibiting osteoclastogenesis and preventing inflammation. Further analysis on the bacterial community revealed that the structure of gut microbiota was dramatically changed by APS, and 13 bacteria (such as c_Bacteroidia, p_Bacteroidetes, and g_Allpprevotella) could serve as biomarkers for APS-improved osteoporosis. Furthermore, five genera (uncultured_bacterium_f_Ruminococcaceae, Alloprevotella, Ruminococcaceae_UCG-014, Blautia and Lactobacillus) were inferred as the key bacteria in APS-improved osteoporosis. In conclusion, APS-modified gut microbiota and the potential key bacteria to alleviate osteoporosis, as well as its relationship with improved osteoporosis, were investigated in our present study. Our results will help to understand how APS improves osteoporosis by regulating gut microbiota and contribute to the development and application of functional foods to alleviate refractory osteoporosis by regulating targeted intestinal bacteria.
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http://dx.doi.org/10.1016/j.foodres.2020.109811DOI Listing
December 2020

Recent advances in pretreating technology for recycling valuable metals from spent lithium-ion batteries.

J Hazard Mater 2021 Mar 21;406:124332. Epub 2020 Oct 21.

Advanced Analysis and Computation Center, China University of Mining and Technology, No.1 Daxue Road, Jiangsu, Xuzhou 221116, China.

In recent years, the amount of spent lithium-ion batteries (LIBs) increase sharply due to the promotion of new energy vehicles and the limited service life. Recycling of spent LIBs has attracted much attention because of the serious environmental pollution and high economic value. Although some established techniques have been presented in spent LIBs recycling process, but most of them focus on cathode material recycling due to its high economic value. Therefore, preparation of high purity cathode material by a proper pretreating technology is an important procedure. In this paper, the technologies used in the pretreating process of spent LIBs are summarized systematically from three main points of discharging procedure, liberation, and separation. The collaborative application of multi-technologies is the key to realize efficient pretreating process, which can lay the foundation for the subsequent metallurgical process. In addition, an alternative pretreating flowchart of spent LIBs is proposed based on the multi-process collaboration. Pretreating procedures in this process are mainly based on the physical property difference, and they include "Discharging-Shredding-Crushing-Sieving-Separation".
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http://dx.doi.org/10.1016/j.jhazmat.2020.124332DOI Listing
March 2021

Recovery of and Expressions in the Colon Alleviates Collagen-Induced Arthritis in Rats by Specific Bioactive Polysaccharide Intervention.

J Agric Food Chem 2020 Dec 23;68(49):14531-14539. Epub 2020 Nov 23.

Department of Food Science and Engineering, Jinan University, Guangzhou 510632, Guangdong, China.

Rheumatoid arthritis (RA) causes swollen joints and irreversible joint damage and may even elevate cancer risks. Several bioactive nonstarch polysaccharides (NSPs) were reported to alleviate RA, but the key colonic genes accountable for this alleviation were elusive. Using collagen-induced arthritis as an RA model, colonic candidate genes related to RA were selected by transcriptome and methylome. The key genes were determined by comparing the transcriptome, methylome, and quantitative reverse transcription polymerase chain reaction profiles in RA rats with and without polysaccharides' treatment and further validated using polysaccharides and polysaccharides for comparison. Both colonic genes γ-glutamyltransferase 7 () and angiotensin-I-converting enzyme () were downregulated by RA, and they were upregulated after polysaccharides' and polysaccharides' intervention that reduced the RA-caused hypermethylation status in nucleotide sites in the exon/promoter region of the two genes. However, the polysaccharides' intervention barely reduced the hypermethylation in the corresponding sites, failing to recover the expressions of these two genes and improve RA. Therefore, the colonic and can be considered as key genes accountable for RA alleviation by bioactive NSP intervention. This study provides a more comprehensive insight into diet intervention to improve RA.
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http://dx.doi.org/10.1021/acs.jafc.0c06252DOI Listing
December 2020

A critical review of current technologies for the liberation of electrode materials from foils in the recycling process of spent lithium-ion batteries.

Sci Total Environ 2021 Apr 16;766:142382. Epub 2020 Sep 16.

Guangdong Guanghua Technology Co., Ltd., No.295 University Road, Shantou, Guangdong 515063, China.

Proper disposal of spent lithium-ion batteries is beneficial for the resource recycling and pollution elimination. Full liberation of electrode materials, including the liberation between electrode material and current collector (copper/aluminum foils) and the liberation among electrode material particles, is the pivotal precondition for improving the recovery efficiency of electrode materials. In this article, authors attempt to carry out a summary of current technologies used in the liberation of electrode materials derived from spent lithium-ion batteries. However, specialized studies about the liberation of electrode materials are insufficient at present. This research clearly shows that: (1) Organic binder must be removed so as to improve the liberation and metallurgy efficiency of electrode materials; (2) A collaboration of varied technologies is the necessary process to achieve high liberation efficiency between electrode materials and copper/aluminum foils; (3) Pyrolysis may be a recommended technology for removal of organic binder because part of pyrolysis products can be recovered. Finally, an alternative recycling flowchart of spent LIBs is proposed.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142382DOI Listing
April 2021

The scavenging capacity of γ-aminobutyric acid for acrolein and the cytotoxicity of the formed adduct.

Food Funct 2020 Sep;11(9):7736-7747

Institute of Food Safety & Nutrition, Jinan University, Guangzhou 510632, China.

Acrolein is a notorious aldehyde with hazardous impacts on humans. γ-Aminobutyric acid (GABA) is a functional amino acid present widely in foods. This study aimed at investigating the protective mechanism of GABA against acrolein. In simulated physiological and thermal processing models, GABA effectively scavenged acrolein by adduct formation. The cytotoxicity of the formed adduct was evaluated in human bronchial epithelial cell line HBE and normal colonic epithelial cell line NCM460. It tremendously decreased acrolein toxicity and exerted protective effects by ROS reduction. Apoptotic staining and signaling analysis showed that it also interfered with apoptosis via extrinsic and intrinsic pathways. Our findings provide the basic knowledge that GABA is an effective acrolein scavenger and it has potential detoxifying capacity for both exogenous and endogenous acrolein sourced cellular damage.
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http://dx.doi.org/10.1039/c9fo02518aDOI Listing
September 2020

Organics removal combined with in situ thermal-reduction for enhancing the liberation and metallurgy efficiency of LiCoO derived from spent lithium-ion batteries.

Waste Manag 2020 Sep 29;115:113-120. Epub 2020 Jul 29.

Research Institute of Tsinghua University in Shenzhen, Shen Zhen 518057, China.

Liberation and reduction of cathode material are the necessary procedures for improving the recycling efficiency of cathode material derived from spent lithium-ion batteries. In this research work, a pyrolysis technology was utilized to remove the organic binder and enhance liberation of electrode materials. At the same time, pyrolysis treatment can facilitate the thermal-reduction of Co in LiCoO to Co with surface organics, which lays a foundation for the subsequent reductant-free acid leaching. Results indicate that the crystal structure of pure LiCoO is not changed at a pyrolysis temperature of 600 °C, but LiCoO transforms to CoO, LiCO, LiF, and LiO under the reduction action of HF, pyrolytic carbon, and additive carbon black. Water-impact crushing is synchronized with water-leaching to separate electrode materials from aluminum foil and recover Li element. Afterwards, reductant-free acid leaching technology can be utilized to recycle Li and Co from spent LiCoO batteries. Recovery efficiency of Li element in water-leaching process was up to 92.17% while the remaining 7.83% of Li and all Co elements were recovered during reductant-free acid leaching process. Based on the foundation analysis, the green chemical process for recovering valuable metals from spent lithium-ion batteries was proposed.
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http://dx.doi.org/10.1016/j.wasman.2020.05.030DOI Listing
September 2020

Based on Histogram Analysis: ADC Derived from Ultra-high b-Value DWI could be a Non-invasive Specific Biomarker for Rectal Cancer Prognosis.

Sci Rep 2020 06 23;10(1):10158. Epub 2020 Jun 23.

Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.

Aquaporins (AQP) are not only water channel protein, but also potential prognostic indicator and therapeutic target for rectal cancer. Some previous studies have demonstrated the AQP expression could be estimated by ADC value derived from ultra-high b-value diffusion-weighted imaging (DWI). We aim to determine whether ADC could be a new and specific biomarker for indicating the AQP expression and prognostic factors of rectal cancer. 76 untreated patients with rectal cancer confirmed by colonoscopy biopsy were enrolled. ADC value was generated from ultra-high b-value DWI with five b-values (1700-3500 s/mm). AQP (AQP1, 3 and 5)staining intensity was estimated by both of software (QuPath) and manual manner. The relationships between histogram features of ADC and AQP staining intensity were analyzed. The correlations between histogram features of ADC and differentiation degrees (good, moderate, poor), T stage (T1-2 vs T3-4), and lymph node status (N+ vs N-) were also evaluated respectively. The mean, 75 percentile and 97.5 percentile of ADC were correlated with AQP1 staining intensity (r = 0.237, 0.323 and 0.362, respectively, all P < 0.05) . No correlation was found between the histogram features of ADC and AQP3 or AQP5 staining intensity. The mean, 50 percentile, 75 percentile and 97.5 percentile of ADC value exhibited significant differences between differentiation status (all P < 0.05). Histogram features of ADC value showed no significant differences in two subgroups of T stage and lymph node status (all P > 0.05). Histogram analysis showed that the ADC value derived from ultra-high b-value DWI of rectal cancer could reflect AQP1's expression and rectal cancer's malignancy degree. ADC might be a new imaging biomarker for evaluating rectal cancer.
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http://dx.doi.org/10.1038/s41598-020-67263-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311405PMC
June 2020

Pectin and inulin stimulated the mucus formation at a similar level: An omics-based comparative analysis.

J Food Sci 2020 Jun 29;85(6):1939-1947. Epub 2020 May 29.

Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong, 510632, China.

Mucin 2 (MUC2) is the skeleton of colonic mucus that comprises the physical intestinal barrier. Different dietary polysaccharides may affect colonic mucus at different extents. The effect of pectin on MUC2 production is contradictory. To investigate whether and how pectin affected hosts' colonic mucus, the amount of MUC2 in colon, the cecal, mucosal microbiota, and metabolites profiles were analyzed and compared with inulin. The results showed pectin stimulated the production of MUC2 at a similar level to inulin. Both interventions increased the abundance of cecal Lachnospira and Christensenellaceae_R-7_group, and enhanced the production of specific metabolites including soyasapogenol B 24-O-b-d-glucoside, lucyoside Q, trans-EKODE-(E)-Ib, and 1,26-dicaffeoylhexacosanediol. Additionally, pectin increased the relative abundance (RA) of cecal Lactobacillus, and induced less RA of potentially harmful bacteria such as Helicobacter in mucosal microbiota than inulin. In conclusion, we first reported that pectin and inulin stimulated the mucus formation at a similar level. Two genera of cecal bacteria and four metabolites may play an important role in enhancing the production of MUC2. Moreover, the MUC2 production may be unrelated to several traditional health-beneficial bacteria; pectin possibly performed as good as or better than the inulin in rats' gut.
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http://dx.doi.org/10.1111/1750-3841.15163DOI Listing
June 2020

Mechanism of Asbt ()-related bile acid malabsorption in diarrhea after pelvic radiation.

Int J Radiat Biol 2020 04 11;96(4):510-519. Epub 2020 Feb 11.

The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.

Radiation is a mode of treatment for many pelvic malignancies, most of which originate in the gynecologic, gastrointestinal, and genitourinary systems. However, the healthy gut is unavoidably included in the irradiation volume, resulting in undesirable results that manifest as radiation-induced diarrhea (RID), which is the most common side effect of radiation therapy and significantly affects the patients' quality of life. This study aimed to investigate the potential mechanism of diarrhea after pelvic radiotherapy in rats based on the effect of radiation on bile acid homeostasis and sodium-dependent bile acid transporter (Asbt). In this experimental study, male Sprague-Dawley rats were divided into the following groups - pelvic irradiation, cholestyramine-concurrent radiation, and control groups. The rats in the pelvic irradiation group were irradiated in the pelvic region with 2 Gy per day for five consecutive days. The total bile acid (TBA) levels in the ileum, colon, and feces were measured using automatic biochemical analyzer, and the levels of individual bile acids were evaluated by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The mRNA and protein expression of Asbt in ileum were assessed by qRT-PCR and Western blot assay. The rats in the cholestyramine-concurrent radiation group were administered with cholestyramine, a bile acid-chelating resin, and concurrent radiation for 5 days. The body weight of rats was monitored daily, and the degree of diarrhea was scored. Diarrhea was observed at 2 and 3 days post-pelvic radiation. The TBA levels were significantly decreased at 4 and 5 days post-radiation in the ileum ( < .01,  < .01) and increased at 4 and 5 days post-radiation in the colon ( < .05,  < .05). The fecal excretions of TBA were significantly increased at 3, 4, and 5 days post-radiation ( < .05). The levels of individual bile acids were significantly decreased in the ileum and increased in the colon and feces, post-radiation. The mRNA and protein expression of Asbt in the ileum gradually decreased with increasing days of pelvic radiation and significantly decreased at 3 and 5 days post-radiation, respectively. Furthermore, a significant decrease in body weight was observed post-pelvic radiation, and cholestyramine administration did not reverse the weight loss. However, the incidence of RID was decreased after administration of cholestyramine. Bile acid malabsorption is partially responsible for RID post-pelvic radiation in rats, and the potential mechanism is related to the downregulation of the ileal Asbt.
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http://dx.doi.org/10.1080/09553002.2020.1707324DOI Listing
April 2020

Guar gum different from Ganoderma lucidum polysaccharide in alleviating colorectal cancer based on omics analysis.

Food Funct 2020 Jan;11(1):572-584

Department of Food Science and Engineering, Jinan University, Guangzhou 510632, Guangdong, China.

It is unclear if guar gum can alleviate colorectal cancer (CRC). We evaluated the effect of guar gum (unmodified) on the mortality, colon status, serous tumor necrosis factor-alpha (TNF-α) concentration, and gut microbial and colonic epithelial cell gene expression profiles in CRC mice and performed omics analyses to compare these with those of Ganoderma lucidum polysaccharide (GLP), whose main component is β-glucan (>90%). We found that guar gum had a CRC alleviating effect. However, it showed a 20% higher mortality rate, shorter colon length, worse colon status, larger number and size of tumors, higher concentration of serous TNF-α and upregulation of epithelial cell genes (Il10, Cytl1, Igkv7-33, Ighv1-14, Igfbp6 and Foxd3) compared to that of GLP. The higher relative abundance of Akkermansia, the alteration of microbial metabolic pathways, especially those involving chaperones and folding catalysts, fatty acid biosynthesis, glycerophospholipid metabolism, glycolysis/gluconeogenesis, lipid biosynthesis and pyruvate metabolism, and the upregulation of specific genes (Mcpt2, Mcpt9, Des and Sostdc1) were also determined in animals fed a guar gum diet. The results suggested that the alleviating effect of guar gum (an inexpensive polysaccharide) on CRC was inferior to that of GLP (a more expensive polysaccharide). This could potentially be attributed to the increased presence of Akkermansia, the alteration of 10 microbial metabolic pathways and the upregulation of 4 epithelial cell genes.
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http://dx.doi.org/10.1039/c9fo02786fDOI Listing
January 2020

Formation and Identification of Two Hydroxmethylfurfural-Glycine Adducts and Their Cytotoxicity and Absorption in Caco-2 Cells.

J Agric Food Chem 2020 Jan 17;68(1):384-389. Epub 2019 Dec 17.

Department of Food Science and Engineering , Jinan University , Guangzhou , 510632 Guangdong , China.

Our previous research showed that thioacetal and Schiff base formed between 5-hydroxymethylfurfural (HMF) and cysteine or lysine considerably decreased the cytotoxicity of HMF. In this study, two adol condensation adducts, named 2β-amino-3α-hydroxy-3-(5-(hydroxymethyl)furan-2-yl)propanoic acid (HGA) and 2α-amino-3β-hydroxy-3-(5-(hydroxymethyl)furan-2-yl)propanoic acid (HGB), were prepared from the reaction products of glycine and HMF, and their cytotoxicities were investigated in Caco-2 cells. Compared with HMF, HGA and HGB displayed lower cytotoxicities against Caco-2 cells with IC values of 36.50 and 43.47 mM, respectively, versus 16.11 mM (HMF). In contrast to our findings in thioacetal and Schiff base products, HGA and HGB underwent a very high metabolism rate (99%) in Caco-2 cells. HGA and HGB may degrade to other products instead of HMF since no extracellular or intracellular HMF was detected.
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http://dx.doi.org/10.1021/acs.jafc.9b06418DOI Listing
January 2020

Effects of soybean oil and dietary copper levels on nutrient digestion, ruminal fermentation, enzyme activity, microflora and microbial protein synthesis in dairy bulls.

Arch Anim Nutr 2020 Aug 13;74(4):257-270. Epub 2019 Nov 13.

College of Animal Science and Veterinary Medicine, Shanxi Agricultural University , Taigu, Shanxi, P R China.

The study evaluated the effects of soybean oil (SO) and dietary copper levels on nutrient digestion, ruminal fermentation, enzyme activity, microflora and microbial protein synthesis in dairy bulls. Eight Holstein rumen-cannulated bulls (14 ± 0.2 months of age and 326 ± 8.9 kg of body weight) were allocated into a replicated 4 × 4 Latin square design in a 2 × 2 factorial arrangement with factors being 0 or 40 g/kg dietary dry matter (DM) of SO and 0 or 7.68 mg/kg DM of Cu from copper sulphate (CS). The basal diet contained per kg DM 500 g of corn silage, 500 g of concentrate, 28 g of ether extract (EE) and 7.5 mg of Cu. The SO × CS interaction was significant ( < 0.05) for ruminal propionate proportion and acetate to propionate ratio. Dietary SO addition increased ( < 0.05) intake and total tract digestibility of EE but did not affect average daily gain (ADG) of bulls. Dietary CS addition did not affect nutrient intake but increased ( < 0.05) ADG and total tract digestibility of DM, organic matter, crude protein and neutral detergent fibre. Ruminal pH was not affected by treatments. Dietary SO addition did not affect ruminal total volatile fatty acids (VFA) concentration, decreased ( < 0.05) acetate proportion and ammonia N and increased ( < 0.05) propionate proportion. Dietary CS addition did not affect ammonia N, increased ( < 0.05) total VFA concentration and acetate proportion and decreased ( < 0.05) propionate proportion. Acetate to propionate ratio decreased ( < 0.05) with SO addition and increased ( < 0.05) with CS addition. Dietary SO addition decreased ( < 0.05) activity of carboxymethyl cellulase, cellobiase and xylanase as well as population of fungi, protozoa, methanogens, and but increased ( < 0.05) α-amylase activity and population of and . Dietary CS addition increased ( < 0.05) activity of cellulolytic enzyme and protease as well as population of total bacteria, fungi, protozoa, methanogens, primary cellulolytic and proteolytic bacteria. Microbial protein synthesis was unchanged with SO addition but increased ( < 0.05) with CS addition. The results indicated that the addition of CS promoted nutrient digestion and ruminal fermentation by stimulating microbial growth and enzyme activity but did not relieve the negative effects of SO addition on ruminal fermentation in dairy bulls.
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http://dx.doi.org/10.1080/1745039X.2019.1679562DOI Listing
August 2020

Alternating consumption of β-glucan and quercetin reduces mortality in mice with colorectal cancer.

Food Sci Nutr 2019 Oct 4;7(10):3273-3285. Epub 2019 Sep 4.

Department of Food Science and Engineering Jinan University Guangzhou China.

The current dietary recommendations for disease prevention and management are scarce and are not well supported. Beta-glucan or quercetin in a diet can alleviate colorectal cancer (CRC) by regulating the gut microbiota and related genes, but the effects of alternating their consumption for routine ingestion during CRC occurrence remain unknown. This study investigated the effects of alternating the consumption of β-glucan and quercetin for routine ingestion on CRC development in mice. The mortality rate, colonic length, inflammatory cytokines, gut microbiota, and colonic epithelial gene expression in healthy and CRC mice that consumed normal and alternate diets were compared and studied. The results showed that alternating the consumption of β-glucan and quercetin (alternating among a β-glucan diet, a normal diet and a normal diet that was supplemented with quercetin) alleviated colon damage and reduced the mortality rate in CRC mice, with a reduction in mortality of 12.5%. Alternating the consumption of β-glucan and quercetin significantly decreased the TNF-α level, increased the relative abundance of and downregulated three genes ( and ) that are associated with inflammation and cancer. Alternating the consumption of some bioactive compounds, such as β-glucan and quercetin, in food can contribute to human health. This experiment provided some experimental evidence for the dietary recommendations for disease prevention and management.
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http://dx.doi.org/10.1002/fsn3.1187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804767PMC
October 2019

The added value of intravoxel incoherent motion diffusion weighted imaging parameters in differentiating high-grade pancreatic neuroendocrine neoplasms from pancreatic ductal adenocarcinoma.

Oncol Lett 2019 Nov 13;18(5):5448-5458. Epub 2019 Sep 13.

Department of Radiology, Ninth Hospital of Xi'an City, Xi'an, Shaanxi 710068, P.R. China.

The aim of the present study was to investigate the potential significance of intravoxel incoherent motion (IVIM)-diffusion weighted imaging (DWI) in differentiating high-grade pancreatic neuroendocrine neoplasms (pNENs) from pancreatic ductal adenocarcinoma (PDAC). A total of 50 patients, including 37 patients with PDAC and 13 patients with high-grade pNENs, underwent pancreatic multiple b-values DWI with 15 b-values including 0, 10, 20, 40, 60, 80, 100, 150, 200, 400, 800, 1,000, 1,200, 1,500 and 2,000 sec/mm. Standard apparent diffusion coefficient (ADC) and IVIM parameter [slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D), fraction of fast apparent diffusion coefficient (ƒ)] values of PDAC and pNENs were compared. P<0.05 was considered to indicate a statistically significant difference. Receiver operating characteristics analysis was performed in order to evaluate the diagnostic potential of IVIM parameters for differentiating high-grade pNENs from PDAC. D of pNENs was significantly lower compared with that of PDAC (0.460 vs. 0.579×10 mm/sec; P=0.001). D of pNENs was significantly higher compared with that of PDAC (13.361 vs. 4.985×10 mm/sec; P<0.001). Area under the curve of D, D and combined D and D was 0.793, 0.863 and 0.885 respectively. The specificity and sensitivity of D≤0.472×10 mm/sec were 97.3 and 53.9%, respectively, for differentiating high-grade pNENs from PDAC. The specificity and sensitivity of D >9.58×10 mm/sec were 91.9 and 69.2%, respectively, for differentiating high-grade pNENs from PDAC. When D and D were combined, the specificity and sensitivity for differentiating high-grade pNENs from PDAC were 76.9 and 100%, respectively. Taken together, these results indicated that the diffusion-associated parameter D and the perfusion-associated parameter D of IVIM-DWI may differentiate high-grade pNENs from PDAC with high diagnostic accuracy, and that IVIM-DWI may be a valuable biomarker in differentiating pancreatic neoplasms.
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http://dx.doi.org/10.3892/ol.2019.10863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781772PMC
November 2019

Identification of a 5-Hydroxymethylfurfural-Lysine Schiff Base and Its Cytotoxicity in Three Cell Lines.

J Agric Food Chem 2019 Sep 27;67(36):10214-10221. Epub 2019 Aug 27.

School of Life Sciences , Guangzhou University , Guangzhou , Guangdong 510006 , People's Republic of China.

5-Hydroxymethylfurfural (HMF) can undergo the Maillard reaction with amino acids. However, the safety of the products remains unknown. In this study, a HMF-lysine Schiff base named ()--((5'-(hydroxymethyl)furan-2'-yl)methylene)lysine (HML) was identified and detected for the first time in baked foods. HML formation significantly decreased the cytotoxicity (IC) of HMF against GES-1 cells (81.81 versus 5.02 mM and 73.76 versus 2.94 mM for HML versus HMF at 24 and 48 h, respectively), EA.hy926 cells (86.05 versus 4.85 mM and 77.22 versus 0.71 mM, respectively), and Caco-2 cells (155.77 versus 36.84 mM and 112.70 versus 18.51 mM, respectively). Exposure of Caco-2 cells to HMF at 10.0 mM triggered cell apoptosis of 14.02% (versus 8.54% in the control), whereas exposure to HML at 10-15 mM hardly increased cell apoptosis. Moreover, the absorption capacities of HMF and HML by Caco-2 cells were equivalent ( > 0.05) at 7.23-12.57% after incubation at 2 mM for 30-150 min.
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http://dx.doi.org/10.1021/acs.jafc.9b04539DOI Listing
September 2019

CuH-Catalyzed Synthesis of 3-Hydroxyindolines and 2-Aryl-3H-indol-3-ones from -Alkynylnitroarenes, Using Nitro as Both the Nitrogen and Oxygen Source.

Org Lett 2019 08 2;21(16):6194-6198. Epub 2019 Aug 2.

Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering , South China University of Technology , Guangzhou , People's Republic of China , 510640.

CuH-catalyzed diasterospecific synthesis of 3-hydroxyindolines and 2-aryl-3H-indol-3-ones have been developed from -alkynylnitroarenes in the presence of hydrosilane as the reductant. The protocol employs nitro as both nitrogen and oxygen sources for the intramolecular simultaneous construction of C-N and C-O bonds.
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http://dx.doi.org/10.1021/acs.orglett.9b01849DOI Listing
August 2019

Antiobesity Effect of Flaxseed Polysaccharide via Inducing Satiety due to Leptin Resistance Removal and Promoting Lipid Metabolism through the AMP-Activated Protein Kinase (AMPK) Signaling Pathway.

J Agric Food Chem 2019 Jun 14;67(25):7040-7049. Epub 2019 Jun 14.

Department of Food Science and Engineering , Jinan University , Guangzhou , 510632 Guangdong , China.

Obesity is a metabolic syndrome worldwide that causes many chronic diseases. Recently, we found an antiobesity effect of flaxseed polysaccharide (FP), but the mechanism remains to be elucidated. In this study, rats were first induced to develop obesity by being fed a high-fat diet. The obese rats were then fed a control diet, AIN-93M (group HFD), or a 10% FP diet (group FPD). The body weight, body fat, adipose tissue and liver sections, serous total triglycerides, levels of fasting blood glucose in serum, serous insulin, inflammatory cytokines in serum, and serous proteins within the leptin-neuropeptide Y (NPY) and AMP-activated protein kinase (AMPK) signaling pathway were determined and analyzed. FP intervention significantly reduced body weight and abdominal fat from 530 ± 16 g and 2.15% ± 0.30% in group HFD to 478 ± 10 g and 1.38% ± 0.48% in group FPD, respectively. This effect was achieved by removing leptin resistance possibly by inhibiting inflammation and recovering satiety through the significant downregulation of NPY and the upregulation of glucagon-like peptide 1. Adiponectin was then significantly upregulated probably via the gut-brain axis and further activated the AMPK signaling pathway to improve lipid metabolism including the improvement of lipolysis and fatty acid oxidation and the suppression of lipogenesis. This is the first report of the proposed antiobesity mechanism of FP, thereby providing a comprehensive understanding of nonstarch polysaccharides and obesity.
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http://dx.doi.org/10.1021/acs.jafc.9b02434DOI Listing
June 2019

Enhancement in leaching process of lithium and cobalt from spent lithium-ion batteries using benzenesulfonic acid system.

Waste Manag 2019 Apr 26;88:191-199. Epub 2019 Mar 26.

Advanced Analysis and Computation Center, China University of Mining and Technology, Xuzhou 221116, Jiangsu, China.

Recycling of valuable metals from spent lithium ion batteries (LIBs) is of great significance considering the conservation of metal resources and the alleviation of potential hazardous effects on environment. Thus, the present work focuses on enhancing the efficiency of leaching process for the recovery of cobalt and lithium from the cathode active materials of spent LIBs. In this study, benzenesulfonic acid (CHSOH) with a reducing agent hydrogen peroxide (HO) was innovatively used as leaching reagents, and the operating variables were optimized to obtain higher leaching efficiencies. Results show the optimized leaching recovery of 99.58% Li and 96.53% Co was obtained under the conditions of 0.75 M benzenesulfonic acid, 3 vol% HO, a solid to liquid (S/L) ratio of 15 g/L, 500 rpm stirring speed, and 80 min leaching time at 90 °C. Moreover, a new kinetic model was introduced to describe the leaching kinetics of LiCoO from the cathode material. The apparent activation energies E for leaching of lithium and cobalt are 41.06 and 35.21 kJ/mol, respectively, indicating that the surface chemical reaction is the rate-controlling step during this leaching process. Further, the proposed recovery mechanism for spent cathode material was raised by analyzing the experimental results and characterizing the morphological and chemical state (i.e. SEM-EDS, XPS and XRD) of raw material and leaching residues. In comparison with the previous leaching process, this research was found to be efficient, low energy consumption, and environmental friendly.
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http://dx.doi.org/10.1016/j.wasman.2019.03.044DOI Listing
April 2019

polysaccharide improves rat DSS-induced colitis by altering cecal microbiota and gene expression of colonic epithelial cells.

Food Nutr Res 2019 12;63. Epub 2019 Feb 12.

Department of Food Science and Engineering, Jinan University, Guangzhou, China.

Background: The effects of β-glucan on colitis mice are contradictory in previous reports. As a result, it is still unclear whether there is an anti-colitis effect in polysaccharide (GLP), which is mainly composed of β-glucan. Moreover, the association between GLP function and gut microbiota remains to be elucidated.

Objective: This study aimed to investigate whether GLP consumption improved rat dextran sodium sulfate (DSS)-induced colitis by regulating gut microbiota and altering colonic epithelial expression.

Design: The disease activity index (DAI) scores and the cecal short chain fatty acid (SCFA) levels of DSS-induced colitis rats fed with a GLP diet (Group GLP, = 6) and a control diet (Group Con, = 6) were investigated and analyzed. Moreover, the profiles of gut microbiota and colonic epithelial expression were analyzed using metagenomics and transcriptomics.

Results: GLP consumption significantly lowered animal DAI scores by producing more SCFAs by increasing SCFA-producing bacteria such as and reducing pathogens such as in both the small intestine and cecum of rat. Moreover, GLP consumption regulated 11 genes, including six upregulated (, , , , , and ) and five downregulated (, , , , and ) genes enriched in six inflammation-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, resulting in enhancement of immunity and reduction of inflammatory response and colonic cancer risk.

Conclusions: GLP consumption alleviated DSS-induced colitis and may have potential for ulcerative colitis relief.
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http://dx.doi.org/10.29219/fnr.v63.1559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387425PMC
February 2019

The Alternate Consumption of Quercetin and Alliin in the Traditional Asian Diet Reshaped Microbiota and Altered Gene Expression of Colonic Epithelial Cells in Rats.

J Food Sci 2019 Mar 15;84(3):678-686. Epub 2019 Feb 15.

Dept. of Food Science and Engineering, Jinan Univ., Guangzhou, 510632, China.

The diet of traditional Asian is similar to the Mediterranean that was considered as a healthy dietary pattern. The report was scarce on whether different plant-derived components with similar anti-oxidative and anti-inflammatory function such as quercetin and alliin in traditional Asian diet consumed in an alternate style cooperatively affect health including the growth of host and the status of the gut microbiota and colonic epithelial immunity. In the present study, the effects of alternate consumption of quercetin and alliin on host health judging by the profile of gut microbiota and gene expression of colonic epithelial cells were investigated with the Illumina MiSeq sequencing (16S rRNA genes) and Illumina HiSeq (RNA-seq) technique, respectively. The results showed that the alternate consumption significantly increased the rat body weight and reshaped the gut microbiota composition. At the phylum level, it significantly increased the relative abundance of fecal Firmicutes and Cyanobacteria but decreased that of Bacteroidetes (P < 0.05) and increased the relative abundance of Candidatus Arthromitus, Lactococcus, Geobacillus, and Ruminococcus at the genus level that benefits the host's health. The alternate consumption of quercetin and alliin also altered 13 genes expression involved in the KEGG pathways of complement and coagulation cascades and hematopoietic cell lineage to improve the gut immunity. Therefore, the alternate consumption of quercetin and alliin in traditional Asian diet can contribute beneficial metabolic effects by optimizing gut microbiota and altering the immunologic function of colonic epithelial cells, resulting in its potential to improve the sub-health status.
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http://dx.doi.org/10.1111/1750-3841.14473DOI Listing
March 2019

The Formation of Acrylamide from and Its Reduction by 3-Aminopropanamide Occur Simultaneously During Thermal Treatment.

J Food Sci 2018 Oct 19;83(10):2662-2668. Epub 2018 Sep 19.

The Dept. of Food Science and Engineering, Jinan Univ., Guangzhou, 510632, China.

3-Aminopropanamide (3-APA) is the direct precursor of acrylamide produced in the Maillard reaction between asparagine and reducing sugars. In this research, we found that 3-APA could reduce acrylamide by the formation of adducts between acrylamide and 3-APA via Michael addition. The effects of temperature, heating duration and 3-APA/acrylamide ratio on the reduction of acrylamide were investigated. Addition of 3-APA to acrylamide at a molar ratio of 5:3 at 160 °C for 20 min reduced acrylamide by up to 47.29%. The major adduct was identified as 3,3',3'-nitrilotris, and its cytotoxicity on Caco-2 cells was evaluated to be much lower than acrylamide. The viability of Caco-2 cells retained at 88.31% and 86.43% after incubation with 16 mM 3,3',3'-nitrilotris for 24 and 48 hr, respectively, while those incubated with the same concentration of acrylamide were 23.33% and 19.12%, respectively.

Practical Application: The current study reported 3-APA could reduce acrylamide through the Micheal addition reaction between 3-APA and acrylamide. The adduct showed significantly reduced cytotoxicity compared to acrylamide. The research is critical in evaluation and control of food contaminants. The results brought new insights in the area of food safety, especially in the mechanism researches on formation and mitigation of endogenous contaminants in thermal-processed foods.
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http://dx.doi.org/10.1111/1750-3841.14355DOI Listing
October 2018

Grading of pancreatic neuroendocrine neoplasms using pharmacokinetic parameters derived from dynamic contrast-enhanced MRI.

Oncol Lett 2018 Jun 29;15(6):8349-8356. Epub 2018 Mar 29.

Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

The present study aimed to evaluate the diagnostic efficacy of pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in prospective evaluation of pancreatic neuroendocrine neoplasms (pNENs) grading. A total of 25 histologically proven patients with pNENs (30 lesions in total) who underwent DCE-MRI were enrolled. Lesions were divided into G1, G2 neuroendocrine tumor (NET) and G3 NET/neuroendocrine carcinoma (NEC) groups based on their histological findings according to 2017 World Health Organization Neuroendocrine Tumor Classification Guideline. In addition, the same numbers of tumor-free regions were selected using as normal control group. For each group, pharmacokinetic DCE parameters: volume transfer constant (); contrast transfer rate constant (); extravascular extracellular space volume fraction (v); and plasma volume fraction (v) were calculated with Extended Tofts Linear model. Receiver operator characteristics analysis was conducted to assess the diagnostic efficacy of these parameters in pNENs grading. There were significant differences of , , v and v between tumor-free areas and G1, G2 NET (P<0.001). The and of G1 NET were significantly lower compared with those of G2 ones (P<0.005). The area under the curve of and in differentiating G2 from G1 NET were 0.767 and 0.846, respectively. When was >0.667 and k >1.644, the sensitivity of diagnosing G2 NET was the lowest (53.85%), but the specificity was the highest (93.75%). When was >0.667 or >1.644, the sensitivity of diagnosing G2 NET was 92.31%, but the specificity was 75.00%. Pharmacokinetic parameters of DCE-MRI, particularly the quantitative values of and , are helpful for differentiating G2 NET from G1 ones.
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http://dx.doi.org/10.3892/ol.2018.8384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5950181PMC
June 2018

Quantitative parameters of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI): potential application in predicting pathological grades of pancreatic ductal adenocarcinoma.

Quant Imaging Med Surg 2018 Apr;8(3):301-310

Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

Background: The aim of this study was to compare intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) parameters such as standard apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D) and perfusion fraction (ƒ) for differentiating pancreatic ductal adenocarcinoma (PDAC) with different pathological grades.

Methods: Institutional Review Board of our hospital approved this study protocol. Subjects comprised 38 PDACs confirmed by pathology. Pancreatic multiple b values DWI with 15 b values of 0, 10, 20, 40, 60, 80, 100, 150, 200, 400, 800, 1,000, 1200, 1,500, and 2,000 s/mm was performed using GE Discovery MR750 3.0T scanner. ADC, D, D and ƒ values of all PDACs were calculated using mono- and bi-exponential models. Parameters of well/moderately differentiated and poorly differentiated PDAC were compared using Independent Sample -test. P values <0.05 were considered significant.

Results: Mean D value of well/moderately differentiated PDAC was significantly lower than that of poorly differentiated PDAC (0.540×10 0.676×10 mm/s, P<0.001). Mean ƒ value of well/moderately differentiated PDAC was significantly higher than that of poorly differentiated PDAC (60.3% 38.4%, P<0.001). The area under curve value of ƒ in differentiating well/moderately differentiated PDAC from poorly differentiated PDAC was slightly higher than that of D (0.894>0.865). When the D value was less than or equal to 0.599×10 mm/s, the sensitivity and specificity were 100% and 84.6% respectively. When ƒ value was greater than 49.6%, the sensitivity and specificity were 92.0% and 84.6% respectively.

Conclusions: D and ƒ derived from IVIM-DWI model can be used to distinguish well/moderately differentiated PDAC from poorly differentiated PDAC. And to serve this purpose, D and ƒ have high diagnostic performance. IVIM-DWI is a promising and non-invasive tool for predicting pathological grade of PDAC.
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http://dx.doi.org/10.21037/qims.2018.04.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941211PMC
April 2018

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer.

Cell Physiol Biochem 2018 31;45(2):692-705. Epub 2018 Jan 31.

Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.

Background/aims: Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer.

Methods: We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer. Then, we examined the influence of hypoxia on TPM2 expression and methylation status using bisulfite sequencing PCR. Furthermore, we performed TPM2-mediated migration and invasion assays in the context of hypoxia and examined changes in matrix metalloproteinase-2 (MMP2) expression. Finally, we detected the influence of TPM2 on survival and chemotherapy drug sensitivity.

Results: We found that TPM2 expression is down-regulated in breast cancer cells compared to that in normal breast cells. The data from TCGA supported these results. Promoter methylation of TPM2, which could be induced by hypoxia, was responsible for its low expression. Hypoxia might regulate cell invasiveness partly by TPM2 down-regulation-mediated changes of MMP2 expression. Importantly, low TPM2 expression was correlated with lymph node metastasis (P=0.031), tumour node metastasis stage (P=0.01), histological grade (P=0.037), and shorter overall survival (P=0.028). Univariate and multivariate analyses indicated that TPM2 was an independent predictor in breast cancer patients. Paclitaxel chemotherapy did not benefit patients with low TPM2 expression (P<0.0001). TPM2 knockdown significantly reduced cell sensitivity to paclitaxel.

Conclusion: TPM2 is a potential novel tumour suppressor gene in breast cancer. TPM2 is associated with poor survival and chemoresistance to paclitaxel in breast cancer, and TPM2 may represent a promising therapeutic gene target for breast cancer patients with chemoresistance.
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http://dx.doi.org/10.1159/000487162DOI Listing
March 2018
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