Publications by authors named "Hongmei Jiang"

132 Publications

Circadian misalignment leads to changes in cortisol rhythms, blood biochemical variables and serum miRNA profiles.

Biochem Biophys Res Commun 2021 Aug 12;567:9-16. Epub 2021 Jun 12.

State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address:

The circadian clock plays a critical role in synchronizing the inner molecular, metabolic and physiological processes to environmental cues that cycle with a period of 24 h. Non-24 h and shift schedules are commonly used in maritime operations, and both of which can disturb circadian rhythms. In this study, we first conducted an experiment in which the volunteers followed a 3-d rotary schedule with consecutive shift in sleep time (rotatory schedule), and analyzed the changes in salivary cortisol rhythms and blood variables. Next we conducted another experiment in which the volunteers followed an 8 h-on and 4-h off schedule (non-24-h schedule) to compare the changes in blood/serum variables. The rotatory schedule led to elevated levels of serum cortisol during the early stage, and the phase became delayed during the early and late stages. Interestingly, both of the schedules caused comprehensive changes in blood/serum biochemical variables and increased phosphate levels. Furthermore, transcriptomic analysis of the plasma miRNAs from the volunteers following the rotatory schedule identified a subset of serum miRNAs targeting genes involved in circadian rhythms, sleep homeostasis, phosphate transport and multiple important physiological processes. Overexpression of miRNAs targeting the phosphate transport associated genes, SLC20A1 and SLC20A2, showed altered expression due to rotary schedule resulted in attenuated cellular levels of phosphate, which might account for the changed levels in serum phosphate. These findings would further our understanding of the deleterious effects of shift schedules and help to optimize and enhance the performances and welfare of personnel working on similar schedules.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.015DOI Listing
August 2021

Progressive back-projection network for COVID-CT super-resolution.

Comput Methods Programs Biomed 2021 May 24;208:106193. Epub 2021 May 24.

College of Electrical Engineering and Information Engineering, Lanzhou University of Technology, Lanzhou 730050, China; Key Laboratory of Gansu Advanced Control for Industrial Processes, Lanzhou 730050, China; National Experimental Teaching Center of Electrical and Control Engineering, Lanzhou University of Technology, Lanzhou 730050, China. Electronic address:

Background And Objective: Recently, the COVID-19 epidemic has become more and more serious around the world, how to improve the image resolution of COVID-CT is a very important task. The network based on progressive upsampling for COVID-CT super-resolution increases the reconstruction error. This paper proposes a progressive back-projection network (PBPN) for COVID-CT super-resolution to solve this problem.

Methods: In this paper, we propose a progressive back-projection network (PBPN) for COVID-CT super-resolution. PBPN is divided into two stages, and each stage consists of back-projection, deep feature extraction and upscaling. We design an up-projection and down-projection residual module to minimize the reconstruction error and construct a residual attention module to extract deep features. In each stage, firstly, PBPN performs back-projection to extract shallow features by two up-projection and down-projection residual modules; then, PBPN extracts deep features from the shallow features by two residual attention modules; finally, PBPN upsamples the deep features through sub-pixel convolution.

Results: The proposed method achieves the improvements of about 0.14~0.47 dB/0.0012~0.0060 for × 2 scale factor, 0.02~0.08 dB/0.0024~0.0059 for × 3 scale factor, and 0.08~0.41 dB/ 0.0040~0.0147 for × 4 scale factor than state-of-the-art methods (Bicubic, SRCNN, FSRCNN, VDSR, LapSRN, DRCN and DSRN) in terms of PSNR/SSIM on benchmark datasets.

Conclusions: The proposed mehtod obtains better performance for COVID-CT super-resolution and reconstructs high-quality high-resolution COVID-CT images that contain more details and edges.
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http://dx.doi.org/10.1016/j.cmpb.2021.106193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142806PMC
May 2021

Epigallocatechin Gallate Can Protect Mice From Acute Stress Induced by LPS While Stabilizing Gut Microbes and Serum Metabolites Levels.

Front Immunol 2021 1;12:640305. Epub 2021 Apr 1.

College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, China.

Epigallocatechin gallate (EGCG) has potent biological activity as well as strong antioxidant and anti-inflammatory effects. This study aims to explore the protective effect of EGCG on LPS-induced acute injury. We randomly divided 18 mice into three groups: CON, LPS, and EGCG-LPS. We gave the EGCG-LPS group gavage treatment with EGCG on day 8-15 and an intraperitoneal injection of LPS on day 16 to induce acute injury. The results showed that, compared with the LPS group, the bodyweight of the mice in the EGCG-LPS group increased significantly and effectively inhibited the morphological damage of the jejunum and liver. We measured liver tissue and found that the EGCG gavage treatment significantly inhibited the pro-inflammatory factors () and oxidation indicators (MPO, NO, ALT, and AST) levels increase. The microbiological results showed that the EGCG gavage treatment reshaped the disturbance done to the intestinal microbial community in the mice by LPS, reversed the changes in the abundance ratio of /, and significantly reduced the abundance of . Finally, the serum metabolomics results showed that, when compared with the LPS group, the gavage treatment of EGCG significantly increased the concentration of sphingomyelin (d17:1/17:0), sphingomyelin (d16:1/20:0), and significantly reduced the content of trans-Hexadec-2-enoyl carnitine, and so on. Therefore, we believe that EGCG can protect mice from acute stress induced by LPS while stabilizing gut microbes in general, improving the metabolism of sphingolipids, and inhibiting the content of harmful metabolites.
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http://dx.doi.org/10.3389/fimmu.2021.640305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047319PMC
April 2021

[Tolerogenic dendritic cells alleviate joint inflammation and arthropathy via reducing Th1 and Th17 cell proportion in CIA rats].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Mar;37(3):193-198

Department of Clinical Microbiology and Immunology, School of Medical Laboratory Science, Guizhou Medical University, Guiyang 550025, China. *Corresponding author, E-mail:

Objective To investigate the effects of tolerogenic dendritic cells (tolDCs) induced by nuclear factor κB oligodeoxynucleotide decoy (NF-κB ODN decoy) on Th1 cells, Th2 cells, Th17 cells and regulatory T cells (Tregs) and the intervention effects on collagen-induced arthritis (CIA) rats. Methods SD female rats used to establish CIA rat models were divided into four groups, including a CIA model group, a bovine type II collagen-decoy-dendritic cell (Col2-decoy DC) treatment group, a blank control group, and a Col2-decoy DC control group. On the 20th days after the first immunization, the rats were injected with tolDCs via the tail vein, and the rats were sacrificed on the 7th weeks. The proportions of Th1 cells, Th2 cells, Th17 cells, and Tregs in the rat spleen were detected by flow cytometry. The ankle joint pathomorphological change was evaluated by HE staining, and the arthritis index (AI) was scored. Results Compared with the CIA model group, the Col2-decoy DC group had lower AI and milder ankle joint pathomorphological change. The percentages of Th1 cells and Th17 cells in the spleen CD4 T cells decreased, while the percentages of Th2 cells and Tregs increased. Conclusion The treatment of tolDCs can alleviate the inflammation and arthropathy of CIA rats by reducing the proportion of Th1 and Th17 cells in CD4 T cells.
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March 2021

Roles of Macrophages in the Development and Treatment of Gut Inflammation.

Front Cell Dev Biol 2021 2;9:625423. Epub 2021 Mar 2.

College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, China.

Macrophages, which are functional plasticity cells, have the ability to phagocytize and digest foreign substances and acquire pro-(M1-like) or anti-inflammatory (M2-like) phenotypes according to their microenvironment. The large number of macrophages in the intestinal tract, play a significant role in maintaining the homeostasis of microorganisms on the surface of the intestinal mucosa and in the continuous renewal of intestinal epithelial cells. They are not only responsible for innate immunity, but also participate in the development of intestinal inflammation. A clear understanding of the function of macrophages, as well as their role in pathogens and inflammatory response, will delineate the next steps in the treatment of intestinal inflammatory diseases. In this review, we discuss the origin and development of macrophages and their role in the intestinal inflammatory response or infection. In addition, the effects of macrophages in the occurrence and development of inflammatory bowel disease (IBD), and their role in inducing fibrosis, activating T cells, reducing colitis, and treating intestinal inflammation were also reviewed in this paper.
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http://dx.doi.org/10.3389/fcell.2021.625423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960654PMC
March 2021

Targeting NSD2-mediated SRC-3 liquid-liquid phase separation sensitizes bortezomib treatment in multiple myeloma.

Nat Commun 2021 02 15;12(1):1022. Epub 2021 Feb 15.

The province and ministry co-sponsored collaborative innovation center for medical epigenetics; Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases; Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Heping, Tianjin, China.

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid-liquid phase separation to supranormally modify histone H3 lysine 36 dimethylation (H3K36me2) modifications on promoters of anti-apoptotic genes. Targeting SRC-3 or interference of its interactions with NSD2 using a newly developed inhibitor, SI-2, sensitizes BTZ treatment and overcomes drug resistance both in vitro and in vivo. Taken together, our findings elucidate a previously unrecognized orchestration of SRC-3 and NSD2 in acquired drug resistance of MM and suggest that SI-2 may be efficacious for overcoming drug resistance in MM patients.
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http://dx.doi.org/10.1038/s41467-021-21386-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884723PMC
February 2021

Potential role of Lactobacillus plantarum in colitis induced by dextran sulfate sodium through altering gut microbiota and host metabolism in murine model.

Sci China Life Sci 2021 Feb 10. Epub 2021 Feb 10.

College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, 410128, China.

Inflammatory bowel disease (IBD) is a chronic lifelong disease characterized by inflammation of the gastrointestinal tract. Although more and more treatment options serve IBD, there is still no cure. It is important to find an effective treatment for IBD. This study aims to investigate whether Lactobacillus plantarum (L. plantarum) could alleviate colitis induced by dextran sulfate sodium (DSS). Following the DSS challenge, L. plantarum on DSS-mediated inflammatory colon lesions in mice, and L. plantarum therapy heightened the relative abundance of the colon-resident Actinobacteria. Analysis of serum metabolomics also indicated that the content of MG (18:4 (6Z, 9Z, 12Z, 15Z)/0:0/0:0) was increased in response to L. plantarum therapy, and this was also the case for indolepyruvate and 1-hydroxyibuprofen. However, 13-oxooctadecadienoic acid (13-oxoODE) and indolylacryloylglycine content fell following the DSS challenge. Based on these results, the study elucidates the mitigatory effects of L. plantarum in colitis, which depend on its regulation of the colonic microbial community and its modification of serum metabolites. The results revealed that L. plantarum mitigated inflammatory colon lesions, reprogrammed the microbial community and altered the level of serum metabolites in a murine model challenged with DSS. The study may present a potential therapeutic strategy for colitis.
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http://dx.doi.org/10.1007/s11427-020-1835-4DOI Listing
February 2021

Degradation and effect of 6:2 fluorotelomer alcohol in aerobic composting of sludge.

Biodegradation 2021 Feb 22;32(1):99-112. Epub 2021 Jan 22.

Department of Environmental Engineering, College of Biology and the Environment, Nanjing Forestry University, Nanjing, 210037, China.

Perfluoroalkyl carboxylates (PFCAs) is toxic to the environment and human health. However, the degradation characteristics of fluorotelomer alcohols (FTOHs), precursors of PFACAs biodegradation, in the sludge during aerobic composting remain unclear. In this study, the degradation characteristics of 6:2 FTOH in sewage sludge by composting were researched and the influences of 6:2 FTOH on the composting process and microbial communities of the sludge were evaluated. After 52 days of composting, 6:2 FTOH retained only 0.73% of its original concentration, and its half-life was less than 1 d; 6:2 FTOH was degraded finally to perfluorohex unsaturated acid, perfluoropentanoic acid, 5:3 polyfluorinated acid (FTCA), 4:3 FTCA, and perfluorobutanoic acid through two pathways; and 6:2 FTCA and 6:2 fluorotel unsaturated acid were the intermediate products. Notably, dosing with 6:2 FTOH affected the composting process of sewage sludge. Additionally, 50 mg/kg 6:2 FTOH resulted in a decrease in the microbial richness and diversity of sludge compost. When compared with the compost without 6:2 FTOH, the proportion of Proteobacteria had increased, and the proportion of Firmicutes had decreased as the concentration of 6:2 FTOH increased. The negative effect of a dosage of 50 mg/kg 6:2 FTOH was more obvious than the effect of other treatments. This study expanded our understanding of the risk of sludge contaminated by 6:2 FTOH being used as a fertilizer after composting.
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http://dx.doi.org/10.1007/s10532-020-09924-9DOI Listing
February 2021

Hypoxia-induced CREB cooperates MMSET to modify chromatin and promote DKK1 expression in multiple myeloma.

Oncogene 2021 02 8;40(7):1231-1241. Epub 2021 Jan 8.

The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases, Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Heping, Tianjin, China.

Myeloma cells produce excessive levels of dickkopf-1 (DKK1), which mediates the inhibition of Wnt signaling in osteoblasts, leading to multiple myeloma (MM) bone disease. Nevertheless, the precise mechanisms underlying DKK1 overexpression in myeloma remain incompletely understood. Herein, we provide evidence that hypoxia promotes DKK1 expression in myeloma cells. Under hypoxic conditions, p38 kinase phosphorylated cAMP-responsive element-binding protein (CREB) and drove its nuclear import to activate DKK1 transcription. In addition, high levels of DKK1 were associated with the presence of focal bone lesions in patients with t(4;14) MM, overexpressing the histone methyltransferase MMSET, which was identified as a downstream target gene of hypoxia-inducible factor (HIF)-1α. Furthermore, we found that CREB could recruit MMSET, leading to the stabilization of HIF-1α protein and the increased dimethylation of histone H3 at lysine 36 on the DKK1 promoter. Knockdown of CREB in myeloma cells alleviated the suppression of osteoblastogenesis by myeloma-secreted DKK1 in vitro. Combined treatment with a CREB inhibitor and the hypoxia-activated prodrug TH-302 (evofosfamide) significantly reduced MM-induced bone destruction in vivo. Taken together, our findings reveal that hypoxia and a cytogenetic abnormality regulate DKK1 expression in myeloma cells, and provide an additional rationale for the development of therapeutic strategies that interrupt DKK1 to cure MM.
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http://dx.doi.org/10.1038/s41388-020-01590-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892339PMC
February 2021

NinimHMDA: Neural integration of neighborhood information on a multiplex heterogeneous network for multiple types of human Microbe-Disease association.

Bioinformatics 2021 Jan 8. Epub 2021 Jan 8.

Department of Statistics, Northwestern University, Evanston, IL, 60208, USA.

Motivation: Many computational methods have been recently proposed to identify differentially abundant microbes related to a single disease; however, few studies have focused on large-scale microbe-disease association prediction using existing experimentally verified associations. This area has critical meanings. For example, it can help to rank and select potential candidate microbes for different diseases at-scale for downstream lab validation experiments and it utilizes existing evidence instead of the microbiome abundance data which usually costs money and time to generate.

Results: We construct a multiplex heterogeneous network (MHEN) using human microbe-disease association database, Disbiome, and other prior biological databases, and define the large-scale human microbe-disease association prediction as link prediction problems on MHEN. We develop an end-to-end graph convolutional neural network-based mining model NinimHMDA which can not only integrate different prior biological knowledge but also predict different types of microbe-disease associations (e.g. a microbe may be reduced or elevated under the impact of a disease) using one-time model training. To the best of our knowledge, this is the first method that targets on predicting different association types between microbes and diseases. Results from large-scale cross validation and case studies show that our model is highly competitive compared to other commonly used approaches.

Availability: The codes are available at Github https://github.com/yuanjing-ma/NinimHMDA.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa1080DOI Listing
January 2021

Leptin correlates with monocytes activation and severe condition in COVID-19 patients.

J Leukoc Biol 2021 07 6;110(1):9-20. Epub 2021 Jan 6.

Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases, School of Basic Medical Science, Tianjin Medical University, Heping, Tianjin, China.

Excessive monocyte activation with the development of excessive or uncontrolled release of proinflammatory cytokines often results in host tissue injury and even death in patients with pneumonia caused by the 2019 novel coronavirus. However, the changes of cytokine profiles of coronavirus disease 2019 (COVID-19) patients, as well as the underlying mechanisms that are involved, remain unknown. Using a cytokine array containing 174 inflammation-related cytokines, we found significantly altered cytokine profiles in severe COVID-19 patients compared with those in mild patients or healthy controls, and identified leptin, CXCL-10, IL-6, IL-10, IL-12, and TNF-α as the top differentially expressed cytokines. Notably, leptin showed high consistency with CXCL-10 and TNF-α in predicting disease severity, and correlated with body mass index, decreased lymphocyte counts, and disease progression. Further analysis demonstrated that monocytes in severe patients with higher leptin levels were inclined toward M1 polarization. Mechanistic studies revealed that leptin synergistically up-regulated expression levels of inflammatory cytokines and surface markers with IL-6 in monocytes through STAT3 and NF-κB signaling pathways. Collectively, our results suggest that overweight COVID-19 patients were prone to have higher leptin levels, which further activated monocytes, resulting in amplified or dysregulated immune responses. Taken together, our findings argue that leptin correlates severity of COVID-19 and may indicate a possible mechanism by which overweight patients have a greater tendency to develop severe conditions.
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http://dx.doi.org/10.1002/JLB.5HI1020-704RDOI Listing
July 2021

DiR-labeled tolerogenic dendritic cells for targeted imaging in collagen- induced arthritis rats.

Int Immunopharmacol 2021 Feb 24;91:107273. Epub 2020 Dec 24.

School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550000, Guizhou, China; Department of Microbiology and Immunology, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou, China. Electronic address:

Tolerogenic dendritic cells (tolDCs) are immunosuppressive cells and play an important role in rheumatoid arthritis (RA) as immunotherapeutic tools. We aimed to investigate whether allogeneic tolDCs (allo-tolDCs) and autologous tolDCs (auto-tolDCs) had long-time tolerogenic potential in vivo and improve arthritis in collagen-induced arthritis (CIA) rats. TolDCs were induced by NF-κB Decoy ODN, and loaded with Bovine Type II collagen (CII- loaded tolDCs) and identified by flow cytometry, and labeled with DiR and injected into CIA rats. The biodistribution of DiR-labeled tolDCs was monitored by IVIS imaging at different time points. Major organs were harvested and analyzed by ex-in vivo cell imaging. The tolDCs were successfully constructed, along with expressing low levels of CD80 and CD86 compared to DCs. The fluorescent signals of all DiR (+) groups were observed at least 25 days, and as long as 35 days. DiR (+) CII- loaded allo-and auto-tolDCs at post injection mainly distributed in the chest and abdomen and gradually moved to limb joints over time. The allo- and auto-tolDCs decreased the expression of IFN-γ and IL-2 in CIA rats with different severity compared to CIA rats without tolDCs treatment, while significantly increased the expression of IL-4 and IL-10. Additionally, these tolDCs ameliorated the ankle joints injury in CIA rats with different severity. The both allo- and auto-tolDCs showed long-time tolerogenic potential in vivo and ameliorated arthritis in CIA rats with different severity.
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http://dx.doi.org/10.1016/j.intimp.2020.107273DOI Listing
February 2021

Increases the Abundance of and Affects the Serum Metabolome to Alleviate DSS-Induced Colitis in a Murine Model.

Front Cell Dev Biol 2020 21;8:591408. Epub 2020 Oct 21.

Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China.

has the beneficial function of regulating the host's immune system and plays an indispensable role in intestinal health. The purpose of this study was to investigate the specific mechanism by which relieves dextran sulfate sodium (DSS) induced ulcerative colon inflammation. We randomly divided 24 mice into three groups, which were administered either a basic diet, drinking water with 2.5% DSS (DSS), or drinking water with 2.5% DSS and intragastric administration of (DSS + ). DSS was added to the drinking water on days 8 to 12, and was administered on days 12 to 19. Serum was collected for metabolomic analysis, colon length and weight were measured, and colon contents were collected to detect microbial structural composition. Compared with the DSS group, the DSS + group had significantly higher levels of indolepyruvate and pantothenic acid in the serum and significantly lower levels of 3,4-dimethyl-5-pentyl-2-furannonanoic acid and 5-oxo-6-trans-leukotriene B4. Moreover, compared with the other two groups, the DSS + group had a significantly greater abundance of . The abundance of was positively correlated with indolepyruvate and pantothenic acid levels. Therefore, can interact with to increase its abundance in the intestinal tract. This results in the production of metabolites that are beneficial for the regulation of intestinal immunity, thereby alleviating DSS-induced ulcerative colon inflammation.
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http://dx.doi.org/10.3389/fcell.2020.591408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609924PMC
October 2020

Facile construction of a molecularly imprinted polymer-based electrochemical sensor for the detection of milk amyloid A.

Mikrochim Acta 2020 Nov 5;187(12):642. Epub 2020 Nov 5.

MOE Joint International Research Laboratory of Animal Health and Food safety, Nanjing Agricultural University, Nanjing, 210095, China.

A molecularly imprinted electrochemical sensor for the detection of serum amyloid A (MAA) in milk was established for early diagnosis of subclinical mastitis in dairy cows. The electrochemical sensor was initially constructed using a nanocomposite material (reduced graphene oxide/gold nanoparticles, [email protected]) to modify the working electrode. The template protein, MAA, was then immobilized using pyrrole as the functional monomer to carry out the electropolymerization. Finally, the template protein was removed to form a molecular imprint film with the capability to qualitatively and quantitatively signaling of MAA. Cyclic voltammetry (CV), differential pulse voltammetry (DPV), and scanning electron microscopy (SEM) were used to characterize the modification process of the molecularly imprinted electrochemical sensors. Under optimized conditions, the sensor shows two well-behaved linear relationships in the MAA concentration range 0.01 to 200 ng/mL. A lower detection limit was estimated to be 5 pg/mL (S/N = 3). Other parameters including the selectivity, reproducibility (RSD 3.2%), and recovery rate (96.1-103%) are all satisfactory. Compared with the traditional methods, detection of MAA to determine the subclinical mastitis of dairy cows can efficiently be diagnosed and hence prevent an outbreak of dairy cow mastitis. The electrochemical sensor can detect MAA more rapidly, sensitively, and inexpensively than the ELISA-based MAA detection. These advantages indicate that the method is promising for early diagnosis of dairy cows.
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http://dx.doi.org/10.1007/s00604-020-04619-7DOI Listing
November 2020

Genetic-Based Hypertension Subtype Identification Using Informative SNPs.

Genes (Basel) 2020 10 27;11(11). Epub 2020 Oct 27.

Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

In this work, we proposed a process to select informative genetic variants for identifying clinically meaningful subtypes of hypertensive patients. We studied 575 African American (AA) and 612 Caucasian hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study and analyzed each race-based group separately. All study participants underwent GWAS (Genome-Wide Association Studies) and echocardiography. We applied a variety of statistical methods and filtering criteria, including generalized linear models, F statistics, burden tests, deleterious variant filtering, and others to select the most informative hypertension-related genetic variants. We performed an unsupervised learning algorithm non-negative matrix factorization (NMF) to identify hypertension subtypes with similar genetic characteristics. Kruskal-Wallis tests were used to demonstrate the clinical meaningfulness of genetic-based hypertension subtypes. Two subgroups were identified for both African American and Caucasian HyperGEN participants. In both AAs and Caucasians, indices of cardiac mechanics differed significantly by hypertension subtypes. African Americans tend to have more genetic variants compared to Caucasians; therefore, using genetic information to distinguish the disease subtypes for this group of people is relatively challenging, but we were able to identify two subtypes whose cardiac mechanics have statistically different distributions using the proposed process. The research gives a promising direction in using statistical methods to select genetic information and identify subgroups of diseases, which may inform the development and trial of novel targeted therapies.
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http://dx.doi.org/10.3390/genes11111265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693873PMC
October 2020

Frequency and clinicopathologic associations of DNA mismatch repair protein deficiency in ampullary carcinoma: Routine testing is indicated.

Cancer 2020 11 28;126(21):4788-4799. Epub 2020 Aug 28.

Department of Pathology, Koç University School of Medicine, Istanbul, Turkey.

Background: The significance of DNA mismatch repair (MMR) deficiency in ampullary cancers (ACs) has not been established.

Methods: In total, 127 ACs with invasive carcinomas measuring ≥3 mmthat had adequate tissue were analyzed immunohistochemically.

Results: MMR loss was detected in 18% of ACs (higher than in colorectal cancers). Twelve tumors with MLH1-PMS2 loss were negative for BRAF V600E mutation, suggesting a Lynch syndrome association. MMR-deficient tumors (n = 23), comparedwith MMR-intact tumors (n = 104), showed a striking male predominance (male:female ratio, 4.7). Although the deficient tumors had slightly larger invasion size (2.7 vs 2.1 cm), they also had more expansile growth and less invasiveness, including less perineural invasion, and they ultimately had lower tumor (T) classification and less lymph node metastasis (30% vs 53%; P = .04). More important, patients who had MMR-deficient tumors had better clinical outcomes, with a 5-year overall survival rate of 68% versus 45% (P = .03), which was even more pronounced in those who had higher Tclassification (5-year overall survival, 69% vs 34%; P = .04). MMR deficiencyhad a statistically significant association with medullary phenotype, pushing-border invasion, and tumor-infiltrating immune cells, and it occurred more frequently in ampullary-duodenal type tumors. Programed cell death-ligand 1 (PD-L1) levels analyzed in the 22 MMR-deficient ACs revealed that all medullary carcinomas were positive. Nonmedullary MMR-deficient carcinomas expressed PD-L1 in 33% of tumors cells according to the criteria for a combined positive score ≥1, but all were negative according to the tumor proportion score≥1 method.

Conclusions: In ACs, MMR deficiency is even more frequent (18%) than in colon cancer and often has a Lynch-suggestive profile, thus routine testing is warranted. Male gender, pushing-border infiltration, ampullary-duodenal origin, medullary histology, and tumor-related inflammation have a significantly higher association with MMR deficiency. MMR-deficient tumors have less aggressive behavior. PD-L1 expression is common in medullary-phenotype ACs, thus immunotherapy should be considered at least for this group.
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http://dx.doi.org/10.1002/cncr.33135DOI Listing
November 2020

The Protective Effect of Polyphenols for Colorectal Cancer.

Front Immunol 2020 10;11:1407. Epub 2020 Jul 10.

Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China.

Colorectal cancer (CRC) is one of the most prevalent cancers that threaten people in many countries. It is a multi-factorial chronic disease caused by a combination of genetic and environmental factors, but it is mainly related to lifestyle factors, including diet. Plentiful plant foods and beverages are abundant in polyphenols with antioxidant, anti-atherosclerotic, anti-inflammatory, and anticancer properties. These compounds participate in host nutrition and disease pathology regulation in different ways. Polyphenolic compounds have been used to prevent and inhibit the development and prognosis of cancer, and examples include green tea polyphenol (-)epigallocatechin-3-O-gallate (EGCG), curcumin, and resveratrol. Of course, there are more known and unknown polyphenol compounds that need to be further explored for their anticancer properties. This article focuses on the fact that polyphenols affect the progression of CRC by controlling intestinal inflammation, epigenetics, and the intestinal microbe in the aspects of prevention, treatment, and prognosis.
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http://dx.doi.org/10.3389/fimmu.2020.01407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366338PMC
April 2021

Microbial community dissimilarity for source tracking with application in forensic studies.

PLoS One 2020 23;15(7):e0236082. Epub 2020 Jul 23.

Interdisciplinary Program in Statistics and Data Science, The University of Arizona, Tucson, Arizona, United States.

Microbial source-tracking is a useful tool for trace evidence analysis in Forensics. Community-wide massively parallel sequencing profiles can bypass the need for satellite microbes or marker sets, which are unreliable when handling unstable samples. We propose a novel method utilizing Aitchison distance to select important suspects/sources, and then integrate it with existing algorithms in source tracking to estimate the proportions of microbial sample coming from important suspects/sources. A series of comprehensive simulation studies show that the proposed method is capable of accurate selection and therefore improves the performance of current methods such as Bayesian SourceTracker and FEAST in the presence of noise microbial sources.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236082PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377425PMC
September 2020

Aberrant expression of miRNA-192-5p contributes to N,N-dimethylformamide-induced hepatic apoptosis.

J Appl Toxicol 2020 12 10;40(12):1683-1693. Epub 2020 Jul 10.

Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Excessive exposure to N,N-dimethylformamide (DMF) can lead to occupational liver poisoning in workers; however, the underlying mechanism is not fully clarified. The importance of microRNAs (miRNAs) in chemical-induced hepatotoxicity has been demonstrated. To determine whether miRNAs are also involved in DMF-induced hepatotoxicity, we systematically analyzed the miRNA expression profiles in DMF-treated (75 and 150 mm) HL-7702 liver cells and controls by high-throughput sequencing. Among the altered miRNAs, miR-192-5p was the most significantly upregulated in HL-7702 cells after DMF exposure and was involved in DMF-mediated cell apoptosis. By contrast, suppression of miR-192-5p in HL-7702 cells attenuated the apoptosis induced by DMF. Furthermore, the anti-apoptotic gene (NIN1/RPN12 binding protein 1 homolog [NOB1]) was predicted to be a potential miR-192-5p target according to bioinformatics analysis. The direct interaction between miR-192-5p and NOB1 was confirmed by the dual-luciferase activity assay in HEK293FT cells. Overexpression of miR-192-5p efficiently reduced NOB1 mRNA and protein expression in HL-7702 cells. Alteration in NOB1 expression influenced DMF-induced hepatotoxicity by affecting hepatic apoptosis. In addition, the inverse correlation between miR-192-5p expression levels and NOB1 expression was further confirmed in DMF-exposed mouse liver tissue samples. These observations demonstrated that promotion of apoptosis from the suppression of NOB1 by miR-192-5p overexpression was responsible for the DMF-induced hepatotoxicity. This work provides the molecular mechanism at the miRNA level for hepatic apoptosis induced by DMF.
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http://dx.doi.org/10.1002/jat.4028DOI Listing
December 2020

TPL2 enforces RAS-induced inflammatory signaling and is activated by point mutations.

J Clin Invest 2020 09;130(9):4771-4790

Division of Oncology, Department of Internal Medicine, and.

NF-κB transcription factors, driven by the IRAK/IKK cascade, confer treatment resistance in pancreatic ductal adenocarcinoma (PDAC), a cancer characterized by near-universal KRAS mutation. Through reverse-phase protein array and RNA sequencing we discovered that IRAK4 also contributes substantially to MAPK activation in KRAS-mutant PDAC. IRAK4 ablation completely blocked RAS-induced transformation of human and murine cells. Mechanistically, expression of mutant KRAS stimulated an inflammatory, autocrine IL-1β signaling loop that activated IRAK4 and the MAPK pathway. Downstream of IRAK4, we uncovered TPL2 (also known as MAP3K8 or COT) as the essential kinase that propels both MAPK and NF-κB cascades. Inhibition of TPL2 blocked both MAPK and NF-κB signaling, and suppressed KRAS-mutant cell growth. To counter chemotherapy-induced genotoxic stress, PDAC cells upregulated TLR9, which activated prosurvival IRAK4/TPL2 signaling. Accordingly, a TPL2 inhibitor synergized with chemotherapy to curb PDAC growth in vivo. Finally, from TCGA we characterized 2 MAP3K8 point mutations that hyperactivate MAPK and NF-κB cascades by impeding TPL2 protein degradation. Cancer cell lines naturally harboring these MAP3K8 mutations are strikingly sensitive to TPL2 inhibition, underscoring the need to identify these potentially targetable mutations in patients. Overall, our study establishes TPL2 as a promising therapeutic target in RAS- and MAP3K8-mutant cancers and strongly prompts development of TPL2 inhibitors for preclinical and clinical studies.
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http://dx.doi.org/10.1172/JCI137660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456254PMC
September 2020

Morphologic Variants of Pancreatic Neuroendocrine Tumors: Clinicopathologic Analysis and Prognostic Stratification.

Endocr Pathol 2020 Sep;31(3):239-253

Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Davutpaşa Caddesi No: 4, Topkapı, 34010, Istanbul, Turkey.

Better prognostication/stratification of pancreatic neuroendocrine tumors (PanNETs) is needed. In this detailed morpheomic study of 163 resected PanNETs, 11 unusual variants, some of which were not previously recognized, and others scarcely documented in the literature, were identified, and their pathologic characteristics were further analyzed. By behavior and clinicopathologic associations, these variants could be grouped into three prognostically different categories. I. More aggressive (20%). Included in this group were the variants that in average showed higher grade and stage and adverse outcome including oncocytic, plasmacytoid, lipid-rich and previously unrecognized hepatoid variants, which often had a more diffuse/broad-band growth pattern, with some also displaying discohesiveness. They were characterized by abundant cytoplasm and often had prominent nucleoli (as seen in metabolically active cells), thus the provisional name "metabolic cell phenotype." Because of their diversion from classical neuroendocrine cytomorphology, these variants created challenges on original diagnostic workup, particularly hepatoid examples, which revealed Arginase 1/Hep Par-1 expression in 50%. II. Less aggressive (10%). These cases either showed signs of maturation, including nested growth, paraganglioid pattern (which was previously unrecognized), and organoid PanNETs such as "ductulo-insular" growth, or showed symplastic/degenerative changes, and despite their paradoxically disconcerting histology, were more benevolent in behavior. III. Undetermined. There were other variants including mammary tubulolobular-like, pseudoglandular, peliotic, and sclerotic PanNETs, which although diagnostically challenging, their biologic significance could not be determined because of rarity or heterogeneous characteristics. Prognostic associations: Features that were significantly different in the more aggressive group than the less aggressive group were median size (5.0 vs 1.6 cm, p < 0.001), percentage of pT3+T4 cases (72% vs 12%, p < 0.001), Ki67 index (5.3% vs 2.3%, p = 0.001), % G2 and G3 cases (77% vs 27%, p < 0.001), and rate of lymph node and distant metastasis (96% vs 27%, p < 0.001). In stepwise logistic regression model using the 3 established prognosticators of T stage, size, and grade along with morphology, only aggressive-morphology (metabolic cell phenotype) was found to be associated with metastatic behavior with an odds ratio of 5.9 with 95% confidence interval (C.I.) 1.688 to 22.945 and p value 0.007. In conclusion, PanNETs display various morphologic patterns that are not only challenging and important diagnostically but appear to have biologic significance. Tumors with more diffuse growth of cells with nucleoli and abundant cytoplasm and/or discohesion (oncocytic, hepatoid, lipid-rich, plasmacytoid PanNETs), provisionally termed "metabolic cell phenotype," show aggressive characteristics and are an independent determinant of adverse outcome and thus may require closer post-surgical follow-up, whereas variants with more degenerative or mature features (ductuloinsular, pleomorphic, paraganglioma-like) appear to be more benevolent despite their more atypical and worrisome morphology.
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http://dx.doi.org/10.1007/s12022-020-09628-zDOI Listing
September 2020

A novel normalization and differential abundance test framework for microbiome data.

Bioinformatics 2020 07;36(13):3959-3965

Department of Statistics, Northwestern University, Evanston, IL 60208, USA.

Motivation: Microbial communities have been proved to have close relationship with many diseases. The identification of differentially abundant microbial species is clinically meaningful for finding disease-related pathogenic or probiotic bacteria. However, certain characteristics of microbiome data have hurdled the accuracy and effectiveness of differential abundance analysis. The abundances or counts of microbiome species are usually on different scales and exhibit zero-inflation and over-dispersion. Normalization is a crucial step before the differential abundance test. However, existing normalization methods typically try to adjust counts on different scales to a common scale by constructing size factors with the assumption that count distributions across samples are equivalent up to a certain percentile. These methods often yield undesirable results when differentially abundant species are of low to medium abundance level. For differential abundance analysis, existing methods often use a single distribution to model the dispersion of species which lacks flexibility to catch a single species' distinctiveness. These methods tend to detect a lot of false positives and often lack of power when the effect size is small.

Results: We develop a novel framework for differential abundance analysis on sparse high-dimensional marker gene microbiome data. Our methodology relies on a novel network-based normalization technique and a two-stage zero-inflated mixture count regression model (RioNorm2). Our normalization method aims to find a group of relatively invariant microbiome species across samples and conditions in order to construct the size factor. Another contribution of the paper is that our testing approach can take under-sampling and over-dispersion into consideration by separating microbiome species into two groups and model them separately. Through comprehensive simulation studies, the performance of our method is consistently powerful and robust across different settings with different sample size, library size and effect size. We also demonstrate the effectiveness of our novel framework using a published dataset of metastatic melanoma and find biological insights from the results.

Availability And Implementation: The R package 'RioNorm2' can be installed from Github athttps://github.com/yuanjing-ma/RioNorm2.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332570PMC
July 2020

An Information-Based Approach for Mediation Analysis on High-Dimensional Metagenomic Data.

Front Genet 2020 13;11:148. Epub 2020 Mar 13.

Interdiciplanary Program in Statistics and Data Science, The University of Arizona, Tucson, AZ, United States.

The human microbiome plays a critical role in the development of gut-related illnesses such as inflammatory bowel disease and clinical pouchitis. A mediation model can be used to describe the interaction between host gene expression, the gut microbiome, and clinical/health situation (e.g., diseased or not, inflammation level) and may provide insights into underlying disease mechanisms. Current mediation regression methodology cannot adequately model high-dimensional exposures and mediators or mixed data types. Additionally, regression based mediation models require some assumptions for the model parameters, and the relationships are usually assumed to be linear and additive. With the microbiome being the mediators, these assumptions are violated. We propose two novel nonparametric procedures utilizing information theory to detect significant mediation effects with high-dimensional exposures and mediators and varying data types while avoiding standard regression assumptions. Compared with available methods through comprehensive simulation studies, the proposed method shows higher power and lower error. The innovative method is applied to clinical pouchitis data as well and interesting results are obtained.
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http://dx.doi.org/10.3389/fgene.2020.00148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083016PMC
March 2020

Precision medicine: Subgroup identification in longitudinal trajectories.

Stat Methods Med Res 2020 09 19;29(9):2603-2616. Epub 2020 Feb 19.

Department of statistics, Northwestern University, Evanston, IL, United States.

In clinical studies, the treatment effect may be heterogeneous among patients. It is of interest to identify subpopulations which benefit most from the treatment, regardless of the treatment's overall performance. In this study, we are interested in subgroup identification in longitudinal studies when nonlinear trajectory patterns are present. Under such a situation, evaluation of the treatment effect entails comparing longitudinal trajectories while subgroup identification requires a further evaluation of differential treatment effects among subgroups induced by moderators. To this end, we propose a tree-structured subgroup identification method, termed "interaction tree for longitudinal trajectories", which combines mixed effects models with regression splines to model the nonlinear progression patterns among repeated measures. Extensive simulation studies are conducted to evaluate its performance and an application to an alcohol addiction pharmacogenetic trial is presented.
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http://dx.doi.org/10.1177/0962280220904114DOI Listing
September 2020

Uterine compression suture is an effective mode of treatment of postpartum haemorrhage.

Pak J Med Sci 2020 Jan-Feb;36(2):131-135

Jing Liang, Binzhou People's Hospital, Shandong, 256600, China.

Objective: To compare the effects of uterine compression suture versus conventional mode of treatment for the management of postpartum haemorrhage after caesarean section.

Methods: This study enrolled 84 women with postpartum hemorrhage who were admitted to Binzhou People's Hospital from August 2017 to October 2018 as the research subjects. They were divided into a control group and an observation group according to random number table method, 42 each group. The patients in the control group were treated by conventional treatment, while those in the observation group were treated by uterine compression suture. The hemorrhage, hemostasis, postoperative recovery and frequency of adverse reactions were compared between the two groups.

Results: The amount of bleeding in the observation group was less than that in the control group, and the bleeding time was shorter than that in the control group; the differences had statistical significance (P<0.05). The success rate of hemostasis in the observation group was significantly higher than that in the control group, and the ineffective rate of hemostasis was significantly lower than that in the control group (P<0.05); the differences were statistically significant. The cleaning time of lochia, the recovery time of uterus and the recovery time of menstruation in the observation group were significantly shorter than that in the control group (P<0.05); the differences between the two groups were statistically significant (P<0.05). The frequency of adverse reactions in the observation group was significantly lower than that in the control group (P<0.05), and the difference was statistically significant (P<0.05).

Conclusion: Uterine compression suture is effective for postpartum hemorrhage of cesarean section, which can effectively reduce postpartum hemorrhage, shorten postpartum hemorrhage time and accelerate the recovery. It is safe and worth clinical promotion.
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http://dx.doi.org/10.12669/pjms.36.2.1072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994861PMC
February 2020

Facile one-pot solvothermal synthesis of magnetic mesoporous carbon for the efficient adsorption of methyl orange.

Environ Sci Pollut Res Int 2020 Mar 3;27(8):8248-8259. Epub 2020 Jan 3.

College of Science, Nanjing Agricultural University, Weigang Street 1#, Nanjing, 210095, China.

A facile one-pot solvent thermal method was proposed to synthesize magnetic mesoporous carbon (MMC) using Fe(NO)·9HO as a precursor, Pluronic copolymer P123 as template, and chitosan as carbon source, and it was applied for the adsorptive remediation of methyl orange (MO). The characterization results of TEM, XRD, and IR showed that MMC consisted of graphitized carbon matrix and some black spherical particle mixture of FeO and Fe, and it was rich in hydroxyl and carbonyl groups. Besides, the effect of the content of Fe and the content of chitosan in MMC on the magnetism and adsorption performance of prepared material were investigated. In addition, the effects of pH value, initial concentration of methyl orange, and contact time on the adsorption performance of MO were studied, respectively. At 318 K, the maximum adsorption capacity of MO calculated from Langmuir isotherm was from 139 to 400 mg g on MMC. Kinetic studies demonstrated that the adsorption process obeyed a pseudo-second-order kinetic model. The regeneration experiments revealed that MMC could be reused at least five times without notable decrease of adsorption performance. These results illustrate that MMC is an efficient and economical adsorbent for the adsorption of MO.
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http://dx.doi.org/10.1007/s11356-019-07492-xDOI Listing
March 2020

[Optimization of tolerogenic dendritic cell preparation technique in rats with collagen-induced arthritis].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Dec;35(12):1076-1081

Department of Microbial Immunology, Medical Laboratory, Guizhou Medical University, Guiyang 550025, China. *Corresponding author, E-mail:

Objective To yield high-quality tolerogenic dendritic cells (TolDCs) for therapeutic intervention by a refined technique of TolDC preparation from the spleen of modified collagen-induced arthritis (CIA) rats. Methods The refinements took place amid monocellular cell isolation process, including both the preparation of single cell suspension and the adjustment of incubation time after plate seeding of mononuclear cells. TolDCs were induced by administration of NF-κB oligonucleotide (ODN) decoy at the initiation of cell culture. Cell morphology was examined under a microscope and cell viability was revealed by trypan blue staining. Expression of classical cell identity and activation makers, CD103 (OX62), CD80 and CD86 was determined by flow cytometry; meanwhile, DC-stimulated lymphocyte proliferation was measured by MTT assay following mixed lymphocyte reaction (MLR). Results With the established approach, the viability ratio of resulting cells reached over 90% and the proportion of OX62 positive ones was above 87.4%, which altogether confirmed their ideal DC phenotype. Functionally, the tolerogenic nature of the NF-κB ODN-treated DCs was further unveiled by the low expression of costimulatory molecules (CD80 and CD86) and the abrogated capacity of lymphocyte stimulation effect. Conclusion Compared with TolDCs generated by conventional protocol, CIA rat spleen-derived TolDCs isolated by the optimized splenic mononuclear cell preparation procedure and induced by NF-κB ODN decoy show the higher regulatory activity, higher phenotypic stability, higher purity and tolerogenic properties.
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December 2019

Retinoid X receptor α (RXRα)-mediated erythroid-2-related factor-2 (NRF2) inactivation contributes to N,N-dimethylformamide (DMF)-induced oxidative stress in HL-7702 and HuH6 cells.

J Appl Toxicol 2020 04 25;40(4):470-482. Epub 2019 Dec 25.

Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.

N,N-dimethylformamide (DMF) is a colorless industrial solvent that is frequently used for chemical reactions. Epidemiologic studies and clinical case reports have consistently indicated that the main toxic effect after exposure to DMF is hepatotoxicity. Previous studies have suggested that oxidative stress is the pivotal molecular event of DMF-mediated hepatotoxicity; however, its underlying mechanism remains unclear. In this study, we found that DMF (0-150 mM) exposure induced an increase in reactive oxygen species (ROS) levels and inhibited the transcriptional activity of nuclear factor erythroid-2-related factor-2 (NRF2) in a dose-dependent manner. Subsequently, our research revealed that the elevated ROS levels and the decline in NRF2-mediated anti-oxidative response in HL-7702 and HuH6 cells might be due to the DMF-induced accumulation of retinoid X receptor α (RXRα) protein. Further investigation demonstrated that phosphorylation of the RXRα protein, which is mediated by the activation of extracellular signal-regulated kinase (ERK), leads to the inhibition of RXRα protein degradation and in turn the accumulation of RXRα after DMF exposure. These findings provide information that improves our understanding of the role of RXRα in DMF-induced hepatotoxicity.
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http://dx.doi.org/10.1002/jat.3919DOI Listing
April 2020

Ultrasound accelerated synthesis of O-alkylated hydroximides under solvent- and metal-free conditions.

Org Biomol Chem 2019 12 28;17(48):10223-10227. Epub 2019 Nov 28.

College of Science, Hunan Agricultural University, Changsha 410128, People's Republic of China.

A novel, sustainable, environmentally friendly, high substrate scope, efficient, solvent-free and metal catalyst-free method for the cross-dehydrogenative coupling (CDC) reaction between N-hydroxyphthalimide (NHPI) and benzyl/ether compounds is described. This coupling reaction proceeds through ultrasound acceleration. Compared to conventional heating conditions, the use of ultrasound techniques not only improves the reaction efficiency and enhances the reaction rate but also minimizes the side reactions.
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http://dx.doi.org/10.1039/c9ob02245gDOI Listing
December 2019

IRW and IQW Reduce Colitis-Associated Cancer Risk by Alleviating DSS-Induced Colonic Inflammation.

Biomed Res Int 2019 24;2019:6429845. Epub 2019 Oct 24.

College of Bioscience and Biotechnology, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, China.

Background And Objective: Bioactive peptides exert great influence in animals and human health by targeting gastrointestinal tracts. The colitis model of mice was induced by dextran sulfate sodium (DSS). Thirty-two 8-week-old mice weighing 23 g on average were randomly assigned to four groups of 8 each: mice fed basal diet (CON), mice fed basal diet with 5% DSS (DSS), mice fed 0.03% IRW with 5% DSS (IRW-DSS), and mice fed 0.03% IRW with 5% DSS (IQW-DSS). After an adaptation period of 3 days, on day 8, all mice were slaughtered. Serum samples were collected to determine the level of amino acids; colonic tissue was quick-frozen for the determination of gene expression.

Methods: The aim of this study was to assess the ability of two kinds of peptides (IRW and IQW) to repair intestinal inflammatory in the DSS-induced model in accordance with serum amino acids and intestinal inflammatory factors.

Results: The results demonstrated that the addition of IRW and IQW had a mitigating effect on DSS-induced intestinal inflammation. The level of Asp decreased in the serum of mice supplemented with IRW-DSS ( < 0.05), and IQW enhanced the level of Leu, but lowered the level of Ser ( < 0.05). IQW and IRW addition reduced the level of TNF- and IL-17 ( < 0.05). No other significant effects were observed.

Conclusions: The present study demonstrated that intracolic administration of IRW and IQW might be a novel option for preventing inflammatory bowel disease via regulating the level of serum amino acid and enhancing the intestinal immune defense.
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http://dx.doi.org/10.1155/2019/6429845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854911PMC
April 2020
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